Purpose: The neoadjuvant chemoradiotherapy (nCRT) might accentuate surgical complications and toxicity in the treatment of locally advanced rectal cancer (LARC) while neoadjuvant chemotherapy (nCT) alone shows promise as an alternative treatment. However, which patients deserve most from the nCT need further clarify. This trial aimed to assess the non-inferiority of nCT with capecitabine plus oxaliplatin (CAPOX) versus nCRT with capecitabine in LARC with uninvolved mesorectal fascia (MRF).
Methods: Patients with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to receive 4 cycles of CAPOX chemotherapy alone (nCT group) or CRT with concurrent Capecitabine (nCRT group). The primary end point is 3-year locoregional recurrence-free survival (LRRFS). Secondary end points, such as 3-year disease-free survival (DFS), 3-year overall survival (OS), and adverse events (AEs), were also reported.
Results: A total of 663 patients were enrolled and 589 patients received the allocated treatment (nCT, n = 300; nCRT, n = 289). LRRFS was analyzed with a median follow-up of 48 months. 3-year LRRFS was 97.4% (95% CI, 95.5 to 99.3) in the nCRT group and 96.3% (95% CI, 94.0 to 98.6) in the nCT group, resulting in a hazard ratio (HR) of 1.40 (95% CI, 0.53 to 3.68). The nCT and nCRT achieved similar 3-year DFS (89.2% v 87.9%; HR, 0.88 [95% CI, 0.54 to 1.44]) and 3-year OS (95.0% v 94.1%; HR, 0.86 [95% CI, 0.42 to 1.76]). The nCT group showed a lower incidence of grade 2 to 4 long-term AEs (16.0% v 26.3%, P = 0.002) and proctitis (33.6% v 41.7%, P = 0.049) compared with nCRT group.
Conclusions: The non-inferiority of nCT was not confirmed with a very low incidence of local recurrence in both group. But nCT offers comparable DFS and OS while mitigating the burden of toxicity as compared to nCRT. These insights shed light on a potential paradigm shift in the treatment for LARC with uninvolved MRF.
Trial registration: ClinicalTrials.gov NCT02288195.