Abstract 624P
Background
Genomic aberrations of the PTEN tumor suppressor gene are among the most common in prostate cancer. PTEN loss and subsequent activation of the PI3K/AKT/mTOR pathway has potential clinical and therapeutic value. However, the prevalence and clinical significance in mHSPC are not well characterized.
Methods
We retrospectively reviewed consecutive pts from two institutions presenting with de novo mHSPC. PTEN expression was assessed via immunoreactivity (IHC) in primary tumor biopsy (loss defined as absence or weak intensity staining in >10% cells). Pts were not selected on the basis of clinical factors and treatments were given according to each center’s standard of care. We assessed the association of PTEN loss on time to CRPC (TTCRPC) and overall survival (OS) from diagnosis.
Results
We identified 56 pts with de novo mHSPC, of whom 22 (39%) harbored PTEN loss. Median age at diagnosis was 69 years (49-87). The majority were classified as high-volume disease (n=48; 86%) with Gleason 9-10 grade (n=30; 53.6%). Median PSA pre-treatment was 48 ng/mL (5.6-2170). Therapies in the HSPC setting included ADT alone (n=15, 27%), ADT + Docetaxel (n=25, 44.6%), ADT + Abiraterone or Enzalutamide (n=8; 14.3%), and ADT + Docetaxel + Abiraterone (n=5; 9%). A greater proportion of pts received ADT alone in the PTEN-intact groups. At a median follow-up of 28.5 months (mos), CRPC occurred in 30 (53.6%) pts with a median TTCRPC of 15.5 mos TTCRPC was numerically shorter among PTEN-loss compared to PTEN-intact pts (18 vs. 26 mos, HR 1.33; p=0.07). Median OS was 75.0 mos with significant difference observed according to PTEN status: median OS was 40 mos in PTEN loss compared to 75 mos in PTEN-intact pts (HR 3.26; p=0.01).
Conclusions
In this real-world study of routine PTEN loss assessment, we found a 39% prevalence in de novo mHSPC – similar to castration resistant disease. PTEN loss was associated with deleterious impact on survival in pts treated with conventional therapies. Support of ongoing prospective studies evaluating targeted therapies in pts harboring PTEN aberrations (e.g. NCT03997123) is warranted to improve clinical outcomes. Larger dataset correlating genomic with outcomes will be presented.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.