Determination of prognostic factors in early rectal cancer and the implications for rectal preservation surgery

Thesis

Local excision of early rectal cancer has benefits to patients, with reduced morbidity compared to radical surgery, but carries a higher risk of local recurrence. A detailed analysis of contemporary outcomes after local excision by TEM is presented. Currently, a coarse estimate of the recurrence risk is made on routine histopathological features and patients are advised regarding the options for subsequent management: radical surgery is the current standard if high risk; adjuvant radiotherapy is used in some places to reduce risk but is unproven; or close surveillance. Better, more accurate, and individualised means of predicting recurrence risk are sought to aid this decision process in this clearly defined group. Potential prognostic factors addressed in this work are sentinel lymph node biopsy (Chapter 3), more detailed histopathological analysis including routine mutation panel testing (Chapter 4), and digital pathology assessment and gene expression (Chapter 5). Areas of promise are perineural invasion, absence of common mutations, artificial intelligence-based assessment of the ratio of desmoplastic to inflamed stroma, and expression levels of certain genes, particularly those involved in the immune response. A search is also made for potential indicators of responsiveness to radiation which would help guide the decision to use this modality and spare patients with unresponsive tumours from potentially harmful exposure; this may also be of benefit to those with more advanced cancers considering neoadjuvant treatment, and some consideration is given to this group. Some of the early cancers display transition from adenoma, and differential molecular features that may cast light on this process are sought (Chapter 6). Finally, an assessment of functional outcomes after various rectal-preserving pathways is also made (Chapter7). More accurate and clinically practical recurrence prediction can be made now using readily accessible information, and further work on some of the gene signatures identified could improve this still further.

Authors: Jones, HJS

• DOI: 10.5287/ora-jvxaoedz5
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: Rectal cancer; Prognostic factors; Organ preservation
• Subjects: Rectal cancer