Patients with cT2-cT3a-b rectal cancer may benefit from a ‘watch and wait’ approach, according to the results of a new study.

Researchers concluded that non-total mesorectal excision (TME) surgical treatment for these individuals is feasible, assuming they are fit and wish to avoid surgery. On the other hand, patients who require surgical intervention can be offered salvage surgery, either immediately for local residual disease or at a later date for local regrowth. 

In a presentation during the 2021 Gastrointestinal Cancers Symposium of the American Society of Clinical Oncology (abstract 12), the investigators noted that non-operative treatment of rectal cancer is becoming increasingly popular among clinicians, as it avoids extirpative TME surgery and a stoma. 

To help compare these two treatment modalities, the researchers embarked on the so-called OPERA trial (NCT02505750). The study was designed to compare dose escalation using contact x-ray brachytherapy (CXB) with the current standard of care -- external beam chemoradiotherapy (EBCRT) plus TME surgery – with respect to improving the likelihood of organ preservation.

“We report on the preliminary surgical salvage data for treatment failures in the OPERA trial,” the authors wrote.

The investigators enrolled 148 patients (mean age 68 years; 61% males) into the pan-European study between July 2015 and June 2020. The majority of patients (63.9%) were at a T stage of CT2; the remainder at cT3a/b (36.1%). More than half of patients (57%) had tumors with a greatest diameter >3 cm, while the remaining 43% had tumors whose greatest diameter was <3 cm.

The participants were randomized to undergo one of two treatment regimens:

• standard care comprising EBCRT 45 Gy/25/5 weeks with oral capecitabine 825 mg/m2 plus a boost of external beam radiation therapy (EBRT) of 9 Gy/5/5 days; or 

• experimental care comprising EBCRT followed by a boost of CXB boost (90 Gy/3/4 weeks). 

Patients were all assessed at weeks 14, 20, and 24. The watch-and-wait policy was adopted for individuals who demonstrated clinical complete response at 24 weeks after randomization. By comparison, those who had residual disease and/or local regrowth were offered surgery, either TME or local excision, at a later date.

According to primary author Arthur Sun Myint, of The Clatterbridge Cancer Centre, United Kingdom, the final study population comprised 144 evaluable patients, 71 of whom underwent standard therapy and 73 of whom underwent experimental therapy. The median follow-up time was 19 months (range 2-36 months). 

Interestingly, organ preservation was achieved in 116 of the 144 patients in the entire cohort (80.5%). What’s more, Kaplan Meier estimates of TME-free survival at 19 months was 76%.

The researchers observed overall clinical complete response in 103 of 127 evaluable patients in both study arms (81%) at 24 weeks. Surgery was performed in 36 of these patients (28%) with suspected residual tumour. Moreover, 13 patients had salvage surgery at a later date for local regrowth. 

By 19 months, 49 of 144 evaluable patients (34%) in the total cohort had undergone surgery. Of these, 24 (49%) underwent local excision, three of whom went on to undergo TME surgery because of R(1) or ypT2 adverse histology. In total, TME surgery was performed in 28 of the 49 patients. Of these, eight (28.6%) underwent abdomino perineal resection, while the remaining 20 (71.4%) had anterior resection. 

In light of these findings, the researchers concluded that non-TME surgical treatment for cT2-cT3a-b rectal cancer is feasible in fit patients who want to avoid surgery. 

“Organ preservation of 80.5% can be achieved without compromising their chance of cure,” the authors wrote.