The clinical and pathological factors influencing outcomes following treatment for locally advanced or locally recurrent rectal cancer by pelvic exenteration

Gould, Laura (2026) The clinical and pathological factors influencing outcomes following treatment for locally advanced or locally recurrent rectal cancer by pelvic exenteration. PhD thesis, University of Glasgow.

Abstract

Rectal cancer remains a significant oncological challenge, particularly when locally advanced or recurrent disease necessitates radical surgery. Pelvic exenteration (PE) offers the greatest potential for cure in carefully selected patients with locally advanced rectal cancer (LARC) or locally recurrent rectal cancer (LRRC), yet it is associated with considerable morbidity and variable long-term outcomes. This thesis explores the clinical, pathological, and host factors influencing outcomes following PE.
Chapters 1& 2 introduce the background, evolution, and rationale for exenteration surgery, outlining the indications, operative techniques, and perioperative management. They highlight the ongoing challenge of balancing oncological clearance with postoperative function and quality of life and identify key knowledge gaps in predicting outcomes in this complex patient group.
Chapter 3 presents a systematic review, exploring the clinicopathological determinants of outcome following resection for locally advanced and recurrent rectal cancer. Margin status consistently emerges as the strongest predictor of survival, yet the biological factors driving local recurrence remain poorly understood. Current literature gaps in defining and characterising locally recurrent tumours are explored. The chapter underscores the need for a more integrated understanding of tumour biology and host response beyond conventional staging.
Chapter 4 describes the creation of a prospectively maintained Complex Cancer Clinic (CCC) database at St Mark’s Hospital. It describes patient inclusion, data collection, and methodology used to assess surgical, clinical, and pathological factors in patients undergoing exenteration. This cohort forms the foundation for subsequent clinical and translational analyses. Included in this chapter are the outcomes for patients who are referred to the CCC but do not undergo PE, which provides a valuable insight into the natural evolution of the disease.
Chapter 5 explores the boundaries of what is achievable with modern PE surgery by presenting the outcomes for patients who have undergone PE with en bloc high sacrectomy and extended lateral pelvic sidewall excision. Despite historical concerns over morbidity, the study demonstrates that R0 resection rates of 95% and 5-year survival exceeding 56% are achievable in specialised centres. Although perioperative morbidity and mortality remain significant, most long-term survivors retain good mobility and independence. These findings challenge traditional contraindications to surgery for high sacral or sidewall involvement and emphasise the importance of centralised multidisciplinary care.
Chapter 6 evaluates outcomes of perineal reconstruction following complex rectal cancer resections, comparing standard versus high-complexity exenterations to assess if a greater magnitude of surgery influences perineal wound-related morbidity. In a cohort of 194 patients, flap-related complications were common but not significantly increased by surgical complexity, with no cases of total flap failure. Obesity and total pelvic exenteration were independent predictors of short-term wound morbidity, while urinary tract leaks drove late complications. The study concludes that gluteal flaps provide a durable, versatile reconstructive option even in high-risk settings, highlighting the importance of multidisciplinary planning and patient optimisation.
Chapters 7 and 8 examine clinical, surgical and tumour-related factors influencing both short- and long-term outcomes. These chapters confirm that achieving an R0 resection remains paramount but demonstrate that other host factors, such as comorbidity, inflammation, and metabolic state, also contribute to postoperative risk and survival variability. They also reveal that the key factors that appear to influence outcome in patients with LARC differ from those in LRRC.
Chapter 9 extends the analysis to host body composition, using computed tomography (CT)–based body composition profiling to assess sarcopenia, myosteatosis, and visceral obesity. Myosteatosis and visceral obesity were significantly associated with increased postoperative morbidity and prolonged hospital stay, while sarcopenia showed a weaker association, likely reflecting selection bias within this fitter surgical cohort. Although no CT-derived body composition measures significantly influenced long-term survival, a trend toward reduced local recurrence-free survival was observed among patients with myosteatosis. These findings emphasise the interplay between tumour biology, systemic inflammation, and host physiology in shaping patient outcomes.
Chapter 10 provides a unique insight into the tumour microenvironment in locally recurrent rectal cancer, focusing primarily on immune cell infiltration and tumour stromal composition. It highlights significant variability in immune and stromal profiles between primary and recurrent disease, suggesting distinct biological behaviour. These findings underscore the importance of tumour–host interactions in influencing local control and recurrence patterns.
In conclusion, this thesis demonstrates that outcomes following pelvic exenteration are determined not only by surgical and pathological factors but also by host-related characteristics, including systemic inflammation and altered body composition. Integrating these elements into preoperative assessment frameworks may enhance patient selection, enable risk-adapted perioperative care, and guide the development of prehabilitation and nutritional optimisation strategies. Future research exploring the molecular mechanisms linking tumour–host interaction, metabolic dysfunction, and immune modulation could provide novel therapeutic insights and refine multidisciplinary management in this complex field.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer); R Medicine > RD Surgery
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Supervisor's Name: Jenkins, Mr. Ian, Steele, Dr. Colin and Roxburgh, Professor Campbell
• Date of Award: 2026
• Depositing User: Theses Team
• Unique ID: glathesis:2026-85841
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 25 Mar 2026 16:45
• Last Modified: 27 Mar 2026 10:48
• Thesis DOI: 10.5525/gla.thesis.85841
• URI: https://theses.gla.ac.uk/id/eprint/85841

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