Metastasis-directed therapy in castration-refractory prostate cancer (MEDCARE): a non-randomized phase 2 trial

Abstract

Background: Patients diagnosed with metastatic castration-refractory prostate cancer (mCRPC) rely on a limited number of therapeutic agents resulting in a median survival of 2-3 years. A subgroup of those patients with mCRPC presents with oligoprogressive disease, with a limited number of progressive lesions while other metastases are still controlled by ongoing systemic treatment. Methods: In this single arm prospective phase II trial, we aim to include 18 patients with oligoprogressive mCRPC (1-3 metastases and/or local recurrence) who will be treated with metastasis-directed therapy to all visible progressive lesions. Progression is based on conventional imaging, as the use of PSMA PET-CT is considered investigational. However all patients will undergo PSMA PET-CT and the images will be blinded until progression. Primary endpoint is the postponement of the start of next-line systemic treatment (NEST) and the additional clinical value of PSMA PET-CT. Recruitment of patients for this trial started in January 2020 and will be completed approximately by December 2020. Discussion: In this phase 2 trial on oligoprogressive mCRPC, we will investigate the benefit of progression-directed therapy while continuing ongoing systemic treatment. We hypothesize that progression-directed therapy (PDT) with surgery or stereotactic body radiation therapy for these oligoprogressive lesions will postpone the start of next-line systemic treatment and therefore serve as a new or add-on therapy in the spectrum of treatments available for mCRPC. The results of this trial will serve as guidance for a later randomized phase 3 trial. All participants are given an information sheet and are required to give written informed consent. Results will be published in a peer-reviewed journal. Trial registration: This study is registered at ClinicalTrials.gov: NCT04222634 (December 18th 2019).

Management of patients with advanced prostate cancer—metastatic and/or castration-resistant prostate cancer: Report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022

“…For patients with PSA doubling time > 10 months, even more (about 67%) panellists recommended MDT, mostly without additional systemic therapy. The available evidence for MDT in nmCRPC is scarce and is limited to small trials or retrospective case series [54][55][56][57][58]. In patient with high-risk features (based on both total PSA and PSA kinetics), the evidence is again best for systemic therapy (showing improvements in both MFS and OS), and any additional benefit of MDT is unproven.…”

“…As discussed previously (in the nmCRPC section), the concept of oligoprogressive disease is not well defined in advanced prostate cancer, and available evidence for MDT is limited [54][55][56][57].…”

Survival Outcomes and Pattern of Relapse After SABR for Oligometastatic Prostate Cancer

“…These questions warrant further exploration in prospective trials using standardized treatments to validate the potential benefit and to define the group of CRPC patients expected to profit from SABR. Ongoing prospective trials, such as the single-arm phase II TRAP trial ( 20 ) and the Medcare trial ( 21 ), are investigating the role of SABR for oligometastatic CRPC. Since immune-checkpoint inhibitor monotherapy has shown only modest benefits in the mCRPC setting, the ICE-PAC trial aimed at improving outcomes by combining the PD-L1 checkpoint inhibitor avelumab with SABR in patients with both low- as well as high-volume mCRPC after prior androgen-receptor pathway inhibitor therapy ( 22 ).…”

68Ga-PSMA-11 PET imaging in patients with ongoing androgen deprivation therapy for advanced prostate cancer

“…In addition, an ongoing prospective phase II trial (NCT 04222634) aims to include patients with oligoprogressive metastatic hormone-resistant PCa who are treated with MDRT to all visible progressive lesions. However, progression in this study performed by Berghen et al is based on conventional imaging and not 68 Ga-PSMA-11 PET imaging [ 31 ]. In our cohort of 84 patients 19 (22.6%) were classified as having oligometastatic PCa.…”