Evaluation of response after chemoradiation for rectal cancer as a predictive factor for the benefit of adjuvant chemotherapy: A pooled analysis of 2,724 individual patients.

Abstract

361 Background: Neoadjuvant chemoradiation (CRT) for rectal cancer increasingly results in pathologic response. It has been suggested that patients with different degrees of response might not have the same benefit of adjuvant chemotherapy. The aim was to determine whether patients with a pathologic complete response (pCR), ypT1-2 or ypT3-4 tumor after CRT for rectal cancer have different benefits of adjuvant chemotherapy for disease-free survival. Methods: Authors from studies evaluating different degrees of response to CRT were contacted to share individual patient data. The collected individual patient data were pooled into one dataset. To evaluate the effect of adjuvant chemotherapy on disease-free survival multivariate analyses according to the Cox proportional hazards model were performed. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated for 3 subgroups: patients with pCR(ypT0N0), ypT1-2 tumor and ypT3-4 tumor after CRT. To determine benefit of adjuvant chemo for different pathologic N-stages we performed subgroup analyses. Results: 2,724 patients were included. 811 had pCR (28%), 863 had ypT1-2 (30%) and 1050 had ypT3-4 (37%). Median follow-up was 50 months (range 0-277). 41% underwent adjuvant chemotherapy, which consisted mostly of 5-FU based chemotherapy. The HR with 95%CI for disease-free survival for adjuvant chemotherapy was 0.94 (0.50-1.78) for patients with pCR, 0.61 (0.40-0.92) for patients with ypT1-2 tumors and 0.97 (0.75-1.25) for patients with ypT3-4 tumors. ypT1-2N0 patients benefited most from adjuvant chemo: HR 0.45 (0.27-0.75) vs. 0.79 (0.31-1.95) for patients with ypT1-2N+. For ypT3-4 patients pN-stage did not alter benefit of adjuvant chemo. Conclusions: Patients with pCR or ypT3-4 residual tumor after CRT do not seem to benefit from adjuvant chemo. This might be due to the already good prognosis of patients with pCR and less responsiveness to 5-FU based chemotherapy in the poor responders (the ypT3-4 tumors). Possibly adjuvant chemotherapy can be omitted or adapted for these patients. Patients with ypT1-2N0 benefit most from adjuvant chemo. No significant financial relationships to disclose.