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An assay to calculate circulating tumor cells may be superior to PSA as a surrogate marker for survival in men treated for castration-refractory prostate cancer, according to a multicenter study.
Observing that circulating tumor cell (CTC) monitoring is an effective outcome and treatment guideline in patients undergoing therapy for metastatic breast cancer, Dr. José Moreno and his colleagues built a trial around men diagnosed with castration-refractory prostate cancer.
The men, who had a mean age of 70, were studied at 65 sites in the United States and Europe, reported Dr. Moreno, a urologist at Thomas Jefferson University Hospital in Philadelphia. All patients had prostate-specific antigen (PSA) progression and Eastern Cooperative Oncology Group scores of 0-2, and were to start initial or salvage chemo- therapy and/or combination therapy.
CTCs were enumerated with the CellSearch system (Veridex LLC) assay in blood drawn before treatment and monthly thereafter for up to 18 months. Of 240 evaluable patients, 142 were alive at the time of study presentation. Mean follow-up was just short of 1 year.
Median overall survival for 40 patients with a CTC reduction to below 5 per 7.5 mL of blood drawn at 2-5 weeks after initiation of therapy was 21 months: significantly longer than the 10 months observed in 78 patients whose CTC counts remained above 5, Dr. Moreno said. Men who had no CTCs after 2-5 weeks of chemotherapy had a median survival of 21 months, whereas the 52% of patients with more than 1 CTC had a median survival of 10 months. Among the 10% of patients with CTC counts exceeding 100 per 7.5 mL, median survival was 4 months.
In multivariate analysis, CTCs were the most significant independent predictor of outcome. Dr. Moreno said that at 13-20 weeks, the assay was more predictive than a PSA decline greater than 50% from baseline. "The results validate our key assumption that survival of patients with less than 5 CTCs before treatment is twice that of patients with greater than or equal to 5 CTCs. Measurement of CTCs at any time point predicts response to therapy," he concluded.
The technique faces certain challenge, said discussant Dr. Daniel P. Petrylak of Columbia-Presbyterian Medical Center in New York. "We do need to correlate pretreatment patient characteristics with their CTC and PSA levels to come up with the best prognostic marker for hormone-refractory prostate cancer," he said.
Moreno J. et al. Multicenter study evaluating circulating tumor cells (CTCs) as a surrogate for survival in men treated for castration refractory prostate cancer (CRPC). Abstract 5016.
Commentary |
The area of circulating tumor cells (CTCs) in prostate cancer has been controversial since groups at Jefferson Medical College and the University of Washington claimed credit in 1991 for the concept of detecting prostate-specific antigen (PSA)-expressing circulating cells by using reverse transcriptase-polymerase chain reaction (RT-PCR). Shortly thereafter, a group at Columbia University coined the term "molecular staging" in prostate cancer, claiming that PSA-expressing cells in blood, as detected by RT-PCR, were a predictor of outcome of radical prostatectomy. Unfortunately, a series of studies from multiple centers failed to confirm molecular staging using RT-PCR of PSA-expressing cells as a reproducible technology. A multicenter trial funded by industry and led by University of Washington investigators (in which my group participated) was a dismal failure, and the results were never published. Over the last few years, technology has progressed away from this focus to examination of blood and bone marrow for the cells themselves. Moreno and colleagues from Jefferson should be congratulated for "sticking with it" in trying to further advance this area of research in prostate cancer. We are 16-plus years into molecular staging in prostate cancer, and still struggling to move from bench to bedside to provide new tools to help better care for our patients. — Judd W. Moul, M.D.
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