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

D Baron; T Pace Loscos; R Schiappa; N Barbet; E Dost; S Ben Dhia; S Soltani; L Mineur; I Martel; S Horn; C Picardi; A Stewart; E Cotte; R Coquard; G Baudin; L Evesque; A Dhadda; A Sun Myint; J P Gérard; J Doyen; ICONE group

doi:10.1016/j.annonc.2024.10.827

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

Ann Oncol. 2024 Nov 10:S0923-7534(24)04904-4. doi: 10.1016/j.annonc.2024.10.827. Online ahead of print.

Authors

D Baron¹, T Pace Loscos², R Schiappa², N Barbet³, E Dost², S Ben Dhia², S Soltani⁴, L Mineur⁵, I Martel⁶, S Horn⁷, C Picardi⁸, A Stewart⁹, E Cotte⁷, R Coquard³, G Baudin², L Evesque², A Dhadda¹⁰, A Sun Myint¹¹, J P Gérard², J Doyen²; ICONE group

Affiliations

¹ Centre Antoine Lacassagne, Université Côte d'Azur, Nice, France. Electronic address: david.baron@nice.unicancer.fr.
² Centre Antoine Lacassagne, Université Côte d'Azur, Nice, France.
³ Centre Oncologie Radiothérapie Bayard, Villeurbanne, France.
⁴ Institut de Cancérologie de la Loire, Saint Etienne, France.
⁵ Institut Sainte Catherine, Avignon, France.
⁶ Le Centre Régional de Lutte Contre le Cancer Léon Bérard, Lyon, France.
⁷ CHU de Lyon, Lyon, France.
⁸ Klinik Bethanien, Swiss Medical Network, Zürich, Switzerland; Hirslanden Klinik, Zürich, Switzerland.
⁹ St Luke's Cancer Centre, Guilford.
¹⁰ Queen's Centre for Oncology, Castle Hill Hospital, Hull, UK.
¹¹ Clatterbridge Cancer Centre, Clatterbridge, UK.

PMID: 39532203
DOI: 10.1016/j.annonc.2024.10.827

Abstract

Background: 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.

Patients and methods: 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.

Results: 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.

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, 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.

Keywords: TME surgery; contact X-ray brachytherapy; neoadjuvant treatment; organ preservation; randomised trial; rectal cancer.