Circulating tumor cells in peripheral blood samples from patients with increased serum prostate specific antigen: initial results in early prostate cancer.

PURPOSE: We evaluated the hypothesis that circulating tumor cells as determined using the CellSearch System would correlate with tumor volume, pathological stage and Gleason score in men with localized prostate cancer. MATERIALS AND METHODS: Samples of blood (30 ml) were drawn from 97 men with localized prostate cancer before radical prostatectomy, on postoperative days 2 to 3 and at 6 weeks. A control group consisted of 25 men with an increased prostate specific antigen and no tumor detected on extended prostate biopsy. Samples were analyzed for circulating tumor cells using the CellSearch System. RESULTS: Circulating tumor cells were detected in 21% of patients with cancer and 20% of controls (p = 0.946). At 6 weeks after prostatectomy circulating tumor cells were detected in 16% and 11% (p = 0.51) of the men positive and negative for circulating tumor cells at baseline, respectively. Of the 20 patients with cancer who had circulating tumor cells at baseline 18 showed no circulating tumor cells after surgery. Circulating tumor cell values did not correlate with tumor volume, pathological stage or Gleason score. Only 3.1% of the men with cancer and 8% of the control group had 3 or more circulating tumor cells per 22.5 ml blood at baseline. CONCLUSIONS: In metastatic breast, prostate and other cancers more than 5 circulating tumor cells are often detected using the CellSearch System, and may correlate with prognosis. However, in the setting of localized prostate cancer the number of detectable circulating tumor cells was low, with findings comparable to those in men who were biopsy negative for cancer. We found no correlation between the number of circulating tumor cells and known prognostic factors in this population.

Evaluation of precursor prostate-specific antigen isoform ratios in the detection of prostate cancer.

OBJECTIVE: Disease-associated isoforms of the prostate-specific antigen (PSA) have recently been identified. We evaluated the efficacy of using precursor isoforms of PSA (pPSA) and their ratios for the detection of prostate cancer. METHODS: Serum concentrations of [-2], [-4], and [-7]pPSA, BPSA, and free PSA (fPSA) were retrospectively measured in 43 selected men. Of the 43 men, 15 had clinical T2 prostate cancer with ultrasound-estimated prostate volumes (PVs) of >50 cm(3), 13 had clinical T2 prostate cancer with (PVs) <25 cm(3), and 15 were prostate cancer-free with PV >50 cm(3). We calculated sum pPSA ([-2]+[-4]+[-7]pPSA). We also compared the ratios of: free/total PSA, [-2]pPSA/fPSA, [-2]pPSA/BPSA, [-2]pPSA/(fPSA-BPSA), [-2]pPSA/(fPSA-sum pPSA), and [-2]pPSA/{fPSA-(sum pPSA+BPSA)} among these three groups. RESULTS: The median [-2]pPSA/(fPSA-sum pPSA) ratio was significantly higher in men with prostate cancer with or without large PV compared with men with large PV without prostate cancer. Values for median [-2]pPSA/free PSA ratio were higher in men with prostate cancer with or without large PV compared with men with large PV, and without prostate cancer, but the differences were not statistically significant. CONCLUSIONS: In this preliminary study, [-2]pPSA/(fPSA-sum pPSA) ratio was not associated with prostate gland volume but was associated with prostate cancer. This ratio may be useful in the detection of prostate cancer, particularly in men with larger glands.

Cancer worry is associated with abnormal prostate-specific antigen levels in men participating in a community screening program.

An accumulating body of research suggests that psychological factors can affect physiological parameters. We assessed the association between the perceived risk of prostate cancer, prostate cancer-specific worry, and cancer-related symptoms and prostate-specific antigen (PSA) levels or the findings from digital rectal examination (DRE) in a large sample of men undergoing a free prostate cancer screening. Participants (n = 1635) completed a background questionnaire and a questionnaire that assessed their prostate cancer history, screening behavior, perceived risk of prostate cancer, and prostate cancer worry. PSA levels were then determined, and a DRE was conducted. A PSA level of >or=4.0 ng/ml was considered abnormal. The sample size for the multivariate analyses was reduced because of missing data on certain items. Participants who had an abnormal PSA level reported a significantly higher perceived cancer risk (P = 0.02), cancer worry (P = 0.004), and a greater percentage indicated the reason for the current screening was cancer-related symptoms (P = 0.014) than did participants who had normal PSA levels. Multivariate logistic regression analyses controlling for age, past screening behavior, past screening results, and reason for current screening revealed that perceived cancer risk [P = 0.01; odds ratio (OR), 1.5; 95% confidence interval (CI), 1.1-2.1], cancer worry (P = 0.001; OR, 3.3; 95% CI, 1.7-6.5), and cancer-related symptoms (P = 0.05; OR, 3.4; 95% CI, 1.1-10.3) remained significantly associated with an abnormal PSA level. When perceived cancer risk, cancer worry, and cancer-related symptoms were entered in the same multivariate analysis, only cancer worry remained in the model. The present findings suggest that prostate cancer-specific worry was associated significantly with an abnormal PSA level.

Volume-based evaluation of serum assays for new prostate-specific antigen isoforms in the detection of prostate cancer.

OBJECTIVES: Recently, disease-specific isoforms of the prostate-specific antigen (PSA) have been identified. We evaluated the efficacy of precursor isoforms of PSA (pPSA) and an internally cleaved form of PSA referred to as the benign prostatic hyperplasia-associated PSA (BPSA) for the detection of prostate cancer. METHODS: Serum concentrations of [-2], [-4], and [-7]pPSA, sum pPSA ([-2] + [-4] + [-7]pPSA), and BPSA were retrospectively measured in 43 selected men. The median total PSA levels in men with and without cancer were 6.5 microg/L (range 0.4 to 12.1 microg/L) and 6.1 microg/L (range 3.7 to 21.5 microg/L), respectively. Of the 43 men, 15 had clinical T2 prostate cancer with an ultrasound-estimated prostate volume (PV) of greater than 50 mL, 13 had clinical T2 prostate cancer with PV less than 25 mL, and 15 were prostate cancer free with PV greater than 50 mL. RESULTS: The median values for BPSA, free-to-total PSA ratio (f/tPSA), and benign-to-total PSA ratio (B/tPSA) differed statistically between men with cancer and a PV less than 25 mL and men with cancer and a PV greater than 50 mL (P <0.05) and between the men with cancer and a PV less than 25 mL and men without cancer and a PV greater than 50 mL (P <0.005). All evaluated variables had no correlation with tumor volume in 15 men who had undergone radical prostatectomy. CONCLUSIONS: In this preliminary study, the level of [-2], [-4], sum pPSA, and BPSA seemed to be PV related, but only BPSA and B/tPSA and f/tPSA were significantly associated with PV. Therefore, pPSA did not aid in better discriminating cancer from noncancer.