Patient Outcomes after Radiotherapy of Prostate Cancer. Impact of Absorbed Dose and Treated Volume

Abstract: Abstract Backgound Prostate cancer is the most common form of cancer in men in Sweden. Radiotherapy, including external beam radiation therapy (EBRT) and brachytherapy (BT), is important treatment alternatives to surgery and active surveillance. Precise delivery of the prescribed absorbed dose to the prostate with minimal irradiation of normal tissue, specifically organs at risk, is crucial for optimal tumour response and limited side effects. The overall aim of this work was to investigate the outcome of radiotherapy for prostate cancer in the clinical settings. A specific aim was to study associations between radiation dose and outcome (tumour response and/or side effects) when applicable. Material and methods The studies were based on clinical patient data.Lymphedema was studied in 22 patients treated with EBRT including large pelvic volumes in combination with high-dose-rate (HDR)-BT and hormonal therapy after lymph-node dissection. Tumour outcome was studied retrospectlively in 195 patients treated with low-dose-rate (LDR)-BT at Skåne University Hospital. Erectile dysfunction (ED) after EBRT was studied in 673 patients, treated in the HYPO-RT-PC randomised phase 3 trial comparing conventional fractionation (CF) with ultrahypofractionation (UHF). Long-term incidence of hip complications after EBRT was studied in 351 patients using outcome data from the National Prostate Cancer Datatbase, PCBaSe. Results: A low rate of lymphedema was found in the group of high-risk node-positive cancer patients, supporting the feasability of this extensive treatment. Excellent outcomes were found in the cohort of low-risk prostate cancer patients treated with LDR-BT showing a biochemical failure-free survival (BFFS) rate of 95.7% at 5 years with few side effects. The dose to the prostate ( D90%) was significantly associated with BFFS. The frequency of ED was similar in the CF and UHF treatment groups. Age was the strongest predictor of severe ED followed by dose to penile bulb (PB) beeing most evident for younger patients. EQD2-corrected doses of D2 % < 50 Gy and Dmean < 20 Gy to PB are suggested as treatement planning objectives in order to minimise ED after EBRT. No increased risk of hip fracture was found after radical radiotherpy but an increased risk of clinically relevant osteoarthritis was observed. These results indicate that osteoarthritis after EBRT is reduced by limiting the volume of the femoral heads receiving more than 40 Gy (EQD2). Conclusions: Toxicity was acceptable after treating pelvic nodes with EBRT. Significant associations were found between dose coverage and tumour-control in LDR-BT, between dose to PB and ED and dose to femoral head and ostearthritis, following EBRT. These findings add valuable information in the design of future radiotherapy regimens.