Contact radiation boost improves EBCRT outcomes in rectal cancer

In the final surgical salvage results of the phase III OPERA* trial, boosting a neoadjuvant external beam chemoradiotherapy (EBCRT) regimen with contact X-ray brachytherapy (CXB) led to better organ preservation (OP) rates than with EB radiotherapy (EBRT) in individuals with rectal cancer.

The primary endpoint of OP rate at 36 months was markedly higher with CXB vs EBRT (81 percent vs 61 percent; hazard ratio [HR], 0.36; p=0.0039), as was the 3-year survival rate with OP (79 percent vs 57 percent; HR, 0.37; p=0.0026). [ASCO GI 2023, abstract 6]

“We set up the OPERA trial to evaluate the role of radiation dose escalation using CXB,” said Professor Arthur Sun Myint from the Clatterbridge Cancer Centre, Merseyside, UK, at ASCO GI 2023. Sun Myint and colleagues randomized 148 participants (median age 68 years, 61 percent male) 1:1 to receive EBCRT 45 Gy/25/5 weeks with oral capecitabine 825 mg/m² and a boost with either CXB 90 Gy/3/4 weeks or EBRT 9 Gy/5/5 days. Median follow up was 38.2 months.

The CXB arm was further stratified by tumour size. Patients with tumours <3 cm received CXB first, while those with tumours >3 cm received EBCRT first. This is so because the applicator used for CXB only allows tumours <3 cm to be treated initially, noted Sun Myint.

The OP rate was higher for tumours <3 vs >3 cm (97 percent vs 63 percent; HR, 0.073; p=0.0124). This implies that starting with CXB first confers significant improvement in OP rate for smaller rectal cancers, noted Sun Myint.

 

Other outcomes

At 6 months, about two-thirds of participants in the EBRT arm achieved clinical complete response (cCR). In the CXB arm, >90 percent were able to achieve this outcome.

Overall, surgery was carried out for 47 percent of participants with suspected residual tumour or local regrowth after achieving cCR. Surgery was either through local excision for small tumours (in 41 percent) or TME** for large, bulky tumours (in 59 percent).

 

Little collateral damage

Although CXB applies a very high radiation dose, it utilizes low-energy X-rays and a very small volume (<5 cc) that is directly targeted on the tumour, Sun Myint explained. “There is very little collateral damage and less side effects.”

Looking at the endoscopic response in one of the CXB recipients, shrinkage was already evident after two fractions of radiation, with normal tissue surrounding the mucosa, he continued. “At 4 weeks from the first fraction, there’s hardly any tumour left.”

 

Watch-and-wait sans surgery: Is it feasible?

“In rectal cancer, surgery is the standard of care for all tumour types. Even in the very early stages, radiation is not included in the [treatment strategy],” said Sun Myint. Radiation is only used for very advanced tumours with involved resection margins. In such cases, CRT is initially given to downstage the tumour and render it operable eventually.

“However, watch-and-wait strategy without surgery for rectal cancer is gaining popularity, as this avoids the need for a stoma,” Sun Myint pointed out.

In OPERA, responders with no residual tumours followed a watch-and-wait protocol. With more patients in the EBRT arm needing surgical salvage for local failures*** than in the CXB arm (70 percent vs 30 percent), this implies that more CXB recipients were able to hold off on surgery. Moreover, only 10 percent of CXB recipients had a stoma, as opposed to 15 percent in the EBRT arm.

“[Our] data suggest that nonsurgical treatment for cT2-cT3a-b rectal cancer is feasible and those who needed surgery for local failures can be salvaged without compromising their chance of cure,” said Sun Myint. “This option should be discussed with patients wishing to avoid surgery and a stoma as an initial treatment.”

He added that they hope these data can provide evidence to change practice in rectal cancer management by accepting an alternative treatment option for these patients.