Ten-Year Update of a Randomized, Prospective Trial of Conventional Fractionated Versus Moderate Hypofractionated Radiation Therapy for Localized Prostate Cancer

Abstract

PURPOSE The previously published single institution randomized prospective trial failed to show superiority in the 5-year biochemical and/or clinical disease failure (BCDF) rate with moderate hypofractionated intensity-modulated radiation therapy (H-IMRT) versus conventionally fractionated IMRT (C-IMRT). We now present 10-year disease outcomes using updated risk groups and definitions of biochemical failure. METHODS Men with protocol-defined intermediate- and high-risk prostate adenocarcinoma were randomly assigned to receive C-IMRT (76 Gy in 38 fractions) or H-IMRT (70.2 Gy in 26 fractions). Men with high-risk disease were all prescribed 24 months of androgen deprivation therapy (ADT) and had lymph node irradiation. Men with intermediate risk were prescribed 4 months of ADT at the discretion of the treating physician. The primary endpoint was cumulative incidence of BCDF. We compared disease outcomes and overall mortality by treatment arm, with sensitivity analyses for National Comprehensive Cancer Network (NCCN) risk group adjustment. RESULTS Overall, 303 assessable men were randomly assigned to C-IMRT or H-IMRT. The median follow-up was 122.9 months. Per updated NCCN risk classification, there were 28 patients (9.2%) with low-risk, 189 (62.4%) with intermediate-risk, and 86 (28.4%) with high-risk prostate cancer. The arms were equally balanced for clinicopathologic factors, except that there were more black patients in the C-IMRT arm (17.8% v 7.3%; P = .02). There was no difference in ADT use ( P = .56). The 10-year cumulative incidence of BCDF was 25.9% in the C-IMRT arm and was 30.6% in the H-IMRT arm (hazard ratio, 1.31; 95% CI, 0.82 to 2.11). The two arms also had similar cumulative 10-year rates of biochemical failure, prostate cancer–specific mortality, and overall mortality; however, the 10-year cumulative incidence of distant metastases was higher in the H-IMRT arm (rate difference, 7.8%; 95% CI, 0.7% to 15.1%). CONCLUSION H-IMRT failed to demonstrate superiority compared with C-IMRT in long-term disease outcomes.

Long-Term Outcomes of Dose-Escalated Hypofractionated Radiotherapy in Localized Prostate Cancer

“…De Vries et al found significant improvement in local control in patients with a Gleason score = 8 treated with HFRT versus conventional schedule, but not in relapse-free survival [35]. Moreover, Avkshtol et al (Fox Chase) reported higher incidence of distant metastases at 10-year follow-up in patients in the HFRT arm (rate difference, 7.8%; 95% CI, 0.7% to 15.1%) and observed no between-group difference in overall survival [36]. Finally, the MD Anderson trial showed a 10.7% biochemical failure incidence in men treated with HFRT versus a 23.7% of incidence in patients treated with CFRT over a 10-year follow-up [25].…”

Optimizing External Beam Radiotherapy as per the Risk Group of Localized Prostate Cancer: A Nationwide Multi-Institutional Study (KROG 18-15)

“…Multiple randomized trials and a meta-analysis evaluated the role of hypofractionated RT and concluded that its efficacy is equivalent to that of CF [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. Data on whether HF increases overall treatment-related toxicity are inconclusive.…”

Radiation oncologists’ attitudes and beliefs about intensity-modulated radiation therapy and stereotactic body radiation therapy for prostate cancer

“…In designing the study, we did not seek to purposefully select participants based on gender since we felt attitudes towards IMRT and SBRT were unlikely to differ based on gender. Third, these interviews occurred in 2016 and more evidence has accumulated since then supporting hypofractionated radiation [33]. Nonetheless, SBRT is still sparingly used and, in the absence of randomized controlled data, these views are still very relevant today.…”