new cancer research 2022

Our top 5 cancer research breakthroughs of 2022

15th December 2022

2022 has likely been your first full year back to ‘normal’ since the COVID-19 pandemic, and that’s no different for cancer researchers. Back into full swing in the lab, Worldwide Cancer Research scientists have been busy making exciting new discoveries about cancer. Here are the top five cancer research breakthroughs made by our scientists in 2022.

1. Stopping the spread of breast cancer

Our scientists in Italy discovered a previously unknown way that breast cancer cells survive treatment . They found that breast cancer cells hiding in places like the lungs seem to rely on specific antioxidants to survive there. This could be a new way to wipe out breast cancer cells that have escaped treatment.

Click here to read more about this incredible discovery, or find out what other ground-breaking work we're funding .

Our hope is that these findings can be translated into a real drug treatment that can kill “sleeping” cancer cells before they awake into full-blown metastases.

2. Stool samples can reveal pancreatic cancer sooner

Our researchers in Spain, led by Dr Núria Malats, have found a new way to spot if someone is at higher risk of pancreatic cancer, and even diagnose patients at an early stage of the disease . Specific microorganisms in a stool sample could signal that there is a problem in a rapid, non-invasive, and affordable way.

Read the full story here , or find out what else our scientists have discovered about pancreatic cancer this year.

This new breakthrough builds on the growing evidence that the microbiome is linked to the development of cancer. Early detection and diagnosis are just as important an approach to starting new cancer cures as developing treatments.

Become a Curestarter today and join us in supporting pioneering cancer research breakthroughs like these in 2023.

3. targeting cancer’s energy supply.

Our scientists in Germany discovered they could prevent head and neck cancer spreading by stopping it getting the extra energy it needs to do so. If they prevented a change happening in the RNA of mitochondria (the powerhouse of the cell), the cancer didn’t spread as much.

Click here to learn more about this breakthrough, or learn how your donations are used to start cancer cures .

The funding from Worldwide Cancer Research helped us to get a step closer to succeeding in fighting cancer metastasis, the leading cause of cancer death.

4. Making radiotherapy work for more patients

Our researchers in Spain made a breakthrough that could help treat people with cancer that has spread to the brain . In the future, a blood test could reveal if patients will respond to radiotherapy or if the cancer will resist it, then a drug called a RAGE inhibitor could make radiotherapy work better for those that would resist it.

Learn more about this important discovery , or read Anne and Cathrin's personal story.

We are very excited about the findings of this study and specifically the drug we have found. We really hope that what we have discovered will lead to a new way to personalise the use of radiotherapy that maximises the benefits for each patient.

5. Engineering immune cells to hunt down cancer

Our researchers in Italy have made a breakthrough that could lead to better, more effective immunotherapy options for cancer patients . They discovered how to engineer a specific type of immune cell to target and kill cancer cells, then boost its cancer-killing ability using a drug delivered with nanotechnology.

Find out the full story , or see how we've contributed to the discovery of new immunotherapies .

We hope we have laid the foundations for an innovative approach of adoptive cell therapy of cancer, hopefully more efficient than the current ones.

Breakthroughs of the future: 2023!

And finally, we were delighted to commit to funding £5.3 million to 25 new research projects that will start in 2023! It is incredibly important to continue supporting ground-breaking discovery cancer research if we hope to end the suffering caused by cancer.

Breakthroughs like these are vital if we hope to end the suffering caused by cancer. Unfortunately, funding for discovery research has dropped by ~25% in recent years.

Become a Curestarter today and you can help start new cancer cures.

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Explore  CRI’s 2023 Cancer Research Impact

Cancer Research Institute Media Room

Cellular Cancer Immunotherapy Development Evolves, Expands with New Technologies and Targets

Latest analysis from the Cancer Research Institute of the global landscape of cellular immunotherapies, including R&D trends and real-world usage, highlights key challenges including effective solid tumor targeting, manufacturing complexities, and commercial access to approved therapies

The Cancer Research Institute (CRI), a nonprofit organization dedicated to the discovery and development of powerful immunotherapies for all types of cancer, announced today the publication of its newest analysis of the global landscape of cellular immunotherapies, including R&D trends and real-world usage data. The report, published today in Nature Reviews Drug Discovery , highlights trends in cellular immunotherapy for cancer including top modalities, targets, clinical development, and data from patients receiving CAR-T therapies in clinical practice. This report is an update to CRI’s prior cellular immunotherapy landscape analysis published in July 2021.

In this analysis, author Samik Upadhaya, PhD, assistant director of scientific affairs and member of the Anna-Maria Kellen Clinical Accelerator team at CRI, and colleagues provide an update on the overall status of the cellular cancer immunotherapy landscape as well as observations on key changes within the field including clinical practice. Findings include:

• As of April 15, 2022, there were 2,756 active cell therapy agents in the global immuno-oncology pipeline, an increase of 36% over the 2021 landscape analysis that identified 2,031 such agents, but also a modest deceleration compared to 43% growth in the prior year
• CAR-T therapeutics continue to dominate the cell therapy pipeline with growth of 24% since 2021
• Development continues for non-T cell therapies including NK cell, dendritic cell, stem cell, and other myeloid-derived cell therapies, with the greatest growth in NK cell therapy, up 55% over the prior year
• Clinical usage of cell therapy for cancer treatment is not keeping pace with regulatory approvals, with clinicians citing cost, travel, and supply limitations as key barriers to patient access

This latest report from the Cancer Research Institute, titled, “Landscape of cancer cell therapies: trends and real-world data,” was generated in collaboration with IQVIA, a leading global provider of advanced analytics, technology solutions, and clinical research services to the life sciences industry, which provided the authors with access to IQVIA’s proprietary clinical trials database. The report is part of a suite of CRI-owned immuno-oncology landscape analyses that includes reports on cell therapy drug development and the broader IO landscape including clinical development of checkpoint inhibitors, cancer vaccines, and oncolytic viruses in addition to bispecific antibodies and other immunomodulators.

To access an interactive dashboard of the Cancer Research Institute’s cancer cell immunotherapy report, visit the CRI website at cancerresearch.org/cell-therapy .

About the Cancer Research Institute The Cancer Research Institute (CRI), established in 1953, is a highly rated U.S. nonprofit organization dedicated exclusively to saving more lives by fueling the discovery and development of powerful immunotherapies for all cancers. Guided by a world-renowned Scientific Advisory Council that includes four Nobel laureates and 27 members of the National Academy of Sciences, CRI has invested $474 million in support of research conducted by immunologists and tumor immunologists at the world’s leading medical centers and universities and has contributed to many of the key scientific advances that demonstrate the potential for immunotherapy to change the face of cancer treatment. To learn more, go to cancerresearch.org .

About the Anna-Maria Kellen Clinical Accelerator CRI’s clinical program, the Anna-Maria Kellen Clinical Accelerator is a unique academic-nonprofit-industry collaboration model that serves an as “incubator” that delivers multicenter clinical trials of promising new immunotherapy combinations. CRI’s venture philanthropy fund supports clinical trials within the program, which fosters a collaborative environment that enables scientists to advance their most ambitious research ideas by accelerating studies that one group or company could not do alone. To learn more, go to cancerresearch.org/clinical-accelerator .

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This experimental drug could change the field of cancer research

Sacha Pfeiffer

Jonaki Mehta

The new treatment is categorized as immunotherapy. skaman306/Getty Images hide caption

The new treatment is categorized as immunotherapy.

A tiny group of people with rectal cancer just experienced something of a scientific miracle: their cancer simply vanished after an experimental treatment.

In a very small trial done by doctors at New York's Memorial Sloan Kettering Cancer Center, patients took a drug called dostarlimab for six months. The trial resulted in every single one of their tumors disappearing. The trial group included just 18 people, and there's still more to be learned about how the treatment worked. But some scientists say these kinds of results have never been seen in the history of cancer research.

Dr. Hanna Sanoff of the University of North Carolina's Lineberger Comprehensive Cancer Center joined NPR's All Things Considered to outline how this drug works and what it could mean for the future of cancer research. Although she was not involved with the study, Dr. Sanoff has written about the results.

This interview has been lightly edited

On her first reaction to the results: I mean, I am incredibly optimistic. Like you said in the introduction, we have never seen anything work in 100 percent of people in cancer medicine.

On how the drug works to treat cancer: This drug is one of a class of drugs called immune checkpoint inhibitors. These are immunotherapy medicines that work not by directly attacking the cancer itself, but actually getting a person's immune system to essentially do the work. These are drugs that have been around in melanoma and other cancers for quite a while, but really have not been part of the routine care of colorectal cancers until fairly recently.

On the kinds of side effects patients experienced: Very, very few in this study - in fact, surprisingly few. Most people had no severe adverse effects at all.

On how this study could be seen as 'practice-changing': Our hope would be that for this subgroup of people - which is only about five percent to 10 percent of people who have rectal cancer - if they can go on and just get six months of immunotherapy and not have any of the rest of this - I don't even know the word to use. Paradigm shift is often used, but this really absolutely is paradigm-shifting.

On why the idea of being able to skip surgery for cancer treatment is so revolutionary: In rectal cancer, this is part of the conversation we have with someone when they're diagnosed. We are very hopeful for being able to cure you, but unfortunately, we know our treatments are going to leave you with consequences that may, in fact, be life-changing. I have had patients who, after their rectal cancer, have barely left the house for years - and in a couple of cases, even decades - because of the consequences of incontinence and the shame that's associated with this.

On next steps for the drug: What I'd really like us to do is get a bigger trial where this drug is used in a much more diverse setting to understand what the real, true response rate is going to be. It's not going to end up being 100 percent. I hope I bite my tongue on that in the future, but I can't imagine it will be 100 percent. And so when we see what the true response rate is, that's when I think we can really do this all the time.

This piece was reported by Sacha Pfeiffer, produced by Jonaki Mehta and edited by Kathryn Fox. It was adapted for the web by Manuela Lopez Restrepo.

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New Research and Treatment Advances From Yale Cancer Center to be Presented at the World’s Largest Cancer Research Conference

2024 asco annual meeting.

Nearly 50 presentations by researchers and clinicians from Yale Cancer Center (YCC) at Yale School of Medicine will be among the more than 5,000 abstracts available during the annual meeting of the American Society of Clinical Oncology (ASCO) May 31 to June 4 in Chicago, Ill.

This year's meeting, themed “The Art and Science of Cancer Care: From Comfort to Cure” will include over 200 sessions. The 48 YCC presentations will include phase II trial results for a cancer vaccine in combination with an immunotherapy drug, a new tool to predict the risk of recurrence of hormone receptor-positive, HER2-negative breast cancer, and the factors affecting sexual function of young women with breast cancer.

