174TiP - SPARKLE: A new spark in treating oligorecurrent prostate cancer: Adding systemic treatment to stereotactic body radiotherapy or metastasectomy: Key to long-lasting event-free survival?

Background

Metastasis-directed therapy (MDT), performed by either metastasectomy or stereotactic body radiation therapy (SBRT) significantly delays the initiation of palliative androgen deprivation therapy (pADT) in patients with oligorecurrent prostate cancer (PCa). This delay positively impacts patient’s quality of life. For this approach, however, it remains unclear whether adding a certain period of ADT improves polymetastatic disease-free survival (PM-DFS) and castration refractory PCa-free survival (CRPC-FS). Multiple trials demonstrated a significantly overall survival benefit when an androgen receptor targeted agent (ARTA) was added to pADT in patients with metastatic hormone sensitive PCa (HSPC). However, whether the addition of an ARTA to MDT in the treatment of oligorecurrent PCa results in better PMD-FS and CRPC-FS has not been proven yet.

Trial design

SPARKLE (a new Spark in treating oligorecurrent Prostate cancer: Adding systemic treatment to stereotactic body Radiotherapy or metastasectomy: Key to Long-lasting Event-free survival?) is a multicenter randomized phase 3 trial which evaluates whether the addition of short-term ADT (1 month) (Arm B) or prolonged administration of ADT with an ARTA (enzalutamide 4x40 mg daily) for 6 months to MDT (Arm C) significantly improves (PM-DFS, primary endpoint) compared to MDT alone (arm A). Patients presenting with oligorecurrent HSPC will be randomized with a 1:1:1 allocation ratio and stratified by PSA doubling time (£ 3 vs. >3 months), number of metastases (1 vs. >1) and initial localization of metastases (M1a vs. M1b and/or M1c). A total of 873 patients will be included to guarantee a family-wise significance level of 5% and to obtain a power of at least 80%. Oligorecurrent disease is defined as a maximum of 5 extracranial metastases on PSMA PET-CT, nodal disease can be included only when accompanied by M1a-c disease. Testosterone level should be within normal range. Primary tumor should be treated and controlled. Patients must have a good performance status (WHO performance 0-2). The first patient has been randomized in April 2022.

Clinical trial identification

NCT05352178.

Legal entity responsible for the study

The authors.

Funding

In progress.

Disclosure

All authors have declared no conflicts of interest.