Improved Survival After Adjuvant Therapy in Locally Advanced Rectal Cancer Patients With Pathologic Complete Response

BACKGROUND: The benefit of adjuvant therapy is unclear in patients with rectal cancer achieving a pathologic complete response after neoadjuvant chemoradiotherapy and total mesorectal excision.OBJECTIVE: This study aimed to assess the benefit of adjuvant chemotherapy on survival among rectal cancer patients with a pathologic complete response after neoadjuvant chemoradiation.DESIGN: Retrospective cohort study.SETTING: National Cancer Database (2004-2017).PATIENTS: Patients with clinical stage 2 or 3 rectal adenocarcinoma who underwent neoadjuvant chemoradiation (50-50.4 Gy in 25-28 fractions) followed by total mesorectal excision with a pathologic complete response were included.INTERVENTION: Adjuvant chemotherapy.MAIN OUTCOME MEASURES: Overall survival.RESULTS: There were 20,518 patients and 2221 (11%) had a pathologic complete response after neoadjuvant chemoradiation. Of 2221 patients, 1441 (65%) did not receive adjuvant therapy and 780 (35%) did. Patients who received adjuvant therapy were more likely to be younger (median 58 vs 62 y), have private insurance (61% vs 49%), and have node-positive disease (57% vs 48%) (all p < 0.05). There were no differences in sex, race, Charlson-Deyo score, clinical T-stage, tumor size and differentiation, adequate lymphadenectomy (12 or more), or sphincter preservation between groups (all p > 0.05). Overall survival at 5, 10, and 14 years was significantly longer in the adjuvant group (93%, 85%, 83%, respectively) compared to patients who did not receive adjuvant therapy (87%, 67%, 51%, respectively) (p < 0.001). In a subgroup analysis, adjuvant therapy was associated with improved survival in patients with clinical stage 2 and 3 rectal cancer (p < 0.001). After adjusting for patient and tumor characteristics, omission of adjuvant chemotherapy was associated with significantly worse survival (HR 1.53, 95% 1.08-2.16).LIMITATIONS: Selection bias, unknown perioperative morbidity, chemotherapy regimen, recurrence status, and other unidentified factors limiting survival analysis.CONCLUSIONS: In patients with clinical stage 2 or 3 rectal cancer, adjuvant chemotherapy was associated with improved overall survival in patients achieving a pathological complete response after neoadjuvant chemoradiotherapy.