PTEN Loss in Metastatic Prostate Cancer: Biology and Prognosis

PTEN loss is associated with worse outcomes in prostate cancer, yet until recently clinicians lacked a targeted treatment option to address this high-risk disease biology. In this video, Scott Sellinger, MD, FACS, discusses the role of PTEN loss in prostate cancer and why this biomarker has become increasingly important with the emergence of targeted therapies such as capivasertib (Truqap). He explains that PTEN normally functions as a regulator of the AKT signaling pathway, which promotes cancer cell growth when activated. When PTEN is lost or significantly reduced, this pathway can become dysregulated, allowing unchecked cellular growth and contributing to more aggressive prostate cancer behavior.

Sellinger notes that PTEN loss occurs in a substantial subset of patients with metastatic prostate cancer and is associated with several adverse disease characteristics. He explains that patients with PTEN-deficient tumors are more likely to present with higher-grade disease, including higher Gleason scores or grade groups, and may have metastatic disease at diagnosis. Additionally, these patients may be more likely to develop visceral metastases, which can be more challenging to treat. Because of this aggressive disease biology, Sellinger emphasizes the importance of identifying patients with PTEN loss early in the metastatic disease course to help inform treatment decisions and risk assessment.

Before the availability of capivasertib, Sellinger explains that PTEN loss served primarily as a prognostic biomarker, helping clinicians identify patients with a higher likelihood of aggressive disease but without a specific targeted intervention. He describes how the identification of PTEN deficiency previously prompted a more aggressive approach to management but did not directly guide the use of a particular therapy. With the approval of capivasertib, PTEN loss has gained an additional role as a predictive biomarker, offering clinicians a treatment strategy designed to target this specific molecular alteration and potentially improve outcomes for this patient population.