Genomic aberrations of the PTEN tumor suppressor gene are among the most common in primary prostate cancer (PCa). Deletion of the PTEN gene and subsequent activation of the PI3K/AKT/mTOR pathway are associated with poor clinical outcomes and a reduced therapeutic response. However, the prevalence and clinical meaningfulness of PTEN loss in Asian patients (pts) with De novo novo metastatic hormone-sensitive prostate cancer have not been comprehensively understood.

A prospective study was conducted with consecutive patients with de novo mHSPC presenting at Cho Ray Hospital, Vietnam. PTEN expression was assessed by Immunohistochemistry (IHC) in primary tumor biopsy. Clinical and subclinical characteristics, as well as treatment outcomes, were recorded. We evaluated the association of PTEN loss on time to CRPC (TTCRPC) and overall survival (OS) from diagnosis.

We identified 20 patients with de novo mHSPC, of whom 5 (25%) harbored PTEN loss. Median age at diagnosis was 66.7 years (53-83). The majority were classified as high-volume disease (n=16; 80%) with Gleason 8-10 (n=15; 75%). Pre-treatment PSA > 100 ng/mL were observed in 15/20 cases (75%). First-line therapies in the mHSPC setting included ADT alone (n=7, 35%), ADT + Docetaxel (n=1, 5%), and ADT + Abiraterone (n=12; 60%). A greater proportion of pts received ADT + Abiraterone in the PTEN loss groups (80% vs 53.3%). At a median follow-up of 22.9 months (mos), CRPC occurred in 13 (65%) pts with a median TTCRPC of 15.5 mos. TTCRPC in PTEN-loss and PTEN-intact was 19.2 vs. 13.2 mos, respectively. Median OS in PTEN-loss and PTEN-intact was 31.9 vs. 25.9 mos, respectively. There was no significant difference between PTEN status groups in terms of PFS and OS.

In the first study of PTEN status assessment in Vietnamese individuals, we found a 25% prevalence of de novo mHSPC, consistent with previous studies in other countries. The correlation between PTEN loss and negative impact on survival and cancer progression was not seen clearly in pts treated with conventional therapies. Therefore, further studies with larger datasets are needed to clarify this association.