Lower PSA levels increase or decrease mortality risk depending on Gleason score

This study evaluated prostate-specific mortality risk based on PSA (prostate specific antigen) levels in men with high-grade disease. Authors reported increased mortality risk with lower PSA levels in men with high-grade disease. A decreased mortality risk was observed with lower PSA levels in men with low-grade disease.

Prostate cancer is often graded based on how agressive the cancer is (called the Gleason score). The higher the Gleason score, the more likely the cancer can grow and spread. This is known as high-grade disease.

PSA (prostate specific antigen) is a protein elevated in the blood in prostate cancer. An increase in PSA levels is a common risk factor associated with a change in the disease status in prostate cancer. PSA levels are, therefore, often used to monitor and calculate disease progression. However, whether the risk of progression based on PSA levels is the same in men with high-grade disease has not been fully studied. 

The aim of this study was to determine mortality risk due to prostate cancer according to PSA levels in men with high-grade disease.

The records of 250,986 men with localized (confined) prostate cancer were analyzed. Men were divided according to PSA levels: very low (less than or equal to 2.5 ng/mL), low (2.6 to 4 ng/mL), medium (4.1 to 10 ng/mL), medium-high (10.1 to 20 ng/mL), high (20.1 to 40 ng/mL), and very high (more than 40 ng/mL). Mortality risk according to PSA levels was compared between men with low-grade (Gleason score of 7 or less) and high-grade disease (Gleason score of 8 to 10). Health outcomes were followed for an average of 38 months.

Overall, the highest mortality risk due to prostate cancer was observed among men with very high PSA levels. However, men with very low or low PSA levels had a higher prostate-cancer specific mortality risk than men with medium-high PSA levels.

Among men with high-grade disease, prostate-cancer specific mortality risk was 2.15 times higher if PSA levels were very low compared to medium PSA levels. Compared to medium PSA levels, low PSA levels increased mortality risk 1.6-fold, high PSA levels increased risk 2.08-fold, and very high PSA levels increased the risk up to 3.23-fold.

Very low PSA levels were not associated with poorer outcomes in men with low-grade disease. Prostate-cancer specific mortality risk steadily increased with higher PSA levels in men with low-grade disease. For example, this risk was increased 5.8-fold in men with very high PSA levels compared to men with medium PSA levels.

The authors concluded that lower PSA levels were associated with higher prostate-cancer specific mortality risk in men with high-grade disease. However, lower PSA levels were associated with better survival in men with low-grade disease.