Short Versus Long-term Androgen Deprivation Therapy With Salvage Radiotherapy in Prostate Cancer. URONCOR 0624

Status

Recruiting

Phase

Phase 3

Enrollment

534 participants (estimated)

Sponsor

Instituto de Investigación en Oncología Radioterápica - Fundación Española de Oncología Radioterápic · Other

Design

Randomized · Open label (no masking)

Countries

1 country

Spain

Start

14 Mar 2023

Primary completion

Dec 2023 (estimated)

Completion

Dec 2032 (estimated)

First posted

23 Mar 2023

Last update posted

18 Nov 2023

Conditions

Prostate Cancer · Salvage Radiotherapy · Biochemical Recurrence · Androgen Deprivation Therapy · Metastases-free Survival

The optimal indication for ADT has long been a point of controversy, at least until the results of randomised trials comparing RT with and without ADT were published. NCCN guidelines and most retrospective series and left the decision to prescribe ADT in combination with RT to the discretion of the treating physician, despite a lack of clear scientific evidence to support this recommendation. The percentage of patients in those retrospective series who received hormone therapy ranged from 33% to 71%, but generally involved patients with adverse prognostic factors (Gleason score \> 7, stage pT3-T4, PSA \> 1 ng/mL in cases with biochemical recurrence \[BCR\], and PSA doubling time \[PSA-DT\] \< 6 months). Despite the heterogeneity in those studies in terms of treatment duration, RT dose, and treatment volumes, most of the studies found that ADT significantly prolonged biochemical relapse-free survival (BRFS), especially in patients with PSA levels \> 1 ng/mL at recurrence. The results of two randomised trials evaluating SRT with or without ADT were published in 2017, with both trials demonstrating a benefit for ADT in this clinical setting. A follow-up study confirmed the value of ADT in combination with SRT in terms of better PFS and, in the RTOG study, an improvement in overall survival (OS). Despite the lack of data from phase III trials regarding the influence of PSA-DT, the BRFS interval, and the Gleason score in terms of their effects on the clinical course of patients who develop BCR, there is strong evidence from other studies to support the use of these variables (together with age and comorbidities). Given the available evidence, we believe that these variables should be considered when determining the indications for ADT. In line with the philosophy underlying the approach used by D'Amico to develop a risk classification system for prostate cancer patients at diagnosis, we propose three risk groups. According to Pollack et al. and Spratt et al., low-risk patients would not benefit from hormone therapy, especially long-term ADT, due to the deleterious effects of such treatment. By contrast, intermediate and high risk patients would be candidates for ADT combined with RT. However, the optimal duration of ADT in these patients (6 months vs. 2 years) remains undefined and needs to be determined prospectively in a randomised trial, similar to the approach used in the DART 05.01 trial. SRT and ADT are widely used in routine clinical practice to treat patients who develop BCR after prostatectomy. In this context, we intend to perform a multicentre, phase III trial to define the optimal duration of ADT (6 vs. 24 months).

• Active comparator

  short-term ADT (6 months)

  ARM 1: LHRH analogues for 6 months + bicalutamide 50 for 30 days

• Active comparator

  long-term ADT (24 months)

  LHRH analogues for 24 months + bicalutamide 50 for 30 days

1. To compare 5-year MFS rates in prostate cancer patients treated with long- versus short-term ADT in combination with salvage radiotherapy

   Time frame · 5 years

   Registry description

   Distant metastasis-free survival: time from administration of the first LHRH analogue (this same starting point applies to all secondary objectives) until the patient develops M1a disease (involved retroperitoneal lymph nodes) or M1b-c disease (bone/visceral involvement) according to RECIST 1.1 criteria based on conventional computed tomography (CT) imaging and bone scans. The use of advanced molecular imaging-PSMA or choline positron-emission tomography (PET)/CT-is subject to the centre-specific protocols in place at the participating hospitals; however, metastatic progression will be determined according to RECIST 1.1 criteria based on conventional imaging tests.