Advanced presentation and early survival loss in early-onset colorectal signet-ring cell carcinoma: a population-based study

Colorectal signet-ring cell carcinoma (SRCC) is rare, often advanced at diagnosis, and associated with poor survival. We assessed whether the association between SRCC and advanced presentation differed across diagnosis eras and quantified the timing of survival loss in early-onset disease. We analyzed SEER Research records of stage I–IV colorectal adenocarcinoma diagnosed at ages 20–49 years during 2000–2023. Baseline-covariate and stage-conditional survival models, competing-risk analyses, sequential tumor-burden adjustment, and crude and stage-standardized landmark restricted mean survival time (RMST) compared SRCC with conventional and mucinous adenocarcinoma. Among 66,916 diagnosis records from 65,595 patients, 1,230 (1.8%) were SRCC and 1,064/1,230 (86.5%) had stage III–IV disease. Baseline-covariate-adjusted SRCC-versus-conventional hazard ratios at 12 and 60 months were 2.91 and 2.44 for cancer-specific survival and 2.83 and 2.33 for overall survival. The crude 60-month overall-survival RMST deficit was 18.5 months (95% CI, 17.2–19.8); after standardization to a common stage distribution it was 13.9 months (12.6–15.3). Among 36-month survivors, the corresponding standardized deficit over the subsequent 24 months was 1.4 months (0.8–2.1). The largest stage-specific 60-month excess risk of colorectal cancer death occurred in stage III (35.2% points; 30.6–40.1). Early-onset colorectal SRCC was a high-risk phenotype characterized by frequent advanced presentation and substantial early survival loss. Stage standardization reduced but did not remove the RMST deficit, and stage III carried the largest absolute excess colorectal cancer-death risk. Landmark RMST further characterized subsequent survival loss among 36-month survivors.