Predictors of Histological Disease Progression in Untreated, Localized Prostate Cancer Ramachandran Venkitaraman, Andrew Norman, Ruth Woode-Amissah, Cyril Fisher, David Dearnaley, Alan Horwich, Robert Huddart, Vincent Khoo, Alan Thompson and Chris Parker* From the Academic Unit of Radiotherapy and Oncology, Institute of Cancer Research (RV, RWA, DD, AH, RH, VK, CP) and Computing (AN) and Pathology (CF) Departments, Urology Unit (AT), Royal Marsden National Health Service Foundation Trust, Sutton, United Kingdom Purpose: Active surveillance for early prostate cancer is a policy of close monitoring with radical treatment targeted at cases with evidence of disease progression. There is no consensus on the need for or optimum timing of repeat biopsies as part of active surveillance. Materials and Methods: In a prospective cohort study of active surveillance 119 patients with untreated localized prostate cancer (T1/2a), prostate specific antigen less than 15 ng/ml, Gleason score 3 + 4 or less and 50% or less positive cores underwent repeat biopsy after 18 to 24 months. Histological disease progression was defined as primary Gleason grade 4 or greater, greater than 50% positive cores or a Gleason score increase from 6 or less to 7 or greater. The risk of histological disease progression was analyzed with respect to baseline clinical factors. Results: Median patient age was 66 years and median initial prostate specific antigen was 6.6 ng/ml. Histological disease progression was seen in 33 of 119 cases (28%). On multivariate analysis prostate specific antigen density (p = 0.002) and maximum percent involvement of any core (p = 0.04) were significant independent determinants of histological disease progression. Progression was seen in 22 of 40 cases (55%) with prostate specific antigen density 0.2 ng/ml/ml or greater and greater than 15% maximum involvement of any core. Progression was seen in 2 of 33 cases (6%) with prostate specific antigen density less than 0.2 ng/ml/ml and 15% or less maximum involvement of any core. Conclusions: Repeat biopsy should be an integral part of active surveillance for untreated localized prostate cancer. Immediate repeat biopsy should be considered in patients who elect active surveillance but who have prostate specific antigen density greater than 0.2 ng/ml/ml. These findings must be validated in a cohort of patients with extended biopsies at diagnosis and followup. Key Words: prostate, prostatic neoplasms, biopsy, prostate-specific antigen A ctive surveillance with selective curative intervention is an approach to low risk, localized prostate cancer. 1 The aim is to individualize management by targeting curative therapy to cases with evidence of disease progres- sion. Repeat prostate biopsy may be used in men on active surveillance to detect adverse histological features, such as an increase in GS or the volume of cancer in the biopsy material, which may be considered indications for curative intervention. Currently there is no consensus on the need for repeat biopsies or their optimum timing as part of active surveillance for localized prostate cancer. 2–7 An ongoing prospective cohort study of active surveil- lance for localized prostate cancer opened at our institution in 2002. Patients with untreated, clinically localized, low to intermediate risk prostate cancer have been followed using frequent serum PSA monitoring and with repeat prostate biopsy performed after 18 to 24 months. We present the repeat biopsy results. We identified the clinical characteris- tics that predict repeat biopsy results with a view to inform- ing the debate concerning the need for and timing of this procedure in patients on active surveillance for localized prostate cancer. PATIENTS AND METHODS Patients eligible for the prospective study of active surveil- lance at our institution had clinical stage T1/2a, N0/x, M0/x, histologically proven adenocarcinoma of the prostate with serum PSA less than 15 ng/ml, GS 7 or less with primary Gleason grade 3 or less and cancer present in 50% or less of the total number of biopsy cores. Participants were 50 to 80 years old and fit for radical treatment but they had elected active surveillance as initial treatment and provided in- formed consent to the study. Baseline staging investigations (bone scan and magnetic resonance imaging of the pelvis) were not mandatory. Our institution is a tertiary referral center, so that diagnostic transrectal ultrasound guided bi- opsies were performed at a wide range of secondary care centers according to standard United Kingdom clinical prac- Submitted for publication December 21, 2006. Study received Royal Marsden Research Ethics Committee ap- proval. * Correspondence: Academic Urology Unit, Institute of Cancer Research, Downs Rd., Sutton, Surrey SM2 5PT, United Kingdom (telephone: +44(0)02086613425; FAX: +44(0)02086438809; e-mail: chris.parker@icr.ac.uk). 0022-5347/07/1783-0833/0 Vol. 178, 833-837, September 2007 THE JOURNAL OF UROLOGY ® Printed in U.S.A. Copyright © 2007 by AMERICAN UROLOGICAL ASSOCIATION DOI:10.1016/j.juro.2007.05.038 833