Among men with palpable prostate cancer (PCa) and normal-range PSA level at diagnosis, the risk of cancer-related death increases as PSA level decreases, a new study suggests.

The finding suggests the existence of clinically detectable, low-PSA-secreting disease with an elevated risk of PCSM and highlights the importance of the digital rectal examination in men with PCa and normal-range diagnostic PSA, Itai Pashtan, MD, of Brigham and Women’s Hospital in Boston, and colleagues concluded in an online report in Cancer Epidemiology.

The study included 9,081 men with non-metastatic PCa and a diagnostic PSA level below 2.5 ng/mL. Of these, 1,710 had non-palpable tumors (clinical stage T1c) and 7,371 men had palpable tumors (clinical stage T2–T4). The groups had a median PSA level at diagnosis of 1.3 and 1.4 ng/mL, respectively. After a median follow-up of 2.8 years, 548 men died, 118 (21.5%) from PCa.

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In men with non-palpable tumors and a Gleason score of 7–10, each 1-point increment in PSA was associated with a significant 2-fold increased risk of PCSM, after adjusting for confounders. Among the men with palpable tumors and any Gleason score, each 1-point decrement in PSA was associated with a significant 34% increased risk of PCSM.

Dr. Pashtan’s group noted that the biology underlying the low PSA secreting yet clinically aggressive PCa in patients with palpable tumors is unclear.

The researchers analyzed 2004–2007 data from the Surveillance, Epidemiology and End Results (SEER) database. The 9,081 men represented 5.5% of all men (163,982) diagnosed with non-metastatic PCa during that time period.