YCC experts will deliver 10 oral presentations and 38 poster presentations. They include:

Poster Session

A randomized phase 2 trial of the IO102-IO103 (IDO and PD-L1) cancer vaccine plus pembrolizumab as neoadjuvant/adjuvant treatment of patients with solid tumors

June 1; 9:00AM CDT

Presenter and Senior Author: Barbara Burtness, MD

Safety and time to response of [177Lu]Lu-DOTATATE in patients with newly diagnosed advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors: Sub-analysis of the phase 3 randomized NETTER-2 study

June 1; 1:30PM CDT

Presenter: Pamela Kunz, MD

Oral Abstract

A phase 1 dose expansion study of a first-in-class KAT6 inhibitor (PF-07248144) in patients with advanced or metastatic ER+ HER2− breast cancer

June 1; 4:24PM CDT

Presenter: Pat LoRusso, DO

ARC-9: A randomized study to evaluate etrumadenant based treatment combinations in previously treated metastatic colorectal cancer (mCRC)

June 2; 10:24AM CDT

Presenter and Senior Author: Michael Cecchini, MD

ARV-766, a proteolysis targeting chimera (PROTAC) androgen receptor (AR) degrader, in metastatic castration-resistant prostate cancer (mCRPC): Initial results of a phase 1/2 study

June 3; 1:27PM CDT

Presenter: Daniel Petrylak, MD

Factors associated with sexual function and sexual satisfaction in young women with breast cancer

June 3; 1:30PM CDT

Presenter: Ana Ferrigno Guajardo, MD

Updated results from COAST, a phase 2 study of durvalumab (D) ± oleclumab (O) or monalizumab (M) in patients (pts) with stage III unresectable non-small cell lung cancer (uNSCLC)

Presenter and Senior Author: Roy Herbst, MD, PhD

Development and validation of RSClin N+ tool for hormone receptor-positive (HR+), HER2-negative (HER2-), node-positive breast cancer

June 3; 5:24PM CDT

Presenter: Lajos Pusztai, MD

Click here to see the full list of YCC presentations.

Yale Cancer Center combines a tradition of innovative cancer treatment and quality care for our patients. A National Cancer Institute (NCI) designated comprehensive cancer center since 1974, Yale Cancer Center is one of only 56 such centers in the nation and the only one in Connecticut. Yale Cancer Center members include national and internationally renowned scientists and physicians at Yale School of Medicine and Smilow Cancer Hospital. This partnership enables the Center to provide the best approaches for prevention, detection, diagnosis, and treatment for cancer. 

Media Contact:

Michael Masciadrelli [email protected]

Featured in this article

• Patricia LoRusso, DO Amy and Joseph Perella Professor of Medicine (Medical Oncology); Chief, Experimental Therapeutics; Associate Cancer Center Director, Experimental Therapeutics
• Roy S. Herbst, MD, PhD Ensign Professor of Medicine (Medical Oncology) and Professor of Pharmacology; Deputy Director, Yale Cancer Center; Chief of Medical Oncology, Yale Cancer Center and Smilow Cancer Hospital; Assistant Dean for Translational Research, Yale School of Medicine; Director, Center for Thoracic Cancers, Yale Cancer Center and Smilow Cancer Hospital; Program Director, Master of Health Science - Clinical Investigation Track (MHS-CI)
• Barbara Burtness, MD Anthony N. Brady Professor of Medicine (Medical Oncology); Chief Translational Research Officer, Yale Cancer Center; Chief, Head and Neck Cancers/Sarcoma; Co-Leader, Developmental Therapeutics, Yale Cancer Center; Associate Cancer Center Director for Translational Research, Yale Cancer Center
• Daniel P. Petrylak, MD Professor of Medicine (Medical Oncology) and of Urology; Chief, Genitourinary Oncology
• Michael Cecchini, MD Assistant Professor of Medicine (Medical Oncology); Co-Director, Colorectal Program in the Center for Gastrointestinal Cancers; Medical Oncology Section Lead for National Accreditation Program for Rectal Cancer, Internal Medicine
• Pamela L. Kunz, MD Associate Professor of Internal Medicine (Medical Oncology); Director, Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center; Chief, GI Medical Oncology
• Lajos Pusztai, MD, DPhil Professor of Medicine (Medical Oncology); Co-Leader, Genetics, Genomics and Epigenetics, Yale Cancer Center
• Ana Ferrigno Guajardo, MD Hospital Resident

Cancer News

Top headlines, latest headlines.

• New Tech: Tailoring Cancer Treatment
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Earlier Headlines

Tuesday, may 7, 2024.

• US Geographic Region Results in Vastly Different Anal Cancer Risk for People With HIV
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Monday, May 6, 2024

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• Expanding a Lymph Node, Boosting a Vaccine

Friday, May 3, 2024

• Newly Discovered Mechanism of T-Cell Control Can Interfere With Cancer Immunotherapies
• Pan-Cancer Analysis Uncovers a New Class of Promising CAR T--Cell Immunotherapy Targets
• New Immunosuppressive Mechanism Found in Brain Cancer

Thursday, May 2, 2024

• Scientists Track 'doubling' In Origin of Cancer Cells
• Gene Signatures from Tissue-Resident T Cells as a Predictive Tool for Melanoma Patients
• Cancer Patients Gain Important Benefits from Genome-Matched Treatments
• Medical School Scientist Creates Therapy to Kill Hypervirulent Bacteria

Wednesday, May 1, 2024

• Therapy to Kill Hypervirulent Bacteria Developed
• Research Breakthrough on Birth Defect Affecting Brain Size
• Unraveling the Roles of Non-Coding DNA Explains Childhood Cancer's Resistance to Chemotherapy
• Biomarkers in Blood to Predict Liver Cancer
• New mRNA Cancer Vaccine Triggers Fierce Immune Response to Fight Malignant Brain Tumor
• Clogged Arteries Worsened by Cells That Behave Like Cancer Cells
• One-Two Punch Treatment Delivers Blood Cancer Knockout

Tuesday, April 30, 2024

• Difference Found in Pancreatic Cancer Cells, Offering New Hope for Immunotherapy Effectiveness
• New and Improved Way to Grow the Cells That Give Rise to the Kidney's Filtration System
• Regulating Cholesterol Levels Might Be the Key to Improving Cancer Treatment
• Scientists Find Cancer-Like Features in Atherosclerosis, Spurring Opportunity for New Treatment Approaches

Monday, April 29, 2024

• Kaposi Sarcoma Discovery Could Facilitate Drug Development
• The Aspirin Conundrum: Navigating Negative Results, Age, Aging Dynamics and Equity
• Blood Samples Enhance B-Cell Lymphoma Diagnostics and Prognosis

Friday, April 26, 2024

• Breast Cancer Rates Rising Among Canadian Women in Their 20s, 30s and 40s
• Component of Keto Diet Plus Immunotherapy May Reduce Prostate Cancer

Thursday, April 25, 2024

• Vitamin D Alters Mouse Gut Bacteria to Give Better Cancer Immunity
• Physical Activity in Nature Helps Prevent Several Diseases, Including Depression and Type 2 Diabetes
• Circadian Rhythms Can Influence Drugs' Effectiveness

Wednesday, April 24, 2024

• Tumor Cells Evade the Immune System Early On: Newly Discovered Mechanism Could Significantly Improve Cancer Immunotherapies
• Mini-Colons Revolutionize Colorectal Cancer Research
• Artificial Intelligence Can Develop Treatments to Prevent 'superbugs'
• Scientists Identify and Show How to Target a Key Tumor Defense Against Immune Attack
• CAR T Cell Therapy Targeting HER2 Antigen Shows Promise Against Advanced Sarcoma in Phase I Trial
• Discovering Cancers of Epigenetic Origin Without DNA Mutation

Tuesday, April 23, 2024

• Researching Cancer by Studying Lipids Cell by Cell
• Genetics Predict Type 2 Diabetes Risk and Disparities in Childhood Cancer Survivors
• New Study Uncovers Lasting Financial Hardship Associated With Cancer Diagnosis for Working-Age Adults in the U.S.
• Liver Cancer: Molecular Signaling Pathway of Tumor Development Decoded

Monday, April 22, 2024

• Breakthrough Rice Bran Nanoparticles Show Promise as Affordable and Targeted Anticancer Agent
• Genetically Engineering a Treatment for Incurable Brain Tumors

Friday, April 19, 2024

• Researchers Develop a New Way to Safely Boost Immune Cells to Fight Cancer
• Study Opens New Avenue for Immunotherapy Drug Development

Thursday, April 18, 2024

• Mutations in Noncoding DNA Become Functional in Some Cancer-Driving Genes
• AI Tool Predicts Responses to Cancer Therapy Using Information from Each Cell of the Tumor
• Siblings With Unique Genetic Change Help Scientists Progress Drug Search for Type 1 Diabetes
• New Urine-Based Test Detects High-Grade Prostate Cancer, Helping Men Avoid Unnecessary Biopsies

Wednesday, April 17, 2024

• Researchers Uncover Human DNA Repair by Nuclear Metamorphosis

Tuesday, April 16, 2024

• Researchers Discover Urine-Based Test to Detect Head and Neck Cancer
• Nanoparticle Delivery of FZD4 to Lung Endothelial Cells Inhibits Lung Cancer Progression and Metastases
• New Insights Could Unlock Immunotherapy for Rare, Deadly Eye Cancer

Monday, April 15, 2024

• Next-Generation Treatments Hitch a Ride Into Cancer Cells
• Epilepsy Drug Prevents Brain Tumors in Mice With NF1
• New Study Sheds Light on the Mechanisms Underlying the Development of Malignant Pediatric Brain Tumors

Friday, April 12, 2024

• Melanomas Resist Drugs by 'breaking' Genes
• Scientists Uncover a Missing Link Between Poor Diet and Higher Cancer Risk

Thursday, April 11, 2024

• Researchers Identify New Genetic Risk Factors for Persistent HPV Infections
• Colorless, Odorless Gas Likely Linked to Alarming Rise in Non-Smoking Lung Cancer
• Scientists Uncover Key Resistance Mechanism to Wnt Inhibitors in Pancreatic and Colorectal Cancers
• Study Lays the Basis for New Knowledge on Gastrointestinal Diseases

Wednesday, April 10, 2024

• Researchers Identify Protein That Controls CAR T Cell Longevity
• New Insight Into Combating Drug-Resistant Prostate Cancer
• A Promising Target for New RNA Therapeutics Now Accessible
• A New Screening Protocol Can Detect Aggressive Prostate Cancers More Selectively
• AI-Assisted Breast-Cancer Screening May Reduce Unnecessary Testing

