Oh, the HORRAD.
The Study: Maybe they were grounding their decision on any one of the myriad pubs de jour: big retrospective databases. One representative SEER analysis of 13,692 patients with metastatic prostate cancer concluded a survival advantage with local therapy for the 313 undergoing radical prostatectomy and 161 brachytherapy. Out of 13,692. The Dutch see these international consensus guidelines and retrospective big data, and they raise them a prospective trial. The phase 3 HORRAD trial enrolled 432 men with untreated prostate cancer metastatic to bone. Note that bone scintigraphy was the only staging study required and PSA had to be at least 20 ng/mL, meaning enrollees weren’t necessarily oligometastatic. All patients received androgen deprivation therapy (ADT) with an AR-antagonist (e.g., bicalutamide) for 4 weeks plus a LHRH-agonist (e.g., leuprolide) indefinitely. The study question comes with a randomization +/- to prostate-directed external radiation delivered 2 Gy x 35 or 3.04 Gy x 19. Kaplan-Meier curves depicting the primary endpoint of overall survival criss-cross with a median of 45 months with radiation and 43 months without. The authors recognize that, in the interim since this study was designed in 2004, standard radiation has become dose-escalated and upfront systemic therapy now includes more than ADT. But on the one hand radiation dose-escalation doesn’t improve overall survival, and on the other improvements in systemic therapy should work only to tighten not separate the survival curves.
Bottom Line: Prospective data does not demonstrate a survival benefit with incorporation of prostate-directed radiation into upfront treatment of all-comer prostate cancer metastatic to bone. | Boevé, Eur Urol 2018