Locally Advanced Rectal Cancer: Characterising Patient-Reported Outcomes and Biomarkers in the Era of Non-Operative Management

Author: Sina Vatandoust

  • Thesis download: available for open access on 3 Apr 2027.

Vatandoust, Sina, 2024 Locally Advanced Rectal Cancer: Characterising Patient-Reported Outcomes and Biomarkers in the Era of Non-Operative Management , Flinders University, College of Medicine and Public Health

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Rectal cancer, accounting for a significant portion of colorectal cancer cases, has distinct characteristics in terms of anatomy, function, and treatment strategies compared to cancers in other regions of the large bowel. The treatment for locally advanced rectal cancer often involves chemoradiotherapy, which has been successful in achieving complete responses in a considerable number of patients. Lately, there has been a paradigm shift towards a non-operative approach (also known as watch-and-wait) for those showing complete responses to chemoradiation, supported by emerging evidence. Despite these advances, there are limited data regarding how this approach affects patient-reported outcomes and the fear of cancer recurrence, as well as the role of biomarkers in this context.

This doctoral thesis addresses these gaps. The overall aim is to characterise the patient-reported outcomes and biomarkers in survivors of rectal cancer who have been managed with a watch-and-wait approach and compare them with survivors who have been managed with a standard surgical approach. The thesis is divided into three sections: the first focuses on patient-reported outcomes in survivors of rectal cancer, the second investigates the fear of cancer recurrence, and the third includes pilot studies exploring novel biomarkers and analyses their correlation with treatment-response and patient-reported outcomes.

To gain insight into the patient-reported outcomes of rectal cancer survivors treated with a watch-and-wait approach, data from two studies were combined to compare survivors who underwent this approach with those who received standard surgical treatment after Chemoradiotherapy (CRT). The main aim was to compare QoL between the cohort of survivors managed with watch-and-wait and the cohort of survivors managed with upfront surgery after completing CRT. The findings revealed that participants who were managed with a watch-and-wait approach had a significantly better quality of life and bowel function compared with participants who had surgery. Additionally, the study provided comprehensive data on various aspects of survivors’ experiences and uncovered previously unstudied interrelations between patient-reported outcome measures (PROMs).

In the second section, fear of cancer recurrence (FCR) was investigated using the largest data set studied thus far in survivors of colorectal cancer. The main aim of this section was to compare FCR between the cohort of survivors of rectal cancer managed with a non-surgical approach and the cohort managed with surgery. The results suggested that a watch-and-wait approach in rectal cancer patients does not lead to an increase in fear of cancer recurrence. In addition, the study provided substantial data on the correlation of different variables with fear of cancer recurrence.

In the third section, various novel biomarkers representing different aspects of the complex tumour-host interaction were investigated for their role in predicting response to treatment as well as their correlation with bowel dysfunction. These biomarkers included tumour non-coding RNAs, tumour infiltrating lymphocytes and the gut microbiota. The number of samples available for the studies in this section was small, and therefore, the studies were redefined as pilot studies aiming for hypothesis generation. Notably, despite the sample size constraints, the studies identified an association between piR-1920878 and the response to chemoradiation, an observed trend toward greater diversity of gut microbiota in participants with improved bowel function and detected a tendency for elevated tumour-infiltrating lymphocytes in participants with a sustained complete response.

Collectively, these findings suggest that a watch-and-wait approach in patients with rectal cancer who achieve a complete response to chemoradiation leads to improvement in different aspects of quality of life. In addition, this approach does not lead to an increased fear of cancer recurrence. Moreover, the analysis revealed complex interrelations between different patient-reported outcomes. It also provides justification for further investigation of potential associations between biomarkers and patient-reported outcomes. The clinical relevance of this study is that it offers insights into rectal cancer survivors' experiences, paving the way for tailored treatment strategies. Ultimately, additional research is necessary to ascertain the connection between patient-reported outcomes, different treatment methods, and biomarkers.

Keywords: rectal cancer, watch-and-wait, non-operative management, patient-reported outcomes, biomarkers

Subject: Medicine thesis

Thesis type: Doctor of Philosophy
Completed: 2024
School: College of Medicine and Public Health
Supervisor: Professor Ross McKinnon