Increased expression of PSA mRNA during brachytherapy in peripheral blood of patients with prostate cancer

Abstract

Objectives. To determine the extent of iatrogenic tumor cell dissemination during brachytherapy by assessing prostate-specific antigen (PSA) mRNA expression in circulating prostate tumor cells using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The instrumentation used in the radioisotope seed placement of the prostate causes trauma to blood vessels and provides a vascular access for tumor cells that can lead to potential iatrogenic dissemination and systemic failure. Methods. Twenty-five patients treated for brachytherapy were recruited in the study. Controls included 4 normal men and 1 woman; case controls included 4 patients who underwent prostate biopsy for prostate cancer diagnosis. Peripheral blood (10 mL) was collected before, during, and after the brachytherapy procedure. Total RNA was isolated from mononuclear cells and phosphorus-32 RT-PCR was performed to analyze the mRNA expression of PSA and G6PDH genes. Results. Of 25 patients, 23 were negative for PSA mRNA expression and 2 were positive for PSA mRNA expression before brachytherapy. Of the 23 patients who were negative for PSA mRNA expression before treatment, 15 patients (65%) turned positive during or after brachytherapy and the remaining 8 patients remained negative throughout the treatment. Eight of the 25 patients developed rising serum PSA levels. Of these 8 patients, 1 (12.5%) did not have PSA mRNA expression in the peripheral blood before, during, or after brachytherapy; the remaining 7 patients who developed rising serum PSA levels had PSA mRNA expression after brachytherapy ( P = 0.03). Conclusions. These findings strongly suggest that iatrogenic shedding of prostate cells occurs as a result of brachytherapy and raises the concern that these cells liberated at the time of brachytherapy increase the risk of metastatic deposits and results in systemic failure, as measured by serum PSA levels.