Charting the Future of Precision Oncology: The Emerging Role of PTEN Testing-Charting the Future of Precision Oncology in Prostate Cancer: The Emerging Role of PTEN Testing

Charting the Future of Precision Oncology in Prostate Cancer: The Emerging Role of PTEN Testing

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Video Summary

The CME program reviews how precision oncology could improve outcomes in metastatic hormone-sensitive prostate cancer (mHSPC), a setting with no FDA-approved biomarker-driven strategies today. Speakers emphasize using biomarkers to better stratify prognosis and treatment, aiming to delay progression to metastatic castration-resistant disease.<br /><br />Current management has expanded from ADT alone to routine doublet therapy (ADT plus an androgen receptor pathway inhibitor) and, for selected high-risk patients, triplet intensification (adding docetaxel). Clinical “biomarkers” already guiding care include disease volume (CHAARTED), high-risk features (LATITUDE), timing (de novo vs metachronous), and PSA kinetics/nadir.<br /><br />The session highlights molecular testing—urging universal germline and somatic testing up front—because actionable alterations are common. HRR mutations (especially BRCA1/2) predict poorer prognosis but strong benefit from PARP-based intensification; the AMPLITUDE trial supports abiraterone plus niraparib in HRR-altered mHSPC, with particularly strong BRCA benefit.<br /><br />A major focus is PTEN (referred to as “P10”) loss, present in ~25% of mHSPC and linked to aggressive biology and relative ARPI resistance via PI3K/AKT pathway activation. CAPItello-281 (PTEN-loss by IHC) showed improved radiographic PFS adding capivasertib to abiraterone, with notable diarrhea, hyperglycemia, and rash; PSA may be unreliable in PTEN-loss patients, so imaging surveillance is important. Emerging concepts include PSMA PET as a biomarker and radioligand intensification (PSMA-Addition).

Keywords

metastatic hormone-sensitive prostate cancer

precision oncology

biomarker-driven therapy

germline and somatic testing

homologous recombination repair mutations

BRCA1/2

PARP inhibitor intensification

PTEN loss

PI3K/AKT pathway