Assessing the impact of PTEN loss on outcomes in high-/very high-risk, advanced hormone-sensitive prostate cancer patients: Institutional retrospective study.

260 Background: Inactivation of tumor suppressor gene, PTEN (Phosphatase and tensin homolog) by deletion or mutation occurs in between 15-20% of localized prostate cancers and up to 50% of castration-resistant prostate cancers. The series of studies has shown a robust correlation between the genomic loss of PTEN and its protein as assessed by immunohistochemistry (IHC). Dysregulation of PI3K/AKT/mTOR signaling pathway has been linked with adverse pathological features and poor oncological outcomes such as the development of disease recurrence, metastasis, and castrate-resistant prostate cancer (CRPC). Here, we aim to study the prognostic and predictive role of PTEN in relation to treatment outcomes in a newly developed retrospective institutional research cohort. Methods: The cases with genomic PTEN loss (FoundationOne CDx, n=190) and protein loss by IHC (BenchMark Ultra, Roche Diagnostics, n=273) were pooled together. A total of 311 patients (PTEN loss=84, PTEN intact=227) that had available clinical and pathological information, including follow-up, were used for downstream statistical analysis. Kaplan-Meier analyses and univariate and multivariate Cox proportional hazard models were used to assess the benefit of RP over definitive RT with or without androgen deprivation therapy (ADT) for high-risk localized cohort as well as the benefit of primary ADT with or without intensification in the patients experiencing the loss of PTEN. Results: Patients with PTEN loss were more likely to present with advanced-stage disease (Stage IV: 33% vs. 19%) and more frequently received RT+ADT (43% vs. 34%) in high-risk patients. In contrast, those with intact PTEN were more likely to undergo radical prostatectomy (34% vs. 28%). Although overall survival (OS) did not differ significantly between all groups (log-rank p=0.51), mortality was higher in the PTEN loss group (32% vs. 22%). There was also a trend toward earlier development of castration-resistant prostate cancer (CRPC) in patients with PTEN loss (log-rank p=0.16). Conclusions: PTEN loss in prostate cancer is linked to more aggressive disease, higher mortality, and earlier CRPC development, consistent with existing literature. Our findings suggest that high-risk/very high patients with PTEN loss may benefit from definitive RT-based treatment over surgery. The study is limited by its retrospective, smaller sample size and single-institution design.