Long-term outcomes of locally advanced rectal cancer after neoadjuvant chemoradiotherapy: A bi-national colorectal cancer audit study

Abstract

Background: There is a great interest in predicting the pathological complete response (pCR) to facilitate patient selection for a “watch and wait” protocol, sparing locally advanced rectal cancer patients from surgical related morbidity and mortality. However, there is a high risk of tumor regrowth with the current assessment of clinical complete response, highlighting the need for a better predictive marker of pCR. Objective: The aim of this study was to assess the short- and long-term outcomes according to tumor response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Design: Retrospective analysis of a prospectively maintained bi-national database. Settings: Multicenter bi-national database. Patients and Methods: This was a retrospective study of a prospectively maintained bi-national colorectal cancer audit database. Inclusion criteria were T3-4 and/or N1-2 rectal cancer patients receiving long course chemoradiotherapy followed by surgery. The primary outcome measure was pathological tumor response. Main Outcome Measures: The primary outcome measure was rate of pathological response and associated local and distant recurrence. Sample Size: There were 929 consecutive locally advanced rectal cancer patients identified within the database. Results: A total of 929 patients were included, with a pCR rate of 29.6% (275 patients). Non-responding tumors had a higher circumferential resection margin positive rate of 20% (33 of 165 patients) compared to partial responding tumors of 5.1% (24 of 475 patients). Local recurrence rates in accordance to tumor regression grade (pCR, partial and no response) were 2.2%, 4.4%, and 4.7% (P = 0.254) respectively, with distant recurrence rates of 2.9%, 4.1%, and 8.1% (P = 0.03) respectively. Independent predictors of pCR were early stage disease on pre-treatment imaging (OR 2.12 95% CI 1.24–3.63, P = 0.005), a rural setting (OR 3.15 [95%] CI 1.63–6.06, P < 0.001) and private insurance (OR 2.06 [95%] CI 1.45–2.93, P < 0.001), with an inverse association to metastatic disease (OR 0.22 [95%] CI 0.1-0.5, P < 0.001). Conclusions: Early-stage tumors had the greatest likelihood of attaining a pCR with a lower risk of local and distant recurrence than partial or non-responding tumors. Limitations: This study is limited by the retrospective nature of the analysis and the lack of data auditing to ensure accuracy of data is maintained. Conflict of Interest: None.