Neoplasms

Symptoms and General Pathology

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Neoplasm Metastasis

Prostatic Neoplasms

Recurrence

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Disease Attributes

All Drugs and Chemicals

Antineoplastic Agents

Reproductive Control Agents

Androgens

Leuprolide

Goserelin

Triptorelin Pamoate

Bicalutamide

Antineoplastic Agents, Hormonal

Contraceptive Agents

Contraceptive Agents, Female

Contraceptive Agents, Hormonal

ARM 1:

LHRH analogues for 6 months + bicalutamide 50 for 30 days

LHRH analogues for 24 months + bicalutamide 50 for 30 days

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.

triptorelin, goserelin, leuprorelin

Pablo Raña, PhD

Anna Maria Boladeras, MD

Victor Duque, MD

Alfonso Gómez, MD

Xavier Maldonado, MD

Joel Mases, MD

Gemma Sancho, MD

Felipe Couñago, MD

Carmen González, MD

Fernando López, MD

Aurora Rodríguez, MD

Noelia Sanmamed, MD

Jesús Oliveira, MD

Luis Alberto Glaria, MD

Antonio José Conde, MD

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).

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

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.

BRFS: time to biochemical progression defined as an increase in PSA confirmed by a second PSA determination (0.2 ng/mL above the salvage radiotherapy nadir or a sustained elevation in PSA levels).

Pelvic PFS: time to local recurrence (prostate bed) and/or N1 disease (positive lymph nodes below the aortic bifurcation) according to RECIST 1.1 criteria by conventional CT imaging and bone scan. The use of advanced molecular imaging (PSMA or choline PET/CT) will depend on centre-specific protocols; determination of metastatic progression will be based on RECIST 1.1 criteria from conventional imaging tests.

Cytotoxic treatment-free interval: time to the start of the first cytotoxic treatment or local treatment for oligorecurrence.

Time interval to castration resistance: the time to biochemical and/or clinical progression with castration levels (testosterone \< 50 ng/dL). Progression to castration resistance is defined as three consecutive increases in PSA (one-week intervals) with at least two PSA increases \> 2 ng/mL and a 50% increase over the PSA nadir, progression of bone lesions (≥ two lesions on the bone scan), progression of soft tissue lesions (RECIST 1.1 criteria), or the development of ≥ one soft tissue or visceral metastases (including lymph nodes).

time to death due to prostate cancer or treatment-related complications

Acute toxicity: toxicity (CTCAE criteria, v. 4.0; https://evs.nci.nih.gov) appearing any time from treatment initiation up to three months after completion of RT.

-Late toxicity: from 3 months to 5 years after completing RT (CTCAE v 4.0).

Quality of life (QoL): from baseline (prior to RT) to five years after completion of RT, assessed with the EORTC QLQ-C30 and QLQ-PR25 questionnaires.

Spots Global Cancer Trial Database for triptorelin, goserelin, leuprorelin