Tuesday, April 9, 2024

• Targeting RAS Proteins May Prevent Relapse in Acute Myeloid Leukemia
• Bacteria in Cancer Unmasked
• Periostin Shows Promise to Help Fight a Common Form of Esophageal Cancer
• Research Could Unlock More Precise Prognoses and Targeted Treatments for Children With Cancer
• Immune Key to Chronic Viral Infections Discovered

Monday, April 8, 2024

• The Surprising Connection Between Male Infertility and Family Cancer Risk
• Targeting Vulnerability in B-Cell Development Leads to Novel Drug Combination for Leukemia
• Opening a New Front Against Pancreatic Cancer

Thursday, April 4, 2024

• Less Extensive Breast Cancer Surgery Results in Fewer Swollen Arms
• Microbial Signature of Colorectal Cancer-Associated Mutations Identified in New Study
• Study Finds Less Invasive, Safer Option for Removing Benign Pancreatic Tumors

Tuesday, April 2, 2024

• Investigators Develop Novel Treatment for T-Cell Leukemias and Lymphomas

Monday, April 1, 2024

• New Antibiotic Class Effective Against Multidrug-Resistant Bacteria
• Exposure to Common Environmental Carcinogens Linked to Decreased Lifespan Happiness

Thursday, March 28, 2024

• Genomic Research May Help Explain Cancer Resistance in Tasmanian Devils
• Cell Division Quality Control 'stopwatch' Uncovered
• 'Exhausted' Immune Cells in Healthy Women Could Be Target for Breast Cancer Prevention

Wednesday, March 27, 2024

• A Combination of Approved Drugs Enhances the Delivery of Anti-Bacterial Medications to Treat Tuberculosis
• Combining Epigenetic Cancer Medications May Have Benefit for Colorectal Cancers and Other Tumor Types
• Researchers Turn Back the Clock on Cancer Cells to Offer New Treatment Paradigm
• New Technique for Predicting Protein Dynamics May Prove Big Breakthrough for Drug Discovery
• Researchers Create Biocompatible Nanoparticles to Enhance Systemic Delivery of Cancer Immunotherapy
• Researchers Discover a Mechanism That Could Improve Platinum-Based Cancer Therapy
• Accelerating CAR T Cell Therapy: Lipid Nanoparticles Speed Up Manufacturing
• Beating by Overheating: New Strategy to Combat Cancer

Tuesday, March 26, 2024

• Genetically Engineered Dendritic Cells Enhance the Power of Immunotherapy Against Lung Cancer

Monday, March 25, 2024

• Cancer Therapies Show Promise in Combating Tuberculosis
• Promising Drug Combination for Multiple Myeloma Treatment

Thursday, March 21, 2024

• An Immunotherapy to Overcome Resistant Leukemia

Wednesday, March 20, 2024

• Bacteria Subtype Linked to Growth in Up to 50% of Human Colorectal Cancers
• In the Fight Against Breast Cancer, Researchers Identify Malignancy Hibernation as the Next Battleground
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After years of lackluster results, cancer vaccines seem poised for success. Finally.

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This article first appeared in The Checkup,  MIT Technology Review’s  weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first,  sign up here .  

Last week, Moderna and Merck launched a large clinical trial in the UK of a promising new cancer therapy: a personalized vaccine that targets a specific set of mutations found in each individual’s tumor. This study is enrolling patients with melanoma. But the companies have also launched a phase III trial for lung cancer. And earlier this month BioNTech and Genentech announced that a personalized vaccine they developed in collaboration shows promise in pancreatic cancer, which has a notoriously poor survival rate.

Drug developers have been working for decades on vaccines to help the body’s immune system fight cancer, without much success. But promising results in the past year suggest that the strategy may be reaching a turning point. Will these therapies finally live up to their promise?

This week in The Checkup, let’s talk cancer vaccines. (And, you guessed it, mRNA.)

Long before companies leveraged mRNA to fight covid, they were developing mRNA vaccines to combat cancer. BioNTech delivered its first mRNA vaccines to people with treatment-resistant melanoma nearly a decade ago. But when the pandemic hit, development of mRNA vaccines jumped into warp drive. Now dozens of trials are underway to test whether these shots can transform cancer the way they did covid. 

Recent news has some experts cautiously optimistic. In December, Merck and Moderna announced results from an earlier trial that included 150 people with melanoma who had undergone surgery to have their cancer removed. Doctors administered nine doses of the vaccine over about six months, as well as  what’s known as an immune checkpoint inhibitor. After three years of follow-up, the combination had cut the risk of recurrence or death by almost half compared with the checkpoint inhibitor alone.

The new results reported by BioNTech and Genentech, from a small trial of 16 patients with pancreatic cancer, are equally exciting. After surgery to remove the cancer, the participants received immunotherapy, followed by the cancer vaccine and a standard chemotherapy regimen. Half of them responded to the vaccine, and three years after treatment, six of those people still had not had a recurrence of their cancer. The other two had relapsed. Of the eight participants who did not respond to the vaccine, seven had relapsed. Some of these patients might not have responded  because they lacked a spleen, which plays an important role in the immune system. The organ was removed as part of their cancer treatment. 

The hope is that the strategy will work in many different kinds of cancer. In addition to pancreatic cancer, BioNTech’s personalized vaccine is being tested in colorectal cancer, melanoma, and metastatic cancers.

The purpose of a cancer vaccine is to train the immune system to better recognize malignant cells, so it can destroy them. The immune system has the capacity to clear cancer cells if it can find them. But tumors are slippery. They can hide in plain sight and employ all sorts of tricks to evade our immune defenses. And cancer cells often look like the body’s own cells because, well, they are the body’s own cells.

There are differences between cancer cells and healthy cells, however. Cancer cells acquire mutations that help them grow and survive, and some of those mutations give rise to proteins that stud the surface of the cell—so-called neoantigens.

Personalized cancer vaccines like the ones Moderna and BioNTech are developing are tailored to each patient’s particular cancer. The researchers collect a piece of the patient’s tumor and a sample of healthy cells. They sequence these two samples and compare them in order to identify mutations that are specific to the tumor. Those mutations are then fed into an AI algorithm that selects those most likely to elicit an immune response. Together these neoantigens form a kind of police sketch of the tumor, a rough picture that helps the immune system recognize cancerous cells.  

“A lot of immunotherapies stimulate the immune response in a nonspecific way—that is, not directly against the cancer,” said Patrick Ott, director of the Center for Personal Cancer Vaccines at the Dana-Farber Cancer Institute, in a 2022 interview .  “Personalized cancer vaccines can direct the immune response to exactly where it needs to be.”

How many neoantigens do you need to create that sketch?  “We don’t really know what the magical number is,” says Michelle Brown, vice president of individualized neoantigen therapy at Moderna. Moderna’s vaccine has 34. “It comes down to what we could fit on the mRNA strand, and it gives us multiple shots to ensure that the immune system is stimulated in the right way,” she says. BioNTech is using 20.

The neoantigens are put on an mRNA strand and injected into the patient. From there, they are taken up by cells and translated into proteins, and those proteins are expressed on the cell’s surface, raising an immune response

mRNA isn’t the only way to teach the immune system to recognize neoantigens. Researchers are also delivering neoantigens as DNA, as peptides, or via immune cells or viral vectors. And many companies are working on “off the shelf” cancer vaccines that aren’t personalized, which would save time and expense. Out of about 400 ongoing clinical trials assessing cancer vaccines last fall, roughly 50 included personalized vaccines.

There’s no guarantee any of these strategies will pan out. Even if they do, success in one type of cancer doesn’t automatically mean success against all. Plenty of cancer therapies have shown enormous promise initially, only to fail when they’re moved into large clinical trials.

But the burst of renewed interest and activity around cancer vaccines is encouraging. And personalized vaccines might have a shot at succeeding where others have failed. The strategy makes sense for “a lot of different tumor types and a lot of different settings,” Brown says. “With this technology, we really have a lot of aspirations.”

Now read the rest of The Checkup

Read more from mit technology review’s archive.

mRNA vaccines transformed the pandemic. But they can do so much more. In this feature from 2023, Jessica Hamzelou covered the myriad other uses of these shots , including fighting cancer. 

This article from 2020 covers some of the background on BioNTech’s efforts to develop personalized cancer vaccines. Adam Piore had the story . 

Years before the pandemic, Emily Mullin wrote about early efforts to develop personalized cancer vaccines—the promise and the pitfalls. 

From around the web

Yes, there’s bird flu in the nation’s milk supply. About one in five samples had evidence of the H5N1 virus. But new testing by the FDA suggests that the virus is unable to replicate. Pasteurization works! ( NYT )

Studies in which volunteers are deliberately infected with covid—so-called challenge trials—have been floated as a way to test drugs and vaccines, and even to learn more about the virus. But it turns out it’s tougher to infect people than you might think. ( Nature )

When should women get their first mammogram to screen for breast cancer? It’s a matter of hot debate. In 2009, an expert panel raised the age from 40 to 50. This week they lowered it to 40 again in response to rising cancer rates among younger women. Women with an average risk of breast cancer should get screened every two years, the panel says. ( NYT )

Wastewater surveillance helped us track covid. Why not H5N1? A team of researchers from New York argues it might be our best tool for monitoring the spread of this virus. ( Stat )

Biotechnology and health

How scientists traced a mysterious covid case back to six toilets.

When wastewater surveillance turns into a hunt for a single infected individual, the ethics get tricky.

An AI-driven “factory of drugs” claims to have hit a big milestone

Insilico is part of a wave of companies betting on AI as the "next amazing revolution" in biology

• Antonio Regalado archive page

The quest to legitimize longevity medicine

Longevity clinics offer a mix of services that largely cater to the wealthy. Now there’s a push to establish their work as a credible medical field.

• Jessica Hamzelou archive page

There is a new most expensive drug in the world. Price tag: $4.25 million

But will the latest gene therapy suffer the curse of the costliest drug?

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New on NCI’s Websites for April 2024

April 12, 2024 , by Daryl McGrath

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Preventable Premature Deaths from the Five Leading Causes of Death in Nonmetropolitan and Metropolitan Counties, United States, 2010–2022

Surveillance Summaries / May 2, 2024 / 73(2);1–11

Macarena C. García, DrPH 1 ; Lauren M. Rossen, PhD 2 ; Kevin Matthews, PhD 3 ; Gery Guy, PhD 4 ; Katrina F. Trivers, PhD 5 ; Cheryll C. Thomas, MSPH 5 ; Linda Schieb, MSPH 5 ; Michael F. Iademarco, MD 1 ( View author affiliations )

Introduction

Limitations, future directions, acknowledgments.

