Consolidation Chemotherapy After Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer: 7-Year Follow-Up Results of a Randomized Multicenter Trial (KCSG CO 14-03).

Abstract

Total neoadjuvant therapy has become the standard treatment for locally advanced rectal cancer. However, the optimal sequence and duration of treatment remain unclear. Hence, the long-term follow-up results from our previous randomized phase 2 trial on consolidation chemotherapy, which demonstrated improved short-term pathologic outcomes, could provide valuable clinical evidence supporting total neoadjuvant therapy. The KCSG CO 14-03 trial is a multicenter, randomized trial involving patients with preoperative cT3-4NxM0 locally advanced rectal cancer. Patients were randomized into 2 arms: (1) preoperative chemoradiation therapy of 50 to 50.4 Gy/25-28 fractions with capecitabine (arm A) and (2) consolidation chemotherapy with 2 capecitabine and oxaliplatin cycles after chemoradiation therapy (arm B). Postoperative adjuvant chemotherapy was administered based on ypStage (ypStage 0-II: capecitabine; III: capecitabine and oxaliplatin) in both arms. The secondary endpoints of this study were disease-free survival (DFS), relapse-free survival, overall survival (OS), cumulative locoregional recurrence rate, long-term safety, and quality of life at 7 years. A total of 110 patients were enrolled between June 2014 and March 2016. DFS at 7 years was 61.2% and 75.6% in arms A and B, respectively (hazard ratio, 0.59; 95% CI, 0.28-1.21; P = .148). OS at 7 years was 78.9% and 83.2% in arms A and B, respectively (hazard ratio, 0.75; 95% CI, 0.27-2.08; P = .587). The 7-year cumulative locoregional recurrence and distant recurrence after total mesorectal excision were 6.1% and 29.9% in arm A and 4.0% and 21.8% in arm B, respectively. Drops in the Functional Assessment of Cancer Therapy for patients with Colorectal Cancer total, physical well-being, and functional well-being scores after preoperative treatment were significantly larger in arm B than in arm A. However, no significant change in Functional Assessment of Cancer Therapy for patients with Colorectal Cancer scores was observed between the 2 arms after surgery. DFS and OS did not differ significantly between the 2 arms, but there was a numerical improvement in 7-year DFS with consolidation chemotherapy. Quality of life deteriorated significantly with consolidation chemotherapy before surgery, but the difference disappeared after surgery.