PROMET-BR - Molecular Profiling of Metastatic Prostate Cancer: a Brazilian Cohort

A Retrospective and Prospective Study Aiming to Characterize Molecular Alterations and Clinical Outcomes of Metastatic Prostate Cancer in a Real-world Cohort of Patients Eligible to Palliative Systemic Therapy at Oncoclínicas & Co Group

PROMET-BR is an observational, retrospective and prospective real-world study in Brazil designed to characterize clinically relevant molecular alterations in metastatic prostate cancer and explore their association with patient outcomes in routine practice. The study will be conducted within Oncoclínicas & Co and will integrate centralized biomarker testing performed at OC Precision Medicine laboratories with retrospectively assembled clinical data from electronic health records (EHRs) from participating sites. Treatments are not assigned by the protocol; patients receive standard-of-care palliative systemic therapy at the discretion of their treating physicians.

PROMET-BR is an observational, retrospective and prospective molecular epidemiology study designed to characterize the prevalence of clinically relevant homologous recombination repair (HRR) gene alterations and PTEN loss of expression in metastatic prostate cancer in Brazil, and to describe associations between these biomarkers and real-world clinical outcomes.

The study is conducted within Oncoclínicas & Co and combines centralized biomarker testing performed at OC Precision Medicine (LOCUS lab, São Paulo) with retrospective clinical data assembled from electronic health records (EHRs) from participating Oncoclínicas & Co sites and integrated by the OC Precision Medicine Big Data team. The protocol does not assign or modify anticancer treatment; systemic therapies are delivered as standard of care at the discretion of treating physicians.

Approximately 100 adult patients (≥18 years) with a clinical diagnosis of metastatic prostate cancer receiving palliative systemic therapy at Oncoclínicas & Co (from 2023 onward) and with sufficient archived FFPE tumor tissue available will be included for the primary analyses. Both primary tumor and metastatic lesions may be used for tissue profiling, provided the patient has metastatic disease and is eligible for palliative systemic therapy. A prospective liquid biopsy subset of up to approximately 30 patients will be enrolled to support evaluation of plasma-based testing, including patients with tissue NGS failure/inconclusive results (expected in a proportion of cases due to pre-analytical tissue limitations) and/or patients enriched for known HRR alterations to enable comparative analyses.

Molecular assessments include a validated tissue NGS assay (GS Focus HRR) for HRR pathway alterations and a validated PTEN immunohistochemistry assay (Ventana PTEN, SP218) for PTEN expression status. For selected cases, a validated plasma NGS assay (GS Focus Liquid) will be performed to evaluate concordance with tissue results for key actionable HRR genes (including BRCA1, BRCA2, ATM, PALB2) and to provide an alternative approach when tissue testing is not informative. Clinical and outcome variables are derived from EHRs (including demographics, disease characteristics, treatment regimens and dates, discontinuation reasons where documented, and survival status). Exploratory endpoints include time to treatment discontinuation (TTD), time to next treatment (TTNT), and overall survival (OS), with subgroup analyses by clinically relevant features (e.g., de novo metastatic vs relapsed, hormone-sensitive vs castration-resistant, and metastatic burden definitions as available).

Analyses are primarily descriptive and exploratory. The primary analyses estimate biomarker prevalences with 95% confidence intervals, with planned stratified descriptions by clinical subgroups. Concordance between tissue and liquid biopsy results will be evaluated in participants with paired results, using concordance metrics (and, where applicable, sensitivity estimates). Exploratory time-to-event outcomes will be summarized using Kaplan-Meier methods and exploratory modeling approaches (e.g., univariate Cox models), acknowledging the heterogeneity of real-world clinical contexts and potential missingness in EHR-derived variables. The study is designed to provide robust local prevalence estimates of HRR alterations and PTEN loss using validated testing methodologies and to inform real-world feasibility considerations for biomarker testing in Brazil.

Ethics committee approval will be obtained prior to study conduct. Informed consent will be obtained where required (including for prospective liquid biopsy procedures); for certain retrospective situations (e.g., deceased or unreachable individuals), an ethics committee-approved consent waiver may be applied in accordance with local requirements. The study does not plan active adverse event collection; any safety information is limited to what is available in routine records for exploratory purposes (e.g., discontinuation due to toxicity when documented).

Inclusion Criteria:

• Adult patients age >= 18 years; clinical diagnosis of metastatic prostate cancer (irrespective of hormone-sensitivity or castration-resistance status); eligible to palliative therapy for metastatic prostate cancer at Oncoclínicas & Co in 2023 onwards; sufficient FFPE tissue available for molecular profiling. For the subset of patients prospectively selected to liquid biopsy cohort, clinical or radiological evidence of disease progression at the sample collection, and with at least 14 days of treatment interval from last dose of systemic anticancer therapy or radiotherapy to liquid biopsy.

Exclusion Criteria:

• No tissue FFPE tissue available for molecular profiling (except in prospective liquid biopsy cohort); less than 3 months follow-up from start of palliative therapy for metastatic prostate cancer at Oncoclínicas & Co.