Data from the phase 3 OPERA trial indicates that escalating doses of contact X-ray brachytherapy (CXB) sustain organ preservation and maintain good bowel function in patients with early rectal adenocarcinoma located in the low-mid rectum. The 5-year findings, published in Annals of Oncology, support CXB boost as a valuable treatment option for preserving organs, especially in smaller tumors.
In the OPERA trial, 141 patients with cT2 to cT3b low-mid rectal early rectal adenocarcinoma were enrolled. All patients underwent radiotherapy with EBRT at 45 Gy in 25 fractions with concurrent capecitabine. Subsequently, patients were randomized 1:1 to receive either a boost of EBRT at 9 Gy in 5 fractions (group A) or a boost with CXB at 90 Gy in 3 fractions (group B).
The primary endpoint was organ preservation at 3 years without non-salvageable pelvic disease and diversion stoma. Secondary endpoints included complete and near-complete clinical tumor response rates, overall survival (OS), disease-specific survival (DSS), bowel function, toxicities, and quality of life.
Organ Preservation and Tumor Response
Among 112 patients without total mesorectal excision included in a wait-and-watch (W&W) strategy, a complete or near complete clinical response was observed in 93% of patients who received a boost with CXB compared to 65% of those who received a boost of external beam radiotherapy (P < .0001). Specifically, for tumors less than 3 cm in diameter, these rates were 97% vs 79%, respectively (P = .04), and for tumors 3 cm or larger, the rates were 90% and 55% (P < .001).
At 5 years, the organ preservation rate was 79% in group B (CXB) compared to 56% in group A (EBRT) (HR, 0.4; 95% CI, 0.21-0.75; P = .003). In patients with tumors smaller than 3 cm, the organ preservation rates were 93% vs 54%, respectively (HR, 0.12; 95% CI, 0.028-0.55; P = .006). For tumors 3 cm or larger, the rates were 67% vs 57% (HR, 0.61; 95% CI, 0.29-1.3; P = .17).
The local regrowth rate in the overall population was 16% in the CXB group compared to 33% in the EBRT group (P = .02).
Survival and Bowel Function
The overall survival rate among all patients was 91%. There was no significant difference in OS rates between group A (91%) and group B (92%; P = .5). The 5-year DSS rate was 60% across the entire study population, with 46% in group A and 73% in group B (P = .003).
Bowel function, assessed using the low anterior resection syndrome (LARS) score, showed that 24% of patients in group A had a LARS score of 30 or higher, compared to 17% in group B (P = .5).
Adverse Events
The incidence of grade 2/3 early or late adverse effects (AEs) was similar between the two groups (P = .7). Common AEs included proctitis (6% in group A vs 13% in group B) and radiation dermatitis (9% vs 1%).
Expert Commentary
"The 5-year results of the OPERA trial are encouraging and position the CXB boost as one of the treatment options of choice for achieving organ preservation in tumors [smaller than 3 cm in diameter]," wrote lead study author David Baron, of Centre Antoine Lacassagne, Université Côte d'Azur, Nice, France, and coauthors. The study highlights the potential of CXB to improve organ preservation rates, especially in smaller tumors, offering a less invasive alternative to total mesorectal excision.
