Acute toxicity and quality of life in high risk prostate cancer patients: Updated results of randomized hypofractionation trial.

PURPOSE: The aim of our study was to perform the final analysis of acute toxicity and quality of life data obtained from 221 consecutive patients who suffered from intermediate-to-high risk prostate cancer. METHODS: In this trial, 221 patients were randomized to receive either hypofractionated (63 Gy in 20 fractions, 4 fractions/week) or conventionally fractionated (76 Gy in 38 fractions, 5 fractions/week) radiotherapy to the prostate and seminal vesicles. Elective pelvic lymph node irradiation with 46 Gy in 23 fractions sequentially and 44 Gy in 20 fractions simultaneously was also applied. RESULTS: There was no statistically significant difference in acute GU and GI toxicity in men treated with hypofractionated (SIB) (Arm 2) in comparison with patients who had conventional fractionation (Arm 1) radiation therapy. Multivariate analysis using logistic regression showed statistical significant association between acute GU ≥ 1 and PTV(LN) (p = 0.008) only. We found out that clinically relevant decrease (CRD) was significantly higher only in the urinary domain of Arm 1 at month 3 (p = 0.02). CONCLUSION: Our study demonstrated that hypofractionated radiotherapy was associated with a small but insignificant increase of acute toxicity. The reduction of overall treatment time has no significant influence on patients' QOL in any domain.

A randomized hypofractionation dose escalation trial for high risk prostate cancer patients: interim analysis of acute toxicity and quality of life in 124 patients.

BACKGROUND: The α/ß ratio for prostate cancer is postulated being in the range of 0.8 to 2.2 Gy, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. To do so, we carried out a randomized trial comparing hypofractionated and conventionally fractionated image-guided intensity modulated radiotherapy (IG-IMRT) in high-risk prostate cancer. Here, we report on acute toxicity and quality of life (QOL) for the first 124 randomized patients. METHODS: The trial compares 76 Gy in 38 fractions (5 fractions/week) (Arm 1) to 63 Gy in 20 fractions (4 fractions/week) (Arm 2) (IG-IMRT). Prophylactic pelvic lymph node irradiation with 46 Gy in 23 fractions sequentially (Arm 1) and 44 Gy in 20 fractions simultaneously (Arm 2) was applied. All patients had long term androgen deprivation therapy (ADT) started before RT. Both physician-rated acute toxicity and patient-reported QOL using EPIC questionnaire are described. RESULTS: There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity. Compared to conventional fractionation (Arm 1), GI and GU toxicity both developed significantly earlier but also disappeared earlier in the Arm 2, reaching significant differences from Arm 1 at week 8 and 9. In multivariate analyses, only parameter shown to be related to increased acute Grade ≥1 GU toxicity was the study Arm 2 (p = 0.049). There were no statistically significant differences of mean EPIC scores in any domain and sub-scales. The clinically relevant decrease (CRD) in EPIC urinary domain was significantly higher in Arm 2 at month 1 with a faster recovery at month 3 as compared to Arm 1. CONCLUSIONS: Hypofractionation at 3.15 Gy per fraction to 63 Gy within 5 weeks was well tolerated. The GI and GU physician-rated acute toxicity both developed earlier but recovered faster using hypofractionation. There was a correlation between acute toxicity and bowel and urinary QOL outcomes. Longer follow-up is needed to determine the significance of these associations with late toxicity.