Acute Toxicity Patterns and Their Management after Moderate and Ultra- Hypofractionated Radiotherapy for Prostate Cancer: A Prospective Cohort Study

Objective: Hypofractionation has become the new clinical standard for prostate cancer. We investigated the management of acute toxicity in patients treated with moderate hypofractionation (MHF) or Ultrahypofractionation (UHF). Methods: In a prospective cohort setting, patients (N=316) received either MHF (20 fractions of 3/3.1 Gy, 5 fractions per week, N=156) or UHF (7 fractions of 6.1 Gy, 3 fractions per week, N=160) to the prostate +/- (base of the) seminal vesicles between 2019 and 2023. UHF was not indicated in case of significant lower urinary tract symptoms (LUTS) or T3b disease. Patient-reported outcomes (PRO) were online distributed at baseline, end of treatment (aiming at last fraction +/- 3 days), 3 months. Acute toxicity rates, management, and associations with baseline factors were analysed using Chi-square test and logistic regression. CTCAE scores (version 5) were calculated. Results: Treatment for acute urinary complaints was prescribed in 46 % (MHF) and 29 % (UHF). Taking into consideration baseline LUTS, MHF and UHF showed similar rates of PROs and management. Medication for acute gastrointestinal (GI) symptoms was prescribed for 21.1 % (MHF) and 14.1 % (UHF) with more loperamide for diarrhea in MHF (9.0 %) vs UHF (1.9 %, p = 0.005). Grade >= 2 (MHF / UHF) was scored in 40% / 28 % for GI (p = 0.03) and 50 % / 31 % for GU (p < 0.01). PROs for GI reported after last fraction of UHF were significantly worse compared to before last fraction. Conclusion: UHF was safe with respect to acute toxicity risks in the selected population. MHF is associated with risks of significant diarrhea which needs further investigation. Furthermore, optimal registration of acute toxicity for UHF requires measurements up to 1-2 weeks after the last fraction.