Studies Show Complexed PSA (cPSA) Test Can Reduce False Diagnoses of Prostate Cancer and Unnecessary Biopsies New studies show that the complexed prostate specific antigen (cPSA) test for detecting prostate cancer has higher specificity than the commonly-used total prostate specific antigen (PSA) test and can be used in distinguishing men who do not have prostate cancer from those who do.(1,2,3) The findings are being presented at the annual meeting of the American Urological Association (AUA) and extend results from previous studies showing improved accuracy with cPSA(4,5,6,7) over PSA. "The results of these new studies are important because the greater specificity of the cPSA test can potentially result in fewer false diagnoses of prostate cancer, sparing many men anxiety and unnecessary biopsies," said Michael Brawer, M.D., Director, Northwest Prostate Institute, Seattle, Washington, and an investigator in one of the studies. "Given this, and the recognition of cPSA in the recently released practice guidelines from the NCCN, physicians should consider cPSA as a first line test to screen for prostate cancer," he added. The National Comprehensive Cancer Network (NCCN) is an alliance of 19 of the world's leading cancer centers and a foremost authority on cancer care. A perfectly predictive test would be one that identifies prostate cancer in every man who has it ("true positives") i.e., is 100 percent "sensitive," and would be negative in every man who does not have it ("true negatives"), i.e., is 100 percent "specific." In reality, determining cutoff PSA values for diagnosing prostate cancer involves a tradeoff: increasing the sensitivity (by lowering the cutoff value) to identify all true positives reduces specificity, since it will also incorrectly identify more men who actually don't have cancer as having it. Studies and Findings One of the studies(1) compared cPSA with other PSA measures in men whose PSA value was 2.5 to 6.0 ng/ml -- a gray zone in which a significant number of men will have prostate cancer but many of whom do not -- making the decision to proceed with a biopsy difficult. The study included 1,362 men who already had prostate biopsies; 605 of whom had PSA within the gray zone. Compared to using the PSA test, the cPSA test with a cutoff value of 2.2 ng/ml would have achieved an eight percent reduction of unnecessary biopsies in the men with PSA values between 2.5 and 6.0 ng/ml. Because of increased specificity of the cPSA assay, the investigators noted it has potential value as a first-line test, particularly in men at the lowest margins of the PSA value scale. Another study(2) combined data from eight studies involving 5,437 men -- 3,493 without cancer, 1,944 with cancer -- and compared the performance of cPSA with PSA, percent of cPSA (%cPSA), and free-to-total PSA (%fPSA). At published cutpoints, which are used by many urologists in daily practice, cPSA gave the highest specificity (e.g., 37.3 percent vs. 34.2 percent for cPSA vs. PSA, respectively). The cPSA test also gave the highest specificity at fixed, high levels of sensitivity (e.g., at 90 percent and 95 percent sensitivity). A third study(3) compared cPSA with other prostate cancer screening tests in African Americans; mortality from prostate cancer is two to three times greater among African-American men between the ages of 50 and 70 than among American- Caucasian men of similar ages.(8) In the study, 108 African American men whose PSA values were 2.5 ng/ml or higher had prostate biopsies; 31.1 percent tested positive for cancer. Within the sensitivity range of 95 to 100 percent for the various tests, the cPSA test had the highest specificity: 31.6 percent compared to 18.9 percent for PSA. Prostate Cancer According to the American Cancer Society, prostate cancer is the most common type of cancer found in American men, other than skin cancer. In the United States alone, there will be an estimated 230,900 new cases of prostate cancer in 2004 and nearly 30,000 men will die from the disease. About cPSA Serum PSA, a protein produced in the prostate, has proven to be an extremely useful marker for early detection of prostate cancer and in monitoring patients for disease progression and the effects of treatment. PSA serum levels of 4.0 ng/ml or less are usually considered normal; higher levels (4 to 10 ng/ml or higher) are often found in men with prostate cancer. However, current PSA testing generates up to 60 percent "false positive" diagnoses because PSA levels can also increase as men get older due to non-cancerous conditions of the prostate and other factors. Testing can also generate "false negatives" because a significant number of cases of prostate cancer have been found in men whose PSA was considered "normal," between 2.5 to 4 ng/ml.