Do nonoperative modality (NOM) treatments of rectal cancer compromise the chance of cure? Final surgical salvage results from OPERA phase 3 randomised trial (NCT02505750).

Abstract

6 Background: Watch and wait strategy without surgery for rectal cancer is gaining popularity as it avoids a stoma. We set up an OPERA trial to evaluate the role of radiation dose escalation using Contact X-ray brachytherapy [CXB] (Papillon). We report on the final surgical salvage results for local failures of non-surgical approach. Methods: OPERA is a European phase 3 randomised trial between (Arm A-standard arm)EBCRT 45Gy/25/5weeks with oral capecitabine 825mg/m2 and EBRT boost of 9Gy/5/5 days randomised against experimental arm (Arm B) EBCRT followed by CXB boost (90 Gy/3/4 weeks). Patients were assessed at 14, 20 and 24 weeks. Watch & wait policy was adopted for patients with cCR and surgery (TME or local excision) offered for residual disease or recurrence after cCR. Results: From July 2015 –June 2020, 148 patients were randomised of which 141 were evaluable. Median age was 68 years and 88 (61%) patients were males. There were 69 patients in Arm A (standard of care with EBRT boost) and 72 patients in Arm B (experimental with CXB boost). All patients received the protocol stratified radiation dose. Median follow-up was 38.2 months (95% CI:34.2-42.5). Clinical complete response (cCR) was observed in 44/69 (64%) in Arm A and 66/72 (92%) in Arm B at 24 weeks (p< 0.001). Surgery was carried out in 66/141 (47%) with suspected residual tumour or local regrowth after achieving cCR. Total 39/66 (59%) patients had TME surgery. Local excision was carried out in 27 /49(41%). Our primary endpoint of organ preservation (OP) rate was 59% (95% CI: 48-72) in Arm A vs. 81% (95% CI: 72-91) in Arm B (HR 0.36, 95% CI: 0.19-0.70; P= 0.0026). When comparing A1(<3cm) vs. B1(<3cm), OP rate was 63% vs. 97% respectively (HR: 0.072, 95% CI 0.0093-0.57; P= 0.0123]). Overall TME free overall survival was 57% for Arm A and 79% for Arm B (HR 0.37,95% CI 0.2-0.71; P=0.0026). Conclusions: OPERA data at 38 months suggest that non-surgical 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. There is significant improvement in OP rate for rectal cancer <3cm to start with CXB followed by EBCRT. This option should be discussed with patients wishing to avoid surgery and a stoma as an initial treatment. Clinical trial information: NCT02505750 . [Table: see text]