Radical surgery versus organ preservation

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

Design

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.

Population

Patients aged 18 or older with early rectal cancer (T2 or lower, N0, a maximum diameter of 30 mm and no metastasis)

Intervention

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).

Control

Radical surgery (TME) without preoperative chemoradiotherapy.

Primary Outcome

The cumulative randomisation at 12, 18, and 24 months.

Secondary Outcomes

The secondary outcomes included different measures of safety and efficacy.

Results

  • 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.

Dukes’ Club review of the year

It has clearly been a difficult year. As the official training arm of the Association of Coloproctology of Great Britain and Ireland, we believe that the Dukes’ Club has strongly supported and represented trainees throughout the year. Here, we review our activities during 2020.

Dukes’ COVID-19 Taskforce

The Dukes’ COVID-19 Taskforce was set up in March. This taskforce has worked alongside ASiT and ACPGBI in representing colorectal trainee views on a range of training issues including progression of training, FRCS examinations, ARCPs and CCT competencies. Our key priorities during the first wave of COVID-19 were to support colorectal surgery trainees to continue delivering high quality emergency and elective services and to maintain trainee well-being. We launched our Keeping Well Podcast series during this time to support and maintain well-being – a total of nine podcasts on a variety of aspects of well-being including managing stress, kindness, human factors, resilience and leadership. We continue to work hard to ensure that high quality training and research is maintained and trainee progression is enabled as the pandemic continues.

Dukes’ Educational Strategy

Throughout the year we worked hard to deliver high quality educational content. In the early new year we delivered subspecialty events across the UK in advanced cancer, pelvic floor and emergency surgery and ran our first ‘Consultant Interview Preparation’ course in February. Unfortunately we had to cancel our annual education weekend, but instead launched our virtual educational strategy. This started with a series of virtual cadaveric sessions, debates on controversial topics and radiology teaching in advanced CRC, delivered in association with the ACPGBI Advanced Malignancy Subcommittee. In July, the Dukes’ Club enjoyed a successful and integrated programme at the virtual ACPGBI Fringe, co-chairing and presenting in many sessions across the busy week’s programme. We are grateful to Professor Nancy Baxter who delivered a stunning lecture for this year’s Dukes’ keynote lecture titled ‘Reflections on a career training tomorrow’s colorectal surgeons.’ More recently we have launched our ‘Colorectal Classroom’ series, with the first two events well attended and very well received. Look out for the next instalment in the early new year!

Dukes’ Virtual Week

The September Dukes’ Club virtual event was our biggest educational event to date, with over 1000 delegates registering for sessions across a jam-packed exhausting but inspiring week. We are hugely grateful to our brilliant speakers and generous sponsors, and to ACPGBI for their support in delivering this fantastic event. Every day of the virtual week saw a varied assortment of operative video sessions, Spotlight sessions, training hacks and keynote lectures. A full report is available here.

Colonoscopy Training

We are delighted that the new UK General Surgical curriculum now includes an indicative requirement of 200 diagnostic colonoscopies for surgical trainees who have declared colorectal as their subspecialty interest. This change reflects years of hard work by the Dukes’ Club and indicates the JCST’s commitment to colonoscopy training. However, we are aware that many of our members have experienced increasing difficulty in accessing colonoscopy training opportunities and achieving accreditation – challenges that have been acutely accentuated by the COVID-19 pandemic. We are working hard together with the ACPGBI Colonoscopy and Education and Training committees to improve exposure and opportunities and will soon publish a joint statement on colonoscopy training in Colorectal Disease.

Industry Partnership

Our platinum industry sponsor during 2020 has been Ethicon. Our expansion in portfolio has been generously supported by a number of industry partners including Ethicon, Cook Medical and THD. We welcome Intuitive Surgical as our latest industry partner in 2020. We have strengthen our relationships with all industry partners over the last 12 months which has enabled us to provide a range of high quality teaching and educational opportunities to our membership.

Future Plans

Overall, we have enjoyed a very successful year despite difficult circumstances, with the significant expansion of our portfolio of physical and virtual activities on a regional and national scale. We will continue to build on our successes over the last 12 months to deliver high quality, innovative educational and research opportunities to our membership. Please do complete our survey to tell us what you want from the Dukes’ Club.

PhD Project: Linking IBD to the hygiene hypothesis

Linking Inflammatory Bowel Disease to the Hygiene Hypothesis.

Professor Simon M. Cutting, Dept. Biological Sciences, Royal Holloway University of London, Egham, Surrey, TW20 0EX. s.cutting@rhul.ac.uk

Mr Philip Bearn MS FRCS, Dept of Colorectal Surgery, Ashford and St Peter’s NHS Foundation Trust, Guildford St, Chertsey Surrey KT16 0PZ. Philip.bearn@nhs.net. Honorary Senior Lecturer, Dept. Biological Sciences, Royal Holloway University of London, Egham, Surrey, TW20 0EX

Inflammatory bowel disease (IBD) broadly covers two inflammatory disorders of the GI-tract, ulcerative colitis and Crohn’s disease. Both cause diarrhoea, abdominal pain and weight loss. In severe cases surgical intervention may be required and in some the disease can be life-threatening. Diet and stress can aggravate the disease but the underlying causes are poorly understood. Immune malfunction is a likely cause and IBD is more common in families with a history of the disease.

What is known is that those at greatest risk of developing IBD are aged >30 years old, have a family history of IBD and are those who live in industrialised countries. Intriguingly rates of IBD have risen dramatically in the last 30 years posing a potentially significant financial burden on public health (Lancet Gastroenterol Hepatol. 2020; 5:17-30).

We are interested in understanding whether the Western lifestyle contributes to the rising rates of IBD? The Hygiene Hypothesis has been shown to play a role in the rise in allergic disorders over the last 50 years (Scudellari, PNAS, 2017, 114:1433-1436; Stiemsma et al, Immunotargets and Therapy, 2015, 4:143-157). In work being concluded in the Cutting lab we have shown that reduced exposure to environmental bacteria contributes to increased susceptibility to C. difficile infection witnessed in the USA and UK. We wonder then whether a sedentary lifestyle and poor diet coupled and a hyper-sanitised environment may also comprise a risk factor for IBD.

In this project you will first establish an animal (murine) model of IBD. Three models of IBD are known (Kiesler et al, http://dx.doi.org/10.1016/j.jcmgh.2015.01.006), and working with skilled staff in the Cutting lab you will establish and validate the model. This will involve analysis of clinical signs, pathology as well as immunological assessment (e.g., FACS analysis of cytokines). Next, you will work on a large collection of environmental bacteria in the Cutting lab and rapidly screen these for potential in vitro activity to markers linked to IBD. Finally, you will evaluate bacteria or bacterial compounds for efficacy against IBD in your animal models.

During the 3 years, the successful candidate will have a contract of employment at ASPH NHS Foundation Trust with on call and clinical commitments at appropriate level. In addition endoscopy training can be provided around laboratory hours.

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