The METANOVA protocol enrolls men with de novo oligometastatic, hormone-sensitive prostate cancer (omHSPC). Eligibility is defined by the extent of metastatic disease: up to 10 sites detected by PSMA PET/CT or up to five sites identified by conventional imaging. All participants receive systemic androgen suppression as part of baseline management and must be candidates for definitive local therapy to the prostate. The protocol allows inclusion of a clinically appropriate predefined subset who may undergo radical prostatectomy instead of prostate radiotherapy.
Participants are randomised in a 1:1 ratio to either standard of care (SOC) alone or SOC plus metastasis-directed radiotherapy (MDRT). The trial aims to recruit 200 patients. Randomisation is stratified by diagnostic imaging modality (PSMA PET/CT versus conventional imaging), number of bone metastases, whether the treating team plans to deliver MDRT to all identified metastatic sites, and the approach to local therapy for the primary tumor. These stratification factors are intended to balance known prognostic variables across arms.
SOC in this trial includes long-term androgen deprivation therapy for 12 months combined with an androgen receptor pathway inhibitor. Definitive treatment to the prostate is required and may be delivered as radiotherapy or, for a subset, radical prostatectomy if clinically appropriate. Prostate radiotherapy may be given using either moderate hypofractionation (20 fractions) or ultra-hypofractionation (five fractions). An optional simultaneous-integrated-boost to dominant intraprostatic lesions is permitted per treating center practice.
MDRT in METANOVA is delivered with stereotactic body radiation therapy (SBRT) to all metastatic sites identified on conventional imaging or PSMA PET/CT. Regimens are designed to achieve a biologically effective dose (BED) of ≥100 Gy, using an α/β of 1.5, delivered across 1 to 5 fractions. Gross tumour volumes for metastatic targets are delineated using multimodality imaging inputs. The protocol specifies dose objectives and fractionation intent to reach the targeted BED, while allowing site-appropriate SBRT approaches consistent with local normal-tissue constraints.
Imaging for staging and target definition incorporates MRI, CT and PSMA PET/CT when available. Gross tumour volumes are contoured using these modalities to guide both prostate-directed therapy and MDRT. The protocol permits radical prostatectomy for a subset of patients when considered clinically appropriate; details of surgical selection criteria were reported in the source protocol. The trial explicitly stratifies by imaging modality to account for differences in lesion detection and burden assessment.
The primary endpoint is failure-free survival, defined using cause-specific prostate cancer death. The study is powered at 80% to detect a hazard ratio of 0.58 using a one-sided alpha of 0.05. Secondary endpoints include radiographic progression-free survival, overall survival (OS), time to next intervention, time to castration-resistant prostate cancer, prostate cancer-specific mortality and patient-reported outcomes. These secondary measures will inform clinical benefit beyond the primary endpoint and capture both oncologic control and patient-centered effects.
METANOVA incorporates prospective biospecimen collection and imaging data archiving to support future translational research and biomarker discovery. The protocol indicates planned translational analyses to investigate biological correlates of response to MDRT, though specific biomarker assays and analytic plans are to be defined in subsequent work. Data from METANOVA are preplanned to be pooled with the STAMPEDE 2 (NCT06320067) phase III randomised trial, which is designed to assess overall survival benefit of MDRT in men with de novo omHSPC.
The trial has institutional review board approval from the Case Comprehensive Cancer Center (STUDY20231440). Trial outcomes and translational findings will be disseminated through peer-reviewed journals and conference presentations. The study is registered on ClinicalTrials.gov under identifier NCT06150417. Details about operational oversight, monitoring and site participation are provided in the protocol document as reported in the source.