Risk Factors for Subsequent Primary Cancers in Colorectal Cancer Survivors: A Systematic Review and Meta-analysis

As colorectal cancer survival improves, survivors face an increased risk of subsequent primary cancers (SPCs). This systematic review assessed associations between cancer treatments, tumor features and other risk factors and the risk of SPCs for colorectal cancer survivors. We searched four databases for peer reviewed articles published up to October 2025. We conducted meta analyses using random effects models to summarize pooled relative risks (RRs) for each SPC. Of 10,577 articles screened, 36 met the inclusion criteria. Radiotherapy was associated with increased risks of uterine (RR 2.65; 95% confidence interval [CI] 1.63-3.67), ovarian (RR 2.26, 95%CI 1.30-3.91), urethral (RR 4.66, 95%CI 1.96-11.06) and lung cancer (RR 1.19, 95%CI 1.04-1.35) but a decreased risk of prostate cancer (RR 0.55, 95%CI 0.47-0.64). In women, chemotherapy was associated with increased risks of uterine (RR 2.26, 95%CI 1.63-3.15) and breast cancer (RR 1.22, 95%CI 1.05-1.43). Colon (vs rectal) and proximal colon (vs distal) cancers were associated with higher SPC risk, whereas stage II/III (vs stage I) was associated with lower SPC risk. Older age, male sex, White race (vs Black/Asian), smoking, alcohol use and metabolic comorbidities were associated with increased SPC risk. These findings support the need for risk based surveillance after colorectal cancer.