CTCs DETECTED IN LOCALIZED PROSTATE CANCER

April 21, 2010 (Washington, DC) — A novel technology that isolates circulating tumor cells (CTCs) from whole blood has detected CTCs in some men with localized prostate cancer.

It is the first time that CTCs have been discovered in men with early-stage prostate cancer, Medscape Oncology learned in an exclusive interview with the technology's inventor, Sunitha Nagrath, PhD. Previously, these cells were found only in men with more advanced disease.

Dr. Nagrath is an instructor in surgery and bioengineering at the Massachusetts General Hospital and Harvard Medical School in Boston.

Her new technology, known as the CTC-Chip Microfluidic Techonology, has also detected CTCs in men with localized disease before and after prostatectomy.

"The presence of CTCs after surgery could potentially differentiate the patients with aggressive versus indolent disease" she said.

Dr. Nagrath explained that previously, CTCs were found in men with metastatic prostate cancer and were considered to be an indicator of disease spread.

Data from a proof of concept study of the CTC-Chip Microfluidic Technology were presented here at the American Association for Cancer Research (AACR) 101st Annual Meeting. The study involved 30 men with metastatic prostate cancer and 20 men with localized disease.

"This is a new and innovative technique" for monitoring prostate cancer treatment and disease development, said Laura J. van 't Veer, PhD, visiting associate professor at the Helen Diller Family Comprehensive Cancer Center of the University of California, San Francisco. Dr. van 't Veer moderated an AACR press conference at which the CTC-Chip was highlighted.

"The study has high-impact implications because it shows the presence of CTCs in men with localized prostate cancer, indicating that CTCs might be present long before metastasis in some patients," said Dr. Nagrath.

But what exactly Dr. Nagrath's discoveries mean clinically is not certain, said Max Wicha, MD, director of the University of Michigan Comprehensive Cancer Center in Ann Arbor.

The clinical significance of these cells in early-stage prostate cancer remains to be determined," said Dr. Wisha.

Currently, there is no device approved by the US Food and Drug Administration for detecting CTCs in men with localized prostate cancer, said Dr. Nagrath. However, the CellSearch CTC Test (Veridex) is approved to be used as an aid in the monitoring of metastatic prostate cancer patients.

No Preprocessing

According to Dr. Nagrath, the CTC-Chip design, in comparison to CellSearch and other technologies, is a case of less is more.

"Other technologies have to do a lot of preprocessing of blood before actually isolating and capturing CTCs," she said. "So there's a possibility that you will lose some CTCs."

The CTC-Chip design does not require preprocessing, Dr. Nagrath said.

The chip contains 80,000 microposts that are smaller in diameter than a strand of human hair. Blood flows around the microposts, which are coated with antibodies for the epithelial cell adhesion molecule, and were chosen because more than 85% of all cancers are epithelial in origin, noted Dr. Nagrath.

"With the microposts, there is no preprocessing; the blood flows through the CTC-Chip," she said.

The CTC-Chip apparently outperforms other technologies in detecting CTCs.

Dr. Nagrath said that, using other technologies, an average of 100 cytokeratin (ck) CTCs are detected per 5 mL of blood for a variety of cancers.

However, using the CTC-Chip, Dr. Nagrath and colleagues found that CTCs were present at a frequency of 113 (ck) CTCs per only 1 mL among 30 men with metastatic prostate cancer in the study. They also found about 51 (ck) CTCs per 1 mL in the 20 men with localized prostate cancer.

Dr. Wisha said that the chip seems to have advantages over existing CTC technologies.

"Previous studies only detected CTCs in men with advanced prostate cancers, and even there only in about 60% to 70% of patients. Dr. Nagrath's method appears to be considerably more sensitive," said Dr. Wicha, who did not attend AACR and was approach by Medscape Oncology for comment.

According to Dr. Nagrath, the new technology has a sensitivity of more than 90% for prostate cancer CTCs in men with metastatic disease, and a specificity of more than 95%.

The authors have disclosed no relevant financial relationships.

American Association for Cancer Research (AACR) 101st Annual Meeting: Abstract 1136. Presented April 20, 2010.