Purpose Prostate cancer (PCA) is highly heterogeneous in terms of its oncologic outcome. We therefore aimed to tailor radiation treatment to the risk status by using three different hypofractionated radiation regimen differing in applied dose, use of rectum spacer, inclusion of pelvic lymph nodes (pLN) and use of androgen deprivation therapy (ADT). Here we report on acute toxicity, quality of life (QOL) and oncologic outcome at a median follow-up of 12 months. Methods A total of 221 consecutive PCA patients received hypofractionated intensity-modulated radiotherapy (IMRT). Low-risk (LR) patients were planned to receive 60Gy in 20 fractions (EQD2(alpha/beta 1.5) = 77.1Gy), intermediate-risk (IR) patients 63Gy in 21 fractions (EQD2(alpha/beta 1.5) = 81Gy), and high-risk (HR) patients 67.5Gy in 25 fractions (EQD2(alpha/beta 1.5) = 81Gy) to the prostate and 50Gy in 25 fractions to the pLN. Acute rectal toxicity was assessed by endoscopy. In addition, toxicity was scored using CTC-AE 4.0 and IPSS score, while QOL was assessed using QLQ-PR25 questionnaires. Results Acute CTC reactions were slightly higher in the HR regimen but reverted to baseline at 3 months. GI G2 toxicity was 4%, 0% and 12% for the LR, IR and HR regimen. Compared to IR patients, the increase in toxicity in HR patients was statistically significant (p = 0.002) and mainly caused by a higher incidence of diarrhea presumably due to pelvic EBRT. QOL scores of all domains were worse for the HR regimen (not significant). Conclusion Risk-adapted moderate hypofractionation is associated with low GI/GU toxicity. Given the higher rate of pelvic metastases in HR patients, slightly higher transient acute reactions should be outweighed by possible oncological benefits.
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