Long-term oncological outcome and health-related quality of life after curative treatment of prostate cancer with HDR-brachytherapy and external beam radiotherapy

Sammanfattning: Prostate cancer (PC) is a major health problem among men in the western world. The prognosis of PC varies, with high mortality rates for high-risk disease in contrast to a mild course in low risk cancers with almost no risk of metastases. Radical treatment options for localized and locally advanced PC are surgery or different radiotherapy (RT) modalities. Randomized trials concerning the therapeutic effect of these treatment options are rare and have so far shown little difference in oncological outcome, but differences in patterns of side effects. Therefore, it is important to consider age, comorbidity and treatment induced effects on Health-Related Quality of Life (HRQoL) in the decision-making process pertaining to curative treatment of PC. The primary aim of this thesis was to evaluate the long-term oncological outcome in terms of local control, PC specific and overall survival and HRQoL after curative treatment for PC with combined high dose-rate brachytherapy (HDRBT) and external beam radiotherapy (EBRT). In a cohort study (Study 1), men treated with curatively intended radical prostatectomy (RP) or combined HDRBT and EBRT in Gothenburg from 1988-97 were investigated concerning long-term HRQoL measured by the EORTC QLQ-c30 and QLQ PR25 questionnaires. Patients reported high levels of general HRQoL comparable to a Swedish reference population. Small differences in the levels of bowel and urinary HRQoL were found in favour of the RP group. The prognostic value of comorbidity for overall and disease-free survival measured by the Charlson comorbidity index (CCI) was investigated in 611 men with localized or locally advanced PC treated with dose-dense combined HDRBT and EBRT (Study 2). Comorbidity and age were found to be the only independent predictors of overall survival (OS) with hazard ratios (HR) of 1.44 and 1.73, respectively. In contrast, clinical factors; PSA, T-stage, Gleason score and comorbidity were prognostic of Disease-free survival (DFS). Ten-year survival was retrospectively investigated in a cohort of men (n=2,387) treated with combined RT from 1998-2010 at the Karolinska University Hospital HDR-brachytherapy unit (Study 3). During a median follow-up of 10.2 years (Y) 30% of the patients died, of whom 6% from PC. The OS was 77% at ten Y and the cumulative incidence of prostate cancer specific death (PCSD) was 5%. The estimated risk of local recurrence was 1.2% in the whole cohort and the risk of prostate cancer specific failure (PCSF) was 68% at ten years. Competing risk regression was used to model the impact of risk group classification on PCSD and PCSF and was found to give prognostic information on PC specific death and failure for up to ten years. In a cross-sectional study, five-year HRQoL was explored in a sub-cohort of men from study 3 treated between 2002 and 2008 (Study 4). The aim was to evaluate long-term effects of combined RT, using the EORTC QLQ-c30 and PR 25 questionnaires. Differences in HRQoL in men treated before and after changes in the HDR-treatment procedure introduced in 2001 were also investigated using data from an earlier study at our institution. General HRQoL was high and, apart from small differences, comparable to normative data. A low level of problems was reported concerning bowel, urinary and hormone-related symptoms. However, urinary symptoms were reported more frequently than bowel problems. In the sexual domain substantial problems were present at five years. No difference in HRQoL was found between men treated before and after the introduction of the new HDR-technique, except for a reduced frequency of nocturia in favour of the present study group. In summary, combined HDRBT and EBRT is an effective treatment that provides high disease-specific and overall survival with excellent local control in men with PC but involves a risk for development of long-term urinary and sexual problems.