Prostate specific antigen (PSA) has been used as a biomarker for prostate cancer for the last 20 years. Traditionally, a serum PSA <4 ng/ml has been used as a general cut-off between normal and abnormal readings. There is evidence to demonstrate that men with a normal serum PSA can develop prostate cancer. The aim of this study was to investigate the clinico-pathological features of prostate cancer in a non-screened Irish cohort with serum PSA <4 ng/ml.

A retrospective analysis was performed of all patients who underwent radical retropubic prostatectomy (RRP) in a tertiary referral unit over a 10-year period (2000–2010). Clinico-pathological characteristics were collated including those from trans-rectal ultrasound-guided (TRUS) prostate biopsies and radical prostatectomy specimens.

Between 2000 and 2010, 651 men underwent an RRP, with 43 (6.6%) having a serum PSA <4 ng/ml. The median PSA was 3.2 ng/ml (range 0.8–4.0). Nineteen (44.2%) had palpable disease on direct rectal examination (DRE). Following prostatectomy, 28 (65.12%) had Gleason 6 disease, 14 (32.56%) had Gleason 7 disease and one (2.32%) had Gleason 8 disease. Five (11.63%) patients were upgraded from TRUS biopsy to final histopathology. Six (13.95%) patients had pathological evidence of extracapsular extension on final pathology. Three (6.98%) patients experienced biochemical recurrence and received salvage radiation therapy after a median time of 24 months. The median follow-up was 106 months (range 36–158). Twenty (46.51%) patients had a first-degree family history of prostate cancer.

A PSA cut-off of 4 ng/ml has commonly been used in the detection of prostate cancer. Our study emphasizes that this cut-off is inappropriate and that no specific level of PSA can be used. Management decisions need to be individualized based on index of suspicion with concomitant counselling and rectal examination.