• Article PDF
• Rural reinvestment: A path forward to addressing geographic health inequities

Problem/Condition: A 2019 report quantified the higher percentage of potentially excess (preventable) deaths in U.S. nonmetropolitan areas compared with metropolitan areas during 2010–2017. In that report, CDC compared national, regional, and state estimates of preventable premature deaths from the five leading causes of death in nonmetropolitan and metropolitan counties during 2010–2017. This report provides estimates of preventable premature deaths for additional years (2010–2022).

Period Covered: 2010–2022.

Description of System: Mortality data for U.S. residents from the National Vital Statistics System were used to calculate preventable premature deaths from the five leading causes of death among persons aged <80 years. CDC’s National Center for Health Statistics urban-rural classification scheme for counties was used to categorize the deaths according to the urban-rural county classification level of the decedent’s county of residence (1: large central metropolitan [most urban], 2: large fringe metropolitan, 3: medium metropolitan, 4: small metropolitan, 5: micropolitan, and 6: noncore [most rural]). Preventable premature deaths were defined as deaths among persons aged <80 years that exceeded the number expected if the death rates for each cause in all states were equivalent to those in the benchmark states (i.e., the three states with the lowest rates). Preventable premature deaths were calculated separately for the six urban-rural county categories nationally, the 10 U.S. Department of Health and Human Services public health regions, and the 50 states and the District of Columbia.

Results: During 2010–2022, the percentage of preventable premature deaths among persons aged <80 years in the United States increased for unintentional injury (e.g., unintentional poisoning including drug overdose, unintentional motor vehicle traffic crash, unintentional drowning, and unintentional fall) and stroke, decreased for cancer and chronic lower respiratory disease (CLRD), and remained stable for heart disease. The percentages of preventable premature deaths from the five leading causes of death were higher in rural counties in all years during 2010–2022. When assessed by the six urban-rural county classifications, percentages of preventable premature deaths in the most rural counties (noncore) were consistently higher than in the most urban counties (large central metropolitan and fringe metropolitan) for the five leading causes of death during the study period.

During 2010–2022, preventable premature deaths from heart disease increased most in noncore (+9.5%) and micropolitan counties (+9.1%) and decreased most in large central metropolitan counties (−10.2%). Preventable premature deaths from cancer decreased in all county categories, with the largest decreases in large central metropolitan and large fringe metropolitan counties (−100.0%; benchmark achieved in both county categories in 2019). In all county categories, preventable premature deaths from unintentional injury increased, with the largest increases occurring in large central metropolitan (+147.5%) and large fringe metropolitan (+97.5%) counties. Preventable premature deaths from CLRD decreased most in large central metropolitan counties where the benchmark was achieved in 2019 and increased slightly in noncore counties (+0.8%). In all county categories, preventable premature deaths from stroke decreased from 2010 to 2013, remained constant from 2013 to 2019, and then increased in 2020 at the start of the COVID-19 pandemic. Percentages of preventable premature deaths varied across states by urban-rural county classification during 2010–2022.

Interpretation: During 2010–2022, nonmetropolitan counties had higher percentages of preventable premature deaths from the five leading causes of death than did metropolitan counties nationwide, across public health regions, and in most states. The gap between the most rural and most urban counties for preventable premature deaths increased during 2010–2022 for four causes of death (cancer, heart disease, CLRD, and stroke) and decreased for unintentional injury. Urban and suburban counties (large central metropolitan, large fringe metropolitan, medium metropolitan, and small metropolitan) experienced increases in preventable premature deaths from unintentional injury during 2010–2022, leading to a narrower gap between the already high (approximately 69% in 2022) percentage of preventable premature deaths in noncore and micropolitan counties. Sharp increases in preventable premature deaths from unintentional injury, heart disease, and stroke were observed in 2020, whereas preventable premature deaths from CLRD and cancer continued to decline. CLRD deaths decreased during 2017–2020 but increased in 2022. An increase in the percentage of preventable premature deaths for multiple leading causes of death was observed in 2020 and was likely associated with COVID-19–related conditions that contributed to increased mortality from heart disease and stroke.

Public Health Action: Routine tracking of preventable premature deaths based on urban-rural county classification might enable public health departments to identify and monitor geographic disparities in health outcomes. These disparities might be related to different levels of access to health care, social determinants of health, and other risk factors. Identifying areas with a high prevalence of potentially preventable mortality might be informative for interventions.

Premature deaths, all-cause mortality, and poor health outcomes are greater among residents of rural counties than of urban counties in the United States ( 1 ). In 2021, the all-cause age-adjusted death rate in the United States was 841.6 per 100,000 population. The gap in all-cause mortality between rural (nonmetropolitan) and urban (metropolitan) areas of the United States continues to widen. In 1999, the death rate in rural areas was 7% higher than in urban areas; by 2019, it was 20% higher ( 2 ). Describing premature mortality rates from the five leading causes of death (cancer, unintentional injury [e.g., unintentional poisoning including drug overdose, unintentional motor vehicle traffic crash, unintentional drowning, and unintentional fall], heart disease, stroke, and chronic lower respiratory disease [CLRD]) and related rural disparities might help guide public health messaging and interventions.

The risk for premature death is associated with modifiable factors that vary by disease ( 3 ). Four of the five leading risk factors for premature death are more prevalent in rural areas of the United States: using tobacco, obesity, physical inactivity, and drinking alcohol or drinking in excess ( 4 , 5 ). Extensive literature on social determinants of health has established the importance of community context in shaping all aspects of health ( 6 ). Structural factors (e.g., lower socioeconomic status, limited access to health care professionals, and limited job opportunities) increase the risk for premature death among rural residents ( 7 ).

Multiple factors influence the rural-urban gap in preventable premature deaths. Because each of the five leading causes of death is age related, these conditions are more prevalent in rural areas of the United States where residents typically are older than their urban counterparts. Working-age adults might leave rural areas to seek better economic opportunities elsewhere ( 8 ), and older persons might be more likely to retire in rural areas ( 9 ). However, the population’s age structure alone does not explain the disparity in mortality. Instead, differences in social circumstances, socioeconomic characteristics, health-related behaviors, and access to health care services affect mortality and potentially contribute to approximately half of all preventable premature deaths ( 10 ). County-level disparities in all-cause premature deaths by rurality, race, and ethnicity have been documented ( 11 ). Data on cause-specific preventable premature deaths from the leading causes of death by rurality, sex, race, and ethnicity are limited, and direct comparisons accounted for by these factors will be reported in subsequent analyses.

Rural public health needs and sociodemographic characteristics of rural populations are changing ( 12 ). Although the proportion of the U.S. population that lives in rural areas is gradually declining, any rural population growth can be attributed to in-migration, which might require sensitivity to cultural differences ( 13 , 14 ). With gradual declines in population, the wealth and tax bases of rural counties also are decreasing, resulting in reduced funding for social and health services ( 15 ).

In this analysis, mortality data were used to estimate the number and percentage of deaths from each of the five leading causes of death that could have been prevented if all states had similarly low death rates. Disparities in premature mortality from the five leading causes of death in rural areas in the United States during 2010–2022 also were estimated. The results of this analysis are intended to serve as a critical resource for policymakers, public health officials, and researchers striving to understand and address the root causes of preventable premature deaths.

This analysis used mortality data for U.S. residents from the National Vital Statistics System ( https://www.cdc.gov/nchs/index.htm ) to calculate preventable premature deaths by urban-rural county classification from the five leading causes of death during 2010–2022 (heart disease, cancer, unintentional injury, CLRD, and stroke). Deaths from COVID-19 were excluded to maintain consistency and facilitate the assessment of trends over time. Data for 2022 are provisional counts from January through June and were annualized for comparability with previous years.

The number of preventable premature deaths for a specific cause (also described as potentially preventable premature or excess deaths) is equal to the difference in the number of observed deaths among persons aged <80 years and the number of deaths expected if the mortality rate in all states were equivalent to the average rate of the three states with the lowest mortality. Rates in the three states define the benchmarks. The benchmark for each cause of death is derived from a unique set of three states.

Rural and urban categories were identified using the National Center for Health Statistics 2013 urban-rural classification scheme for counties ( 16 ). County of residence of the decedent was used to determine urban-rural county classification. The categories are 1: large central metropolitan (most urban), 2: large fringe metropolitan, 3: medium metropolitan, 4: small metropolitan, 5: micropolitan, and 6: noncore (most rural).

Preventable premature deaths were calculated individually for the two nonmetropolitan categories (micropolitan and noncore) and the four metropolitan categories (large central metropolitan, large fringe metropolitan, medium metropolitan, and small metropolitan) as well as for the broader categories of metropolitan and nonmetropolitan. Analyses were restricted to deaths with an underlying cause of death from the five leading causes of death based on the International Classification of Diseases, 10th Revision (ICD-10): heart disease (I00–I09, I11, I13, and I20–I51), cancer (C00–C97), unintentional injury (V01–X59 and Y85–Y86), CLRD (J40–J47), and stroke (I60–I69). The analysis of preventable premature deaths during 2010–2022 was restricted to persons aged <80 years at the time of death. The age restriction is consistent with the average life expectancy for the U.S. population in 2010, which was approximately 79 years ( 17 ).

Age-specific mortality rates for each of the five leading causes of death were used to derive the number of preventable premature deaths using methods described elsewhere ( 18 ). Age groupings varied by cause of death. (Most were 10-year age groups; however, the size of the youngest age group ranged from 0 to 9 years for unintentional injury to 0 to 49 years for CLRD and cerebrovascular disease because deaths from those causes are rare among younger persons.) For each age group and cause of death, the death rates of the three states with the lowest rates during 2008–2010 (benchmark states) were averaged to produce benchmark rates ( 18 ) ( https://stacks.cdc.gov/view/cdc/42342 ). These benchmarks were chosen to represent the lowest death rates achievable by states at the beginning of the study period and did not vary by year to allow for the examination of trends over time. Although using time-varying benchmarks would better account for potential improvements over time in the benchmark rates, time-varying benchmarks also would make temporal and geographic comparisons more difficult. The same benchmarks were applied to both nonmetropolitan and metropolitan counties, and benchmarks were not adjusted for other characteristics that might affect death rates (e.g., race, ethnicity, socioeconomic status, and urbanicity). Deaths attributed to COVID-19 from 2020 through June 2022 were excluded from this study.

The numbers of preventable premature deaths for each cause of death were assumed to follow a Poisson distribution. SEs were calculated using standard formulas that incorporated the variance around both the observed and the expected counts ( 18 ), and pairwise z-tests were performed to determine whether the differences during 2010–2022 were statistically significant (p<0.05). All differences during 2010–2022 are statistically significant unless otherwise noted. The percentage of preventable premature deaths was calculated by dividing the number of preventable premature deaths by the total observed number of premature deaths.

