PREDICTORS OF PROSTATE CANCER AFTER INITIAL NEGATIVE SYSTEMATIC 12 CORE BIOPSY HERB SINGH, EDUARDO I. CANTO, SHAHROKH F. SHARIAT, DOV KADMON, BRIAN J. MILES, THOMAS M. WHEELER AND KEVIN M. SLAWIN* From the Baylor Prostate Center, Scott Department of Urology (HS, EIC, DK, BJM, TMW, KMS) and Department of Pathology (TMW), Baylor College of Medicine and The Methodist Hospital, Houston and Department of Urology, University of Texas Southwestern Medical Center (SFS), Dallas, Texas ABSTRACT Purpose: We determined the cancer detection rate at initial systematic 12 core (S12C) biopsy and identified features associated with cancer at repeat S12C biopsy after an initial negative S12C biopsy in patients with prostate specific antigen (PSA) parameters associated with a higher risk of prostate cancer. Materials and Methods: Between February 1999 and June 2002, 841 patients underwent initial S12C biopsy. Of these patients 99 underwent repeat S12C biopsy after initial negative S12C because of a percent free-to-total PSA of 15.0 or less and/or a yearly PSA velocity of 0.75 ng/ml or greater. The association between parameters revealed by initial biopsy and cancer at repeat biopsy was assessed. Results: Of the 99 patients 21 (21.2%) had cancer at repeat biopsy. Age (p = 0.01), PSA transitional zone density (p = 0.05), and high grade PIN at initial biopsy (p = 0.01) were associated with cancer at repeat biopsy. Conclusions: In this select group of patients with PSA parameters associated with a higher risk of prostate cancer the cancer detection rate after initially negative S12C biopsy was 21%. Patients with high grade PIN on initial biopsy, advanced age and higher PSA transition zone density are at increased risk for cancer at repeat biopsy. Larger prospective studies are required to confirm these results and construct a nomogram that determines the probability of finding prostate cancer at subsequent biopsy. KEY WORDS: prostate, biopsy, prostatic neoplasms, prostate-specific antigen Several studies have shown that the cancer detection rate is as high as 24.3% to 36.2% using a systematic 10 or 12 core template that samples the lateral peripheral zone in patients who have previously had a negative sextant biopsy. 1, 2 Chon et al recommended that patients with negative sextant bi- opsy undergo repeat biopsy using an extended field template weighted to the lateral aspect of the prostate, presumably because of the high false-negative rate associated with sex- tant biopsy. 2 However, increasingly patients undergo initial 10 or 12 core biopsy, which already includes additional cores directed to the lateral peripheral zone. To our knowledge the false-negative rate and indications for repeat biopsy in such a population of patients are unknown. Stewart et al reported that saturation needle biopsy in patients under anesthesia with a mean of 23 cores obtained detected cancer in 34% who had previously had a negative sextant biopsy. 3 The 10 or 12 core template showed cancer in a similar percent of patients who had previously undergone sextant biopsy with no evidence of cancer. The similar cancer detection rates in saturation biopsies and systematic 10+ core templates following negative sextant biopsy suggest that systematic 12 core (S12C) biopsy may have a clinically neg- ligible false-negative rate. For this reason we selectively rec- ommended re-biopsy to patients who showed no cancer at initial S12C biopsy but who had a persistently suspicious clinical presentation. In this study we evaluated patients who had an initial S12C biopsy without cancer but who met criteria for repeat biopsy based on serum prostate specific antigen (PSA) velocity (PSAV) and/or percent free prostate specific antigen (fPSA) cutoff values. We hypothesized that by using these serum based triggers we would identify pros- tate cancers at repeat S12C biopsy in an appreciable propor- tion of patients with an initial S12C showing no evidence of malignancy, while minimizing the overall repeat biopsy rate. In addition, we identified parameters that were associated with cancer at repeat biopsy. PATIENTS AND METHODS Study population. Informed consent was obtained from each patient. All 841 patients suspected of having T1c-cT2 cancer because of abnormal digital rectal examination (DRE) and/or PSA greater than 2.5 ng/ml who underwent S12C biopsy at the Scott Department of Urology, Baylor College of Medicine, Houston, Texas between February 1999 and June 2002 were potential candidates for this analysis. Patients were generally scheduled to undergo DRE, and serum total and free PSA evaluation within 3 to 6 months after negative S12C biopsy and every 6 months thereafter. Repeat S12C biopsy was generally recommended for patients meeting cer- tain trigger criteria, namely percent fPSA 15.0 or less with total PSA persistently greater than 3.0 ng/ml and/or PSAV 0.75 ng/ml yearly or greater. Clinical measurements. We used the Tandem-E PSA and Tandem-R free PSA immunoenzyme assay until May 2000, when we changed to the chemiluminescent method using an Access analyzer with Hybritech free and total antibodies (Hybritech Beckman-Coulter Corp., San Diego, California). Accepted for publication December 12, 2003. Study received institutional review board approval. * Correspondence: Scott Department of Urology, Baylor College of Medicine, The Baylor Prostate Center, 6560 Fannin, Suite 2100, Houston, Texas 77030 (telephone: 713-798-8670; FAX: 713-798-8030; e-mail: kslawin@bcm.tmc.edu). 0022-5347/04/1715-1850/0 Vol. 171, 1850 –1854, May 2004 THE JOURNAL OF UROLOGY ® Printed in U.S.A. Copyright © 2004 by AMERICAN UROLOGICAL ASSOCIATION DOI: 10.1097/01.ju.0000119667.86071.e7 1850