Preoperative Radiotherapy with a Simultaneous Integrated Boost Compared to Chemoradiotherapy for cT3-4 Rectal Cancer: Long-Term Results of a Multicenter Randomized Study

Simple Summary An international multicenter randomized trial in 174 patients with T3-4 rectal cancer was conducted by the RectumSIB consortium (located at UZ Brussel-VUB in Brussels, Belgium). In this trial, they compared standard 5FU-chemoradiotherapy (CRT) and radiotherapy with a simultaneous integrated boost (SIB) without concomitant chemotherapy in a non-inferiority design. The primary endpoint (metabolic response rate) and secondary endpoints (local control, progression-free survival, survival, pathological response and acute/late toxicity) revealed the equivalence of both treatments. Radiotherapy with an SIB is an appealing treatment strategy for patients with T3-4 rectal cancer that are too frail for chemotherapy. Background: Preoperative chemoradiotherapy (CRT) is the standard treatment for T3-4 rectal cancer. Here, we compared image-guided and intensity-modulated RT (IG-IMRT) with a simultaneous integrated boost (SIB) (instead of concomitant chemotherapy) versus CRT in a multi-centric randomized trial. Methods: cT3-4 rectal cancer patients were randomly assigned to receive preoperative IG-IMRT 46 Gy/23 fractions plus capecitabine 825 mg/m(2) twice daily (CRT arm) or IG-IMRT 46 Gy/23 fractions with an SIB to the rectal tumor up to a total dose of 55.2 Gy (RTSIB arm). Results: A total of 174 patients were randomly assigned between April 2010 and May 2014. Grade 3 acute toxicities were 6% and 4% in the CRT and RTSIB arms, respectively. The mean fractional change in SUVmax at 5 weeks after completion of preoperative RT were -55.8% (& PLUSMN;24.0%) and -52.9% (& PLUSMN;21.6%) for patients in the CRT arm and RTSIB arm, respectively (p = 0.43). The pathologic complete response rate was 24% with CRT compared to 14% with RTSIB. There were no differences in 5-year overall survival (OS), progression-free survival (PFS) or local control (LC). Conclusions: The preoperative RTSIB approach was not inferior to CRT in terms of metabolic response, toxicity, OS, PFS and LC, and could be considered an available option for patients unfit for fluorouracil-based CRT.