Two Cytokines May Aid CRPC Patient Outcome Predictions

CHICAGO—Risk group classification based on two serum cytokines may help predict survival in men with progressive castration-resistant prostate cancer (CRPC), according to a new study presented at the 2013 American Society of Clinical Oncology annual meeting.

American researchers reported that these two cytokines—macrophage colony-stimulating factor (M-CSF) and interleukin (IL)-10—may reflect the biology within the tumor microenvironment. They may also serve as biomarkers for clinical benefit.

“M-CSF has previously been shown in prostate cancer to predict bone metastasis and IL-10 is known to be an immunosuppressive cytokine,” said investigator Sumit Kumar Subudhi, MD, PhD, a medical oncology fellow at Memorial Sloan-Kettering Cancer Center in New York. “So biologically this assay makes sense. If you have both high levels of both of those cytokines, you theoretically would have a higher tumor burden and theoretically you would do worse.”

Dr. Subudhi and colleagues analyzed a panel of 10 cytokines (M-CSF, interferon-gamma, tumor necrosis factor-alpha, IL-1-beta, IL-4, IL-5, IL-6, IL-10, IL-12, and IL-13) using clinically validated enzyme linked immunosorbent assays. M-CSF and IL-10 predicted survival in progressive metastatic CRPC; the predictive value was improved by adding circulating tumor cell (CTC) enumeration.

“It is fast and it something that could be as easy as a PSA [test] and that is what makes it so attractive,” Dr. Subudhi told Renal & Urology News. “The [existing] nomograms do help a lot and they do help influence our treatment decisions. However, there is a great deal of variability in survival rates. Some therapies may work for years in a subset of patients, but may only work for weeks in another.”

Serum cytokines have been proposed as immunologic biomarkers of clinical responses based on their role in tumor biology, Dr. Subudhi said, adding that two whole-blood mRNA signatures recently were found to be predictive of survival in CRPC patients.

For the latest investigation, Dr. Subudhi and his colleagues collected serum from 75 patients with progressive CRPC at MSKCC. The group had a mean age of 73 years and a mean PSA level of 13 ng/mL. Thirty-nine patients (52%) had been treated with surgery and 17 patients (23%) received radiotherapy.

Along with the two cytokines, PSA, LDH, albumin, hemoglobin and CTC enumeration were independently prognostic.

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