Evaluation of the Patient With Prostate Cancer

Ashutosh Tewari, MD, MCh, Badrinath Konety, MD, Akshay Bhandari, MD, James Peabody, MD, Hans Stricker MD, Christine Johnson, PhD, Raymond Demers, MPH, Mani Menon, MD, FACS, the Josephine Ford Cancer Center and Department of Urology, Henry Ford Health System, Detroit, Michigan.

In This Article

Molecular Staging

Polymerase chain reaction (PCR) is a powerful tool for expanding minute quantities of DNA for detailed study. Reverse transcriptase PCR (RT-PCR) involves the initial conversion of messenger RNA (mRNA) to complementary DNA (cDNA), followed by the amplification of the cDNA product for molecular analysis. Prostatic cells express high levels of mRNA for PSA. RT-PCR can detect extraprostatic or circulating prostatic cells in peripheral blood, lymph nodes, and bone marrow in many patients with prostate cancer. According to various studies, the sensitivity of detection of PSA-expressing cells in the peripheral blood ranges from 0% to 88%. For identification of prostatic tissue, the RT-PCR assay seems to be more reliable than immunohistochemistry in patients with lymph node metastasis.

Some studies that analyzed specimens of radical prostatectomy (RP) suggest a strong correlation between a positive RT-PCR and capsular invasion, whereas others do not support its usefulness in determining pathological stage.[12,13,14] Katz and colleagues[12,13] applied an enhanced RT-PCR assay using oligonucleotide primers specific for human PSA. This assay is very sensitive, as it can recognize 1 PSA-expressing cell among up to 100,000 lymphocytes. In a study of 148 patients and controls, Katz and colleagues found the assay to be 66% sensitive and 86% specific in differentiating patients with organ-confined cancer from those with extra-capsular extension, positive margins, and distant metastasis.

However, in spite of the initial enthusiasm for RT-PCR-based staging, recent studies have not found it very useful in routine evaluation because the presence of circulating malignant cells does not always correlate with the development of metastasis.[15] A recent study using the RT-PCR assay in 156 patients concluded that there was no correlation between a positive RT-PCR and clinical stage, pretreatment PSA, biopsy Gleason score, or surgical Gleason score. In multivariate logistic regression analysis, no factor, including treatment with RP, could significantly predict a positive RT-PCR. The authors concluded that a positive RT-PCR result occurs in about 25% of early stage prostate carcinomas and is independent of other established prognostic factors. They also noted that a positive RT-PCR assay is a strong predictor of pathologic upstaging in patients with clinically organ-confined disease.[16]

The current diagnostic and prognostic role of PSA detection by RT-PCR is, therefore, still investigational. The practical utility of this modality is being evaluated by many academic centers and the results of these studies will establish whether it indeed has a significant role in the routine management of patients with prostate cancer.


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