Molecular prediction of progression in patients with conservatively managed prostate cancer.

Abstract

OBJECTIVES: To report our results with the use of reverse transcriptase-polymerase chain reaction (RT-PCR) as a potential predictor of prostate cancer (CaP) progression in patients managed with watchful waiting. There has been much recent debate about the safety of treating older patients with localized CaP with watchful waiting. The RT-PCR is an assay that can detect small numbers of prostate cells in circulating blood. METHODS: Blood samples were taken from male and female control patients and from patients with advanced, hormone-treated and untreated localized (watchful-waiting) CaP. Sensitive nested RT-PCR assays were carried out on these samples using primers for both prostate-specific antigen (PSA) and prostate-specific membrane antigen mRNA. RESULTS: Fifty-one blood samples were taken from patients managed with watchful waiting. Fourteen of these had positive RT-PCR results. These patients had a significantly higher PSA velocity than did the patients with negative RT-PCR results. Circulating prostate cells were detected in 18 of 24 patients with advanced CaP, 2 of 34 patients with stable, hormone-treated CaP, and in none of the negative controls. The assay was able to detect 20 LNCaP cells reliably when added to a 5-mL volunteer blood sample. CONCLUSIONS: A significant minority (27%) of patients with untreated localized CaP had detectable circulating prostate cells, and these patients tended to have a progressively rising serum PSA level. Despite low-grade disease and sometimes low serum PSA values, these patients may be at risk of early metastatic progression. RT-PCR, in conjunction with existing prognostic tests, may be of use in predicting which "watchful-waiting" patients are at risk of early progression.