Background

The OPERA trial aims to evaluate whether dose escalation using Contact X-ray brachytherapy [CXB] (Papillon) improves the chance of organ preservation compared to external beam chemoradiotherapy (EBCRT) in patients who are suitable but wish to avoid surgery or a stoma. Attainment of equivalent oncological outcomes using an organ preserving strategy depends on early and effective surgery in patients who do not achieve a clinical complete response (cCR) following radiotherapy or who develop local tumour regrowth after cCR. However, there remain concerns about safety and feasibility of surgery following radiotherapy with dose escalation. We report preliminary data on the safety and feasibility of surgical salvage in 142 patients from OPERA.

Method

OPERA is a European phase 3 RCT (NCT02505750) comparing EBCRT 45Gy/25/5weeks with oral capecitabine 825mg/m² and EBRT boost of 9Gy/5#/5 days (Arm A- standard arm), against EBCRT followed by CXB boost (90 Gy/3#/4 weeks) (Arm B- experimental arm). Patients were assessed at 14, 20 and 24 weeks. A watchful waiting strategy was adopted if patient achieved cCR. Surgery (Total mesorectal excision- TME, or Local excision- LE) was offered for residual disease and local regrowth. Trial complete in June 2020.

Results

From July 2015 –January 2020, 142 patients were evaluable. There were 71 patients in Arm A and 71 patients in Arm B. Kaplan Myer TME free survival at 18 months was 76%.

Surgery was needed in 47/ 142 (33%) patients. LE was undertaken in 20 /47 (42%). TME in 27/47(58  %) of which 8/27(29.6%) had abdominoperineal excision. No residual tumour (ypT0) was found in 21% and 91% had R0 resections. Three patients with R1 following L.E had TME surgery.  Local regrowth occurred in 13/142 (9%). 7/142 (4.9%) patients developed distant metastases. Organ preservation was achieved in 115/142(80.9%) at 18 months.

Conclusion

Non-surgical management of rectal cancer is feasible in patient who wish to avoid surgery or a stoma.  Patients who needed surgery the R0 resection rate, chance of organ preservation and early oncological outcomes were not compromised.

Impact statement

It will change the standard of care in the management of retal cancer in patients who are suitable but wish to avoids surgery and a stoma.