Patients with prostate cancer who have low prostate antigen (PSA) levels ≤2.5 ng/mL or 2.6 to 4 ng/mL have a higher risk for cancer-specific death compared with patients whose PSA levels are 10.1 to 20 ng/mL, according to a new study published online ahead of print in the journal Cancer.1

The study was conducted in order to establish whether a very low PSA level was linked with greater prostate cancer-specific mortality (PCSM) among men with a Gleason score of 8-10.

Researchers used the Surveillance, Epidemiology, and End Results program to identify 328,904 men with clinical T1 (cT1)-4N0M0 prostate cancer between 2004 and 2010.

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A multivariate Fine-Gray competing risks regression analysis was used to determine PCSM as a function of the PSA level (≤2.5, 2.6-4, 4.1-10, 10.1-20, 20.1-40, or > 40 ng/mL) and GS (8-10 vs ≤ 7).

With a median follow-up of 38 months, the adjusted hazard ratio for PCSM was 2.15 with a PSA level ≤2.5 ng/mL (95% confidence interval [CI], 1.65-2.79; P<0.001), 1.60 with a PSA level of 2.6 to 4 ng/mL (95% CI, 1.22-2.10; P=0.001), 1.60 with a PSA level of 10.1 to 20 ng/mL (95% CI, 1.41-1.82; P<0.001), 2.08 with a PSA level of 20.1 to 40 ng/mL (95% CI, 1.81-2.38; P<0.001), and 3.23 with a PSA level >40 ng/mL (95% CI, 2.85-3.65; P<0.001).

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This suggested a U-shaped distribution. There was a significant interaction between the PSA level and GS (P interaction <0.001) such that only a PSA level ≤2.5 ng/mL significantly predicted poorer PCSM among patients with GS 8-10 disease.

Results support the idea that low PSA levels in GS 8 to 10 disease may be a sign of aggressive and very poorly differentiated or anaplastic low PSA-producing tumors.

Those with low PSA, GS 8-10 disease should be considered for clinical trials studying the use of chemotherapy and other novel agents for very high-risk prostate cancer.


  1. Mahal BA, Aizer AA, Efstathiou FA, Nguyen PL. Association of very low prostate-specific antigen levels with increased cancer-specific death in men with high-grade prostate cancer. [published online ahead of print September 15, 2015]. Cancer. doi: 10.1002/cncr.29691.