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Research Update

New, more accurate test for prostate cancer

Researchers at the U-M Comprehensive Cancer Center have identified 22 biomarkers that together provide a more accurate basis for prostate cancer screening than the current prostate specific antigen, or PSA, test. Their findings were published in the September 22 issue of the New England Journal of Medicine.

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A heatmap image reveals how the 22 biomarkers identified are analyzed to indicate prostate cancer. Horizontal rows each correspond to one of the biomarkers, while vertical columns correspond to 128 sets of serum samples from prostate cancer patients and controls. Positive immunoreactivity, represented in yellow, predicts the presence of cancerous cells. Black and blue indicate no immunoreactivity.

The U-M team looked at blood samples from 331 prostate cancer patients prior to surgery, and from 159 men with no history of cancer. They began by testing the samples against a library of 2,300 bacteriophage, organisms that express proteins on their surface, and were able to narrow the field to the 22 biomarkers that most often pinpointed the cancerous blood samples.

"Initially, we envision this new test could be used as a supplement to PSA. A physician might suggest a patient with an elevated PSA have this test before a biopsy to better determine whether it's a cancerous or benign condition. In the future, I think this could replace PSA," says lead study author Arul Chinnaiyan, M.D., Ph.D., the U-M Medical School's S.P. Hicks Collegiate Professor of Pathology.

The results of this study proved to be more reliable at predicting cancer than prostate specific antigen, which relies on a single biomarker. Although the PSA test is currently the accepted screening method, it is controversial. A high PSA level does not always indicate prostate cancer, and some experts suggest a rise in PSA is more significant than a consistently high PSA level, which can also indicate benign prostate conditions.

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Testing for these 22 biomarkers is reliable in identifying the presence of prostate cancer in patients with PSA levels between 4 and 10 ng/ml. Within this range, the PSA level alone (in green) may or may not suggest cancer, while the biomarkers (in red) result in higher sensitivity (the proportion of positive results for patients who have the disease) and greater specificity (the proportion of negative results for patients who do not have the disease).

Moreover, PSA testing results in a false positive approximately 80 percent of the time, leading to unnecessary prostate biopsies. The normal range for the PSA test is less than 4.0 nanograms per milliliter (ng/mL) in most men. For men over 40 years old with a family history of prostate disease or for African-American men over 40 years old, some doctors suggest that a level higher than 2.5 ng/mL should be checked with more tests, because these two groups of men have an increased risk of prostate cancer.

The 22-biomarker test was reliable at identifying prostate cancer even in the PSA ranges of 4-10 ng/ml or 2.5-10 ng/ml, intermediate PSA scores that do not always suggest cancer. (See above.) The study authors suggest the 22 biomarkers could be used for patients in this range to help determine whether to undergo a biopsy.

The new test would require only a routine blood draw for patients. Most blood-processing laboratories could easily be equipped to scan for these 22 biomarkers, Chinnaiyan says. Researchers are conducting further studies to validate the findings with a larger, community-based group of patients.The test is not currently being offered to patients.

"These 22 biomarkers appear to be the right number. If you used too many or too few, the accuracy went down a bit. Our findings held up when we tested the model on an independent set of blood serum samples," says Chinnaiyan.

In addition to Chinnaiyan, U-M study authors included Xiaoju Wang, Ph.D., research associate; Jianjun Yu, research assistant; Arun Sreekumar, Ph.D., research investigator; Sooryanarayana Varambally, Ph.D., Ronglai Shen, research assistant; Donald Giacherio, Ph.D., clinical associate professor of pathology; Rohit Mehra, M.D., pathology research fellow; James Montie, M.D.,Valassis Professor of Urologic Oncology and professor and chair of urology; Kenneth Pienta, M.D., professor of internal medicine and director of Urologic Oncology; John Wei, M.D., associate professor of urology; and Debashis Ghosh, Ph.D., assistant professor of biostatistics. Additional authors were Martin Sanda, M.D., Beth Israel- Deaconess Medical Center; Philip Kantoff, M.D., Dana Farber Cancer Institute; and Mark Rubin, M.D., Dana Farber Cancer Institute and Brigham and Women's Hospital.

For more information about prostate cancer, visit Prostate Cancer Information or call the Cancer AnswerLine™ at 800-865-1125.

U-M among first to offer new lung surgery technique

A new surgical technique offered at the University of Michigan Comprehensive Cancer Center is helping people with early stage lung cancer recover more quickly with less pain. U-M is one of a select few centers nationwide offering the procedure.

The minimally invasive technique involves removing a portion of the lung without cutting large muscles or spreading open the ribs.

