STAR-TREC phase II: Can we save the rectum by watchful waiting or transanal surgery following (chemo)radiotherapy versus total mesorectal excision for early rectal cancer?

Abstract

3502 Background: No randomised trials have compared non-operative organ preservation (OP) therapy for early-stage rectal cancer versus standard of care (SoC) using total mesorectal excision (TME) alone. STAR-TREC evaluated the feasibility of recruiting to a study comparing contrasting OP therapies, optimised for treatment of early tumours, versus SoC. Methods: STAR-TREC was a prospective, randomised, open-label, feasibility study in the UK, Netherlands and Denmark. Patients with biopsy proven adenocarcinoma of the rectum, staged ≤mrT3b N0 M0, ≤40mm diameter, ECOG 0-1 were randomised in a 1:1:1 ratio to TME, OP via mesorectal short-course radiotherapy (5x5 Gy), or OP via mesorectal chemo-radiotherapy (25x2 Gy + capecitabine) (Peters FP et al. Mesorectal radiotherapy for early stage rectal cancer: A novel target volume. Clin Transl Radiat Oncol 2020; 21: 104-11). Standardised response assessment classified OP cases as complete response for no further treatment, partial response for transanal endoscopic microsurgery or poor response for TME by 20 weeks. Surveillance following OP consisted of 3-monthly endoscopy/MRI. All cases had CT thorax/abdomen/pelvis at 24 months (m). The primary outcome was recruitment rate over 2 years, with randomisation of 120 international cases calculated as sufficient to support a phase III trial. Secondary outcomes included acute toxicity, stoma and OP rates at 12m, disease free survival (DFS) and non-regrowth DFS (NRDFS) at 24m and EORTC QLQ-C30 summary score at 12 and 24m. Phase II analysis was pre-specified, approved by the data monitoring committee conditional upon grouping of OP arms to inform phase III design, without prejudicing the outcome (STAR-TREC Phase III protocol. Colorectal Disease 2022). Results: Recruitment endpoints were met on 28 Oct 2019. Key secondary outcomes are tabulated by intention to treat. No 6-month mortality occurred. Conclusions: OP pathways optimised for early tumours reduce acute surgical morbidity without introducing substantial radiation toxicity to achieve OP in 60% with no increase in NRDFS at 24m compared to SoC. Overall quality of life was evenly matched. STAR-TREC phase III will determine the optimal strategy for achieving OP (STAR-TREC Phase III protocol. Colorectal Disease 2022). Clinical trial information: NCT02945566. [Table: see text]