Total neoadjuvant therapy with six versus four cycles of CAPOX in locally advanced rectal cancer: A real-world study

The optimal number of systemic chemotherapies for total neoadjuvant therapy (TNT) in locally advanced rectal cancer (LARC) is controversial. This retrospective study, conducted at Fujian Medical University Union Hospital from January 2018 to April 2024, compared the efficacy and safety of TNT with radiotherapy plus six cycles of CAPOX (CAPOX-6, n = 105) versus four cycles of CAPOX (CAPOX-4, n = 124) in 229 patients with LARC. The CAPOX-6 group achieved a significantly higher complete response (CR) rate (53.3% vs. 28.2%, p <.001) and pathological complete remission rate (55.1% vs. 28.3%, p <.001) compared to the CAPOX-4 group. The CAPOX-6 group had higher anal preservation rates (95.9% vs. 85.8%, p = .01) and lower enterostomy rates (59.2% vs. 89.2%, p <.001). Furthermore, the CAPOX-6 group had a higher proportion of less invasive transanal local excision (35.7% vs. 4.2%, p <.001) and lower postoperative complications (12.2% vs. 23.3%, p = .04). The 2-year DFS was similar (79% for CAPOX-6 vs. 75.9% for CAPOX-4, p = .92), but the 2-year recurrence rate was significantly lower in patients achieving CR (4.2% vs. 36.7% in non-CR, p <.001). Multivariate analysis identified six cycles of CAPOX and EMVI negative as independent predictors of CR. Grade 3-4 adverse events were comparable (36% vs. 28%, p = .2), with higher grade 1-2 leukopenia, neutropenia, and neurotoxicity in the CAPOX-6 group. The study concludes that TNT with radiotherapy plus six cycles of CAPOX is a preferred treatment strategy for LARC, particularly when prioritizing organ preservation and quality of life.