1645P - Tumour suppressor gene signature predicts early progression in metastatic hormone-sensitive metastatic prostate cancer (mHSPC) patients

Background

Alterations on the tumor suppressor genes (TSG) RB1, PTEN and TP53 are associated with treatment resistance, decreased survival and aggressive variants of prostate cancer (APC). In our previous work we developed and validated a signature of low expression of TSG that was associated with poor outcomes in mHSPC patients (pts) treated with androgen deprivation therapy (ADT) +/- docetaxel (Jimenez, Eur Urol Oncol, 2024). Here, we assessed our TSG signature in mHSPC pts treated with androgen receptor signaling inhibitors (ARSI) and explored clinical characteristics at progression.

Methods

This is a multicenter retrospective biomarker study in mHSPC pts, treated with ADT + ARSI. TSG expression was assessed by nCounter platform in HSPC tumor samples. TSG_low was considered when ≥2 out of 3 TSG presented low expression of a previously stablished cut-off, and TSG_wt in the remaining cases. TSG signature was correlated with castration resistance-free survival (CRPC-FS) (primary endpoint) by Kaplan Meier and multivariate Cox analysis. APC was considered if pts met ≥1 of the previously reported criteria at CRPC progression (Aparicio, Clin Cancer Res, 2013).

Results

140 pts were included. Median age was 71.6 years (range 29-92.8), 76.8% presented de novo stage IV, 15.9% visceral metastasis and 53% high volume disease. With a median follow-up of 27 months (m) (2.4 - 91), 32% of pts died and 32.6% developed CRPC. TSG_low (17.4 %) was independently associated with shorter CRPC-FS (28.5m vs NR, HR 2.1, p=0.024). Among the 45 pts that developed CRPC, 30 had available data at time of CRPC progression. 12 of them (40%), presented at least 1 APC criteria. 66.6% of pts with TSG_low tumors presented APC vs 38% of the TSG_wt (Fisher p=0.12). Four pts (13.3%) harbor PTEN_low + RB1_low tumors and all of them developed APC criteria at progression. Metastatic tumor biopsy at progression was available for 4 pts (13.3%); all of them showed neuroendocrine differentiation.

Conclusions

TSG_low expression is associated with early CRPC progression in mHSPC pts treated with ARSI and could help to predict de development of APC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

O. Reig Torras: Financial Interests, Personal, Invited Speaker: Pfizer, BMS, Ipsen, Astellas; Financial Interests, Personal, Other, Travel costs: MSD. L. Ferrer Mileo: Financial Interests, Personal, Other, speaker, travel accommodation: Pfizer; Financial Interests, Personal, Invited Speaker, speaker, travel accommodation: Kyowa Kirin; Financial Interests, Personal, Invited Speaker, Speaker: Ipsen, Janssen. C. Aversa: Financial Interests, Personal, Invited Speaker: Pfizer, Janssen, BMS, Roche, Astellas, Bayer, MSD, Ipsen, AstraZeneca; Other, Travel funding: Jansen. A. Rodriguez-Vida: Financial Interests, Personal, Invited Speaker: Roche, BMS, Janssen, AstraZeneca, Ipsen; Financial Interests, Personal, Advisory Board: MSD, Pfizer, Astellas, Bayer, Merck. M. Figols Gorina: Financial Interests, Personal, Invited Speaker: Merck, Ipsen, MSD, Astellas. All other authors have declared no conflicts of interest.