Underestimation of Gleason score at prostate biopsy reflects sampling error in lower volume tumours

OBJECTIVE To determine the influence of tumour and prostate gland volumes on the underestimation of prostate cancer Gleason score in diagnostic core biopsies. PATIENTS AND METHODS Patients undergoing radical prostatectomy with matched diagnostic biopsies were identified from a prospectively recorded database. Tumour volumes were measured in serial whole-mount sections with image analysis software as part of routine histological assessment. Differences in various metrics of tumour and prostate volume between upgraded tumours and tumours concordant for the lower or higher grade were analysed. RESULTS In all, 684 consecutive patients with Gleason score 6 or 7 prostate cancer on diagnostic biopsy were identified. Of 298 patients diagnosed with Gleason 6 tumour on biopsy, 201 (67.4%) were upgraded to Gleason 7 or higher on final pathology. Similarly, of 262 patients diagnosed with Gleason 3 + 4 = 7 prostate cancer on initial biopsy, 60 (22.9%) were upgraded to Gleason score 4 + 3 = 7 or higher. Tumours upgraded from Gleason 6 to 7 had a significantly lower index tumour volume (1.73 vs 2 mL, P = 0.029), higher calculated prostate volume (41.6 vs 39 mL, P = 0.017) and lower relative percentage of tumour to benign glandular tissue (4.3% vs 5.9%, P = 0.001) than tumours concordant for the higher grade. Similarly, tumours that were Gleason score 3 + 4 on biopsy and upgraded on final pathology to 4 + 3 were significantly smaller as measured by both total tumour volume (2.3 vs 3.3 mL, P = 0.005) and index tumour volume (2.2 vs 3, P = 0.027) and occupied a smaller percentage of the gland volume (6.3% vs 8.9%, P = 0.017) compared with tumours concordant for the higher grade. On multivariate analysis, lower prostate weight (hazard ratio 0.97, 95% confidence interval 0.96-0.99, P < 0.001) and larger total tumour volume (hazard ratio 1.87, 95% confidence interval 1.4-2.6, P < 0.001) independently predicted an upgrade in Gleason score from 6 to 7. In tumours upgraded from biopsy Gleason 3 + 4, only higher index tumour volume (hazard ratio 3.1, 95% confidence interval 1.01-9.3, P = 0.048) was a significant predictor of upgrading on multivariate analysis. CONCLUSIONS Under-graded tumours are significantly smaller than tumours concordant for the higher grade, indicating that incomplete tumour sampling plays a significant role in Gleason score assignment error. Surrogate measures of tumour volume may predict those at greatest risk of Gleason score upgrade.