OBJECTIVE Prostate cancer patients with surprisingly high prostate-specific antigen (PSA) are encountered clinically. However, descriptions of this group of patients are extremely rare in the published literature. This study reports treatment outcome and long-term prognosis for this group of patients. METHODS Between January 2007 and December 2012, 2,064 patients with PCa diagnosed at a tertiary medical center were retrospectively reviewed. A total of 90 PCa cases were identified with initial PSA (iPSA) >1,000 ng/mL at diagnosis. A retrospective study was conducted in this cohort, with comparison among stratified patient age groups, PSA, treatment options, and overall survival. RESULTS The mean PSA at PCa diagnosis in this cohort was 3,323 ng/mL (1,003-23,126, median: 2,050 ng/mL). Most patients were in the age group 65-79 years (55/90, 61%). Males older than 80 years had a poor prognosis (P<0.001). Forty-six patients (51%) underwent orchiectomy with a median follow-up period of 16.2 (1.3-72.7) months, compared to 44 patients treated with medical castration and a median follow-up of 9.1 (0.3-70.5) months. Kaplan-Meier analysis revealed survival benefit from treatment with orchiectomy (P<0.001). PSA reduction >90% of iPSA following primary androgen deprivation therapy (reaching true nadir) could be a predictor of longer survival (P<0.001). Cox regression revealed the hazard ratio (HR) of variables were age (HR: 4.57, 95% confidence interval [CI]: 1.45-14.37, P=0.009), reaching true nadir (HR: 0.12, 95% CI: 0.03-0.58, P=0.008), and the treatment option with orchiectomy (HR: 0.22, 95% CI: 0.65-0.76, P=0.016). CONCLUSIONS Age ≥80 years indicated poor overall survival in PCa patients with iPSA >1,000 ng/mL. Reaching a true nadir of PSA following primary androgen deprivation therapy could be a predictor of longer survival. Bilateral orchiectomy is recommended for this group of patients.