Thomas Wiegel1, Peter Albers2, Detlef Bartkowiak3, Roswitha Bussar-Maatz4, Martin Härter5, Glen Kristiansen6, Peter Martus7, Stefan Wellek8, Heinz Schmidberger9, Klaus Grozinger10, Peter Renner11, Fried Schneider12, Martin Burmester13, Michael Stöckle14. 1. Department of Radiotherapy and Radiation Oncology, University Hospital Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany. thomas.wiegel@uniklinik-ulm.de. 2. Department of Urology, University Hospital Düsseldorf, Düsseldorf, Germany. 3. Department of Radiotherapy and Radiation Oncology, University Hospital Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany. 4. PREFERE Project Management, German Cancer Society, Berlin, Germany. 5. Department of Medical Psychology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 6. Institute of Pathology, University Hospital Bonn, Bonn, Germany. 7. Department of Clinical Epidemiology and Applied Biostatistics, University Hospital Tübingen, Tübingen, Germany. 8. Department of Medical Biostatistics, Epidemiology and Informatics, University of Mainz, Mainz, Germany. 9. Department of Radiotherapy and Radiation Oncology, University Hospital Mainz, Mainz, Germany. 10. Department of Urology, Klinikum Leverkusen, Leverkusen, Germany. 11. Center for Urology, Lübeck, Germany. 12. Department of Urology, Klinikum Lippe Detmold, Detmold, Germany. 13. Department of Urology, Vinzenzkrankenhaus, Hannover, Germany. 14. Department of Urology, University Hospital Homburg/Saar, Homburg, Germany.
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 receivedradical 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.
RCT Entities:
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 ASpatients with follow-up received radical treatment. Median follow-up was 19 months. Five patientsdied, 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.
Authors: Karl-Friedrich Kowalewski; Marie Angela Sidoti Abate; Manuel Neuberger; Marietta Kirchner; Regina Krisam; Luisa Egen; Caelan Max Haney; Fabian Siegel; Maurice-Stephan Michel; Patrick Honeck; Philipp Nuhn; Niklas Westhoff; Maximilian Christian Kriegmair Journal: BMJ Open Date: 2021-11-03 Impact factor: 2.692
Authors: Thomas Wiegel; Peter Albers; Detlef Bartkowiak; Roswitha Bussar-Maatz; Martin Härter; Glen Kristiansen; Peter Martus; Stefan Wellek; Heinz Schmidberger; Klaus Grozinger; Peter Renner; Fried Schneider; Martin Burmester; Michael Stöckle Journal: J Cancer Res Clin Oncol Date: 2021-04 Impact factor: 4.553
Authors: Matthias Moll; Andreas Renner; Christian Kirisits; Christopher Paschen; Alexandru Zaharie; Gregor Goldner Journal: Strahlenther Onkol Date: 2021-08-05 Impact factor: 3.621