Results of a randomized trial of treatment modalities in patients with low or early-intermediate risk prostate cancer (PREFERE trial)

Abstract

Purpose The optimal treatment for patients with low to early-intermediate risk prostate cancer (PCa) remains to be defined. The randomized PREFERE trial (DRKS00004405) aimed to assess noninferiority of active surveillance (AS), external-beam radiotherapy (EBRT), or brachytherapy by permanent seed implantation (PSI) vs. radical prostatectomy (RP) for these patients. Methods PREFERE was planned to enroll 7600 patients. The primary endpoint was disease specific survival. Patients with PCa stage ≤ cT2a, cN0/X, M0, PSA ≤ 10 ng/ml and Gleason-Score ≤ 3 + 4 at reference pathology were eligible. Patients were allowed to exclude one or two of the four modalities, which yielded eleven combinations for randomization. Sixty-nine German study centers were engaged in PREFERE. Results Of 2251 patients prescreened between 2012 and 2016, 459 agreed to participate in PREFERE. Due to this poor accrual, the trial was stopped. In 345 patients reference pathology confirmed inclusion criteria. Sixty-nine men were assigned to RP, 53 to EBRT, 93 to PSI, and 130 to AS. Forty patients changed treatment shortly after randomization, 21 to AS. Forty-eight AS patients with follow-up received radical treatment. Median follow-up was 19 months. Five patients died, none due to PCa; 8 had biochemical progression after radical therapy. Treatment-related acute grade 3 toxicity was reported in 3 RP patients and 2 PSI patients. Conclusions In this prematurely closed trial, we observed an unexpected high rate of termination of AS and an increased toxicity related to PSI. Patients hesitated to be randomized in a multi-arm trial. The optimal treatment of low and early-intermediate risk PCa remains unclear. Electronic supplementary material The online version of this article (10.1007/s00432-020-03327-2) contains supplementary material, which is available to authorized users.

ROBOCOP II (ROBOtic assisted versus conventional open partial nephrectomy) randomised, controlled feasibility trial: clinical trial protocol

“…The importance of conducting feasibility trials has been shown multiple times, with warning examples such as the PREFERE prostatic cancer trial. 56 The RCT was designed to show non-inferiority of active surveillance, external-beam radiotherapy and brachytherapy by permanent seed implantation to radical prostatectomy with a planned sample size of 7600 patients. However, the trial was stopped early due to poor accrual as only 459 patients agreed to participate within a time period between 2012 and 2016.…”

Active surveillance in favorable intermediate risk prostate cancer: outstanding questions and controversies

“…To date, there have been no randomized controlled trials comparing modern-day active surveillance inclusive of protocol-driven repeat prostate biopsies to upfront treatment of prostate cancer other than the recent PREFERE study [6] published in 2021; however, this study suffered from poor accrual and the trial was terminated prematurely. There are three randomized trials comparing active monitoring or watchful waiting to treatment, which has given some insight into which patients may be offered active surveillance.…”

Pattern of Radiotherapy Treatment in Low-Risk, Intermediate-Risk, and High-Risk Prostate Cancer Patients: Analysis of National Cancer Database

“…Much of the available clinical data remains inconclusive due to the lack of concrete control groups and the possibility of confounding variables [ 29 , 30 ]. There were also some attempts to assess the effectiveness of the different treatment modalities, but such studies were prematurely closed due to decreases in longitudinal active surveillance and thus potential resulting toxicity-related concerns [ 31 ]. Hence, randomized data directly comparing the efficacies and outcomes of survival for various RT techniques are currently lacking on a national scale [ 20 ].…”