Prostate Cancer
REVIEWING THE LITERATURE News and Views from the Literature Prostate Cancer Early Detection of Prostate Cancer Reviewed by Yan Kit Fong, MD, Bob Djavan, MD, PhD Department of Urology, University of Vienna, Vienna, Austria [Rev Urol. 2005;7(1):63-64] © 2005 MedReviews, LLC arly detection and treatment of prostate cancer when it is still localized provide the greatest chance of cure. Lowering the total prostate-specific antigen (PSA) threshold for prostatic biopsy results in a greater number of localized cancers detected but increases the number of unnecessary biopsies and morbidities associated with the procedure. The search for a novel tumor marker continues. The following 3 recent studies report on urinary and serum tests for prostate cancer detection. E 201 urine samples collected after digital rectal examinations, 158 (79% adequacy rate) were suitable for analysis because they contained a sufficient number of prostate cells. With a prostate cancer detection rate of 39%, the overall sensitivity, specificity, positive predictive value, and negative predictive value for the uPM3 assay at a cutoff of 0.5 probability were 82%, 76%, 67%, and 87%, respectively. The uPM3 assay outperformed total PSA (tPSA) in all PSA categories (< 4, 4-10, and > 10 ng/mL). The authors conclude that the uPM3 assay shows excellent clinical performance and a specificity far superior to that of tPSA. uPM3, a New Molecular Urine Test for the Detection of Prostate Cancer Fradet Y, Saad F, Aprikian A, et al. Urology. 2004;64:311-316. Eur Urol. 2004;46:182-187. Similarly, Fradet and associates conducted a multicenter trial to evaluate the diagnostic performance of this new molecular test, uPM3. Of 517 patients undergoing biopsy at 5 centers, 443 (86%) had an assessable sample. The overall sensitivity, specificity, positive predictive value, and negative predictive value for the assay were 66%, 89%, 75%, and 84%, respectively. Compared with tPSA cutoffs of 2.5 ng/mL and 4.0 ng/mL, the accuracy of this novel urine molecular test was almost doubled at 81%. The DD3PCA3 gene is highly specific for prostate cancer and is detectable in prostate cancer cells shed into urine after rectal palpation. Tinzl and colleagues prospectively evaluated a newly developed nucleic acid–based amplification assay (uPM3) for detecting DD3PCA3 RNA in urine samples. Among These 2 studies from different regions of the world clearly demonstrate the superiority of urinary uPM3 assay to tPSA. With a significantly higher positive predictive value, unnecessary biopsies can be minimized, and rebiopsy can be better planned. Unfortunately, this assay is limited to a DD3PCA3 RNA Analysis in Urine—A New Perspective for Detecting Prostate Cancer Tinzl M, Marberger M, Horvath S, Chypre C. VOL. 7 NO. 1ºº2005ººREVIEWS IN UROLOGYºººº63 Prostate Cancer continued degree by the adequacy rate, which is dependent on the amount of manipulation of the prostate (digital rectal examination) before urine collection. Additional technical refinement will further enhance the test’s sensitivity. Complexed Prostate-Specific Antigen (PSA) Reduces Unnecessary Prostate Biopsies in the 2.6-4.0 ng/mL Range of Total PSA Parsons JK, Brawer MK, Cheli CD, Partin AW, Djavan R. BJU Int. 2004;94:47-50. The complexed prostate-specific antigen (cPSA) assay, which measures the amount of PSA bound to serum proteins (primarily -1 antichymotrypsin), is emerging as an With a significantly higher positive predictive value for the uPM3 assay, unnecessary biopsies can be minimized and rebiopsy can be better planned. important test for prostate cancer detection. The rationale for cPSA testing is that the proportion of cPSA is greater in men with prostate cancer. Parsons and colleagues analyzed data from 2 multicenter trials, one from Europe and the other from the United States, to compare the performance of cPSA with tPSA and percentage-free PSA (f/t PSA) in the diagnosis of prostate cancer for the tPSA range 2.6-4.0 ng/mL. Of 316 men with tPSA levels in this range, 82 (26%) were diagnosed with prostate cancer on biopsy. Receiver operating curve analysis of all 316 men showed an area under curve (AUC) of 0.63, significantly greater than the AUC for tPSA of 0.56. At a sensitivity of 95%, threshold values of 2.3 ng/mL for cPSA and 2.73 ng/mL for tPSA provided specificities of 20.1% and 9.8%, respectively. Compared with f/t PSA, the AUC values of both tests were similar (0.63 vs 0.64). With these data from the largest analysis to date of the diagnostic performance of cPSA at a tPSA of 2.6-4.0 ng/mL, the authors conclude that cPSA is an excellent single test that provides improved specificity over tPSA and comparable specificity to f/t PSA for detecting prostate cancer, and may reduce the number of unnecessary prostate biopsies in the 2.6-4.0 ng/mL tPSA range. cPSA has shown potential to replace tPSA as a screening test for prostate cancer. However, further studies are required to determine the ageadjusted values (cutoffs) for screening. 64ºººVOL. 7 NO. 1ºº2005ººREVIEWS IN UROLOGY Fertility Effect of Testis Biopsy on Testosterone Production Reviewed by Jacob Rajfer, MD The David Geffen School of Medicine at UCLA and Division of Urology, Harbor-UCLA Medical Center, Los Angeles, CA [Rev Urol. 2005;7(1):64-65] © 2005 MedReviews, LLC ver since Tash and Schlegel1 published their observation that a testis biopsy for sperm extraction “shocks” the spermatogenic compartment such that it takes 6 months to recover normal spermatogenesis, very little attention has been paid to what happens to the interstitial compartment in this setting. Because testosterone is made in the interstitial compartment, it would be important to know whether such a shock occurs within this compartment and whether testosterone production is affected. Because testosterone in high local concentrations is necessary for normal spermatogenesis, a local drop in this level with a testis biopsy could be the reason spermatogenesis is delayed post testis biopsy and does not recover until testosterone production returns to normal. E Serum Testosterone Levels in Patients with Nonmosaic Klinefelter Syndrome After Testicular Sperm Extraction for Intracytoplasmic Sperm Injection Okada H, Shirakawa T, Ishikawa T, et al. Fertil Steril. 2004;82:237-238. To provide insight into this issue, Okada and colleagues measured the serum testosterone levels in patients with Klinefelter syndrome who were undergoing some form of testicular sperm extraction for in vitro fertilization. In this procedure, which is analogous to a testis biopsy, the authors found that serum testosterone levels were reduced between 25% and 40% (approximately) at 6 months and recovered very little at 12 months following the testis surgery. Similar results were observed for the patients who had a conventional testis biopsy for sperm extraction and those who underwent a microscopic microdissection, in which minimal testis tissue is excised.2 This finding suggests that the effects on the testis following such a biopsy may be more permanent