Molecular Marker Detects Occult Micromets in Prostate Cancer

NEW YORK—Expression of prostate-specific antigen (PSA) in the messenger RNA (mRNA) of pelvic lymph nodes appears to be a promising marker for occult micrometastases in patients with localized prostate cancer, said Anna C. Ferrari, MD, assistant professor, Medical Oncology Associates of the Derald R. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York.

Interim results of an ongoing study suggest that the new molecular marker may prove useful in selecting patients for systemic therapy, Dr. Ferrari said at the Chemotherapy Foundation Symposium XVIII.

Absence of such a diagnostic tool, she noted, results in undertreatment of some patients because their disease appears to be localized and in over-treatment of others based on an estimated risk of occult micrometastases.

The messenger RNA is detected by a reverse transcription polymerase chain reaction (RT-PCR) assay for PSA, Dr. Ferrari said. The assay has been shown to have the sensitivity to detect "one prostate cancer cell among 10 million non-prostate cancer cells," she said.

When tested in pathologically positive pelvic lymph nodes and normal lymph nodes, the number of false-positive and false-negative findings was extremely small, she added, suggesting that "this was a reliable approach to use to detect occult micrometastases."

The current ongoing study seeks to determine if mRNA is an independent risk factor for micrometastases and if it correlates with outcomes, Dr. Ferrari said. At the time of her presentation, the researchers had enrolled 109 patients. The number with PSA levels above and below 10 ng/mL is nearly equal, as are the number with tumor stages above and below stage IIb. "We have a high proportion of patients with high-risk features," she said.

The pelvic lymph nodes are sampled systematically whether the patient is scheduled for surgery or radiation therapy. Laparoscopic lymph node dissection is employed for those whose treatment is to be radiation therapy (79 of 109 to date).

Correlation With Gleason Score

RT-PCR assays of the lymph node samples showed positive signals for PSA mRNA in 30 (28%) of the 109 patients, Dr. Ferrari reported. Dr. Ferrari and her colleagues then tried to correlate this finding with the patients’ high-risk factors.

No linkage was found between the positive signals and tumor stage or serum PSA levels. "However, when we correlated with one of the strongest predictors, the Gleason score in the primary tumor, we found that, in fact, there was a predominance of PSA RT-PCR signals in the high-risk group—those with Gleason 7 or higher," Dr. Ferrari said. There was a strong trend toward statistical significance for this finding.

She noted that the number of patients in this category (26) is small and accrual continues. "But this was extremely encouraging," she said, "and suggests that this may become an important marker."

In follow-up to determine if the new assay correlates with outcomes, disease progression is defined as a serum PSA increase of more than 1.0 ng/mL at 18 months or longer after radiation treatment or 0.1 ng/mL at 12 months or longer after radical prostatectomy.

A total of 62 patients have been followed for a median of 24 months. Progression was seen in 7 of the 26 patients positive for PSA mRNA, Dr. Ferrari reported, and in 5 of the 36 with negative results on the assay.

Follow-up over 5 years will be required, she noted, to determine if the assay identifies an independent marker of micrometastases in patients with localized prostate cancer. The ultimate goal of the research, Dr. Ferrari emphasized, is to "be able to select patients for treatment to prevent progression on the basis of molecular proof of micrometastases rather than conventional indicators of small tumor burden."