Identification of bone marrow micrometastases in patients with prostate cancer

Background. Thirty percent of patients with clinically localized prostate cancer and a negative bone scan will experience relapse with recurrent disease despite treatment of the primary tumor. This may be due to the presence of metastatic prostate cancer cells at the time of treatment undetected by conventional methods, radionu‐cleotide bone scan, and serum prostatic specific antigen blood test. Methods. The authors used polymerase chain reaction (PCR) amplification of the prostate‐specific antigen (PSA) mRNA sequence reverse‐transcriptase PCR (RTPCR) and immunohistochemistry using a PSA antibody to identify metastatic prostate cancer cells in the bone marrow of patients with prostate cancer. Results. Micrometastases were found in the bone marrow of 29 of the 55 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 metastases contained micrometastases. Of the samples taken from 43 patients undergoing radical prostatectomy and with no evidence of metastatic disease, 19(44%) had micrometastases. Four of the 20 samples (20%) from patients with pathologically localized disease and 15 of the 23 samples (65%) from patients with extraprostatic disease had micrometastases (P = 0.003). Bone marrow slides were available on 24 of the 29 patients who were positive for micrometastases by RTPCR. Immunohisto‐chemistry using the PSA antibody identified metastatic cells in 19 of these 24 patients. Conclusions. Reverse‐transcriptase polymerase chain reaction of bone marrow samples from patients with clinically localized prostate cancer may improve the accuracy of prostate cancer staging and identify patients at high risk for metastatic disease.