This month’s Paper of the Month on early-stage rectal cancer compares radical surgical resection with short-course radiotherapy and TREC.
Radical surgery versus organ preservation via short-course radiotherapy followed by transanal endoscopic microsurgery for early-stage rectal cancer (TREC): a randomised, open-label feasibility study. Published: The Lancet 10 Dec 2020, https://doi.org/10.1016/S2468-1253(20)30333-2
What is known about this subject?
The standard care for early rectal cancer is radical surgical resection according to the total mesorectal excision (TME) principles which comes with a mortality risk of around 2% and considerable short-term morbidity as well as long term bowel, bladder, and sexual dysfunction affecting patients’ QOL. There has been an increasing interest in the primary organ preservation approach for early rectal cancer, but this lacked the support of high-quality evidence.
Method and outcomes
Multicentre randomised, open-label feasibility study done at 21 tertiary referral centres in the UK.
The study also included a non-randomised prospective registry including patients for whom randomisation was considered inappropriate because of a strong clinical indication for one treatment group.
Patients aged 18 or older with early rectal cancer (T2 or lower, N0, a maximum diameter of 30 mm and no metastasis)
Organ preservation (via short-course (25 Gy over 5-7 days) radiotherapy followed by delayed transanal endoscopic microsurgery (8-10 weeks following completion of RT).
Radical surgery (TME) without preoperative chemoradiotherapy.
The cumulative randomisation at 12, 18, and 24 months.
The secondary outcomes included different measures of safety and efficacy.
- From 152 eligible patients identified:
- 55 randomised, 68 recruited to non-randomised registry, and 29 (19%) declined.
- Randomised group: 27 organ preservation and 28 TME at 15 sites.
- Non-randomised registry: 61 organ preservation and 7 TME at 17 sites.
- The cumulative randomisation at 12, 18, 24, and 36 months was 18, 31, 39, and 55 patients.
- Organ preservation:
- Compliance with the decision to organ preservation was high in both groups: 85% in randomised and 90% in the non-randomised group.
- Organ preservation was achieved in 19 (70%) in randomised and 56 (92%) in the non-randomised group.
- High-risk features were present in 24 (86%) of TME (no radiotherapy) versus 16 (59%) of organ preservation (after radiotherapy) group (p=0.03)
- Pathological complete response in organ preservation groups:
- 8 (30%) of the randomised group. 25 (41%) of non-randomised group
- Survival (Median follow-up 4.28 years) in the randomised group:
- Overall survival and DFS: no significant difference between groups
- Local recurrence: 3 (11%) in organ preservation (2 salvageable) vs 0 in TME
- Systemic metastasis: 3 (11%) in organ preservation vs 2 (7%) in TME
- Serious adverse events:
- Randomised group: 4 (15%) in organ preservation vs 11 (39%) in TME (p=0.04)
- Non-randomised group: 10 (16%) in organ preservation vs 1 (14%) in TME
- PROMS (overall QOL, role, social and emotional function, body image and health anxiety) and symptoms (diarrhoea, stool frequency, urinary incontinence, embarrassment about bowel function):
- 90% or greater probability of superiority for organ preservation at 36 months in many PROMs when compared to TME group.
Implications for colorectal practice?
The TREC study is the first study to randomly assign 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.
The study has shown the feasibility of developing multidisciplinary organ preservation teams, opening sites and recruiting patients into a randomised trial design.
The study has also shown that short-course radiotherapy followed by transanal endoscopic microsurgery (TEMs) achieves a high level of organ preservation with less morbidity and better QOL when compared to TME surgery for early rectal cancer. 37.5% of patients in this group achieved pathological complete response following short-course radiotherapy.
These results support the use of organ preservation surgery in patients considered unfit for radical surgery, and also the need for further research to look at the oncological outcomes of different organ preservation surgery for early rectal cancer.