BEYOND BRCA AND PSMA: MAPPING THE EMERGING BIOMARKER LANDSCAPE IN METASTATIC PROSTATE CANCER (MPC) USING LIVING EVIDENCE
Author(s)
Stacy Grieve, PhD1, Anna Forsythe, MBA, MSc, PharmD1, Jessicca Rege, PhD1, Saro Sarkisian, MD, MHA2.
1Oncoscope, Miami, FL, USA, 2Frederick Health, Frederick, MD, USA.
1Oncoscope, Miami, FL, USA, 2Frederick Health, Frederick, MD, USA.
OBJECTIVES: Precision oncology has transformed several cancer types through biomarker-driven treatment strategies that improve patient outcomes while reducing unnecessary toxicity. In mPC, currently established biomarker-driven approaches primarily include prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals and poly(ADP-ribose) polymerase (PARP) inhibitors for homologous recombination repair (HRR)-altered tumors. More recently, capivasertib received regulatory approval for PTEN-deficient metastatic castration-resistant PC (mCRPC), signaling expansion of biomarker-directed treatment strategies. We used a Real-Time AI-Assisted Living Systematic Literature Review (REAL-SLR) to characterize the evolving biomarker landscape in metastatic prostate cancer and identify emerging populations relevant to future health technology assessment (HTA) and Joint Clinical Assessment (JCA) planning.
METHODS: A PRISMA-compliant continuously updated REAL-SLR was conducted using protocol-driven searches for PC. Evidence from interventional trials, regulatory sources, clinical guidelines, and technology assessments was systematically identified, screened, and structured. Studies were stratified by clinical stage, castration status, biomarker, risk, treatment path, and intervention category.
RESULTS: As of June 19, 2026, the REAL-SLR identified 862 studies in PC, including 467 conducted in the metastatic setting. Among these, 134 reported outcomes in biomarker-defined populations. Beyond tumor-agnostic biomarkers such as microsatellite instability-high (MSI-H) and tumor mutational burden-high (TMB-H), most studies focused on PSMA-targeted population (n=58) and HRR pathway alterations including BRCA1/2, PALB2, ATM, and ATR (n=43). Emerging biomarker-defined populations included androgen receptor (AR) alterations (n=8); AR-v7 splice variants (n=11), PTEN alterations (n=12), PDL1 expression (n=3), RB1-positive populations evaluating CDK4/6 inhibitors (n=2), and PIK3CA-mutated tumors (n=1).
CONCLUSIONS: Living evidence mapping identified a rapidly expanding biomarker landscape in metastatic prostate cancer extending beyond established PSMA- and HRR-directed treatment paradigms. The emergence of PTEN-, AR-, and RB1-defined populations suggests future changes in treatment sequencing, comparator selection, and evidence requirements. Continuous evidence monitoring may support earlier identification of emerging biomarker populations and inform HTA, JCA, and reimbursement planning in precision oncology.
METHODS: A PRISMA-compliant continuously updated REAL-SLR was conducted using protocol-driven searches for PC. Evidence from interventional trials, regulatory sources, clinical guidelines, and technology assessments was systematically identified, screened, and structured. Studies were stratified by clinical stage, castration status, biomarker, risk, treatment path, and intervention category.
RESULTS: As of June 19, 2026, the REAL-SLR identified 862 studies in PC, including 467 conducted in the metastatic setting. Among these, 134 reported outcomes in biomarker-defined populations. Beyond tumor-agnostic biomarkers such as microsatellite instability-high (MSI-H) and tumor mutational burden-high (TMB-H), most studies focused on PSMA-targeted population (n=58) and HRR pathway alterations including BRCA1/2, PALB2, ATM, and ATR (n=43). Emerging biomarker-defined populations included androgen receptor (AR) alterations (n=8); AR-v7 splice variants (n=11), PTEN alterations (n=12), PDL1 expression (n=3), RB1-positive populations evaluating CDK4/6 inhibitors (n=2), and PIK3CA-mutated tumors (n=1).
CONCLUSIONS: Living evidence mapping identified a rapidly expanding biomarker landscape in metastatic prostate cancer extending beyond established PSMA- and HRR-directed treatment paradigms. The emergence of PTEN-, AR-, and RB1-defined populations suggests future changes in treatment sequencing, comparator selection, and evidence requirements. Continuous evidence monitoring may support earlier identification of emerging biomarker populations and inform HTA, JCA, and reimbursement planning in precision oncology.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
SA27
Topic
Study Approaches
Topic Subcategory
Literature Review & Synthesis
Disease
Oncology