Impact of tumor sidedness and social determinants of health on survival in early-onset colon cancer: A SEER 2004–2022 study.

e15705 Background: Right- and left-sided colorectal cancers (CRC) differ biologically, clinically, and prognostically, but most evidence is derived from patients ≥50 years. Early-onset CRC (< 50 years) is rapidly rising in incidence, yet survival disparities by tumor sidedness in this population remain poorly defined. Moreover, survival disparities related to social determinants of health (SDH) remain poorly defined in young adults, despite emerging signals of inequity in broader CRC populations. We therefore investigated sidedness-specific survival disparities in young adults using modern SEER data and proportional-hazards–robust approaches. Methods: We performed a retrospective cohort study using SEER (2004–2022). Eligible patients were 20–49 years old with a first or only primary colon adenocarcinoma, excluding rectum, rectosigmoid junction, appendix, and large intestine NOS. Tumor sidedness was defined using ICD-O-3 site recodes: right-sided (cecum through transverse colon) and left-sided (splenic flexure through sigmoid). Left side was used as reference in mortality analysis. Outcomes were overall survival (OS) and cause-specific survival (CSS). Restricted mean survival time (RMST) at 60 months was calculated to quantify absolute survival differences independent of proportional hazards. Results: The cohort included 35,788 patients (57.3% left-sided; 42.7% right-sided), with 12,607 OS deaths; CSS analyses included 35,546 patients with 10,954 cancer-attributable deaths. Sidedness violated proportional hazards, and adjusted time-varying models showed a front-loaded survival penalty for right-sided primaries. Adjusted HR(t) (right vs left) for OS was 1.510 (95% CI 1.437–1.587) at 6 months and 1.200 (1.158–1.244) at 24 months, attenuating by 60 months (1.022 [0.974–1.073]) and reversing by 120 months (0.903 [0.847–0.964]); estimated crossover ≈67.8 months. CSS showed a similar pattern: HR(t) 1.551 (1.471–1.636) at 6 months, 1.188 (1.142–1.236) at 24 months, 0.985 (0.932–1.042) at 60 months, and 0.854 (0.792–0.920) at 120 months; crossover ≈55.9 months. Absolute effects were clinically meaningful: adjusted RMST (60) differences (right−left) were −2.50 months for OS and −2.35 months for CSS. SDH remained prognostic after adjustment: nonmetro residence (vs metro) was associated with worse OS (HR 1.071), and higher median household income was protective (per +$10,000: OS HR 0.958; CSS HR 0.962); the early right-sided hazard excess persisted across income and rurality strata. Conclusions: Tumor sidedness in early-onset colon cancer is a time-dependent prognostic factor, with an early right-sided survival disadvantage that diminishes by 5 years, alongside persistent independent effects of income and rurality.