Abstract 5780: Prognostic implications of prostatic gonadotropin releasing hormone receptor and androgen receptor expression in non-metastatic prostate adenocarcinoma

Abstract Background: Suppression of pituitary gonadotropin releasing hormone receptor (GnRHR) is the mainstay systemic therapy for prostate cancer. GnRHR is also expressed in the prostate and its correlation with direct anti-tumorigenic effects have been demonstrated. The inhibition of prostatic androgen receptor (AR) signaling is another potent therapeutic option. Despite their crucial role in prostate cancer proliferation, prognostic implications of prostatic GNRHR and AR expressions remain uncertain. To investigate the prognostic utility of GNRHR and AR expressions, a public prostate cancer transcriptomic profile and progression-free survival (PFS) data were reviewed. Methods: The Cancer Genome Atlas (TCGA) Pan-Cancer project batch-corrected treatment-naïve primary tumor mRNA expression profiles (RNA Seq V2 RSEM) of 324 non-metastatic (M0) prostate adenocarcinoma cases and their associated clinical data were retrieved from the cBioPortal. Log-rank Kaplan-Meier was used for survival analysis. The “low” vs. “high” expression cutoffs for GNRHR and AR were defined as the cohort’s lower 30th and 25th percentiles, respectively. Results: Prostatic GNRHR and AR mRNA expressions were heterogeneous, but apart from low AR expression in Gleason grade group (GGG) 1, levels were similar across age, anatomical T N stage or all other GGGs. For T2b-4 N0 disease, neither GNRHR nor AR expression alone was significantly associated with PFS. However, in a subgroup of patients with T2b-3a N0 disease with high GNRHR, those with concomitant low AR (n=21) were associated with superior 4-year PFS compared to high AR (n=119) with hazard ratio (HR) 0.28 (95% CI 0.080-0.976, p=0.046). The composition of GGG was similar between these groups. GNRHR or AR expression-dependent differential PFS was not observed in patients with T3b-4 N0 disease. For N1 disease, high GNRHR (n=38) was associated with superior 4-year PFS compared to low GNRHR (n=25) with HR 0.32 (95% CI 0.12-0.85, p=0.007), independent from AR expression levels. Conclusions: High GNRHR and low AR expression were associated with superior PFS in an anatomical stage-dependent manner. The superior PFS of low AR was more pronounced for localized T2b-3a N0 disease, while high GNRHR was most pronounced in regional node-positive N1 disease. Prostatic GNRHR and AR mRNA expression levels may allow tailored strategies in utilizing GnRH agonist/antagonist and AR signaling inhibitors in treating non-metastatic castrate-sensitive disease. Further investigation is warranted. Citation Format: Donghyun Kim. Prognostic implications of prostatic gonadotropin releasing hormone receptor and androgen receptor expression in non-metastatic prostate adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5780.