Progression-directed Therapy in Oligoprogressive Castration-resistant Prostate Cancer: Final Results from the Prospective, Single-arm, Phase 2 MEDCARE Trial

Kato Rans; Steven Joniau; Charlien Berghen; Karolien Goffin; Herlinde Dumez; Karin Haustermans; Gert De Meerleer

doi:10.1016/j.euo.2024.04.003

Progression-directed Therapy in Oligoprogressive Castration-resistant Prostate Cancer: Final Results from the Prospective, Single-arm, Phase 2 MEDCARE Trial

Eur Urol Oncol. 2024 Apr 24:S2588-9311(24)00092-0. doi: 10.1016/j.euo.2024.04.003. Online ahead of print.

Authors

Kato Rans¹, Steven Joniau², Charlien Berghen¹, Karolien Goffin³, Herlinde Dumez⁴, Karin Haustermans¹, Gert De Meerleer⁵

Affiliations

¹ Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium.
² Department of Urology, University Hospitals Leuven, Leuven, Belgium; Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
³ Department of Nuclear Medicine, University Hospitals Leuven, Leuven, Belgium; Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
⁴ Department of Medical Oncology, University Hospitals Leuven, Leuven, Belgium.
⁵ Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium. Electronic address: gert.demeerleer@uzleuven.be.

PMID: 38664137
DOI: 10.1016/j.euo.2024.04.003

Abstract

Background and objective: Next-line systemic treatment (NEST) is the standard of care for patients presenting with progressive metastatic castration-resistant prostate cancer (mCRPC). Progression-directed therapy (PDT), defined as a lesion-directed approach in patients with a limited number of progressive and/or new lesions, could postpone the need for NEST in these patients with so-called oligoprogressive mCRPC. Our aim was to investigate the feasibility of postponing NEST initiation in oligoprogressive mCRPC by using PDT.

Methods: MEDCARE was a prospective, single-arm, nonrandomized phase 2 trial. Eligible patients had oligoprogressive mCRPC and were treated with PDT while their ongoing systemic therapy was continued. The primary endpoint was NEST-free survival (NEST-FS). Secondary endpoints were prostate-specific antigen response, clinical progression-free survival (cPFS), prostate cancer-specific survival (PCSS), overall survival (OS), and PDT-induced toxicity.

Key findings and limitations: Twenty patients underwent PDT for 38 oligoprogressive lesions. At median follow-up of 28 mo, median NEST-FS was 17 mo and the 2-yr NEST-FS rate was 35%. Median PCSS and median OS were not reached. The PCSS and OS rates at 2 yr were 80% and 70%, respectively. The 2-yr local control rate was 95%. No patient experienced early or late grade ≥3 toxicity. NEST-FS was longer for patients who received PDT to all lesions visible on ¹⁸F-PSMA positron emission tomography/computed tomography (30 vs 13 mo; p = 0.002).

Conclusions and clinical implications: This single-center, single-arm, phase 2 trial demonstrated that PDT in oligoprogressive mCRPC resulted in median NEST-FS of 17 mo without any early or late grade ≥3 toxicity.

Patient summary: For patients with metastatic prostate cancer no longer responding to hormone therapy, we investigated radiotherapy targeted at progressive cancer lesions while continuing their ongoing systemic treatment. The results show that this targeted therapy had very low toxicity and delayed the need to start a new line of systemic treatment by 17 months.

Keywords: Castration-refractory prostate cancer; Next-line systemic treatment; Oligoprogression; Positron emission tomography/computed tomography; Progression-directed therapy; Prostate cancer; Prostate-specific membrane antigen; Stereotactic body radiotherapy.