Adjuvant Chemotherapy Does Not Improve Recurrence-Free Survival in Patients With Stage 2 or Stage 3 Rectal Cancer After Neoadjuvant Chemoradiotherapy and Total Mesorectal Excision

BACKGROUND: Current guidelines for locally advanced stage 2/3 rectal cancer recommend neoadjuvant chemoradiotherapy followed by total mesorectal excision and adjuvant chemotherapy. The oncologic benefit of adjuvant chemotherapy has not been consistently demonstrated. OBJECTIVE: The purpose of this study was to evaluate disease recurrence and survival in patients with rectal cancer who received adjuvant chemotherapy after chemoradiotherapy and total mesorectal excision. DESIGN: This was a retrospective review of patients with stage 2/3 rectal cancer after chemoradiotherapy and surgery, based on receipt of adjuvant chemotherapy. SETTINGS: The study was conducted at the Kaiser Permanente Southern California system of 14 hospitals and associated clinics. PATIENTS: A total of 862 patients with stage 2/3 rectal cancer diagnosed and treated between January 1, 2005, and December 31, 2016, were included in this study. INTERVENTIONS: The study involved neoadjuvant chemoradiotherapy followed by total mesorectal excision with or without adjuvant chemotherapy. MAIN OUTCOME MEASURES: The primary end point was recurrence-free survival. RESULTS: A total of 348 stage 2 and 514 stage 3 patients were included; 660 patients (76.6%) underwent adjuvant chemotherapy. Mean patient follow-up after surgery was 63.0 months (range, 3-160). Multivariable analysis showed that yp stage (HR for yp stage 2 = 4.74; yp stage 3 = 8.83) and en bloc resection (HR = 1.76) were the only variables that significantly predicted disease recurrence. Neither pretreatment tumor stage nor receipt of adjuvant chemotherapy was significantly associated with recurrence-free survival. Log-rank testing failed to demonstrate significant recurrence-free survival improvement after receipt of adjuvant chemotherapy in any patient subgroup. LIMITATIONS: The study was limited by selection bias attributed to the nature of a retrospective study without patient randomization or predefined treatment protocol. CONCLUSIONS: In stage 2/3 rectal cancer treated with chemoradiotherapy and surgery, the addition of adjuvant chemotherapy was not associated with decreased recurrence-free survival in the entire cohort or in any subgroup, whereas tumor response to chemoradiotherapy is closely associated with disease recurrence. These findings have important consequences for treatment and surveillance decisions for patients with rectal cancer. Presurgical efforts that maximize tumor downstaging, such as total neoadjuvant therapy, may produce better oncologic outcomes than traditional adjuvant chemotherapy. See Video Abstract at .