The percentage of preventable premature deaths from cancer decreased from 2010 through June 2022 (from 21% to 0.3%) ( Figure 1 ). Regardless of urban-rural classification, all county categories experienced decreases ( Figure 2 ). However, the decreases in urban counties were larger than those in rural counties, which widened the rural-urban disparities in preventable premature deaths from cancer (Figure 2) ( Table ). The percentage of preventable premature deaths from cancer in noncore counties in 2022 (18.1%) was similar to the percentage in large central metropolitan counties in 2010 (17.9%).

The percentage of preventable premature deaths from heart disease decreased from 2010 through 2019 (from 33.5% to 28.8%), followed by a steep increase to 33.6% from 2020 through June 2022 (Figure 1). Increases from 2020 through June 2022 occurred across all rural-urban categories except for large central metropolitan counties, which experienced a decrease from 32.9% in 2020 to 30.1% in 2021 (Figure 2) (Table). Rural counties had the highest percentage of preventable premature deaths from heart disease in 2022 (45.8% in micropolitan counties and 49.4% in noncore counties) (Figure 2) (Table). Most states experienced an increase in preventable early deaths from heart disease and stroke (96% and 88% of states, respectively) from 2019 through June 2022 (Supplementary Table, https://stacks.cdc.gov/view/cdc/147842 ).

The percentage of preventable premature deaths from unintentional injury increased from 2010 to 2019 (from 38.8% to 53.8%), followed by a steep increase from 2019 to 2021 and a slight decrease through June 2022 to 63.5% (Figure 1). Increases in preventable premature deaths from unintentional injury during 2010–2022 were statistically significant for all metropolitan categories except micropolitan. Rural percentages were higher than in urban areas, but the gap narrowed (Figure 2). The percentages increased in all states except Wyoming, but the increase varied widely at the state level (Supplementary Table, https://stacks.cdc.gov/view/cdc/147842 ).

The percentage of preventable premature deaths from CLRD decreased from 2010 through 2022 (from 38.6% to 25.5%) (Figure 1). The percentage of preventable premature deaths varied widely when stratified by rural-urban county category, but all county categories except for noncore counties experienced decreases. Rural-urban disparities widened when large central metropolitan percentages decreased from 23.4% in 2010 to 0% in 2022, whereas the rural percentages hovered between 50.7% and 54.8% in 2022 (Figure 2) (Table).

The percentage of preventable premature deaths from stroke decreased slightly from 2010 through 2019 (32.4% to 26.4%), followed by an increase to 33.9% through June 2022 (Figure 1). Each rural-urban category experienced steep increases from 2019 to June 2022, except for noncore counties that experienced a slight decrease from 2021 to June 2022; rural counties had the highest percentages from January to June 2022 (42.0% in micropolitan counties and 40.9% in noncore counties) (Figure 2) (Table). The highest percentages of preventable premature deaths from stroke in 2022 were in southern states (Supplementary Table, https://stacks.cdc.gov/view/cdc/147842 ).

Rural residents, particularly those in noncore counties, experienced high percentages of preventable premature deaths during the study period. The rural-urban disparities in premature deaths varied by cause of death. However, disparities were not limited to place of residence. Disparities in all-cause premature deaths also were associated with other demographic factors (e.g., sex, race, and ethnicity) ( 11 ). For example, the highest rates of premature deaths were observed in rural counties where a majority of the population was Black, African American, American Indian, or Alaska Native ( 11 ). To address disparities in preventable premature deaths across rural and urban counties, data on disparities in cause-specific premature deaths from the five leading causes by rural-urban county category, race, and ethnicity are needed to inform interventions and health care policies for specific racial and ethnic groups. A follow-up of this analysis stratified by race and ethnicity will be published in subsequent reports, further contributing evidence to guide existing and new programs and policies.

Overall, the decrease in preventable premature deaths from cancer was substantial and was greatest in urban counties where access to preventive services, treatment, survivor care, and specialty care is much higher than in rural counties ( 19 ). Large central metropolitan and fringe metropolitan areas achieved the benchmark rates in 2019. This is consistent with overall declines in cancer mortality, which decreased 27% between 2001 and 2020 ( 20 ). The decrease in preventable premature deaths likely reflects multiple factors. Increases in recommended screening for the leading causes of deaths from cancer (e.g., lung, colon, cervical, and female breast) have led to earlier detection, when treatment is more effective, and prevention by detecting cellular changes before they turn into cancer, as in the case of colorectal cancer ( 21 ). Increases in vaccination rates for cancer-causing viruses and decreases in prevalence of risk factors (e.g., combustible tobacco use) also have driven cancer mortality downward ( 22 ). Access to these cancer prevention and early detection strategies was increased with the expansion of Medicaid ( 23 ). New cancer treatments and therapies, specifically for lung cancer and melanoma, also have led to longer survival for those with a cancer diagnosis ( 24 ). CDC conducted a demonstration project on how to best provide care for persons living in rural areas who had cancer diagnosed ( 25 ). Although cancer is categorized as a single disease group in this analysis, each cancer site has different risk factors, has varying treatment methods, and can manifest itself in different ways among groups by sex, age, race, and ethnicity. Preventable premature death might vary depending on the cancer site and might not have decreased for cancers with increasing prevalence of risk factors (e.g., obesity), no recommended screening modalities, or therapies that have not changed. Lung cancer, the leading cause of cancer mortality, accounted for 23% of all cancer deaths in 2020 ( 20 ). Geographic differences in combustible tobacco use and use of lung cancer screening likely partially drive differences in lung cancer mortality. Access to lung cancer screening facilities is more limited in rural counties than in urban counties ( 26 ). Despite overall reductions in preventable premature deaths from cancer, premature deaths surpass the national average in micropolitan and noncore counties, highlighting the need in rural areas to reduce cancer-related premature deaths. Because more urban areas surpassed the 2010 benchmarks for cancer death rates in 2019, future updates to the cancer-specific benchmarks using more recent years of data might better reflect the lowest achievable death rates.

Unintentional Injury

The worsening and expanding drug overdose epidemic, increases in motor vehicle traffic fatalities, and falls drive the growth in preventable premature deaths from unintentional injury ( 27 ). Narrowing rural-urban disparities in the percentage of preventable premature deaths from unintentional injury were driven by worsening rates of preventable mortality in more urban areas, with the percentage more than doubling in large central metropolitan areas over the study period. For drug overdoses, access to medications for opioid use disorder continues to be more limited in rural counties, as evidenced by low buprenorphine dispensing rates and reduced treatment capacity ( 28 ). For motor vehicle traffic crashes, rural residents have an increased risk for death and are less likely than urban residents to wear seat belts ( 29 ). Evidence-based interventions reduce rural-urban disparities in seat belt use and motor vehicle death rates ( 30 ). Many fall risk factors are modifiable, implying that many falls can be prevented ( 31 ).

Heart Disease and Stroke

Disparities in preventable premature deaths from heart disease and stroke between rural and urban areas existed across the study period. These gaps increased from 2019 to June 2022, except in large central metropolitan counties where a decrease of three percentage points was observed from 2020 to 2021. Increases in preventable premature deaths from heart disease and stroke in 2020 and 2021 were likely associated with COVID-19–related conditions that contributed to risk-associated increased mortality from heart disease and stroke ( 32 ). Increases in systolic and diastolic blood pressure, a leading risk factor for heart disease and stroke, were observed among all age groups when comparing 2020 with 2019 ( 33 ). Inequities in control of hypertension (i.e., systolic blood pressure values of ≥130 mm Hg, diastolic blood pressure of >80 mm Hg, or both) were observed during the COVID-19 pandemic and are related to insufficient health care access, medication adherence, and monitoring ( 34 ). Patients might have delayed or avoided seeking emergency care when experiencing a life-threatening event during the height of the COVID-19 pandemic ( 35 ). Emergency department visits for heart attack and stroke decreased by 20% during the weeks after the declaration of COVID-19 as a national emergency on March 13, 2020, and hospital admissions for heart attack and stroke decreased during the pandemic ( 35 ). In addition, COVID-19 was associated with an increased risk for stroke and heart disease ( 36 , 37 ).

Chronic Lower Respiratory Disease

Despite the overall decrease during 2010–2020 (because of decreases observed in larger urban areas), the percentage of preventable premature deaths from CLRD was relatively stable in medium and small urban counties and rural counties during 2010–2015. During 2010–2022, the sharpest decline in preventable premature death from CLRD in urban areas occurred from 2019 through 2021 and could be the result of deaths from COVID-19 that otherwise would have been attributable to CLRD. Persons with CLRD (e.g., chronic obstructive pulmonary disease) are at increased risk for death from COVID-19 ( 38 ).

The findings in this report are subject to at least six limitations. First, applying benchmarks (e.g., the three states with the lowest rates) to all urban-rural county categories facilitates comparisons but might not represent the lowest death rates achievable by certain subgroups. For example, large metropolitan areas met the benchmarks for cancer in 2019 and, therefore, had negative estimates of preventable premature deaths during 2019–2022. In these instances, negative estimates were truncated at zero to indicate that the 2010 benchmarks had been achieved. Using urban-rural–specific benchmarks would likely result in larger numbers of preventable premature deaths in certain categories and larger rural-urban disparities in certain cases. However, using benchmarks specific to state, age, cause, and subgroup (e.g., urban-rural, sex, race, and ethnicity) also could lead to less stable estimates because of smaller numbers of deaths when stratifying by multiple demographic and geographic dimensions. Second, the differences cannot be attributed solely to population size and geographic location because risk factors do not occur randomly in populations and are related to well-known social, demographic, environmental, economic, and geographic attributes of the neighborhoods in which persons live and work ( 39 ). Third, estimates of preventable premature deaths using historical benchmarks (e.g., 2008–2010) might not reflect improvements in mortality that could have occurred in a later year. For example, the 2010 benchmarks for cancer are higher than if benchmarks were based on 2022 data because of decreases in cancer deaths during 2010–2022. Fourth, the numbers of preventable premature deaths by cause are not necessarily independent, and the numbers of potentially excess deaths from the five causes cannot be combined to generate a total. For example, the number of preventable premature deaths from cancer might be lower because persons with cancer died from another cause (e.g., heart disease). Fifth, deaths from certain causes might have increased partly because of COVID-19 and the pandemic. Specifically, misclassification of deaths from COVID-19 that were attributed to other causes (because of lack of testing or reporting on the death certificate) could have contributed to a greater number of deaths across other causes and by rural and urban areas. In addition, certain causes of death might have increased because of indirect pandemic-related effects (e.g., reduced access to emergency care or life-saving treatments). Finally, data for 2022 were based on provisional data from the first half of the year, and results might differ when the final data for the full year are available.

