Clinical application of free/total PSA ratio in the diagnosis of prostate cancer in men over 50 years of age with total PSA levels of 2.0-25.0 ng ml-1 in Western China

Abstract

The goal of this study was to investigate the clinical application of free/total prostate-specific antigen (F/T PSA) ratio, considering the new broad serum total PSA (T-PSA) "gray zone" of 2.0-25.0 ng ml^-1 in differential diagnosis of prostate cancer (PCa) and benign prostate diseases (BPD) in men over 50 years in Western China. A total of 1655 patients were included, 528 with PCa and 1127 with BPD. Serum T-PSA, free PSA (F-PSA), and F/T PSA ratio were analyzed. Receiver operating characteristic curves were used to assess the efficiency of PSA and F/T PSA ratio. There were 47.4% of cancer patients with T-PSA of 2.0-25.0 ng ml^-1. When T-PSA was 2.0-4.0 ng ml^-1, 4.0-10.0 ng ml^-1, and 10.0-25.0 ng ml^-1, the area under the curve (AUC) of F/T PSA ratio was 0.749, 0.769, and 0.761, respectively. The best AUC of F/T PSA ratio was 0.811 when T-PSA was 2.0-25.0 ng ml^-1, with a specificity of 0.732, a sensitivity of 0.788, and an optimal cutoff value of 15.5%. The AUC of F/T PSA ratio in different age groups (50-59 years, 60-69 years, 70-79 years, and ≥80 years) was 0.767, 0.806, 0.815, and 0.833, respectively, and the best sensitivity (0.857) and specificity (0.802) were observed in patients over 80 years. The T-PSA trend was in accordance with the Gleason score, tumor node metastasis (TNM) stage, and American Joint Committee on Cancer prognosis group. Therefore, the F/T PSA ratio can facilitate the differential diagnosis of PCa and BPD in the broad T-PSA "gray zone". Serum T-PSA can be a Gleason score and prognostic indicator.

Keywords: free/total prostate-specific antigen ratio; gray zone prostate-specific antigen; prostate cancer; total prostate-specific antigen.

Figure 1

Serum T-PSA, F-PSA, and F/T PSA ratio analysis in patients with prostate diseases. (a) Serum T-PSA, F-PSA, and F/T PSA ratio in patients with PCa and BPD. (b) The F/T PSA ratio in groups with different T-PSA ranges. (c) ROC analysis of T-PSA, F-PSA, and F/T PSA ratio in differentiating PCa from BPD in the whole population. T-PSA: total prostate-specific antigen; F-PSA: free prostate-specific antigen; PCa: prostate cancer; BPD: benign prostate disease; ROC: receiver operating characteristic; AUC: area under the curve; F/T PSA: free/total prostate-specific antigen.

Figure 2

ROC analysis of T-PSA, F-PSA, and F/T PSA ratio in different T-PSA ranges. ROC analysis of T-PSA, F-PSA, and F/T PSA ratio in serum T-PSA (a) <2.0 ng ml⁻¹, (b) ≥2.0 ng ml⁻¹ and <4.0 ng ml⁻¹, (c) ≥4.0 ng ml⁻¹ and <10.0 ng ml⁻¹, (d) ≥10.0 ng ml⁻¹ and <25.0 ng ml⁻¹, (e) ≥25.0 ng ml⁻¹ and <50.0 ng ml⁻¹, and (f) ≥50.0 ng ml⁻¹ and <100.0 ng ml⁻¹, respectively. T-PSA: total prostate-specific antigen; AUC: area under the curve; F-PSA: free prostate-specific antigen; ROC: receiver operating characteristic; F/T PSA: free/total prostate-specific antigen.

Figure 3

ROC analysis of T-PSA, F-PSA, and F/T PSA ratio for serum T-PSA ≥2.0 ng ml^-1 and <25.0 ng ml^-1 in different age groups. ROC analysis of T-PSA, F-PSA, and F/T PSA ratio for (a) 50–59 years, (b) 60–69 years, (c) 70–79 years, and (d) age ≥80 years, respectively. ROC: receiver operating characteristic; T-PSA: total prostate-specific antigen; F-PSA: free prostate-specific antigen; F/T PSA: free/total prostate-specific antigen; AUC: area under the curve.

Figure 4

Analysis of serum T-PSA, F-PSA concentration, and F/T PSA ratio in patients with different (a) Gleason scores and (b) TNM stages, and (c) in AJCC prognosis groups. T-PSA: total prostate-specific antigen; F-PSA: free prostate-specific antigen; F/T PSA: free/total prostate-specific antigen; AJCC: American Joint Committee on Cancer; TNM: tumor node metastasis.