Preliminary surgery salvage data after watch & wait policy from OPERA trial

Conference

ASCO GI 2021

Trial

Phase 3, OPERA

Non-surgical treatment of rectal cancer is becoming more popular as it avoids the morbidity of extirpative TME surgery and a stoma. Preliminary data from the OPERA phase 3 trial shows that organ preservation is feasible in patients who received chemoradiotherapy with capecitabine and two different types of radiotherapy boosts .

As non-operative modality treatment of rectal adenocarcinoma is gaining popularity, a phase 3 randomised trial (OPERA, NCT02505750) was set up to assess a dose escalation contact x-ray brachytherapy (CXB) which could potentially improve organ preservation rates compared to the standard of care.

Inclusion criteria were MRI-stage cT2, cT3a, or b, up to 3 affected lymph nodes (<8 mm), and a maximum tumour diameter of 5 cm. A total of 148 patients were enrolled and randomised between Arm A (standard arm), treated with external beam chemoradiotherapy (EBCRT) 45 Gy/25/5 weeks with oral capecitabine 825 mg/m² and external beam boost of 9 Gy/5/5 days, and Arm B (experimental arm) treated with EBCRT followed by CXB boost (90 Gy/3/4 weeks). Patients were assessed at 14, 20, and 24 weeks. Watch and wait policy was adopted for patients with complete clinical response at 24 weeks after randomisation. Surgery (TME or local excision) was offered for residual disease and also for local recurrence at a later date. The primary endpoint was organ preservation at 3 years.

Preliminary surgical salvage data from OPERA was presented. Median follow-up was 19 months (range 2-36 months). Overall complete clinical response was observed in 103 patients (81%) at 24 weeks, both arms combined (blinded). At 19 months, surgery was performed in 49/144 patients (34%): in 36 because of suspected residual tumour and in 13 as salvage surgery at a later date for local regrowth. Surgery included local excision in 24/49 patients (49%; of which 3 patients proceeded to TME surgery due to R1 or ypT2 adverse histology) and TME surgery in 28/49 (57%). In total, organ preservation was achieved in 116/144 patients (80.5%), again both arms combined (blinded). Overall TME-free survival was 76% at 19 months.

In summary, nonsurgical treatment of cT2, cT3 rectal cancer seems feasible in those who are fit but wish to avoid surgery. Those who failed with residual tumour or those who have a local recur after achieving a complete response, can be offered surgical salvage. Organ preservation of over 80% can be achieved without compromising the chance of cure.

Myint AS, et al. Does non-TME surgery of rectal cancer compromise the chance of cure? Preliminary surgical salvage data from OPERA phase III randomized trial. ASCO Gastrointestinal Cancers Symposium 2021, 15-17 January. Abstract 12.

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