The findings in this report demonstrate the value of analyzing preventable premature deaths according to the six National Center for Health Statistics 2013 urban-rural county classifications. Reporting trends in preventable premature deaths over a 12-year period highlights differences over time and might aid in understanding underlying structural, environmental, and social risk factors. Because of increasing percentages of preventable premature deaths in recent years for specific causes of death and certain demographic groups, these data might augment traditional rate comparisons and help guide focused public health interventions. Comparing the findings in this report with data from tools such as the CDC Interactive Atlas of Heart Disease and Stroke ( https://www.cdc.gov/dhdsp/maps/atlas/index.htm ) might help identify social determinants of health, health care infrastructure, and public policies that could be related to increases or decreases in preventable premature deaths in specific nonmetropolitan areas. Detailed community-based evaluations might clarify how various risk factors and social determinants of health relate to premature mortality and related rural-urban disparities. In addition, other methods for developing benchmark rates might be helpful, including using benchmarks based on the nonmetropolitan areas with the lowest death rates, or updating benchmarks based on more recent data, especially for causes of death (e.g., cancer) that have decreased substantially over time. In addition, more detailed analyses by race, ethnicity, and age, along with examining preventable deaths among persons aged >80 years, and preventable premature deaths from other causes (especially causes that are more prevalent in rural counties) might be informative.

Defining preventable premature deaths within the context of the five leading causes of death does not capture the full spectrum of preventable mortality. The degree to which these deaths could be prevented is related to various factors, including distinct prevention strategies, varying risk factors, and the availability of effective interventions, all of which vary by cause. Not all premature deaths are equally preventable among the leading causes or even within each specific leading cause category, as exemplified by certain types of cancer ( 40 ).

Routine tracking of preventable premature deaths by urban-rural county classification might facilitate the identification of areas with high prevalence of preventable premature mortality along with related geographic and urban-rural disparities in health outcomes. These disparities might be related to different levels of access to health care, social determinants of health, and other risk factors. Findings might help guide more focused interventions to reduce premature death from the five leading causes of death and reduce disparities by rural-urban residence and geographic region.

Health care professionals, medical examiners, coroners, vital registrars, and vital statistics offices across the United States.

Corresponding author: Macarena C. García, Office of Science and Medicine, Office of the Assistant Secretary of Health, U.S. Department of Health and Human Services, Washington, DC. Telephone: 678-770-6220; Email: [email protected] .

1 Office of Science and Medicine, Office of the Assistant Secretary of Health, U.S. Department of Health and Human Services, Washington, DC; 2 National Center for Health Statistics, CDC, Hyattsville, Maryland; 3 National Center for State, Tribal, Local, and Territorial Public Health Infrastructure and Workforce, CDC, Atlanta, Georgia; 4 National Center for Injury Prevention and Control, CDC, Atlanta, Georgia; 5 National Center for Chronic Disease Prevention and Health Promotion, CDC, Atlanta, Georgia

Conflicts of Interest

All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

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FIGURE 1 . Percentages of preventable premature deaths* among persons aged <80 years from the five leading causes of death, by year — National Vital Statistics System, United States, 2010–2022 †

* Preventable premature deaths are defined as deaths among persons aged <80 years in excess of the number that would be expected if the death rates for each cause in all states were equivalent to those in the benchmark states (i.e., the three states with the lowest rates).

† Data for 2022 are provisional counts from January through June and were annualized for comparability with previous years.

FIGURE 2 . Percentages of preventable premature deaths* among persons aged <80 years from the five leading causes of death, by rural-urban county classification and year — National Vital Statistics System, United States, 2010–2022 †

* Preventable premature deaths are defined as deaths among persons aged <80 years in excess of the number that would be expected if the death rates for each cause in all states were equivalent to those in the benchmark states (i.e., the three states with the lowest rates). Estimates of potentially excess deaths that were negative were set to zero. These negative excess estimates occurred in cases where deaths were fewer than expected (i.e., mortality was lower than benchmark rates). † Data for 2022 are provisional counts from January through June and were annualized for comparability with previous years. § Includes unintentional poisoning (e.g., drug overdose), unintentional motor vehicle traffic crash, unintentional drowning, and unintentional fall ( https://www.cdc.gov/injury/wisqars/animated-leading-causes.html ).

Suggested citation for this article: García MC, Rossen LM, Matthews K, et al. Preventable Premature Deaths from the Five Leading Causes of Death in Nonmetropolitan and Metropolitan Counties, United States, 2010–2022. MMWR Surveill Summ 2024;73(No. SS-2):1–11. DOI: http://dx.doi.org/10.15585/mmwr.ss7302a1 .

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Clinical trials: A significant part of cancer care

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Editor's note: May is National Cancer Research Month.

By Mayo Clinic staff

A cancer diagnosis is an emotional experience. Learning that you have cancer can create feelings of hopelessness, fear and sadness. This is especially true if your cancer is advanced or available treatments are unable to stop or slow its growth.

"Often, when patients are diagnosed with cancer , they feel hopeless and scared. Clinical trials are one way patients can be proactive. They can make a choice in how their care is going to be," says Matthew Block, M.D., Ph.D. , a Mayo Clinic medical oncologist.

Cancer clinical trials help physician-scientists test new and better ways to control and treat cancer. During a clinical trial, participants receive specific interventions, and researchers determine if those interventions are safe and effective. Interventions studied in clinical trials might be new cancer drugs or new combinations of drugs, new medical procedures, new surgical techniques or devices, new ways to use existing treatments, and lifestyle or behavior changes.

Clinical trials provide access to potential treatments under investigation, giving options to people who otherwise may face limited choices. "Clinical trials open the door to a new hope that maybe we can fight their cancer back and give them a better quality of life," says Geoffrey Johnson, M.D., Ph.D. , a Mayo Clinic radiologist, nuclear medicine specialist and co-chair of the Mayo Clinic Comprehensive Cancer Center Experimental and Novel Therapeutics Disease Group.

You will receive cancer treatment if you participate in a clinical trial. "I think one common misperception about clinical trials is that if you enter a clinical trial, you may not get treatment (receive a placebo). And that's actually very much not true. Most clinical trials are looking at one treatment compared to another treatment," says Judy C. Boughey, M.D. , a Mayo Clinic surgical oncologist, chair of Breast and Melanoma Surgical Oncology at Mayo Clinic in Rochester, Minnesota, and chair of the Mayo Clinic Comprehensive Cancer Center Breast Cancer Disease Group.

"I think one common misperception about clinical trials is that if you enter a clinical trial, you may not get treatment (receive a placebo). And that's actually very much not true. Most clinical trials are looking at one treatment compared to another treatment." Judy C. Boughey, M.D.

Watch this video to hear the experiences of people who have participated in cancer clinical trials and to hear Drs. Block, Johnson and Boughey discuss the importance of clinical trials in cancer care:

Clinical trials are a significant part of cancer care at Mayo Clinic Comprehensive Cancer Center. Cancer care teams work together across specialties to make sure the right clinical trials are available to serve the needs of people with cancer who come to Mayo Clinic.

"We are very particular in how we select the clinical trials that we have available for patients," says Dr. Boughey. "We want to have the best trials available for our patients. Some of the clinical trials are evaluating drugs — we are so excited about those drugs, but we can't prescribe those drugs for patients without having that trial. And so we will actually fight to try to get that trial open here to have it available as an opportunity for our patients."

If you choose to participate in a clinical trial, you will continue to receive cancer care. "For most patients that we evaluate, there's always the standard of care treatment option for those patients. And then, in many situations, there's also a clinical trial that the patient can participate in," says Dr. Boughey.

People who participate in clinical trials help make new and better cancer care available for future patients. The treatments available for cancer patients today exist because of the clinical trial participants of yesterday. "We couldn't advance medicine if it wasn't for people volunteering for trials. And the promise from our side is to say we're not going to put patients on trials or offer trials for them to consider unless we think there's a good chance that they'll get a benefit or that society at large will get a benefit," says Dr. Johnson.

"We couldn't advance medicine if it wasn't for people volunteering for trials. And the promise from our side is to say we're not going to put patients on trials or offer trials for them to consider unless we think there's a good chance that they'll get a benefit or that society at large will get a benefit." Geoffrey Johnson, M.D., Ph.D.

Participating in a clinical trial may give you access to cutting-edge treatment, improve your quality of life and extend your time with loved ones.

"It's definitely worth reaching out to your healthcare provider and asking, 'What clinical trials could I be a potential candidate for?'" says Dr. Boughey. "And remember, you can ask this of your surgical oncologist, your medical oncologist, your radiation oncologist, or any of the physicians you're seeing because there are trials in all disciplines. There are also ongoing trials that require the collection of tissue or the donation of blood. They can also be important in trying to help future generations as we continue to work to end cancer."

Participating in a clinical trial is an important decision with potential risks and benefits. Explore these FAQ about cancer clinical trials, and ask your care team if a clinical trial might be right for you.

Learn more about cancer clinical trials and find a clinical trial at Mayo Clinic.

Join the Cancer Support Group on Mayo Clinic Connect , an online community moderated by Mayo Clinic for patients and caregivers.

Read these articles about people who have participated in clinical trials at Mayo Clinic:

• A silent tumor, precancerous polyps and the power of genetic screening
• Mayo Clinic’s DNA study reveals BRCA1 mutations in 3 sisters, prompts life-changing decisions

Read more articles about Mayo Clinic cancer research made possible by people participating in clinical trials.

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Home > Cancer Research Catalyst > AACR Annual Meeting 2024: A Global View on Cancer 

AACR Annual Meeting 2024: A Global View on Cancer 

With more than 23,200 registrants, the American Association for Cancer Research (AACR) Annual Meeting 2024 not only set a record number of registrants but witnessed the highest international participation to date.  

As the world’s largest professional organization dedicated to advancing cancer research, the AACR has members in 141 countries and territories around the world and offers numerous opportunities to help investigators in the international community. 

In fact, 62 out of 67 grants at the AACR are open globally including the AACR Scholar-in-Training Awards , the Global Scholar-in-Training Awards (GSITA), Women in Cancer Research (WICR) Scholar Awards , the Beginning Investigator Grant for Catalytic Research (BIG Cat) , and Maximizing Opportunity for New Advancements in Research in Cancer (MONARCA) . Additionally, education and training opportunities include AACR on Campus and several conferences around the world. 

Even domestic conferences like the Annual Meeting provide international researchers with the opportunity to exchange knowledge and new ideas with other scientists dedicated to cancer research. This year’s meeting welcomed more than 8,000 international registrants—representing 36% of participants—from 78 countries and multiple territories.

