PREDICTING THE PRESENCE AND SIDE OF EXTRACAPSULAR EXTENSION: A NOMOGRAM FOR STAGING PROSTATE CANCER MAKOTO OHORI, MICHAEL W. KATTAN, HIDESHIGE KOH, NORIO MARU, KEVIN M. SLAWIN, SHAHROKH SHARIAT, MASATOSHI MURAMOTO, VICTOR E. REUTER, THOMAS M. WHEELER* AND PETER T. SCARDINO† From the Departments of Urology (MO, MWK, HK, PTS), Epidemiology and Biostatistics (MWK), and Pathology (VER), Memorial Sloan- Kettering Cancer Center, New York, New York, and Departments of Urology (KMS, SS) and Pathology (NM, MM, TMW), Baylor College of Medicine, Houston, Texas ABSTRACT Purpose: We developed a model to predict the side specific probability of extracapsular exten- sion (ECE) in radical prostatectomy (RP) specimens based on the clinical features of the cancer. Materials and Methods: We studied 763 patients with clinical stage T1c-T3 prostate cancer who were diagnosed by systematic needle biopsy and subsequently treated with RP. Candidate predictor variables associated with ECE were clinical T stage, the highest Gleason sum in any core, percent positive cores, percent cancer in the cores from each side and serum prostate specific antigen (PSA). Receiver operating characteristic (ROC) analyses were performed to assess the predictive value of each variable alone and in combination. We constructed and internally validated nomograms to predict the side specific probability of ECE based on logistic regression analysis. Results: Overall 30% of the patients and 17% of 1,526 prostate lobes (left or right) had ECE. The areas under the ROC curves (AUC) of the standard features in predicting side specific probability of ECE were 0.627 for PSA, 0.695 for clinical T stage on each side and 0.727 for Gleason sum on each side. When these features were combined predictive accuracy increased to 0.788. The highest value (0.806) was achieved by adding the percent positive cores and the percent cancer in the biopsy specimen to the standard features. The resulting nomograms were internally validated and had excellent calibration and discrimination accuracy. Conclusions: Standard clinical features of prostate cancer in each lobe—PSA, palpable indu- ration and biopsy Gleason sum— can be used to predict the side specific probability of ECE in RP specimens. The predictive accuracy is increased by adding information from systematic biopsy results. The predictive nomograms are sufficiently accurate for use in clinical practice in deci- sions such as wide versus close dissection of the cavernous nerves from the prostate. KEY WORDS: prostatic neoplasms, cell surface extensions, biopsy, classification When prostate cancer extends laterally through the cap- sule posterior in the region of the neurovascular bundle, the nerve might have to be partially or fully resected to excise the cancer completely. Resection of the cavernous nerves sub- stantially decreases the chance of recovering erectile func- tion 1 but preservation of the nerve may lead to a positive surgical margin. Knowledge of the presence and location of extracapsular extension (ECE) before treatment would help patients and physicians make better informed decisions. Armed with such knowledge surgeons would be able to plan the procedure more carefully, striving to resect the cancer completely with minimal risk of damage to the surrounding tissue so important to recovery of normal function. Yet pre- dicting the presence or location of ECE remains challenging. Imaging studies generally lack the sensitivity to detect mi- croscopic ECE typically found in radical prostatectomy spec- imens. Currently the likelihood of ECE is best estimated from staging nomograms that estimate pathological stage from pretreatment prostate specific antigen (PSA), clinical stage and Gleason grade in the biopsy specimen. 2, 3 However, the predicted probabilities obtained from these staging tables do not fully reflect the risk of ECE since the predicted patholog- ical stages are mutually exclusive categories. Furthermore the tables provide no information about the location of ECE. Systematic biopsy results improve the prediction of ECE by adding information about the percent positive cores and per- cent cancer to clinical stage, serum PSA and biopsy Gleason score. 4–7 Biopsy results have also been used to predict the side specific probability of ECE. 8 –10 However, the concept of a nomogram, a mathematical model to provide an accurate predicted probability from multiple factors, has not been applied to predicting side specific probability of ECE. Since the presence and location of ECE are so crucial for optimal cancer control with preservation of quality of life, we con- structed a model to predict the presence and location of ECE better by incorporating a detailed, quantitative assessment of biopsy results into a nomogram to predict the likelihood of ECE on each side of the prostate. MATERIALS AND METHODS Patient population. All patients treated for clinically local- ized prostate cancer at our institutions from 1989 to 2000 were eligible for analysis. Inclusion criteria were treatment with pelvic lymphadenectomy and radical retropubic prosta- tectomy, no androgen deprivation therapy or radiotherapy Accepted for publication November 14, 2003. Supported by the Leon Lowenstein Foundation and National Can- cer Institute CA 58204 SPORE in prostate cancer. * Financial interest and/or other relationship with Pintex Phar- maceuticals. † Correspondence: Department of Urology, Memorial Sloan- Kettering Cancer Center, 1275 York Ave., New York, New York 10021 (telephone: 646-422-4322; FAX: 212-988-0874; e-mail: scardinp@mskcc.org). 0022-5347/04/1715-1844/0 Vol. 171, 1844 –1849, May 2004 THE JOURNAL OF UROLOGY ® Printed in U.S.A. Copyright © 2004 by AMERICAN UROLOGICAL ASSOCIATION DOI: 10.1097/01.ju.0000121693.05077.3d 1844