A phase III randomized 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.

Abstract

Background: The OPERA trial has shown that a contact X Ray Brachytherapy 50kV (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.

Patients and methods: OPERA was a multicenter, phase III trial that included operable patients (pts), with cT2-cT3b low-mid rectal ADK, tumors <5 cm, cN0 or cN1 <8 mm. All pts received external beam radiotherapy (EBRT): 45Gy in 25 fractions with concurrent capecitabine. Pts were randomly assigned (1:1) to receive a boost of EBRT in group A (9Gy/5 fractions) or a boost with CXB (90Gy/3 fractions) in group B. The primary end point was OP rate.

Results: Out of 148 patients randomized, 141 were eligible. Between week 14-24, a clinical complete (or near) response was observed in 44 pts in group A (64%) vs 66 in group B (92%); p<0.001. The 3-year OP rate was 59% in group A vs 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% vs B 79% (p=0.004). The difference was more significant if tumors < 3cm, 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, disapeared most of the time after three years. Bowel function was not worsened by the CXB boost.

Conclusion: 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, specially in small early-stage tumors. The occurrence of some local regrowth after 3 years necessitates close surveillance of these pts during the 5-year period.