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

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.

Termination rates and histological reclassification of active surveillance patients with low- and early intermediate-risk prostate cancer: results of the PREFERE trial.

PURPOSE: Active surveillance (AS) strategies for patients with low- and early intermediate-risk prostate cancer are still not consistently defined. Within a controlled randomized trial, active surveillance was compared to other treatment options for patients with prostate cancer. Aim of this analysis was to report on termination rates of patients treated with AS including different grade groups. METHODS: A randomized trial comparing radical prostatectomy, active surveillance, external beam radiotherapy and brachytherapy was performed from 2013 to 2016 and included 345 patients with low- and early intermediate-risk prostate cancer (ISUP grade groups 1 and 2). The trial was prematurely stopped due to slow accrual. A total of 130 patients were treated with active surveillance. Among them, 42 patients were diagnosed with intermediate-risk PCA. Reference pathology and AS quality control were performed throughout. RESULTS: After a median follow-up time of 18.8 months, 73 out of the 130 patients (56%) terminated active surveillance. Of these, 56 (77%) patients were histologically reclassified at the time of rebiopsy, including 35% and 60% of the grade group 1 and 2 patients, respectively. No patients who underwent radical prostatectomy at the time of reclassification had radical prostatectomy specimens ≥ grade group 3. CONCLUSION: In this prospectively analyzed subcohort of patients with AS and conventional staging within a randomized trial, the 2-year histological reclassification rates were higher than those previously reported. Active surveillance may not be based on conventional staging alone, and patients with grade group 2 cancers may be recommended for active surveillance in carefully controlled trials only.

[PREFERE - Study on the rise]. / PREFERE-Studie im Aufwind.

The PREFERE study, which compares the treatment options for prostate cancer with low and early intermediate risk, has recorded a noticeable upswing in recruitment since mid-2015. Responsible for this are the revised inclusion criteria and the wide support for this study in Germany. The inclusion criteria opened the study to the use of imaging techniques (MRI, C­Trus / Anna) and the inclusion of all Gleason 3 + 3 = 6 cancers, regardless of tumor extent. In addition, patients can now be included who, for example due to the size of the prostate or existing obstructive micturition disorders, had a contraindication to percutaneous radiotherapy or brachytherapy - these can now be randomized between active surveillance and radical prostatectomy. With the increased recruitment numbers, it seems realistic that the required milestones in recruiting will be achieved.

[Localised prostate cancer: the PREFERE trial]. / Organbegrenztes Prostatakarzinom - PREFERE-Studie.

Prostate cancer is the most common carcinoma of the elderly man and holds the third place in the ranking of cancer-specific mortality. However, mortality rates of 3 % are low, and half of the patients will die from intercurrent disease. Due to the significantly improved diagnostic methods and the increasing use of PSA screening, there has been a stage migration towards early tumour stages that are prognostically heterogeneous and require differentiated treatment. Based on the discussions of the Joint Federal Committee (G-BA) and the conceptual work of the MDS, the Competence Centre Oncology of the MDK, the IQWIG and the National Association of Statutory Health Insurance Funds (GKV-Spitzenverband), a prospective randomised multicentre trial was developed comparing the four treatments actually recommended by the German and European guidelines for localised prostate cancer (radical prostatectomy, percutaneous radiotherapy and permanent seed implantation and active surveillance) allowing a rejection of one or two treatment options. The trial is expected to start at the beginning of next year.