Neoadjuvant Chemoradiotherapy and Tumor Recurrence in Patients with Early T-Stage Cancer of the Lower Rectum
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 ≤ 8 cm from the anal verge, with final histopathology ≤ T2 (≤ ypT2/≤ pT2), 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 (≤ 1 year and > 1 year postsurgery) by nCRT.
Long-course nCRT was associated with a 5.6-fold increase in the hazard of recurrence ≤ 1 year postsurgery [hazard ratio (HR) 5.6; 95% confidence interval (CI) 1.2–24.9; P = 0.02], but there was no increase in recurrence hazards > 1 year (HR 0.84; 95% CI 0.4–2.0; P = 0.70). In subgroup analysis restricted to ≤ mrT2/≤ ypT2 and ≤ pT2 tumors (omitting > mrT2 tumors), the effect of nCRT on recurrence no longer varied over time, indicating that tumor heterogeneity was responsible for the observed increased recurrence hazards ≤ 1 year postsurgery; That is, > mrT2 tumors that were downstaged to ≤ ypT2 after nCRT were responsible for the time-varying effects of nCRT and increased recurrence hazards ≤ 1 year postsurgery. Subsequently, no difference was found in prognostic outcomes either with or without nCRT before surgery in the homogeneous population of ≤ mrT2/≤ ypT2 and ≤ pT2 tumors.
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.
The authors would like to acknowledge BioGrid Australia for providing the data for this study.
All authors contributed substantially to conception and design, analysis of data, and drafting, critical revision, and final approval of the manuscript.
J.C.R. is a recipient of a National Health Medical Research Council (NHMRC) Peter Doherty early career research fellowship (APP1120081). E.M. is funded by the Victorian Centre for Biostatistics.
The authors declare no conflicts of interest.
Ethics Approval and Consent to Participate
BioGrid data were collected from patients’ clinical notes, supported by radiology and histopathology reports. Study ethics approval was obtained from Melbourne Health/BioGrid HREC, No. BG-201709/1. This study was performed in accordance with the Declaration of Helsinki.
Consent for Publication
This manuscript does not contain any individual personal data in any form, so consent for publication is not required.
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