New Test to Find Prostate Cancer Spread at the Earliest

Detects Occult Lymph Node Metastases in Locally Advanced Node-Negative Prostate Cancer

June 20, 2006. A new test for prostate cancer patients who undergo surgery can detect cancer cells hidden in the pelvic lymph nodes. This test could be useful for high risk patients whose nodes look cancer free (not macroscopically positive for cancer). When used to check for occult (hidden) cancer, the test may warn of likely recurrence and enable patients to obtain adequate treatment.

Richard Cote, professor of pathology and urology at the Keck School of Medicine of USC, who has helped run a trial on this test, says it "appears to be a very powerful test and better than anything else we know of for predicting recurrence." Similar trials are evaluating the test for detection of hidden metastases in lymph nodes and bone marrow for breast and lung cancers.

Prostate cancer is the most common non-skin cancer in America. One in six American men will be diagnosed with prostate cancer, making men 35 percent more likely to be diagnosed with prostate cancer than women are to be diagnosed with breast cancer.

Dr. Richard Cote"Thanks to greater awareness, as well as increased and improved screening, we see men increasingly diagnosed with prostate cancer in its early stages," Cote says. "Most of these patients will do very well and will not require treatment beyond surgery or radiation therapy to cure their disease."

But even when the lymph nodes removed at the time of the cancer surgery appeared negative for cancer, Cote says, in a significant number of patients, metastases of the prostate cancer appear later.

Cote and his colleagues looked at 3,914 lymph nodes from 180 patients who were staged as having stage pT3 lymph node negative (NO) prostate cancer based on standardized visual scan of node biopsy samples under a microscope. The lymph nodes were then evaluated for occult (hidden) metastases using new specific tissue staining tests using antibodies and antigens that can detect cancer on a cell-by-cell level.

This test -- an immunochemical analysis -- checks for cells that react with antibodies to cytokeratins and, if positive, PSA. The team found occult tumor cells in the lymph nodes of 24 of the patients whose nodes had been previously been diagnosed as cancer-free.

The test used to detect the occult tumor cells is more sensitive than any clinical, pathologic or radiographic techniques, Cote says.

The group then compared cancer recurrence and survival in those patients with the hidden tumor cells versus those without the cells. The presence of occult tumor cells was associated with increased prostate cancer recurrence and decreased survival. In fact, "the outcome for patients with occult tumor cells was similar to those who were identified as having positive lymph nodes at the time of the surgery," Cote says.

"We have shown that occult tumor spread in lymph nodes is a significant predictor of disease recurrence," he says. "Once surgery is performed, the primary form of treatment is adjuvant systemic therapy. In patients with no evidence of metastasis, success of such therapy is assumed to be due to killing of occult tumor before it becomes clinically evident. Therefore, the ability to detect occult metastasis is pivotal to identification of patients who would most benefit from systemic therapy and also identify patients who may be spared from unnecessary therapy."

Other options for detecting occult positive nodes include High-resolution MRI with magnetic nanoparticles (see Noninvasive Detection of Clinically Occult Lymph-Node, NEJM, June 19, 2003).

Work was supported by grants from the National Institutes of Health and National Cancer Institute, from the Department of Defense, and from the California Cancer Research Program.

Sources and links:

Dr. Cote in labJournal of Clinical Oncology, 24: 2735-2741, 2006. Vincenzo Pagliarulo, Debra Hawkes, Frank Brands, Susan Groshen, Jie Cai, John P. Stein, Gary Lieskovsky, Donald G. Skinner, Richard J. Cote, "Detection of Occult Lymph Node Metastases in Patients with Locally Advanced (pT3) Node Negative Prostate Immunochemical Cancer," From the Departments of Pathology, Urology, and Preventive Medicine, University of Southern California, Keck School of Medicine; and the University of Southern California/Kenneth Norris Comprehensive Cancer Center, Los Angeles, CA .

Credits: Photo of Dr. Cote at work, above, USC. News source, Monika Guttman, University of Southern California.

Dr. Cote's homepage at USC. Dr. Cote has worked on this problem for about ten years.

More than you might want to know about cytokeratins (CK) from NordiQC: Cytokeratin in normal cells

Another way of finding occult metastasis in prostate cancer patients' lymph nodes, tested at Baylor, uses an assay for human glandular kallikrein 2 (hK2) mRNA (RT-PCR/hK2).

See also:

Clinical Cancer Research Vol. 10, 5808-5814, September 1, 2004 Prognostic Value of Combined "Triple"-Reverse Transcription-PCR Analysis for Prostate-Specific Antigen, Human Kallikrein 2, and Prostate-Specific Membrane Antigen mRNA in Peripheral Blood and Lymph Nodes of Prostate Cancer Patients. Ralf Kurek et al. Philipps-University, Marburg, Germany; and Fred Hutchinson Cancer Research Center, Seattle, Washington

This page made and last UPDATED by J. Strax, June 20, 2006.

Information on this web site is not intended as medical advice nor to be taken as such. Consult qualified physicians specializing in the treatment of prostate cancer. Neither the editors nor the publisher accepts any responsibility for the accuracy of the information or consequences from the use or misuse of the information contained on this web site.

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