BETHESDA, MdUp 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
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
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. Were 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
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 its possible that
these are just prostate cells that have gotten there but dont
really have the molecular machinery to set up shop and metastasize.
Further investigation is needed.