Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost

To report the primary endpoint of biochemical progression-free survival (b-PFS) and secondary survival endpoints from ASCENDE-RT, a randomized trial comparing 2 methods of dose escalation for intermediate- and high-risk prostate cancer.

ASCENDE-RT enrolled 398 men, with a median age of 68 years; 69% (n=276) had high-risk disease. After stratification by risk group, the subjects were randomized to a standard arm with 12 months of androgen deprivation therapy, pelvic irradiation to 46 Gy, followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. Of the 398 trial subjects, 200 were assigned to DE-EBRT boost and 198 to LDR-PB boost. The median follow-up was 6.5 years.

In an intent-to-treat analysis, men randomized to DE-EBRT were twice as likely to experience biochemical failure (multivariable analysis [MVA] hazard ratio [HR] 2.04; P=.004). The 5-, 7-, and 9-year Kaplan-Meier b-PFS estimates were 89%, 86%, and 83% for the LDR-PB boost versus 84%, 75%, and 62% for the DE-EBRT boost (log-rank P<.001). The LDR-PB boost benefited both intermediate- and high-risk patients. Because the b-PFS curves for the treatment arms diverge sharply after 4 years, the relative advantage of the LDR-PB should increase with longer follow-up. On MVA, the only variables correlated with reduced overall survival were age (MVA HR 1.06/y; P=.004) and biochemical failure (MVA HR 6.30; P<.001). Although biochemical failure was associated with increased mortality and randomization to DE-EBRT doubled the rate of biochemical failure, no significant overall survival difference was observed between the treatment arms (MVA HR 1.13; P=.62).

Compared with 78 Gy EBRT, men randomized to the LDR-PB boost were twice as likely to be free of biochemical failure at a median follow-up of 6.5 years.

International journal of radiation oncology, biology, physics. 2016 Nov 24 [Epub ahead of print]

W James Morris, Scott Tyldesley, Sree Rodda, Ross Halperin, Howard Pai, Michael McKenzie, Graeme Duncan, Gerard Morton, Jeremy Hamm, Nevin Murray

Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada; BC Cancer Agency-Vancouver Centre, Vancouver, British Columbia, Canada. Electronic address: ., Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada; BC Cancer Agency-Vancouver Centre, Vancouver, British Columbia, Canada., Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada., Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada; BC Cancer Agency-Centre for the Southern Interior, Vancouver, British Columbia, Canada., Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada; BC Cancer Agency-Vancouver Island Centre, Vancouver, British Columbia, Canada., Department of Radiation Oncology, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada., Department of Population Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada., BC Cancer Agency-Vancouver Centre, Vancouver, British Columbia, Canada; Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.