Long-term survival and clinical characteristics of colon and rectal cancer: a comprehensive 47-year retrospective analysis using the SEER database

Background: Population screening and therapeutic advances have changed colorectal cancer (CRC) incidence and survival over recent decades, yet important differences exist by anatomic subsite, histology, and population subgroup. This study describes long-term trends in incidence and survival for colon and rectal tumors. Methods: We analyzed 501 094 primary colon and rectal tumor records from the Surveillance, Epidemiology, and End Results (SEER) Incidence database (1975–2022). Age-adjusted rates used the 2000 U.S. standard population. Outcomes were overall survival (OS) and CRC-specific mortality. OS was estimated using Kaplan–Meier methods and compared between groups by log-rank tests. CRC-specific mortality was evaluated using cause-specific Cox regression based on SEER cause-of-death recodes, adjusting for age, sex, race, histology, primary site, and surgery status. Results: Age-adjusted incidence was 48.3 per 100 000. Median OS improved across eras [Era 1 (1975–1994) 3.83 years, Era 2 (1995–2009) 5.58 years, and Era 3 (2010–2022) 6.92 years, all Eras had P value < 0.001). Left- versus right-sided colon cancers and rectal versus colon primaries showed fixed survival differences across eras. Regarding histology, the signet-ring tumors had markedly worse survival, while neuroendocrine/carcinoid tumors showed better long-term survival. In the adjusted Cox model, several colonic subsites showed a higher hazard of CRC-specific death compared to the appendix. Signet-ring cell histology conferred the greatest mortality risk (HR = 2.206, 95% CI 2.113–2.304; P < 0.001). Conclusions: Over a 47-year period, survival in CRC has significantly improved, but outcomes remain influenced by anatomic subsite and histology. These findings confirm that tumor subsite and histology remain important determinants of long-term prognosis in CRC and highlight the need for risk-adapted management strategies, continued population-based surveillance, and ongoing efforts to address disparities in outcomes.