Title: Surgical complexity and the effect of timing of surgery after chemo-radiotherapy for rectal cancer, a pilot RCT
Funder: Department of Health (England)

Abstract: Background Surgery is the mainstay of treatment for rectal cancer, but the addition of neo-adjuvant chemo-radiotherapy (CRT) results in down-staging, decreased local recurrence and improved survival. However, radiotherapy also causes inflammation that makes surgery particularly challenging, which can have a detrimental effect on clinical outcomes. The ideal time interval between CRT and surgery should allow adequate time for resolution of the inflammatory changes and optimize tumour response. This may make surgery less challenging, improve rates of sphincter preserving surgery and reduce intra- and post-operative complications, therefore improving patient/clinical outcomes. Surgeons offer surgery at various times from 4 to 12 weeks after CRT, with scant clinical evidence to support their decision. Aims The overall aim of the study is to pave the way for a definitive randomised controlled trial by confirming its rationale and piloting all necessary components of that trial. The twin objectives are: (1) To assess the efficacy of an interval of 12 (rather than 6) weeks between CRT and surgery for the reduction of surgical technical complexity, and therefore surgical errors. (2) To test processes and gather information for the planning of a large RCT investigating the impact of the timing of surgery following neo-adjuvant chemo-radiotherapy for locally advanced rectal cancer. The aim of the future large RCT will be to assess the clinical- and cost-effectiveness of delaying surgery following neo-adjuvant chemo-radiotherapy for patients with locally advanced rectal cancer. Plan of Investigation Fifty patients needing surgery for rectal cancer following neo-adjuvant CRT will be recruited from 6 centres across the Avon, Somerset and Wiltshire Cancer Services Network (ASWCS). Consenting patients will be randomised to receive surgery either 6 or 12 weeks after standard neo-adjuvant CRT. Surgical practice and care (eg open or laparoscopic, use of an enhanced recovery programme) will be at the discretion of the surgeon and according to local policy. Surgical complexity will be assessed by a standardised tool recording errors and near-misses. Other outcomes include blinded radiological and pathological assessment of response to CRT and quality of resection, surgical complications and quality of life. Qualitative interviews will assess psychological impact and patient experience. Potential Impact Delaying surgery from 6 weeks to 12 weeks post CRT has the potential to reduce the technical complexity of surgery and the number of intra-operative complications. This may increase the rate of sphincter-sparing surgery, improve nerve preservation, reduce post-operative complication rates and improve recovery and other patient outcomes. It may also produce savings through reduced operating times, length of stay and care needs. Given the number of cases and deaths from rectal cancer, the challenging nature of the surgery and numbers of complications typically arising, the potential impact for patients and the NHS is considerable. The direct impact from this proposal is in enabling the definitive trial to proceed to answer the key questions with confidence.


Research activity codes: 6.4 SURGERY
Health categories: CANCER AND NEOPLASMS