Less Is More: Risk Factors and Survival Outcomes of Overtreatment for Early-Stage Colorectal Cancer.

Background and objectives: After cT1-2N0M0 colorectal cancer (CRC) definitive resection (colectomy/proctectomy) without pathologic upstaging, only observation is recommended given the lack of benefit from adjuvant treatment, which would constitute overtreatment. This study aims to determine risk factors and overall survival (OS) associated with overtreatment in early-stage CRC.

Methods: This National Cancer Database study included cT1-T2N0M0 CRC patients who underwent definitive resection between 2010 and 2020. Multivariable logistic regressions were performed to assess overtreatment risk factors. After propensity-matching, Kaplan-Meier survival analyses and multivariable Cox proportional-hazards analyses were performed to assess the association of overtreatment with OS.

Results: Of 22 875 colon cancer and 4198 rectal cancer cases, 144 (0.6%) and 82 (2.0%) were overtreated, respectively. Colon cancer overtreatment was associated with younger age (aOR = 0.96, 95% CI = 0.95-0.98), Black race (aOR = 1.94, 95% CI = 1.26-2.99), and pT2 vs. pT1 (aOR = 1.66, 95% CI = 1.19-2.33). Rectal cancer overtreatment was associated with pT2 (aOR = 2.58, 95% CI = 1.59-4.19), poor/undifferentiated grade (aOR = 2.61, 95% CI = 1.44-4.76), and high-risk histology (aOR = 3.20, 95% CI = 1.22-8.40). In the propensity-matched cohorts, overtreatment was associated with worse OS for colon (HR = 1.40, 95% CI = 1.01-1.93) but not rectal cancer (HR = 1.05, 95% CI = 0.66-1.68).

Conclusions: Patient and tumor characteristics predicted early-stage CRC overtreatment. Overtreatment was associated with worse OS for colon but not rectal cancer.