Purpose/Objective(s): Early-onset prostate cancer (EOCaP), as defined by diagnosis ≤55 years of age, comprises ~10% of all CaP diagnoses. In EOCaP subgroups with high-risk disease, data has demonstrated worse disease-specific survival compared to older patients. Given the limited representation of high-risk EOCaP in the literature, further phenotypical clinicopathologic analysis of this entity is warranted. This study delineates the associations between preoperative clinical characteristics and pathologic findings following radical prostatectomy (RP) for high-risk EOCaP.

Materials/Methods: Patients ≤55 years old, treated from 2008-2016 with RP for clinical high-risk CaP (without evidence of nodal or distant metastases), were collected from our IRB-approved multi-institutional tumor registry. Pre-operative characteristics included age, clinical T stage (cT), initial PSA (iPSA), percent positive biopsy cores (PPC), and biopsy primary tumor grade and biopsy total Gleason score (G1 and GS, respectively). Post-operative findings included pathologic T stage (pT), extracapsular extension (ECE+), seminal vesicle invasion (SVI+), margin positivity (SM+), positive lymph nodes (LN+), surgical G1 and GS, and post-op PSA positivity (PSA+). Predictive models were generated by both univariate analysis (UVA) and multivariate analysis (MVA) via generalized linear regression with statistical software R. P-value of <0.05 was considered significant.

Results: There were 117 patients included with a median age of 52, median year of diagnosis 2011, median iPSA of 18.1 ng/mL, median biopsy GS of 8, and median PPC 58%. On MVA, cT≥2a and PPC≥50% were predictive for the following characteristics: cT≥2a for pT≥3a (OR 1.27 [95% CI 1.06-1.52]), ECE+ (OR 1.25 [1.04-1.51]), and SM+ (OR 1.30 [1.09-1.55]), PPC≥50% for pT≥3a (OR 1.25 [1.04-1.51]), ECE+ (OR 1.20 [0.99-1.46]), SVI+ (OR 1.38 [1.18-1.63]), and SM+ (OR 1.17 [0.87-1.47]). IPSA was significantly predictive for the following characteristics: SVI+ (OR 1.39 [1.19-1.63]), SM+ (OR 1.34 [1.12-1.59]), LN+ (OR 1.18 [1.01-1.38]), and post-op PSA+ (OR 1.20 [1.03-1.40]). Biopsy G1 was significantly predictive for the following characteristics: pT≥3a (OR 1.26 [1.00-1.59]), ECE+ (OR 1.30 [1.02-1.65]), SVI+ (OR 1.33 [1.09-1.63]), and post-op PSA+ (OR 1.26 [1.03-1.57]). Biopsy GS was a negative predictor for multiple local factors, trending toward significance on MVA (p = 0.0692), but significant on UVA for SVI+ (OR 0.77 [0.65-0.91]) and SM+ (OR 0.76 [0.64-0.92]).

Conclusion: For high-risk EOCaP, PPC≥50% and cT≥2a predicted for upstaging of disease. Biopsy GS≥8 predicted for downstaging of disease after RP, perhaps reflecting a tendency toward early metastatic disease. iPSA may positively predict for more clinically aggressive disease (SVI+, LN+, post-op PSA+). These results may provide information to guide treatment options including RP or radiotherapy combined with androgen deprivation therapy for high-risk EOCaP.