NCT05781217

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

Short Versus Long-term Androgen Deprivation Therapy Combined With Salvage Radiotherapy in Prostate Cancer Patients With Biochemical Recurrence After Prostatectomy: a Multicentre Phase III Randomised Controlled Trial

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 534 (estimated)
• Sponsor: Instituto de Investigación en Oncología Radioterápica - Fundación Española de Oncología Radioterápic · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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).

Conditions

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

Interventions

Type	Name	Description
DRUG	triptorelin, goserelin, leuprorelin	ADT will consist of LHRH analogues (triptorelin, goserelin, leuprorelin) with bicalutamide 50 mg/day started 10 days before the first ADT injection to avoid LHRH-related flare-ups. Bicalutamide will be discontinued after 30 days. The LHRH analogue will be initiated prior to the start of radiotherapy and administered for 6 or 24 months depending on treatment allocation. The maximum time permitted between randomisation and administration of the first LHRH dose is 30 days. The maximum time from the first LHRH dose to the start of SRT is 60 days.

Timeline

• Start date: 2023-03-14
• Primary completion: 2023-12-01
• Completion: 2032-12-01
• First posted: 2023-03-23
• Last updated: 2023-11-18

Locations

17 sites across 1 country: Spain