Finding the Optimal Treatment for Stage IV Rectal Cancer: A Nationwide Comparison of Two Strategies

Abstract

Introduction: The M1-schedule (short-course pelvic radiotherapy (5x5Gy) followed by systemic therapy and subsequent local treatment of tumour sites) was compared to the liver first approach (LFA: systemic therapy, local treatment of liver metastases with subsequent (chemo)radiotherapy and rectum surgery) for patients with stage IV rectal cancer. Methods: Consecutive patients with stage IV rectal cancer and potentially resectable liver metastases who were treated with the M1-schedule or LFA between 2006 and 2018 were analysed in nine tertiary referral centres in the Netherlands. Survival and oncological outcome were assessed. Results: Of the 281 patients, 117 of the 147 (79.6%) patients completed the M1-schedule and 94 of the 134 patients (70.1%) completed the LFA (p = 0.068). Most patients failed completion due to disease progression. The 3-year OS was 59.7% (95% CI: 51.6-69.1) and 53.9% (95% CI: 45.9-63.3, p=0.370) and the median PFS was 16.6 and 16.2 months for M1-schedule and LFA, respectively (p=0.753). Radiologic complete response rates were higher in M1-schedule (10% vs. 4.3%), but did not reach significance (p=0.253). Pathologic complete responses were similar (13% vs. 11.5%, p=0.829). The duration of the M1-schedule was 7 weeks shorter than the LFA (37 vs 45 weeks, p=< 0.001). Surgical and oncological complication rates were comparable in both groups. Conclusion: Both schedules have similar overall and progression free survival outcomes but the M1-schedule is 7 weeks shorter. Although significance was not reached, radiological complete responses were higher with M1-schedule. This schedule could lead to more rectum sparing treatment for stage IV rectal cancer patients.