Multi-Decade Analysis Reveals Shifting Patterns of Subsequent Primary Cancer Risk Among Survivors
Key Insights
A study of over 3 million U.S. cancer survivors from 1975–2021 found that subsequent primary cancer (SPC) risks vary by cancer type, sex, and generation.
SPC risks have generally declined in recent decades, though female lung cancer (search) and male bladder cancer (search) survivors remain notable exceptions.
Survivors diagnosed at older ages continue to face persistent or rising SPC risks, while breast cancer (search) survivors showed stable risks across ages.
A team of researchers from VCU Massey Comprehensive Cancer Center (search) has published a sweeping multi-decade analysis of subsequent primary cancer (SPC) incidence among cancer survivors, drawing on registry data from over three million individuals in the United States spanning 1975 to 2021. The study, published in PLOS Medicine, examines how the risk of developing a new, unrelated cancer changes over time, across generations, and by cancer type—offering critical insights for survivorship care and public health planning.
"Cancer survivors are surviving longer, and that gives them a higher chance of developing a subsequent primary cancer, but literature in that area is limited," said Hui Cheng, Ph.D., a member of Massey's Cancer Prevention and Survivorship Outcomes Research Lab and the article's primary author. Cancer survivorship has risen 34% since 1991, amplifying the clinical relevance of understanding SPC risk trajectories.
Risk Patterns Vary by Cancer Type, Sex, and Age at Diagnosis
The analysis revealed that SPC risks are not uniform. Researchers found that risks varied significantly by cancer type, sex, and generation. In recent decades, SPC risks have generally declined among cancer survivors—yet notable exceptions persist. Female lung cancer (search) survivors and male bladder cancer (search) survivors continue to face elevated risks that have not followed the broader downward trend.
Age at first diagnosis emerged as a key factor. The risk of developing a subsequent primary cancer increased among those who were older when first diagnosed. Breast cancer (search) survivors, however, demonstrated a distinct pattern, showing stable SPC risks across ages—a finding that may inform tailored monitoring strategies for this population.
Implications for Long-Term Monitoring and Prevention
The study's findings highlight that SPC risks remain substantial and that long-term monitoring of cancer survivors is essential. "This is an opportunity to really evaluate your risk factors, your lifestyle and really become a survivorship warrior," said Oxana Palesh, Ph.D., Massey Cancer Center Chair in Cancer Research, co-leader of Massey's Cancer Prevention and Control research program, and co-author of the study. "It is important to remind people that they have a lot of control over their individual cancer risk and prevention."
These results can directly inform prevention strategies, survivorship care models, and public health planning efforts aimed at the growing population of cancer survivors.
A Holistic Survivorship Model
Massey's cancer survivorship program takes a comprehensive approach that integrates personalized medical strategies with resources addressing stress reduction, nutrition, sleep improvement, and other lifestyle factors that influence cancer risk. "Whether it be our work in germline genetic testing, stress reduction or general lifestyle improvements, our program is incredibly impactful," said Susan Hong, M.D., director of the cancer survivorship program at Massey and co-author of the study.
Hong also highlighted the program's embedded food-as-medicine initiative, noting that it is one of the few programs nationwide that systematically targets every cancer center patient reporting food insecurity. "We have studies that demonstrate that cancer patients with food insecurity have higher rates of mortality, anxiety and depression, and are less likely to complete treatment," Hong said. The program is supported by a three-year grant from the McKesson Foundation (search) examining how food access affects cancer patients receiving active treatment.
Future Directions
The research team plans to seek a supplemental grant to expand data collection beyond the clinic, incorporating home monitoring of patients to increase the breadth and depth of data available for future analyses. This next phase aims to further refine understanding of SPC risk and enhance survivorship care delivery across cancer centers in the United States.