508MO - Organ preservation in early rectal adenocarcinoma: 5-year results of the randomized opera trial

Background

The OPERA trial has shown that a contact X Ray Brachytherapy 50kV (CXB) boost with chemoradiotherapy (CRT) was able to increase the 3-year rate of organ preservation (OP) for early rectal adenocarcinoma (ADK) of low-mid rectum. We report the results at 5 years.

Methods

OPERA was a multicenter, phase III trial that included operable patients (pts) ≥ 18 years old, with cT2-cT3b low-mid rectal ADK, tumors < 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. Tumor evaluation was made at week 14, 20 and 24 after treatment start, using clinical exam, endoscopy and magnetic resonance imaging. The primary end point was OP at 3 years. Late follow-up was performed every 3 months for up to 2 years and then every 6 months.

Results

141 pts were evaluable. The median age was 69 years old, 106 pts had distal tumor (75%), 29 pts had a tumors < 3cm in arm A and 32 in arm B. Between week 14-24, a clinical complete (or near) response was observed in 44 pts in group A (65.7%) vs 66 in group B (94.3%) ; p<0.001. The 3-year OP rate was 59% in group A vs 81% in group B (p=0·003). For pts with tumors < 3 cm in diameter, the 3-year OP rate was 63% in group A versus 97% in group B1 (p=0·01).

After update the median follow-up is 61.1 months [56.8-64.5]. The 5-year local relapse was 39% in group A and 17% in group B (p=0.1). The 5-year distant metastasis rate was 14% in group A vs 13% in group B (not significant). At 5 years, the difference in OP was still highly significant between both groups : A 56% vs B 79% (p=0.004). The difference is more significant if tumors < 3cm, with an OP rate of 93% in group B compared to 54% in group A. Rectal bleeding disapeared most of the time after three years.

Conclusions

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 maintained. Occurrence of some local relapses after 3 years make mandatory a close surveillance of these pts during the first 5 years.

Clinical trial identification

NCT02505750.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.