(9) Because of the trade off between sensitivity and specificity, much research has focused on ways to improve the accuracy of PSA testing. Some studies have shown that the cPSA test is equivalent to the PSA test while others have shown it is better than PSA.(10) Other PSA tests include those that measure free (vs. complexed) PSA and the percentage of PSA comprised of free PSA and of cPSA. About NCCN The NCCN (www.nccn.org) recently said that cPSA can be used as an alternative to PSA when testing for cancer. The new guidelines also pointed to some studies showing that the cPSA test can be more predictive of prostate cancer at a lower threshold and can result in fewer false diagnoses and unnecessary biopsies compared to the PSA test.(11) References (1) Naya Y, Fritsche HA, Cheli C, Babaian J. Should complexed prostate- specific antigen be the first line test for prostate cancer early detection: impact on sensitivity, rate of unnecessary biopsies and direct biopsy costs? Podium Presentation, Abstract 5962, presented at: American Urological Association annual meeting, San Francisco, California, Monday, May 10, 2004. (2) Trock BJ, Miller MC, Cheli CD, Brawer MK, Filella X, Mitchell IDC, Babaian RJ, Partin AW. International multi-center comparison of complexed prostate specific antigen (cPSA) with total PSA, percent cPSA, and percent free PSA. Discussed poster, Abstract 4291, presented at: American Urological Association annual meeting, San Francisco, California, Wednesday, May 12, 2004. (3) Martin BJ, Finlay JA, Cheli CD, Sterling K, Ward M, Lifsey D, Mercante D, Jainto JM, Martin L, Rayford W. Prostate specific antigen (PSA) isoforms and human glandular kallikrein 2 (hK2): which offers the best screening performance in a predominantly African American population? Discussed poster, Abstract 3328, presented at: American Urological Association annual meeting, San Francisco, California, Wednesday, May 12, 2004. (4) Okihara, et. Al. Can complexed prostate specific antigen and prostatic volume enhance prostate cancer detection in men with total prostate specific antigen between 2.5 and 4.0 ng/ml. J of Urol. 2001;165(6):1930-1936. (5) Okegawa, et al.. Comparison of two investigative assays for the complexed prostate specific antigen in total prostate specific antigen between 4.1 and 10.0ng/ml. Urol. 2000; 55(5): 700-704. (6) Brawer, et. al., Complexed prostate specific antigen provides significant enhancement of specificity compared with total prostate specific antigen for detecting prostate cancer. J of Urol. 2000; 163(5): 1476-1480. (7) Zhang Z, Cheli C, Bartsch G, Horninger W, Babaian R, Fritsche H, Taneja S, Lepor H, Childs S, Stamey T, Sokoll LJ, Partin AW, Brawer M, Chan DW. A nonlinear model combining complexed psa, total prostate gland volume, and age provides the best prediction of prostate cancer in the 2.0-4.0 ng/ml total psa range. Abstract presented at: American Urological Association annual meeting, Chicago, 2003. (8) Powell IJ et al. Prostate cancer and African American men. Oncology. Vol 11, No 5. May 1997. (9) Catalona WJ, Smith DS, Ornstein DK. Prostate cancer detection in men with serum PSA concentrations of 2.6 to 4.0 ng/mL and benign prostate examination. Enhancement of specificity with free PSA measurements. JAMA. 1997 May 14; 277(18):1452-5. (10) Bayer Diagnostics. Bayer Immuno 1(R) System: complexed prostate specific antigen (cPSA). Bayer Corporation, Tarrytown, New York. Revised October 2002. (11) Horninger W. Cheli C, Babaian RJ, et al. Complexed prostate- specific antigen for early detection of prostate cancer in men with serum prostate specific antigen levels of 2-4 nanograms per millileter. Urology 2002; 60 (suppl 4A): 31-35. Okihara K, Fritsche HA, Ayala A, et al. Can complexed prostate specific antigen and prostatic volume enhance prostate cancer detection in men with total prostate specific antigen between 2.5 and 4.0 ng./ml. J Urol 2001; 165: 1930-1936. Web sites: http://www.nccn.org SAN FRANCISCO, May 10 /PRNewswire/ Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.