Adjuvant Chemotherapy Is Associated With Improved Overall Survival in Locally Advanced Rectal Cancer After Achievement of a Pathologic Complete Response to Chemoradiation

Abstract

Background: In locally advanced rectal adenocarcinoma, 15% to 20% of patients treated with neoadjuvant chemoradiation (nCRT) achieve a pathologic complete response (pCR). The benefit of adjuvant chemotherapy is controversial in rectal cancer. Our objective was to evaluate the effect of clinical risk factors and adjuvant chemotherapy usage on the outcomes of the pCR patient population.

Patients and methods: We performed a retrospective study using the National Cancer Data Base from 2006 to 2013. The primary outcome was overall survival (OS). The association between OS and patient characteristics (demographics, tumor variables, and treatment) was examined using multivariable Cox regression modelling.

Results: A total of 2891 patients were identified who had achieved a pCR. Of these 2891 patients, 2102 received nCRT and 789 received nCRT followed by adjuvant chemotherapy. The median follow-up duration was 43.2 months. The factors significantly associated with OS included age (P < .001), gender (P = .011), Charlson-Deyo comorbidity score (P < .001), grade (P = .029), clinical T stage (P = .030), carcinoembryonic antigen negativity (P = .002), and receipt of adjuvant chemotherapy (P < .001). Nodal status was not significantly associated with survival. The 5-year OS rate was 94% in the nCRT plus adjuvant group compared with 84% in the nCRT-alone group. Adjuvant chemotherapy was more likely to be given to younger patients (aged < 60 years), higher grade, lower Charlson-Deyo comorbidity score, elevated carcinoembryonic antigen level, higher clinical T stage, and higher clinical N stage.

Conclusion: Our findings showed a significant improvement in OS for patients who received nCRT plus adjuvant chemotherapy compared with those who received nCRT alone. The nCRT plus adjuvant patients were more likely to be younger, have a lower comorbidity score, have clinical ≥ T3 disease, and have clinical node-positive disease. Thus, a selection bias could have been present. Nonetheless, even in the setting of already excellent outcomes, for patients with locally advanced rectal adenocarcinoma who achieve a pCR, the additional benefit of adjuvant chemotherapy should be weighed against the potential for toxicity.

Keywords: Adjuvant chemotherapy; Chemoradiotherapy; Colorectal cancer; nCRT; pCR.