Minimally invasive tissue-sparing surgery safe in Early Rectal Cancer: Lancet

Cancer survivors report long-term bowel, bladder, and sexual dysfunction following total mesorectal excision that impairs quality of life (QOL). Interest in primary organ preservation for early-stage rectal cancer is gathering momentum but there is a lack of high quality, prospective, randomised evidence to justify its adoption. To address the lack of randomised evidence describing the trajectory of symptomatic toxicity and health-related quality of life (HRQOL) following organ preservation and total mesorectal excision researchers conducted a first feasibility study (TREC) in patients with early-stage rectal cancer to organ preservation (via short-course radiotherapy and delayed transanal endoscopic microsurgery) or radical surgery (total mesorectal excision) without preoperative chemoradiotherapy. Researchers conducted this study to determine the feasibility of randomisation between two markedly different treatment options. They also aimed to explore the impact of the novel organ preservation intervention to inform the design of a larger phase 3 study comparing radical surgery with organ preservation.

Trial details are:

♦It was a randomised, open-label feasibility study done at 21 tertiary referral centres in the UK between Feb 22, 2012, and Dec 19, 2014. A total of 55 patients (>18 years) with rectal adenocarcinoma, staged T2 or lower, with a maximum diameter of 30 mm or less were included in the study. whereas, patients with lymph node involvement or metastases were excluded.

♦Patients were randomly assigned to either organ preservation with short-course radiotherapy followed by transanal endoscopic microsurgery after 8–10 weeks (n=27) or total mesorectal excision (n=28).

♦The cumulative randomisation at 12, 18, and 24 months was determined as a primary endpoint. Secondary endpoints assessed were safety, efficacy, and health-related quality of life assessed with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and CR29 in the intention-to-treat population.

♦The mean age of patients in both arms was 65. No patients died within 30 days of initial treatment, but one in the organ-preservation group died within 6 months of conversion to total mesorectal excision, which led to anastomotic leakage.

Key findings of the study were:

♦Eight patients (30%) required conversion to total mesorectal excision, and four of 27 (15%) had serious adverse events compared with 11 of 28 (39%) in the surgical arm.

♦Serious adverse events associated with organ preservation were most commonly due to rectal bleeding or pain following transanal endoscopic microsurgery (reported in three cases). In contrast, radical total mesorectal excision was associated with medical and surgical complications including anastomotic leakage (two patients), kidney injury (two patients), cardiac arrest (one patient), and pneumonia (two patients).

♦As for tumor recurrence, histopathological features associated with increased risk after transanal endoscopic microsurgery alone were present in 16 of 27 patients (59%) who underwent organ preservation, and 24 of 28 (86%) patients who underwent total mesorectal excision.

♦The researchers noted, patients who underwent organ preservation showed improvements in patient-reported bowel toxicities and quality of life and function scores in multiple items compared to those in total mesorectal excision, which were sustained over 36 months' follow-up.

♦In a concomitant 17-site non-randomized study, 61 patients underwent organ preservation and seven had radical surgery. The non-randomized patients who had organ preservation were older than the randomized patients and were more likely to have life-limiting comorbidities.

♦Researchers reported 10 of 61 (16%)Serious Adverse events in non-randomized patients who underwent organ preservation arm vs one of seven (14%) patient who underwent total mesorectal excision.

♦They noted 24 (39%) of 61 non-randomised patients assigned to organ preservation treatment had high-risk histopathological features, while 25 (41%) of 61 achieved a complete response.

♦Overall, organ preservation was achieved in 19 (70%) of 27 randomised patients and 56 (92%) of 61 non-randomised patients.

The authors concluded, "TREC provides evidence to support further evaluation of organ preservation strategies that incorporate short-course radiotherapy as an alternative to radical surgery for early-stage rectal cancer. This is a feasible and acceptable approach for patients. Further evaluation of short-course radiotherapy is justified because of the excellent compliance, low toxicity, benefits in HRQOL, and high organ preservation rates observed in TREC".

For further information:

https://www.thelancet.com/journals/langas/article/PIIS2468-1253(20)30333-2/fulltext