PTEN’s Role in Treatment Planning for mHSPC

Precision oncology increasingly requires clinicians to recognize biologically distinct disease subsets within metastatic prostate cancer. Gordon A. Brown, DO, FACOS, an associate professor at Rowan University School of Osteopathic Medicine, program director of Urologic Surgery at Rowan University School of Osteopathic Medicine, and director of New Jersey Urology’s Center for Advanced Therapeutics, highlights that PTEN deficiency represents a validated prognostic biomarker associated with aggressive clinical behavior across both localized and metastatic settings. Evidence from large meta-analyses demonstrates significantly higher risks of recurrence, faster progression, and reduced survival among patients harboring PTEN-deficient tumors.

According to Brown, recognizing PTEN-deficient mHSPC as a separate biologic subgroup has important therapeutic implications. These patients frequently demonstrate earlier escape from androgen deprivation therapy and androgen receptor pathway inhibition, suggesting the need for treatment intensification strategies. Emerging evidence indicates that some patients may benefit from earlier chemotherapy or combination approaches incorporating AKT inhibition alongside standard hormonal therapy.

Data from the phase 3 CAPItello-281 trial (NCT04493853) further reinforce the clinical value of PTEN testing. Brown explains that PTEN-deficient patients exhibit more aggressive radiographic progression patterns, sometimes progressing on imaging despite stable prostate-specific antigen levels. As a result, clinicians may need to adjust monitoring strategies, imaging intervals, and patient counseling, integrating biomarker status into everyday treatment planning and longitudinal disease management.