1643P - Impact of PTEN alterations on clinical outcomes in patients (pts) with de novo metastatic prostate cancer (mPC)

Background

Compound alterations in TP53, RB1, and/or PTEN have been correlated with poor outcomes in pts with mPC; however, there is limited data regarding whether PTEN alterations(alt) by next generation sequencing (NGS) are prognostic in isolation. PTEN -null de novo mPC is currently being investigated in CAPItello-281 and may represent a clinically actionable subtype. As such, we sought to characterize outcomes of this genomically defined subgroup.

Methods

PROMISE is a multi-institutional database including mPC pts (N=2027) with NGS. Using PROMISE, we analyzed outcomes based on PTEN status in de novo mPC pts.

Results

Among 1036 pts with de novo mPC, 212 (20%) had PTEN alt by NGS. Median age at diagnosis was 64 yrs, 21% were Black, 53% had high volume (HV) disease. Compared to the PTEN-wildtype (wt) group, PTEN-altered mPC had higher co-occurrence of TP53 and/or RB1 mutations (57% vs 37%); lower median PSA (38 vs 63 ng/ml); and more visceral disease (18 vs 11%). Groups were otherwise similar. The table shows univariate (UVA) outcomes based on PTEN status. Outcomes were similar in men with high volume disease on UVA. On multivariable analysis controlling for clinical prognostic features and TP53/RB1 alterations, PTEN status remained independently associated with overall survival (OS) [HR 1.27, 95% CI (0.99, 1.63) p=0.05]. Table: 1643P