“We are proud to highlight cutting-edge research from groups of scientists from around the world,” said Elizabeth M. Jaffee, MD, FAACR , chair of the AACR Global Affairs Committee. “Global collaboration enables strong scientific contributions to research, and we trust that the Annual Meeting provides a platform for researchers globally, to absorb and share new knowledge on emerging research, therapies, and treatment with colleagues and communities at home.”  

The Annual Meeting also offers a platform to shine a light on cancer researchers and journalists through a number of awards with several international attendees among this year’s recipients. We asked a few of these award recipients about their experience attending the meeting and the importance of global collaboration in the conquest of cancer. 

Exploring the International Perspective    

Hellen Shikanda from Kenya became a journalist because she wanted to be a voice for the voiceless. 

“Speaking to people who would not ordinarily get an opportunity to have their stories out there helps in empowering communities that they come from,” Shikanda said. “I have learnt that their stories, if told well, always have an impact on the policies that are enacted after those in leadership positions realize that there has been a gap that urgently needed to be filled.”   

One of her stories was honored with the AACR June L. Biedler Award for Cancer Journalism , which was given to five journalists in four categories. Her article, “New Drug Promises Better Treatment for Cancer Patients,”  relays a patient’s journey through five countries to get properly diagnosed with colon cancer and ultimately find hope for treatment in a clinical trial.  

“I was happy to work on a story that explored clinical trials for a new drug that tackles a specific gene mutation—and the research was done in Africa for the first time,” she explained. “Global collaboration means that there will be funding opportunities for all researchers who can share insights on how they can help defeat cancer.” 

Anshika Chauhan, PhD , from India, is the recipient of one such funding opportunity as one of the many international winners of the AACR-WICR Scholar Awards. This award is given to members of WICR, a constituency group focused on women scientists within the AACR that celebrated its 25th anniversary at the meeting , who are scientists-in-training and presenters of meritorious scientific papers at AACR Annual Meetings. She presented her research on increased mitochondrial DNA copy number via EPOR signaling as a potential mechanism for metastatic dissemination in head and neck squamous cell carcinoma. 

“The AACR gives women from different backgrounds, different geographical regions, and different phases of their career the platform to work together, learn from each other, and make a difference in fighting cancer,” Chauhan said. “So, it’s important to welcome women from all over the world into cancer research. By working together and sharing our ideas, we can make a big impact in the fight against this disease.” 

Seifegebriel Feleke Teshome, from Ethiopia, was one of 15 early-career scientists from nine countries who were offered the chance to attend the meeting and present their work as a 2024 GSITA recipient . His poster focused on profiling the CpG methylation patterns of Epstein-Barr virus DNA in lymphoma patients from Ethiopia. 

“During the meeting, numerous scientific researchers and young scientists from different parts of the world gathered to share their findings, achievements, and innovative approaches in cancer research,” he said. “This diverse community of attendees created a vibrant atmosphere conducive to engaging discussions and fruitful interactions.” 

Many of these award recipients will share what they learned about the AACR’s global programs and initiatives with their colleagues back home as they work to overcome the worldwide challenge of cancer through scientific research. 

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Focus  19 April 2022

The Future of Cancer Research

Nature Medicine presents a special Focus dedicated to the future of cancer research and care. We take stock of the latest exciting developments, as well as the challenges, gaps and inequities that must be resolved as we navigate the cancer research landscape of the next decade.

Call for papers - Nature Medicine is inviting submission of innovative research on the prevention, detection and treatment of cancer. We welcome in particular clinical trials leveraging new technologies and designs to address unmet clinical needs, as well as population-based studies with global impact. Find out more here .

Focus Issue: The Future Of Cancer Research

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FIGO 2023 endometrial staging: a leap of faith into the new “prognostic based’ rather than “anatomical based” staging—too fast too furious??

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In 2023 FIGO revised the endometrial cancer staging system after 13 years. There is a lacuna of data regarding the performance and practicality of the revised 2023 FIGO staging schema for endometrial cancer from Low Middle-Income Countries (LMIC).

To estimate the shift of stage and adjuvant management of endometrial cancer based on the FIGO 2023 system compared to the FIGO 2009 system and assess the predictive potential of the FIGO 2023 system.

Material and methods

A retrospective study was conducted from 1st January 2017 to 31st December 2022. All patients with endometrial cancer were staged according to the FIGO 2023 and FIGO 2009 staging system. Follow-up of patients was done to determine recurrence.

A total of 152 patients were included. Aggressive histology was seen in 66 (45%) patients. Eighteen (11%) had subserosal involvement. Substantial LVSI was noted in 23 (15%) of patients. Twenty-four (47%) patients of FIGO 2009 Stage IA and 26 patients (63%) of FIGO 2009 Stage IB were upstaged. Eleven (50%) patients of FIGO 2009 Stage IIIA were down staged to IA3. Overall 23 patients (15%) had a shift of stage. Fifteen out of 152 patients (15%) would have had a possible risk stratification change which would imply 23 patients (15%) would have needed a more radical treatment. Molecular classification was done in 32 patients; however, only 2 patients could afford POLE testing. Kaplan–Meier curves showed significant PFS differences in FIGO 2009 Stage IB and Stage IIIA when restaged according to the FIGO 2023 system.

The FIGO 2023 endometrial staging is a more robust prognosticator; however, the practicality of molecular classification in LMICs is still a distant dream.

Avoid common mistakes on your manuscript.

Introduction

Staging systems are the backbone of any cancer treatment. They are meant to be valid, reliable and practical (Odicino et al. 2008 ). Stage is a strong predictor of patient prognosis. The main bodies for cancer staging include the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) (Brierley. 2006 ). Concerning gynaecological cancer, The International Federation of Gynaecology and Obstetrics (FIGO) takes centre stage and a collaborative arrangement between the three staging systems ensures synchrony with changes in FIGO staging manifesting in the AJCC and UICC versions (Greene and Sobin 2009 ).

The earlier anatomy-based staging was the norm earlier, however, over the years staging has included histological prognostic factors, biomarkers and molecular data as evident in breast, head-neck and prostate cancers (Odicino et al. 2008 ; Amin et al. 2017 ). Keeping with this trend a radical shift in endometrial cancer (EC) staging was formulated by FIGO in June 2023 (Berek 2023 ). The changes in the FIGO 2023 endometrial staging system compared to the FIGO 2009 endometrial staging system are described in Table  1 . It has created quite a stir in the oncology fraternity on its inception. Keeping this background in mind, we devised a retrospective study to study the impact of the FIGO 2023 endometrial staging system compared to its predecessor FIGO 2009 endometrial staging system.

Primary objective

To determine the percentage change in stage and risk stratification of patients with endometrial cancer from the FIGO 2009 endometrial staging system to the FIGO 2023 endometrial staging system.

Secondary objective

To determine the possible impact of the stage shift on the management of patients and assess the prognostic impact of the FIGO 2023 endometrial staging system.

Materials and methods

Study design.

All patients who were diagnosed with EC and initially underwent surgery at the Dr. Bhubaneswar Borooah Cancer Institute (BBCI), Guwahati, Assam, India between 1st January 2017 and 31st December 2022 were included in the study. All patients underwent surgical staging which included a total hysterectomy and bilateral salpingo-oophorectomy. Lymph node dissection was conducted in all patients except in patients with Stage IA—Grades I and II endometrioid endometrial cancer with a tumor size of less than 2 cm. Patients who received neoadjuvant chemotherapy, had recurrent endometrial cancer, operated outside BBCI, had multiple cancers, had no available formalin fixed paraffin embedded samples and whose tissue samples were inadequate were excluded. We had incorporated immunohistochemistry testing for MMR proteins (mismatch repair proteins MLH 1, MSH 2, MSH 6 and PMS 2) and p53 from 1st January 2023. POLE testing is not done in our institute due to the cost factor and depending on the affordability of the patient it was outsourced. The patients were divided into four groups—POLEmut, MMR-D, p53abn and NSMP. In the event of a patient testing positive for multiple IHCs the algorithm of ProMisE study was followed (Kommoss et al. 2018 ). Patients who were treated before molecular testing were classified without the molecular testing. All the histopathology reports were reviewed by two expert oncopathologists and were reported as per the 2020 World Health Organization tumor classification criteria which included the histopathological type, extent of LVSI and size of lymph node metastasis. The histopathological slides were reviewed where a discrepancy or doubt occurred regarding the findings. Demographic and clinical data were obtained retrospectively from the electronic medical registry (EMR). In this study the patients who were previously stratified based on FIGO 2009 endometrial staging system were restratified based on FIGO 2023 endometrial staging system. Upstaging was described as the reclassification to a higher group and downstaging was the reclassification to the lower group in the FIGO 2023 staging system compared to the FIGO 2009 staging system.

Operational definitions as per the FIGO 2023 endometrial staging system (Berek 2023 )

Non-aggressive histological types are composed of low-grade (Grades 1 and 2) endometrioid cancers, while aggressive histological types are composed of high-grade endometrioid cancer (Grade 3), serous carcinoma, clear cell carcinoma, mixed carcinoma, undifferentiated variant, carcinosarcoma and mesonephric-like and gastrointestinal type mucinous carcinomas.

Lymphovascular space invasion (LVSI):

Involvement of ≥ 5 vessels is considered as substantial LVSI and less than 5 vessels is considered as focal LVSI.

Involvement of sub-serosa:

As per the ISGYP recommendations (Singh 2019 ) uterine serosa involvement is defined as a tumour reaching submesothelial fibro connective tissue or the mesothelial layer, regardless of whether tumour cells may or may not be present on the serosal surface of the uterus.

Adnexal involvement:

The 2023 FIGO staging for endometrial carcinoma assigns the category of Stage IA3 when the following criteria are met in a low-grade endometrioid endometrial cancer:

No more than superficial myometrium invasion is present (< 50%).

The absence of substantial LVSI.

The absence of additional metastases.

The ovarian tumour is unilateral, limited to the ovary, without capsule invasion/breach (equivalent to pT1a).

The cases not fulfilling these criteria were interpreted as extensive spread of the endometrial carcinoma to the ovary (Stage IIIA1).

All patients underwent risk stratification as per standard guidelines existing (Concin et al. 2021 ; Colombo et al. 2016 ; Endometrical Cancer 2024 ) and received appropriate adjuvant radiotherapy and chemotherapy. We also studied the possible change in risk stratification when patients were stratified as per the ESMO 2022 risk stratification system (Endometrical Cancer 2024 ) using the FIGO 2023 staging system.

