Oxaliplatin-based adjuvant chemotherapy rather than fluorouracil-based chemotherapy in rectal cancer is more efficient to decrease distant metastasis and increase survival after preoperative chemoradiotherapy and surgery: a meta-analysis

Purpose The standard treatment of stage II–III rectal cancer is preoperative chemoradiotherapy (CRT), followed by total mesorectal excision (TME). However, the rate of metastasis is still high following this treatment. Therefore, several adjuvant chemotherapy studies have been conducted on reducing subsequent metastases and increasing survival, although there are still no definite conclusions. Methods We searched for published prospective randomized controlled trials comparing adjuvant chemotherapy regimens following standard preoperative CRT and curative surgery in stage II–III rectal cancer. We systematically searched Medline, Embase, and the Cochrane Library for relevant trials done from January 2004 to January 2021. Review Manager (RevMan, version 5.3) was used to analyze the data. Results We initially searched 1955 studies. We screened and carefully selected four randomized controlled trials with 2897 patients. Compared to the 5-FU-based regimen group, the oxaliplatin-added regimen group attained a higher 3-year locoregional control rate (relative risk [RR] of 0.64, 95% confidence interval [CI], 0.48–0.86; p = 0.003) and 3-year distant metastasis control rate (RR of 0.82, 95% CI, 0.71–0.95; p = 0.007). The oxaliplatin-added regimen group had significantly increased 3-year disease-free survival with a hazard ratio (HR) of 0.85 (95% CI: 0.74–0.97, p = 0.020), but not overall survival ( p = 0.740). Grade 3 or higher acute toxicity rates did not differ between the two groups ( p = 0.190). Conclusion The addition of oxaliplatin to adjuvant therapy for stage II–III rectal cancer following preoperative CRT and TME may increase disease-free survival without significant increases in toxicity, but not overall survival.