Background

In pts with mCSPC undergoing intensified ADT, achieving a PSA nadir ≤0.2 ng/mL “anytime” after the start of treatment was associated with a significantly improved overall survival (OS) versus those with a PSA >0.2 ng/mL: HR 0.17 (95% CI, 0.13-0.23) (Chi AUA 2021, abstract 1281). Our objective was to validate these findings in a real-world population and characterize the clinical and tumor genomic landscape according to PSA response.

Methods

In this IRB-approved study, patient-level data were collected retrospectively. Eligibility: presence of mCSPC undergoing intensified ADT with either docetaxel or novel hormonal therapy (NHT) started within 3 months of diagnosis, availability of PSA nadir, and availability of tumor comprehensive genomic profiling (CGP) prior to start of ADT. Variants of unknown significance and genomic aberrations present in <5% pts were excluded. Optimal PSA response (OR): PSA≤0.2 ng/mL. Study endpoints: PFS was calculated per PCWG-2 defined PSA progression or radiographic progression or clinical progression whichever occurred first; OS was defined as start of therapy to date of death or censored after last follow-up. The relationship between PSA nadir and both PFS and OS was assessed in the context of Cox proportional hazards. Gene prevalence was compared using a chi square test.

Results

134 pts were eligible and included. Optimal responders (OR) (n=104) and non-OR (n=30): median age at diagnosis 63 vs 65 years; median PSA at ADT start 18.1 vs 74.5 ng/mL; high volume of disease 48% vs 77%. For OR and non-OR: median PFS, 60.6 vs 13.2 (P<0.001); median OS, 94.9 vs 35.2 months (P<0.001) respectively. Multivariate analysis is described in the table.

Conclusions

Only a minority of pts with mCSPC do not achieve an optimal PSA response with intensified ADT. Those non-OR have worse outcomes on treatment with intensified ADT. Herein we externally validate that achieving a PSA nadir ≤0.2 ng/mL is correlated with superior OS. Detailed genomic landscape of these pts will be presented in the meeting.

 
Variable PFS
HR (95% CI, P-value)
OS
HR (95% CI, P-value)
PSA nadir ≤ 0.2 ng/mL 0.28 (0.15 - 0.53, P <0.001) 0.21 (0.09 - 0.50, P<0.001)
Age at Diagnosis 0.99 (0.96 - 1.03, P = 0.71) 0.97 (0.93 - 1.02, P = 0.23)
Gleason Score 1.50 (1.07 - 2.10, P = 0.02) 0.13 (0.81-2.23, P = 0.25)
PSA at Baseline 1.00 (1.00 - 1.00, P = 0.37) 1.00 (1.00 - 1.00, P = 0.04)
NHT vs Docetaxel 0.35 (0.17 - 0.69, P = 0.003) 0.26 (0.11 - 0.66, P = 0.004)
Disease Volume 0.53 (0.25 - 1.12, P = 0.10) 0.56 (0.18 - 1.71, P = 0.31)
De-novo 0.61 (0.30 - 1.23, P = 0.17) 1.17 (0.41 - 3.34, P = 0.77)