Key Takeaways
- Order matters: The sequence of colorectal cancer (CRC) diagnosis matters for patients with multiple primary cancers. Patients diagnosed with CRC first fared better than those diagnosed with a different cancer first.
- Better prognosis than CRC alone: CRC diagnosed as the first of multiple primary malignancies is associated with better overall and cancer-specific survival compared to just CRC or CRC as a second primary cancer.
- Hope, with a caveat: Patients who survive CRC have better prospects when facing another cancer. However, the authors caution that regular screening remains essential.
CHICAGO (June 17, 2025) — A new study using one of the world's largest cancer registries shows that patient outcomes can be significantly impacted depending on when colorectal cancer (CRC) is diagnosed related to other cancers. The results are published in the Journal of the American College of Surgeons (JACS).
The Surveillance, Epidemiology, and End Results (SEER) Program is a cancer database established by the National Cancer Institute. Researchers studied data from 2000-2020 and defined three different groups:
- Group A: Patients with only a CRC diagnosis (71.8%)
- Group B: CRC diagnosed first, followed by another cancer (11.9%)
- Group C: CRC diagnosed after another cancer (16.3%)
Key Findings:
- Best survival: Group B (CRC first) had the highest overall survival (50.4 months) and cancer-specific survival (51.3 months).
- More surgery, better outcomes: Group B was more likely to receive surgical treatment (20.5%) than Group A (13.0%) or Group C (14.3%).
- Worst prognosis: Group C (CRC second) more often had right-sided tumors (linked to aggressive biology) and the poorest survival.
"We expected isolated CRC patients to fare best, but patients with CRC diagnosed first, followed by another cancer had the best survival rates. This was surprising; we hypothesized patients with only a CRC diagnosis would do best," said first author Anjelli Wignakumar, MBBS, BSc (Hons), a clinical research fellow at the Department of Colorectal Surgery, Ellen Leifer Shulman & Steven Shulman Digestive Disease Center at Cleveland Clinic Florida.
Potential Explanations
There are multiple potential reasons why Group B patients, with multiple cancers, would fare better than Group A, who only had CRC. The first is the increased surveillance and interaction with the medical system that comes with cancer diagnosis. Increased monitoring leads to cancers being caught earlier. Prior cancer treatment may prime the immune system to fight subsequent cancers. Healthier habits post-diagnosis could also improve outcomes.
Another difference was that "Group A patients were younger, presented more aggressively (higher liver metastases), and were less likely to receive surgery — possibly because their disease was further along," said Dr. Wignakumar.
Clinical Implications
For providers, the researchers emphasize that patients with a prior history of non-CRC cancer may require more intensive CRC screening. "Group C (CRC as the second cancer) had the worst outcomes. Clinicians must treat these as high-risk cases and consider aggressive therapy," said Sameh H. Emile MBBCh, MSc, MD, FACS, co-author and a project scientist at the Department of Colorectal Surgery, Ellen Leifer Shulman & Steven Shulman Digestive Disease Center, Cleveland Clinic Florida.
For patients: "Surviving CRC doesn't make you immune to other cancers, but the next one could have better outcomes," emphasized Steven D. Wexner, MD, PhD (Hon), FACS, senior author, and director of the Ellen Leifer Shulman & Steven Shulman Digestive Disease Center at Cleveland Clinic Florida. "Follow all recommended screenings — catching the next cancer early saves lives."
Disclosure: Dr. Wexner is a consultant for ActivSurgical, Arthex, Baxter, Becton, Dickinson and Co., Intuitive Surgical, OstomyCure, Takeda, Virtual Ports, has consulting Agreements with stock options for consulting with GI View, OstomyCure, and Virtual Ports, is the Data Safety Monitoring Board chair of Polypid (chair), and receives royalties from Intuitive Surgical, Karl Storz Endoscopy America Inc., and Unique Surgical Solutions, LLC. Dr. Emile is a consultant for Becton, Dickinson and Co. Dr. Boutros receives teaching honoraria from Ethicon, Johnson and Johnson. The remaining authors report no financial disclosures.
Citation: Wignakumar A, Emile S, Dourado J, et al. Does the sequence of colorectal cancer diagnosis matter for patients with multiple primary cancers? A SEER Database Cohort Study. Journal of the American College of Surgeons, 2025. DOI: 10.1097/XCS.0000000000001413
