The Clinical Trajectory of Prostate Cancer Patients Harboring Rare Histological Subtypes-A Retrospective Cohort Trial

Acinar adenocarcinoma is the most common histological subtype of prostate cancer (PCa). However, 5% of cases present with unconventional histological subtypes (UHs), which have inconsistent clinical characteristics.

600 patients underwent a radical prostatectomy (RP) at our institution between 2003 and 2023. 50% had UHs, while other 50% age-matched patients (median age 63 years), with pure acinar adenocarcinoma served as comparison group. Collected parameters included age at diagnosis, PSA levels, imaging results, ISUP (International Society of Urological Pathology) Grade Group at biopsy and RP, TNM-stage and biochemical recurrence rates (BCR). Statistical analysis was conducted using SPSS and Excel, applying Mann-Whitney-U, Chi-Square tests, and Cox proportional hazards models to assess associations with recurrence-free survival.

All patients with UHs presented mixed histological forms (P < .001). Importantly, UHs were previously identified only in 9% of biopsy specimens (P < .001). Patients with UHs had more aggressive disease reflected by higher ISUP Grade Group (P < .001), higher prevalence of ≥pT3a tumors as well as higher rates of positive resection margins (P < .001) although fewer nerve-sparing procedures were performed (P < .001). Patients with UH had a higher risk of PSA persistence after RP (P = .04) and higher BCR rates (P < .001) after a median follow-up of 54.8 months. Notably, multivariate Cox regression analysis indicated that the presence of UHs is the most significant risk factor for BCR (HR 1.972, 95% CI 1.210-3.312).

Patients with UH exhibit more aggressive disease and have an increased risk of disease relapse following curative therapy.