Dose Escalation with High Dose Rate Brachytherapy or Protons in Curative Radiotherapy of Prostate Cancer

The aim of the thesis was to study the outcome and side effects after dose-escalated radiotherapy with high dose rate brachytherapy (HDR-BT) or proton beam therapy (PBT) boost in prostate cancer. The first cohorts of men in Sweden treated with either HDR-BT or PBT in combination with conventional photon beam therapy (2 Gray (Gy) fractions to 50 Gy) were analysed. The HDR-BT was given with two 10 Gy fractions, and the PBT with four fractions of 5 Gy. The analyses included 823 men in two HDR-BT cohorts, and 265 men in the PBT cohort. A large proportion of the cohorts, from 38% to 53%, were classified as high risk. After a follow-up between four and eleven years, both combinations showed low risks for relapse. The overall 5-year risk for PSA relapse was 0% for men with low risk. After PBT, the 5-year PSA relapse risk for intermediate and high risk were 5% and 26% respectively. After HDR-BT the 10-year risks for PSA relapse were 0%, 21% and 33% for low, intermediate, and high risk, respectively. The risk for early and late toxicity was low. Genitourinary (GU) toxicity was more frequent than gastrointestinal (GI) toxicity. GU toxicity may have a late onset and progress slowly with time after HDR-BT. The 5- and 10-year actuarial incidences of urethral stricture were 6% and 10% respectively after HDR-BT. With applied dose constraints to the urethra the 10-year risk was 5%. The actuarial prevalence of GI toxicity declined slowly with time after HDR-BT as well as after PBT. A PSA bounce after HDR-BT was seen in 26% of the patients, more frequent with younger age and lower Gleason score, and followed by a low risk for relapse. For dose-escalated radiotherapy with HDR-BT or PBT: long-term tumour control was achieved, not only for low- and intermediate risk, but also for the majority of high risk patients, a PSA bounce after HDR-BT was folled by a good prognosis, levels of late toxicity were low, genitourinary toxicity was more frequent than gastrointestinal toxicity, dose constraints to risk organs must be applied to minimise risks for late toxicity