5-year results from the multicentre, phase III OPERA study in which the patients with early rectal cancer received external radiotherapy with capecitabine and were randomised to external beam radiotherapy or contact X-ray brachytherapy boost, demonstrate that increasing the dose of the radiotherapy boost from 9 Gy to 90 Gy significantly increased the organ preservation rate, 79% versus 56%. The efficacy was particularly high in patients with tumours less than 3 cm, with a 5-year preservation rate of 93%.
Contact X-ray brachytherapy boost has been included in the therapeutic options in the French recommendations for the management of rectal tumours under 3 cm diameter according to Dr. David Baron of the Radiotherapy unit, Antoine Lacassagne Center, Université Côte d'Azur in Nice, France and colleagues, who published the findings on 10 November 2024 in the Annals of Oncology.
The authors wrote in the background that contact x-ray brachytherapy is an endocavitary brachytherapy technique that allows for rapid and safe irradiation with high doses in direct contact with the rectal tumour, while preserving the healthy pelvic organs. Watch-and-wait strategies can preserve organs in patients with rectal cancer who achieve a complete clinical response (cCR) after neoadjuvant therapy.
To optimise the chances of achieving a cCR, the OPERA trial compared neoadjuvant chemoradiotherapy with dose escalation by contact x-ray brachytherapy or external beam radiotherapy. The results, with a median follow-up of 3 years, showed a significant improvement in organ preservation rates with neoadjuvant chemoradiotherapy and contact x-ray brachytherapy boost, especially for patients with tumours of less than 3 cm, compared to the external beam radiotherapy boost.
For incomplete response after neoadjuvant treatments or local regrowth, salvage total mesorectal excision surgery can be performed safely and effectively. As the risk of local regrowth is low but persists beyond three years in the watch-and-wait strategy, longer follow-up was needed and the study team reports updated results of the OPERA trial, with a median follow-up of 5 years.
OPERA included operable patients with cT2-cT3b low-mid rectal adenocarcinoma, tumours < 5 cm, cN0 or cN1 < 8 mm. All patients received external beam radiotherapy 45Gy in 25 fractions with concurrent capecitabine. Patients were randomly assigned (1:1) to receive a boost of external beam radiotherapy in group A (9 Gy in 5 fractions) or a boost with contact X-ray brachytherapy (90 Gy in 3 fractions) in group B. The primary endpoint was organ preservation rate.
Among 148 randomised patients, 141 were eligible. Between 14 to 24 week, a clinical complete (or near) response was observed in 44 patients in group A versus 66 in group B (64% versus 92%; p < 0.001). The 3-year organ preservation rate was 59% in group A versus 81% in group B (p = 0.003).
After update the median follow-up was 61.1 months. The 5-year local regrowth was 39% in group A and 17% in group B (p = 0.1). The difference in organ preservation was still highly significant between both groups: 56% in group A versus 79% in group B (p = 0.004). The difference was more significant in tumours less than 3 cm, with an organ preservation 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 with the contact X-ray brachytherapy boost.
The authors concluded that the OPERA was the first study to demonstrate that contact X-ray brachytherapy dose escalation was increasing the organ preservation rate with good bowel function at 3 years. At 5 years, these results are sustained, specially in small early-stage tumours. The occurrence of some local regrowth after 3 years necessitates close surveillance of these patients during the 5-year period.
The 5-year results of the OPERA trial are encouraging and position the contact X-ray brachytherapy boost as one of the treatment options of choice for achieving organ preservation in tumours less than 3 cm. The investigators will provide an update of the OPERA trial at 10 years, considering data from the Lyon R96-02 phase III study, which showed a colostomy-free survival rate of 83% at 10 years for patients with an initial complete clinical response in T2-T3 lower rectal tumours treated with a combination of contact X-ray brachytherapy boost and external beam radiotherapy.
Reference
Baron D, Pace Loscos T, Schiappa R, et al. on behalf of the ICONE Group. 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. Annals of Oncology; Published online 10 November 2024. DOI: https://doi.org/10.1016/j.annonc.2024.10.827