STUDY TYPEPrognosis (case series).LEVEL OF EVIDENCE4.OBJECTIVETo assess the DNA content in benign-adjacent and cancer-tissue areas of a diagnostic biopsy, to predict which patients would subsequently develop an unfavourable biopsy necessitating treatment for prostate cancer in the expectant management (EM) programme.PATIENTS AND METHODSOf 71 patients who had benign-adjacent and cancer-tissue areas of diagnostic biopsies available, 39 developed unfavourable biopsies (Gleason score > or =7, Gleason pattern 4/5, three or more cores positive for cancer, >50% of any core involved with cancer), while 32 maintained favourable biopsies on annual surveillance examination (median follow-up 3.7 years). DNA content was measured on Feulgen-stained biopsy sections using an automatic imaging system (AutoCyte(TM), TriPath Imaging Inc, Burlington, NC, USA). Cox proportional-hazard regression and Kaplan-Meier plots were used to identify significant predictors for unfavourable biopsy conversion.RESULTSUnivariately, DNA content measurements i.e. an excess of optical density (OD) in the benign-adjacent tissuer area, and the sd of the OD in the cancer tissue were significant, with a hazard ratio and 95% confidence interval of 2.58 (1.17-5.68; P = 0.019) and 5.36 (1.89-15.24; P = 0.002), respectively, for predicting unfavourable biopsy conversion that required intervention. Also, several other DNA content measurements in benign-adjacent and cancer-tissue areas showed a trend to statistical significance. Further, benign-adjacent excess of OD (3.12, 1.4-6.95; P = 0.005) and cancer sd of OD (5.88, 2.06-16.82; P = 0.001) remained significant in the multivariate model to predict unfavourable biopsy conversion. Patients with benign-adjacent excess of OD > 25.0 and cancer sd of OD of >4.0 had the highest risk for unfavourable biopsy conversion (P < 0.001).CONCLUSIONSDNA content measurements in the benign-adjacent and cancer-tissue areas appear to be useful for predicting unfavourable biopsy conversion (a recommendation for intervention) on annual surveillance examinations in the EM programme.