Understanding the impact of perineal reconstruction after extended margin cancer surgery on longer-term quality of life, morbidity and health economic outcomes: protocol for the UK REMACS observational cohort study.

introductionAdvanced and recurrent pelvic cancers pose significant public health challenges due to their invasive nature, affecting pelvic structures like the pelvic floor, other organs and the perineum. Treatment involves chemoradiotherapy followed by extended margin cancer surgery (EMCS) to achieve cancer cure. EMCS results in an empty pelvis prone to major complications like collections, abscesses, bowel obstruction, fistulae and perineal wound breakdown. Known as the empty pelvis syndrome (EPS), this affects >50% of patients. EPS leads to poor quality of life (QoL), reduced return to function and significant financial burden to patients and healthcare services. Perineal reconstruction using myocutaneous flaps or biological meshes may mitigate these complications, but their longer-term clinical outcomes and effectiveness are not well-documented. This study addresses key unmet needs and aligns with strategic healthcare priorities.The Reconstruction after Extended Margin Cancer Surgery (REMACS) study aims to assess the effects of EMCS and perineal reconstruction on QoL, complications and health economic utilisation up to 12 months post-surgery.Objectives include:a. Providing real-world data on 12-month QoL and complications to aid shared decision-making consultations regarding reconstructive techniques post-ECMS.b. Informing clinical practice and patient expectations, improving communication and reducing regret throughout the initial stages of cancer survivorship.c. Evaluating economic impacts on patients and healthcare settings, optimising resource utilisation.d. Uncovering hidden treatment toxicities post-ECMS. METHODS AND ANALYSIS: Design: Multi-centre observational cohort study.

participants236 patients undergoing EMCS with perineal reconstruction in tertiary cancer centres, ensuring diverse representation. DATA COLLECTION: Patients will complete QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30), EuroQol-5 Dimension 5-Level Questionnaire (EQ-5D-5L), Locally Recurrent Rectal Cancer-QoL (LRRC-QoL)) and Decision-Regret questionnaires pre-surgery and 3, 6, 12 months post-surgery. Patient economic impact (COST, patient employment, health resource utilisation), quality-adjusted life years, incremental cost-effectiveness ratios (EQ-5D-5L) and healthcare economic impact will be recorded over 12 months after surgery. Complications (Clavien-Dindo) and pathology outcomes. 5-year survival and cancer recurrence will also be recorded as part of standard of care. Purposefully selected patients (n=30) representing different cancer types and from different geographical regions in the UK, ensuring the inclusion of different ethnic and under-represented minority backgrounds (ie, sexual and gender minorities and those from low socio-economic groups) will be interviewed at 3 and 12 months post-surgery. Patient experiences including preparedness, complex decision-making, complications, regret and hidden cancer treatment toxicities will be explored. ANALYSES: EORTC-QLQ-C30 global health scores at 12 months will be compared between groups (primary outcome: flap versus mesh reconstruction). Descriptive statistics, causal inference techniques and regression modelling will be used to account for allocation bias and heterogeneity. Propensity scoring will weight cases and causal inference techniques will be used to visualise and understand confounding effects. Cost-utility economic analyses will compare reconstructive techniques. Longitudinal interview analyses will use constant comparative methods using reflexive thematic analysis. ETHICS AND DISSEMINATION: REMACS is approved by HRA REC (22/NE/0032). The study is funded by Penguins Against Cancer (Registered Charity Number 1159905), Bowel Research UK (BRUK SG 23019), PLANETS Cancer Charity (Registered Charity Number 1175572) and an NIHR Research for Patient Benefit Grant (NIHR207881).This study will benefit patients internationally by providing real-world outcomes to improve shared decision-making around complex consultations, informing patient expectations and clinical outcomes for QoL, complications and cost after EMCS and perineal reconstruction. Results will be disseminated to researchers, healthcare professionals, patients, carers, charities and policymakers through online platforms, media, scientific conferences and journals. This will raise awareness of late effects of cancer treatment, influence international guidelines and cancer commissioning. TRIAL REGISTRATION NUMBER: Clinical Trials.gov registration number-NCT05219058 and ISRCTN registry number-ISRCTN81241096.