The management and treatment of prostate cancer in 1996 is dependent on several factors. When the clinician has determined that a patient has prostate cancer, the initial evaluation includes a series of diagnostic tests to determine the extent of the disease. Traditionally, ultrasonography, CT scan, bone scan, and endorectal coil MR imaging have been used to stage patients with prostate cancer.<sup>11 Iwakiri J., Granbois K., Wehner N. , e al. An analysis of urinary prostate specific antigen before and after radical prostatectomy: Evidence for secretion of prostate specific antigen by the periurethral glands J Urol 1993 ;  149 : 783

Cliccare qui per andare alla sezione Riferimenti, 33 Salo J.O., Kivisarri L., Rannikko S. , e al. Computerized tomography and transrectal ultrasound in the assessment of local extension of prostatic carcinoma before radical retropubic prostatectomy J Urol 1987 ;  137 : 435

Cliccare qui per andare alla sezione Riferimenti, 34 Scaletscky R., Koch M.O., Eckstein C.W. , e al. Tumor volume and stage in carcinoma of the prostate detected by elevations in prostate specific antigen J Urol 1994 ;  152 : 129

Cliccare qui per andare alla sezione Riferimenti</sup> If the cancer is organ-confined, radical retropubic prostatectomy has been the shown to result in effective disease-free status in the long term.<sup>30 Ravery V., Boccon-Gibod L.A., Meuleman A. , e al. Predictive value of pathological features for progression after radical prostatectomy Eur Urol 1994 ;  26 : 197

Cliccare qui per andare alla sezione Riferimenti41</sup> Unfortunately, almost half of all patients initially considered to have clinically localized disease at the time of diagnosis are found to be pathologically upstaged after radical surgery.<sup>25 Noguchi S., Aihara T., Nakamori S. , e al. The detection of breast carcinoma micrometastases in axillary lymph nodes by means of reverse transcriptase-polymerase chain reaction Cancer 1994 ;  74 : 1595  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> The inability of the urologist to determine the extent of the cancer preoperatively is based on the low sensitivity of the available imaging modalities in detecting microscopic extension of tumor beyond the prostatic capsule.

Recently, we developed an assay that uses reverse-transcriptase polymerase chain reaction (RT-PCR) technology that allows us to detect small numbers of cells expressing prostate-specific antigen (PSA), even when extensively diluted in a population of non–PSA-expressing cells.<sup>16 Klobeck H.G., Combriato G., Schulz P. , e al. Genomic sequence of human prostate specific antigen (PSA) Nucleic Acids Res 1989 ;  17 : 3981

Cliccare qui per andare alla sezione Riferimenti</sup> When this assay was peripheral blood obtained from untreated patients with confirmed metastatic prostate cancer, it was positive in 89% of the cases. In striking contrast, when this assay was applied to bloods from a large number of control patients without prostate cancer, it was never found to be positive. These results imply that the majority of metastatic prostate cancer patients shed prostate cells into the blood stream. We then theorized that this assay might be useful in identifying patients with extracapsular prostate cancer at earlier stages. As a test of this hypothesis, the assay was applied to a cohort of 94 patients.<sup>15 Katz A.E., Olsson C.A., Raffo A.J. , e al. Molecular staging of prostate cancer with the use of an enhanced reverse transcriptase-PCR assay Urology 1994 ;  43 : 765  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> All were candidates for radical prostate surgery based on available diagnostic testing modalities that predicted prostate cancer localized to the prostate gland. The results of this survey supported the use of the RT-PCR for PSA test for detecting patients with early extraprostatic spread of prostate cancer. In this group of patients, a positive test correlated significantly with surgical pathology reports identifying that tumor had spread beyond the prostatic capsule.

An extension of the original study of radical prostatectomy patients, now with 160 subjects, is presented here. Comparison between preoperative RT-PCR results, surgical pathology, and postoperative serum PSA progression demonstrates the potential roles that RT-PCR for PSA may play in the selection of treatment for clinically localized prostate cancer. Additionally, the biologic significance of the RT-PCR–detected cells in the circulation is discussed and the potential future directions for RT-PCR technology in the staging of prostate and other cancers are examined.