Optimization of the radiotherapy management of patients with high-risk prostate cancer

UoM administered thesis: Doctor of Medicine

  • Authors:
  • Hannah Tharmalingam

Abstract

High-risk prostate cancer is an adverse form of the disease accounting for a significant proportion of the 300,000 prostate cancer deaths occurring annually worldwide. Radical radiotherapy has very good long-term outcomes for patients with high-risk disease although its efficacy may be limited by sub-optimal dose to the primary tumour and occult lymph node metastases outside of the radiation field. Side effects can be significant with many having to cope with long-term urinary or bowel toxicity. Moreover, patients with high-risk prostate cancer represent a heterogeneous group, some of whom present with very aggressive disease characterized by rapid distant progression and high mortality. There is a need to improve the stratification of high-risk patients such that this cohort can be selected for and treatment potentially intensified. Two prospective cohort studies were conducted. One comparing the effects of whole pelvis radiotherapy (WPRT) with prostate-only radiotherapy (PORT) in patients treated with combination EBRT and high-dose rate (HDR) brachytherapy and a second evaluating the outcomes of patients treated with single dose 19Gy HDR brachytherapy as monotherapy for localised disease. Magnetic resonance (MR) imaging radiomics analysis was performed on MR imaging of patients before and after neoadjuvant androgen deprivation therapy (nADT) to explore their potential as prognostic imaging biomarkers. In high-risk prostate cancer patients treated with combined EBRT and HDR brachytherapy, WPRT significantly improved five-year biochemical progression-free survival (bPFS) compared to PORT (84% vs 77%) with acceptable late radiation toxicity. Three-year bPFS for high-risk patients treated with single dose 19Gy HDR brachytherapy as monotherapy was 75%. MR radiomic features of homogeneity and energy changed in high-risk patients in response to nADT and in cancerous prostate tissue these changes were positively associated with underlying vascular changes. With optimization of dose escalation to the prostate when combining EBRT and HDR brachytherapy, prophylactic pelvic nodal irradiation may be of clinical benefit in those with high-risk disease. For this cohort of patients, single dose 19Gy HDR brachytherapy is suboptimal as monotherapy and further whole or partial gland dose escalation is required. MR radiomic features in benign and malignant prostate tissue are reproducible and show reciprocal change in response to nADT. Validation of these changes and the strong association in tumour with ADT-induced physiological effects confirms their potential as imaging biomarkers in high-risk disease.

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Original languageEnglish
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Award date1 Aug 2020