Does non-TME surgery of rectal cancer compromise the chance of cure? Preliminary surgical salvage data from OPERA phase III randomized trial.

Abstract

12 Background: Non-operative modality (NOM) treatment of rectal cancer is gaining popularity as it avoids extirpative TME surgery and a stoma. OPERA trial was set up to evaluate the role of dose escalation using Contact X-ray brachytherapy [CXB] in improving the chance of organ preservation compared to the standard of care (EBCRT and TME surgery). We report on the preliminary surgical salvage data for treatment failures in the OPERA trial (NCT02505750). 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 (Arm B- experimental arm) 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 at 24 weeks after randomisation and surgery (TME or local excision) was offered for residual disease and also for local regrowth (recurrence) at a later date. Results: From July 2015 –June 2020, 148 patients were randomised of which 144 were evaluable (table). There were 71 patients in Arm A (standard) and 73 patients in Arm B (experimental). Median follow-up was 19 months (range 2-36 m). Overall clinical complete response (cCR) was observed in 103 out of 127 evaluable patients (81%) at 24 week in both arms (blinded). Surgery was carried out in 36/ 127 (28%) patients with suspected residual tumour. Further 13 patients had salvage surgery at a later date for local regrowth. At 19 months, 49/144 (34%) patients in total cohort had surgery. Local excision was carried out in 24 /49(49%) of which 3 proceeded to TME surgery due to R (1) or ypT2 adverse histology. TME surgery was carried out in 28/49 of which 8/28 (28.6%) had APER and 20/28(71.4%) had AR. In total, organ preservation (blinded) was achieved in 116/144 (80.5%) for the whole cohort. Kaplan Meier estimate of TME free survival is 76% at 19 months. Conclusions: Non-TME surgical treatment for cT2-cT3a-b rectal cancer is feasible in those who are fit and wish to avoid surgery (Watch & Wait). Those who needed surgery can be offered salvage surgery immediately for local residual disease or for local regrowth at a later date. Organ preservation of 80.5% (blinded) can be achieved without compromising their chance of cure. Clinical trial information: NCT02505750. [Table: see text]