RT-PCR PSA Assay in Marrow Predicts Early PSA Recurrence

BETHESDA, Md—Up to 40% to 50% of prostate cancer patients who undergo radical prostatectomy for localized prostate carcinomas will relapse. Traditional prognostic markers, such as clinical stage or pretreatment levels of prostate-specific antigen (PSA), are of limited value in predicting which individuals will have relapsed disease.

In a recent study, the use of a new technique for detecting prostate cells has been shown to have some value in predicting the early recurrence of prostate cancer.

The technique, reverse transcriptase polymerase chain reaction (RT-PCR) assay for PSA, was used to detect the presence of prostate cells in the bone marrow at the time of surgery. Those patients who had a positive RT-PCR PSA assay were more likely to have early disease recurrence during follow-up after surgery.

“The most important finding was that the men who had prostate cells in the bone marrow had a much higher rate of recurrence,” Judd W. Moul, MD, told Oncology News International. Dr. Moul is the director of the Department of Defense Center for Prostate Disease Research (CPDR) at the Uniformed Services University of Health Sciences, Bethesda.

Further investigation is needed to determine if bone marrow RT-PCR PSA positivity has value as an independent prognostic marker. Previous studies with the RT-PCR PSA assay have produced conflicting results, perhaps because standardization of laboratory procedures is lacking. Bone marrow samples, rather than blood, were tested in this study because earlier studies were unable to find a correlation between stage or recurrence in men with RT-PCR PSA positivity of peripheral blood.

The ability to identify those individuals who are at risk for recurrence would allow physicians to devise an appropriate treatment plan. “If we knew that the men who were positive had a high likelihood of recurring, maybe right after surgery we could use adjuvant hormonal treatment for a year,” Dr. Moul said. “Right now, you hate to treat everybody because many of them are cured and may not need that treatment. The RT-PCR PSA assay would identify the high-risk group much earlier, and maybe we could do adjuvant therapy right away in that group.”

In this blinded prospective study, physicians performed preoperative unilateral anterior iliac bone marrow aspiration on 116 patients immediately before radical prostatectomy. The RT-PCR PSA assay was performed three times on each bone marrow sample. Although these men had apparently localized prostate cancer, PSA-expressing cells were found in the bone marrow of 51 (44%) of the patients (Chun-Ling Gao et al: J Urol 161:1070-1076, 1999).

Bone marrow RT-PCR PSA positivity was said to occur when at least two of three assays were positive. When any positive assay result was considered, the rate of positivity was much higher. Seventy-seven men (66.3%) had at least one positive test, said Shiv Srivastava, PhD, the scientific director for CPDR.

Bone marrow RT-PCR PSA positivity failed to predict pathological stage. Of 51 patients testing positive, 25 (49%) had organ-confined disease and 26 (51%) had non-organ-confined disease. Positivity also failed to predict margin status as determined from whole mount prostate cancer specimens.

However, bone marrow RT-PCR PSA positivity was correlated with early PSA recurrence. Patients were seen every 3 months in the first year after surgery and every 6 months thereafter. Mean follow-up was 14.7 months. Using Kaplan-Meier analysis, researchers determined that the 2-year disease-free survival was 96.6% for RT-PCR PSA negative patients and 77.5% for positive patients (P = .054).

Extraprostatic extension of tumor and bone marrow RT-PCR PSA positivity were both associated with early recurrence. Bone marrow RT-PCR PSA positivity was superior to Gleason score and pretreatment PSA for predicting PSA recurrence.

The long-term value of the assay is being studied, Drs. Moul and Srivastava said. “We’re continuing to follow these men to see if this test positivity has longer-term prognostic value. In other words, as we follow the men longer, will all the men who had a positive test end up recurring? Will the men who had a negative test stay clean?”

Researchers also hope that their work will lead to a better understanding of prostate cancer metastatic disease. At this time, the metastatic potential of the prostate cells found in the bone marrow at the time of prostatectomy is poorly understood.

“There are two possibilities,” Dr. Moul said. “Either these men have true occult metastases or it’s possible that these are just prostate cells that have gotten there but don’t really have the molecular machinery to set up shop and metastasize. Further investigation is needed.”