Prognostic significance of PSA in the outcomes of patients with high risk localized prostate cancer.

347 Background: Patients diagnosed with localized high-risk prostate adenocarcinoma (LHRPC) with high Gleason scores (8-10) and prostate-specific antigen (PSA) levels ≤ 4 may experience an altered clinical course. In these patients, low PSA levels may reflect cellular dedifferentiation, indicating more aggressive tumor behavior despite appearing to have a low disease burden. We aim to investigate the impact of PSA levels in patients with LHRPC to better understand prognosis and optimize treatment strategies. Methods: We included patients diagnosed with LHRPC based on TNM stage (T1-T4, N0, M0) and Gleason 8–10 from 2004 to 2020, using data from the National Cancer Database. We stratified patients based on PSA levels (≤4 and >4 ng/dl) and treatment approaches. We utilized Kaplan-Meier analysis and Cox proportional hazard model to study survival outcomes in patients with LHRPC. Results: We included 160,971 patients diagnosed with LHRPC, of which 86.69% (139,546) had PSA >4 ng/dl, while only 13.31% (21,425) had PSA ≤4 ng/dl. Our cohort had 69.55% (111,953) patients aged ≥ 65 years and 30.45% (49,018) aged < 65 years. Regarding race, the cohort was predominantly white, comprising 81.69% (131,497), followed by black at 14.47% (23,292), and other racial categories at 3.84% (6,182). In our cohort 34.43% (55,425) underwent surgery only (S), 9.62% (15,484) received radiation therapy only (RT), 46.81% (75,350) had radiation therapy combined with androgen deprivation therapy (RT + ADT), and 9.14% (14,712) received androgen deprivation therapy only (ADT). In our multivariate cox proportional hazard analysis, LHRPC patients with PSA >4 ng/dL had a 7% (HR 0.93, 95% CI: 0.90–0.95; p<0.001) decreased risk of death compared to those with PSA ≤4 ng/dL. Conclusions: In our study, LHRPC patients with PSA ≤4 ng/dL had poorer survival outcomes after adjusting for the treatment approach, race, age category, income, insurance status, facility type, and location. Further research is required to explore potential biological differences in patients with low PSA-secreting LHRPC. Cox proportional hazard analysis in patients with LHRPC, GS 8-10. Categories Hazard Ratio (95% CI) P-value Treatment type: Surgery only reference RT only 2.27 (2.19, 2.36) <0.001 RT + ADT 2.37 (2.30, 2.44) <0.001 ADT only 5.68 (5.49, 5.87) <0.001 Charlson Deyson score : 0 reference >=1 1.43 (1.40, 1.46) <0.001 Facility type : Academic reference Non-Academic 1.20 (1.17, 1.23) <0.001 PSA ≤ 4 ng/dl reference PSA > 4 ng/dl 0.93 (0.90, 0.95) <0.001