"It's a way of treating cancer with a less invasive procedure that will get patients back to their regular activities sooner," says Allan Pickens, M.D., a thoracic surgeon at the U-M Comprehensive Cancer Center. The procedure allows patients to leave the hospital in half the time of conventional lung surgery.

thoracoscopic lobectomy
The video-assisted thoracoscopic lobectomy requires only four small incisions, each from one to four centimeters long. This is compared with traditional thoracotomy, which requires an incision of approximately 20 centimeters.

Traditional lung cancer surgery is a thoracotomy, in which the surgeon cuts through the muscles into the chest and spreads open the ribs to access the lungs. The incision is large, about 20 centimeters, and recovery is slow and painful. With the new technique, thoracoscopic lobectomy, the surgeon makes three small incisions of two centimeters to four centimeters each. A camera is inserted through a fourth incision that is only half a centimeter long. The camera allows the surgeon to see inside the chest.Very little muscle is cut and the ribs do not need to be spread.

"Thoracotomy is one of the more painful operations surgeons perform. It cuts into the muscles in a dynamic part of the body, an area that moves a lot from breathing. This makes it harder to heal afterward," Pickens says.

Surgeons are seeing better pulmonary function in patients who have the minimally invasive procedure compared to thoracotomy patients. Recovery also requires fewer narcotic painkillers. Initial research suggests cancer survival rates are similar for both procedures.

Thoracoscopic lobectomy is primarily done in patients with stage I or stage II disease, meaning the nodule is smaller than five centimeters, has not invaded the chest wall and has not spread to distant organs. More advanced cancer will still require traditional thoracotomy.

Results to date have been positive. Among the first 1,100 patients to receive this surgery nationally, mortality rates were below one percent. The most common complication was air leaking through staple lines, a condition that typically resolves on its own.

"This is the way thoracic surgery is moving forward for lung cancer treatment. It's a technology I think in my heart improves medical care," Pickens says.

For more information about the thoracic oncology clinic at the Cancer Center, visit their webpage or call the Cancer AnswerLine™ at 800-865-1125.

People taking cholesterol-lowering drug faced half the risk of colon cancer

People who took a type of cholesterol-lowering drug for five years had nearly half the risk of developing colon cancer, even when they had a family history of the disease or other risk factors. This finding was reported by researchers at the University of Michigan Comprehensive Cancer Center in the May 26, 2005 issue of the New England Journal of Medicine. Statins, such as Zocor, Pravachol or Lipitor, are typically used for lowering cholesterol and have been shown to be effective at preventing cardiovascular disease.

"This is an important piece of the puzzle. This piece helps bring together evidence that statins may have the potential to prevent chronic diseases other than heart disease, and helps us consider ways to study these powerful drugs for more than one purpose," says study author Stephen Gruber, M.D.,Ph.D.,M.P.H., associate professor of internal medicine and human genetics at the U-M Medical School and associate professor of epidemiology at the U-M School of Public Health.

Data was based on the Molecular Epidemiology of Colorectal Cancer study, a population-based case-control study of colorectal cancer in northern Israel. The researchers analyzed 1,953 people with colorectal cancer and 2,015 control subjects who did not have colon cancer.

Researchers analyzed the data taking into account increased or decreased risk associated with demographic factors such as age, sex and ethnic background, and with lifestyle factors such as taking aspirin, participating in sports and eating vegetables. They also considered family history of colon cancer, which increases a person's risk. Even considering all these additional factors, statins were still associated with a 47 percent reduced risk of colorectal cancer.

It's not known or well understood why statins show a protective effect against cancer. Recent research has suggested a similar connection between statins and other types of cancer, including breast, prostate, pancreatic and esophageal cancers. Researchers suspect something in the cholesterol pathway may affect a person's risk of colon cancer.

But the researchers caution, it's not advisable for everyone to begin taking statins to prevent cancer. "We are now working to identify those groups who are likely to benefit most. In order to proceed to clinical trials, it is important to know who is most likely to benefit, and who isn't," says Gruber, co-director of the Biomedical Prevention Program at the U-M Comprehensive Cancer Center.

In addition to Gruber, U-M study authors are Peter Higgins, M.D., Ph.D., lecturer in gastroenterology; Joel Greenson, M.D., assistant professor of pathology; Joseph Bonner, a programmer analyst in internal medicine, and Jenny Poynter, M.P.H., of the U-M School of Public Health. Other authors are Ronit Almog, M.D., M.P.H.; Hedy Rennert, M.P.H., Marcelo Low, M.P.H., and Gad Rennert, M.D., Ph.D., all from the Technion-Israel Institute of Technology and Clalit Health Services National Cancer Control Center in Haifa, Israel.

For more information on colorectal cancer, visit the Colon or Rectal Cancer Information webpage or call the Cancer AnswerLine™ at 800-865-1125.

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This article is part of the Cancer Center's News Archive, and is listed here for historical purposes.

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