Statistical analysis

Demographic and clinical data were expressed as the number of patients and percentage (%). Progression-free survival (PFS) was calculated from the date of completion of treatment to the date of recurrence or last contact. The Kaplan–Meier method was used to analyze the PFS and the log-rank test was used to evaluate the between-group differences in PFS. The cutoff p value for statistical significance was < 0.05. SPSS version 29.0 was used for statistical analysis.

A total of 152 patients were included in the study. The median age of the patients was 52 years (range 23–84 years). The majority of patients (144, 95%) underwent open surgery whereas eight patients (5%) underwent minimally invasive surgery. Table 2 shows the histo-pathological data of all 152 patients. The majority (57%) had non-aggressive histology. Substantial LVSI was noted in 15% of cases. Out of 28 women who had adnexal involvement with low-grade endometrioid carcinoma only eleven patients fulfilled the criteria to be reclassified as Stage IA3 as shown in Fig.  1 . Metastasis to the pelvic nodes was seen in 13% of patients whereas para-aortic nodal metastasis was documented in 3% of cases.

Bar diagram depicting the 28 women with adnexal involvement with characteristics about unilaterality, capsule involvement, LVSI and presence of metastasis

Figure  2 shows the Sankey diagram depicting the change in staging of patients as per the FIGO 2009 and FIGO 2023 endometrial staging systems. Due to reclassification number of patients in Stage I decreased from 92 to 38. There was a sharp increase in Stage II patients (39) in the 2023 system and a decline in Stage III with a dramatic decrease in number of patients with Stage IIIA from 22 to 5 patients. Overall 35 out of 152 (23%) patients had a change in the stage.

Sankey diagram showing the difference in staging of patients as per the FIGO 2009 and FIGO 2023 endometrial staging systems

Table 3 shows the stage shift concerning the individual sub-stages of FIGO 2009 and FIGO 2023 endometrial staging systems. It was seen that 24 out of 51 patients (47%) were staged in Stage IA whereas 26 out of 41 patients (67%) in Stage IB were upstaged. In Stage IIIA 11 out of 22 patients (50%) were down staged to IA3 whereas in Stage IVB 5 out of 8 patients (62.5%) were upstaged.

Figure  3 a shows the possible shift in the risk stratification category and Fig.  3 b shows the possible change in adjuvant treatment that would have resulted by the application of the ESMO 2022 risk scoring and FIGO 2023 staging system. It was observed that 15 out of 152 patients (10%) would have had a change in the risk stratification score as shown in Fig.  3 a. In Fig.  3 b as shown 7 out of 152 patients (5%) would have been undertreated whereas 23 out of 152 patients (15%) would have been overtreated.

a The possible change in risk stratification between FIGO 2009 and FIGO 2023 staging systems. b The possible change in adjuvant treatment that would have been needed by patients when restaged as per FIGO 2023 staging system. The cream shade refers to the FIGO 2009 system and the green and red refer to the FIGO 2023 system wherein green depicts a decrease in numbers and red depicts the increase in numbers

Table 4 shows the risk stratification shift between FIGO 2009 and FIGO 2023 staging systems using the ESMO 2022 stratification system. It is observed that 16 out of 37 patients (43%) had increased risk stratification in the FIGO 2009 intermediate risk strata group whereas 10 out of 55 patients (18%) had decreased risk stratification in FIGO 2009 high-risk strata group.

When we analyzed the molecular profiling of 32 patients in the 2023 as shown in Fig.  4 a and b it was observed only two patients could afford POLEmut testing and both of the reports were negative for POLE mutation. It was observed that 3 out of 32 patients (9%) would have had their risk stratification strata changed as seen with the high-risk strata group increasing from 9 to 12 cases. We treated those patients with sequential chemotherapy and radiation therapy as dictated by the high-risk group management guidelines.

a The impact of molecular profiling on risk stratification. b The change in adjuvant treatment based on the risk strata

When patients were followed up for a median duration of 45 months, restaging of FIGO 2009 Stage IB and Stage IIIA as per the new FIGO 2023 staging system using the Kaplan–Meier analysis was found to be statistically significant for PFS (p 0.01) as shown in Fig.  5 . When we compared the other groups the values were not statistically significant.

The PFS curves for the FIGO 2009 endometrial staging system when reclassified as per the FIGO 2023 staging system for Stage IB and IIIA

Figure  5 depicts the PFS curves for the FIGO 2009 endometrial staging system when reclassified as per the FIGO 2023 staging system for Stages IB and IIIA.

FIGO presented their revised staging of endometrial cancer nearly 14 years after their last update in 2009. This staging was different from its predecessor in that it moved from an anatomy-based staging into a prognosis-based staging system and was based on new molecular stratification. This created quite a furore among the medical fraternity concerning several factors (McCluggage 2023 ). In the subsequent sections, we will analyze the results of our study with respect to the above factors.

In a study done by Kobayashi et al. they observed a stage migration in 23.4% of the patients which included a larger shift in Stage I to Stage II as per the FIGO 2023 system (Kobayashi-Kato et al. 2023 ). Schwameis et al. showed 27.6% of patients had a stage shift of which 23.6% were upstaged (Schwameis et al. 2023 ). We observed that 23% of the patients had a stage shift in our study with the majority of the shifts occurring to Stage II as per FIGO 2023 endometrial system.

Molecular classification is not widely available in many parts of the world, especially in Low Middle-Income Countries (LMICs) and POLEmut testing has no defined surrogate IHC marker like MMRd or p53 groups (McCluggage 2023 ). This adds to the extra pinch of the patient’s wallet in an already economically backward community. This was evident in our study where only two patients could afford the POLE testing out of 32 patients. This also created an issue while analyzing the other patients as we could not rule out the multiple classifiers which account for 10–15% of the population. It is preferred to keep the molecular classification out of the staging system until a day comes when medical resources are equally available all around the globe. This is not to say that molecular classification is not prognostic (Gilks 2013 ) but it would be prudent to avoid it in staging and reserve it for the prognostic scoring systems. It would be helpful if a collaborative laboratory system is developed in LMIC countries which can reduce the costs involved as the tests would be done in larger numbers making it cheaper for the general population.

The FIGO 2023 staging system being a “heavy-weight” pathology-based system leads to a phenomenon called “stage migration” where the patient with the same disease has a high probability of being accorded a different stage when reviewed at an advanced diagnostic center due to the availability of molecular testing, determination of depth of sub-serosa involvement (Gilks 2013 ) and use of certain confusing histological parameters like absence of myometrium invasion and ≤ 50% myometrium invasion. It is well known that the depth of myometrium invasion has poor interobserver variation due to irregular endometrial/myometrium interface (Singh 2019 ; Gilks 2013 ). These factors lead to difficulty and confusion while assigning the stage of the patient as it keeps changing during the review of the histopathological report. This was evident in our study as we analyzed all the cases of endometrial cancer and whenever in doubt especially concerning subserosal involvement the opinion of two senior oncopathologists was taken. Not all centres can afford to have this luxury. Moreover, there is no definite consensus in terms of absolute distance from serosa to what constitutes as subserosal involvement. This could be a point that would need further clarification in the subsequent updates of the FIGO staging system.

As per the FIGO 2023 staging system the 5-year mortality in the IA3 group was lower when compared to the IIIA1 group (Berek 2023 ; McCluggage 2023 ). This was also shown in a study done by Matsuo et al. (Matsuo 2017 ). We were not able to study the overall survival due to the shorter follow-up duration in our study. However, we observed the PFS was significantly different for the IA3 Stage compared to IIIA1 Stage. We observed a significant difference in PFS when restaging of FIGO 2009 Stage IB was done. Matsuo et al. demonstrated the prognostic significance of the size of lymph nodal metastatic focus and the nature of peritoneal metastases (Matsuo 2017 ). With adoption of newer technologies such as sentinel node mapping and ultrastaging, micro metastasis are detected which are missed on routine histopathological analysis (Bogani et al. 2019 ).

We analyzed the possible impact on adjuvant risk stratification according to the new FIGO 2023 staging system based on the latest ESMO risk stratification system which had not been studied prior. It revealed that seven out of eleven (63%) patients who would have needed adjuvant chemotherapy and radiotherapy but had received lesser form of adjuvant therapy and later developed distant recurrences. We postulate that had this group of patients received more radical treatment we could have prevented these recurrences.

The role of molecular analysis has been exemplified in the latest therapeutic trials of the GARNET study and KEYNOTE -775 study which highlighted the beneficial effect of dostarlimab and a combination of pembrolizumab plus lenvtinib, respectively, in the treatment of endometrial cancer (Oaknin et al. 2022 ; Makker 2022 ).

However, keeping the above-discussed limitations of costly molecular profiling in mind it is time we explore an upcoming technology of radiomics (Bogani et al. 2022a ). Radiomics is a novel technology that uses a large number of quantitative features from radiological images from ultrasound, contrast-enhanced computed tomography(CECT) and magnetic resonance imaging(MRI) using data characterization algorithms (Rizzo et al. 2018 ; Jong et al. 2019 ). Correlation of this information with clinical data and molecular profiling can open up a new frontier in the management of endometrial cancer which will be cost-effective and widely available in the long run if proven to be an effective prognostic indicator (Bogani et al. 2020 ; Leone Roberti Maggiore et al. 2019 ). Proper use of radio genomics knowledge can reduce the health expenditure on upcoming molecular testing of new molecular targets such as PI3K/Akt/mTOR pathway which are well beyond the reach of the common man (Bogani et al. 2022b ).

The merits of this study include the application of the present ESGO 2022 risk stratification system to analyze the impact of the new staging system on adjuvant treatment. An accurate picture of the fallacies of the staging system performance in LMICs was also discussed.

There are important limitations in this study. The retrospective nature of the study combined with the smaller sample size and limited follow-up meant we could not analyze the impact on overall survival. Our data reflect the availability of resources in this part of the world and need not be applicable in other developed areas.

There are both advantages and drawbacks of the FIGO 2023 endometrial staging system. While it serves as a radical shift to the prognostic implication of the staging system it still has grey areas which can be resolved through proper appraisal at the global community level to ensure its acceptability to the wider scientific community. Hence we recommend universal adoption of the FIGO 2023 endometrial staging system as it is prognostic in nature and it should be followed by validation studies of the system from various parts of the globe.

Data availability

No datasets were generated or analysed during the current study

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Bassetty, K.C., Begum, D., Barmon, D. et al. FIGO 2023 endometrial staging: a leap of faith into the new “prognostic based’ rather than “anatomical based” staging—too fast too furious??. J Cancer Res Clin Oncol 150 , 251 (2024). https://doi.org/10.1007/s00432-024-05739-w

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Received : 09 March 2024

Accepted : 02 April 2024

Published : 11 May 2024

DOI : https://doi.org/10.1007/s00432-024-05739-w

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