High-Grade Prostate Cancer Shows U-Shaped Relation Between PSA, Mortality

Prostate-specific antigen level may have a U-shaped relationship with prostate cancer-specific survival in men with Gleason score of 8 to 10

  • Date: 17 Sep 2015
  • Author: Lynda Williams, Senior medwireNews Reporter
  • Topic: Prostate Cancer

medwireNews: Study findings published in Cancer challenge the belief that a low prostate-specific antigen (PSA) level is associated with a good prognosis in men with high-grade clinical T1 to 4 prostate cancer without positive lymph nodes or metastases.

Data from the Surveillance, Epidemiology, and End Results programme for 250,986 men revealed a U-shaped relationship between prostate cancer-specific mortality (PCSM) and PSA level for the 29.1% of patients with Gleason score of 8 to 10 (GS 8–10).

Multivariate analysis showed that GS 8–10 patients in the lowest and highest PSA categories (≤2.5 ng/mL and ≥40.0 ng/mL) had the highest hazard ratios for PCSM relative to men with a PSA of 4.1–10.0 ng/mL, at 2.15 and 3.21, respectively.

Those with values between these two extremes had lower hazard ratios, at 1.60, 1.60 and 2.08 for those with levels of 2.6–4.0, 10.1–20.0 and 20.1–40.0 ng/mL, respectively.

“These findings in a large, national, contemporary cohort with survival endpoints provide strong clinical evidence for the idea that a low presenting PSA level should be considered an adverse clinical feature when it is coupled with the finding of high-grade disease”, write Paul Nguyen, from Brigham and Women’s Hospital in Boston, Massachusetts, USA, and co-authors.

The team also found a significant interaction between PSA level and GS, whereby a PSA of 2.5 ng/mL or less significantly predicted poor PCSM in men with high-grade GS 8–10 but not those with a GS of 7 or less.

By contrast, for men with GS of 7 or less there was a trend towards better PCSM with lower PSA, with adjusted hazard ratios of 1.0 and 0.87 for those with levels of 2.5 ng/mL or below and 2.6–4.0 ng/mL, compared with the reference group of 4.1–10.0 ng/mL, rising to 1.99, 3.41 and 5.80 for 10.1–20.0 ng/mL, 20.1–40.0 ng/mL and above 40.0 ng/mL, respectively.

“The poor prognosis observed for patients with high-grade, low-PSA prostate cancer in this large, national cohort suggests that a low PSA level may be a sign of underlying aggressive and extremely poorly differentiated or anaplastic low PSA–producing tumors, which may be less sensitive to traditional androgen-deprivation therapy”, the researchers conclude.

“These findings are concerning and could lead to a paradigm shift in clinical practice with respect to low-PSA, high-grade prostate cancer.”


Mahal BA, Aizer AA, Efstathiou JA, Nguyen PL. Association of very low prostate-specific antigen levels with increased cancer-specific death in men with high-grade prostate cancer. Cancer 2015; Advance online publication 15 September. DOI:10.1002/cncr.29691

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