A phase III randomised trial on the addition of a contact X-ray brachytherapy boost to standard neoadjuvant chemo-radiotherapy for organ preservation in early rectal adenocarcinoma: 5 year results of the OPERA trial

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The OPERA trial has shown that a contact X-ray brachytherapy 50 kV (CXB) boost with neoadjuvant chemoradiotherapy (NCRT) can increase organ preservation (OP) rate for early rectal adenocarcinoma (ADK) of low-mid rectum. We report the results after 5 years of follow-up. OPERA was a multicentre, phase III trial that included operable patients (pts), with cT2-cT3b low-mid rectal ADK, tumours <5 cm, cN0 or cN1 <8 mm. All pts received external beam radiotherapy (EBRT): 45 Gy in 25 fractions with concurrent capecitabine. Pts were randomly assigned (1:1) to receive a boost of EBRT in group A (9 Gy/5 fractions) or a boost with CXB (90 Gy/3 fractions) in group B. The primary end point was OP rate. Out of 148 patients randomised, 141 were eligible. Between week 14-24, a clinical complete (or near) response was observed in 44 pts in group A (64%) versus 66 in group B (92%); P < 0.001. The 3-year OP rate was 59% in group A versus 81% in group B (P= 0.003). After update the median follow-up was 61.1 months [56.8-64.5]. The 5-year local regrowth was 39% in group A and 17% in group B (P= 0.1). The difference in OP was still highly significant between both groups: A 56% versus B 79% (P= 0.004). The difference was more significant if tumours <3 cm, with an OP rate of 93% in group B compared to 54% in group A. Of the 28 local regrowths, 3 occurred after 3 years of follow-up. Rectal bleeding (grade 1-2), which was the most prevalent toxicity during follow-up, disappeared most of the time after three years. Bowel function was not worsened by the CXB boost. The OPERA trial was the first trial to demonstrate that CXB dose escalation was increasing the OP rate with good bowel function at 3 years. At 5 years, these results are sustained, especially in small early-stage tumours. The occurrence of some local regrowth after 3 years necessitates close surveillance of these pts during the 5-year period.