Moderate Hypofractionation in High-Risk, Organ-Confined Prostate Cancer: Final Results of a Phase III Randomized Trial

Abstract

Purpose To report the final results on treatment outcomes of a randomized trial comparing conventional and hypofractionated radiotherapy in high-risk, organ-confined prostate cancer (PCa). Patients and Methods This single-institution, randomized clinical trial, conducted from January 2003 to December 2007, enrolled 168 patients with high-risk PCa who were randomly assigned in a 1:1 ratio to conventional (80 Gy in 40 fractions in 8 weeks) or hypofractionated radiotherapy (62 Gy in 20 fractions in 5 weeks) to prostate and seminal vesicles. The primary outcome measure was late toxicity. Additional outcomes were freedom from biochemical failure (FFBF), prostate cancer-specific survival (PCaSS), and overall survival (OS), evaluated on an intention-to-treat basis. Results A total of 85 patients were assigned to conventional and 83 to hypofractionated radiotherapy. At a median follow-up of 9 years (interquartile range, 7.5 to 10.1 years), no differences was observed in physician-assessed late gastro intestinal and genitourinary toxicity greater than or equal to grade 2 ( P = .68 and .57, respectively) were found between the two arms. The 10-year FFBF rate was 72% in the hypofractionation group and 65% in the conventional fractionation group ( P = .148). Ten-year OS rates were 75% in the hypofractionation group and 64% in the conventional group, respectively ( P = .22). The same features for 10-year PCaSS were 95% and 88%, respectively ( P = .066). Hypofractionation, pretreatment prostate-specific antigen level, Gleason score, and clinical tumor stage for FFBF, and hypofractionation and Gleason score for PCaSS were significant prognostic variables on the multivariate analysis. Conclusion Long-term findings showed that hypofractionated radiotherapy failed the intent of either reducing physician-assessed late toxicity or maintaining the same efficacy. A postrandomization analysis, however, revealed that hypofractionation was a significant prognostic factor for FFBF and PCaSS, when adjusted for clinical prognostic variables.

Moderately HRT vs. CRT for localized prostate cancer using image-guided VMAT with SIB: evaluation of acute and late toxicities

“…In the context of a meta-analysis, Datta et al summarized data from randomized trials with follow-up periods ranging from 6 to 10 years to compare moderate HRT with CRT using doses from 57.0 to 62.0 Gy for the HRT arm and 74.0 to 80.0 Gy for the CRT arm. Datta et al conclude that in the investigated trials, such as the PROFIT [14], IRE [28][29][30][31], RTOG [30], CHHiP [17], and HYPRO [32] studies, HRT leads to similar or even improved results regarding biochemical outcomes and toxicity. Also, Schörghofer et al [33] report that moderate HRT lowers GU and GI toxicity through all risk classifications.…”

Radiotherapy in elderly patients with prostate cancer

“…The study showed that the five-year biochemical control rate was non-inferior in the trial arm compared to conventional fractionation; 23 similar results were achieved in the HYPRO study. 24 Further studies have demonstrated good biochemical control rates in high-, medium-and low-risk prostate cancer patients, 25,26,27 although the low-risk data reported an increase in late ECOG Grade 2 and 3 genitourinary and gastroenterological toxicities. Importantly, none of these studies were tailored specifically to the elderly population, although all included a proportion of patients aged over 70 years.…”

Refinement & validation of rectal wall dose volume objectives for prostate hypofractionation in 20 fractions

“…In the last decade, external beam radiotherapy (RT) for localized prostate cancer has leaned towards shorter schedules in order to decrease both patient logistic load and health care costs [1]. Several clinical trials support the use of moderately hypofractionated RT (MHRT) in 20-28 fractions over conventionally fractionated RT in 35-40 fractions [2][3][4][5][6][7].…”

“…Moreover, since the a/b ratio of late responding tissues is considered to be higher than the one of prostate cancer [10,11], (moderate) hypofractionation is expected to be less toxic on late responding tissues than an isoeffective tumor dose at 2 Gy/fraction. However, despite technical improvements and a favorable radiobiological scenario, the rectum remains a dose-limiting organ for prostate external beam radiotherapy, including MHRT [2,6,[12][13][14][15].…”