Neoadjuvant Chemoradiotherapy and Tumor Recurrence in Patients with Early T-Stage Cancer of the Lower Rectum

Abstract

Background The role neoadjuvant chemoradiotherapy (nCRT) plays in oncological outcomes in early T-stage rectal cancer is uncertain. The present work aims to clarify prognostic outcomes by estimating the effect of nCRT on tumor recurrence prior to major surgery compared with major surgery alone. Patients and Methods Prospectively collected data were retrospectively analyzed for patients diagnosed with localized rectal adenocarcinoma ≤\u20098\xa0cm from the anal verge, with final histopathology ≤\u2009T2 (≤\u2009ypT2/≤\u2009pT2), regardless of magnetic resonance imaging staging, between 1990 and 2017. As the effect of nCRT on recurrence varied over time, thereby violating the Cox proportional hazards assumption, the effect of nCRT on recurrence hazards was estimated using a time-varying multivariate Cox model over two separate time intervals (≤\u20091\xa0year and >\u20091\xa0year postsurgery) by nCRT. Results Long-course nCRT was associated with a 5.6-fold increase in the hazard of recurrence ≤\u20091\xa0year postsurgery [hazard ratio (HR) 5.6; 95% confidence interval (CI) 1.2–24.9; P \u2009=\u20090.02], but there was no increase in recurrence hazards >\u20091\xa0year (HR 0.84; 95% CI 0.4–2.0; P \u2009=\u20090.70). In subgroup analysis restricted to ≤\u2009mrT2/≤\u2009ypT2 and ≤\u2009pT2 tumors (omitting >\u2009mrT2 tumors), the effect of nCRT on recurrence no longer varied over time, indicating that tumor heterogeneity was responsible for the observed increased recurrence hazards ≤\u20091\xa0year postsurgery; That is, >\u2009mrT2 tumors that were downstaged to ≤\u2009ypT2 after nCRT were responsible for the time-varying effects of nCRT and increased recurrence hazards ≤\u20091\xa0year postsurgery. Subsequently, no difference was found in prognostic outcomes either with or without nCRT before surgery in the homogeneous population of ≤\u2009mrT2/≤\u2009ypT2 and ≤\u2009pT2 tumors. Conclusions No evidence was found to indicate that nCRT prior to surgery reduces tumor recurrence in early T-stage lower rectal cancer compared with surgery alone.