Low-intensity induction chemotherapy before chemoradiotherapy for rectal cancer: 10-year overall survival in the LARC-RRP trial

Abstract Objectives Total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC) often uses intensive oxaliplatin-based chemotherapy alongside standard radiotherapy to prevent metastatic progression. The optimal intensity of the chemotherapy component, given a contribution of radiotherapy to clonogenic cell elimination in the primary tumor, remains uncertain. We aimed to assess long-term outcomes of a TNT regimen with low-intensity induction chemotherapy before chemoradiotherapy, as evaluated in the LARC-RRP trial. Methods Between 2005 and 2010, 87 LARC patients (36% with T4 organ-infiltrating tumor) were enrolled in the single-arm trial. Induction chemotherapy was given over 4 weeks prior to chemoradiotherapy and surgery. We report 10-year overall survival by tumor regression grade (TRG) and performed descriptive comparisons with contemporary trials whose experimental TNT arms used more intensive chemotherapy. Results At 10 years, overall survival was 83% (95% confidence interval, 71-90) for patients with complete or near-complete tumor cell elimination in the surgical specimen (TRG 1-2; 70% of the cohort) versus 52% (95% confidence interval, 31-69) for others (log-rank P = .0005). LARC-RRP survival outcomes were comparable with those reported in more contemporary TNT trials. Conclusions The LARC-RRP results raise the possibility that shorter-duration chemotherapy combined with standard radiotherapy may suffice to protect against systemic recurrence of high-risk LARC. Advances in knowledge These long-term data support investigation of less intensive chemotherapy within TNT regimens and may guide the design of risk-stratified TNT trials.