IDENTIFICATION OF BONE-MARROW MICROMETASTASES IN PATIENTS WITH PROSTATE-CANCER

Background. Thirty percent of patients with clinically localized prost ate cancer and a negative bone scan will experience relapse with recur rent disease despite treatment of the primary tumor. This may be due t o the presence of metastatic prostate cancer cells at the time of trea tment undetected by conventional methods, radionucleotide bone scan, a nd serum prostatic specific antigen blood test. Methods. The authors u sed polymerase chain reaction (PCR) amplification of the prostate-spec ific antigen (PSA) mRNA sequence reverse-transcriptase PCR (RTPCR) and immunohistochemistry using a PSA antibody to identify metastatic pros tate cancer cells in the bone marrow of patients with prostate cancer. Results. Micrometastases were found in the bone marrow of 29 of the 5 5 patients (51%) with prostate cancer and in 0 of the 5 patients with benign prostatic hyperplasia. Samples from five of the seven patients with lymph node metastases and from all five patients with bony metast ases contained micrometastases. Of the samples taken from 43 patients undergoing radical prostatectomy and with no evidence of metastatic di sease, 19 (44%) had micrometastases. Four of the 20 samples (20%) from patients with pathologically localized disease and 15 of the 23 sampl es (65%) from patients with extraprostatic disease had micrometastases (P = 0.003). Bone marrow slides were available on 24 of the 29 patien ts who were positive for micrometastases by RTPCR. Immunohistochemistr y using the PSA antibody identified metastatic cells in 19 of these 24 patients. Conclusions. Reverse-transcriptase polymerase chain reactio n of bone marrow samples from patients with clinically localized prost ate cancer may improve the accuracy of prostate cancer staging and ide ntify patients at high risk for metastatic disease.