Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Due to sampling error, the Gleason score of clinically localized prostate cancer is frequently underestimated at the time of initial biopsy. Given that this may lead to inappropriate surveillance of patients with high‐risk disease, there is considerable interest in identifying predictors of significant undergrading. Recently PSAD has been proposed to be an accurate predictor of subsequent upgrading in patients diagnosed with Gleason 6 disease on biopsy. We examined the predictive characteristics of PSAD in patients with low‐ and intermediate‐risk disease on biopsy subsequently treated with radical prostatectomy. We found that although PSAD was a significant predictor of upgrade of biopsy Gleason 6 and 3 + 4 = 7 tumours, it failed to predict upgrading in patients with Gleason 7 tumours taken as a whole. When we explored reasons for this discrepancy, we found that the amount of PSA produced per unit tumour volume decreased with increasing Gleason score, thereby diminishing the predictive value of PSAD. OBJECTIVES To analyse the performance of PSA density (PSAD) as a predictor of Gleason score upgrade in a large cohort stratified by Gleason score. We and others have shown that an upgrade in Gleason score between initial prostate biopsy and final radical prostatectomy (RP) pathology is a significant risk factor for recurrence after local therapy. PATIENTS AND METHODS Patients undergoing RP with matching biopsy information were identified from two prospective databases. Patients were analysed according to the concordance between biopsy and final pathology Gleason score in three paired groups: 6/>6, 3 + 4/>3 + 4, 7/>7. Receiver‐operating characteristic (ROC) curves were generated stratified by Gleason score, and the area under the curve (AUC) calculated. Logistic regression models were fitted to identify significant predictors of tumour upgrade. RESULTS From 1516 patients, 435 (29%) had an upgrade in Gleason score. ROC analysis showed a decline in AUC with increasing biopsy Gleason score, from 0.64 for biopsy Gleason score 6, to 0.57 for Gleason score 7. In logistic regression models containing pretreatment variables, e.g. clinical stage and number of positive cores, for Gleason score 6 and 3 + 4, PSAD was the strongest predictor of subsequent tumour upgrade (odds ratio [OR] 1.46, 95% confidence interval [95% CI] 1.18–1.83, P= 0.001 and OR 1.37, 95% CI 1.14–1.67, P= 0.002, respectively). Surprisingly, in tumours upgraded from Gleason score 7 to >7, PSAD was not predictive even on univariable analysis, whereas clinical stage and number of positive cores were significant independent predictors. To explore the relationship between serum PSA and Gleason score, tumour volume was calculated in 669 patients. There was a strong association between Gleason score and tumour volume, with the median volume of Gleason score 7 and Gleason score >7 tumours being approximately twice and four‐times that of Gl...
What ' s known on the subject? and What does the study add? The Gleason score of prostate cancer is frequently underestimated at the time of diagnostic biopsy, although the contribution of sampling error to its incidence is unknown.We show that under-graded tumours are signifi cantly smaller that tumours concordant for the higher grade, indicating that incomplete tumour sampling plays a signifi cant role in Gleason score assignment error. OBJECTIVE• To determine the infl uence 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 identifi ed 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 identifi ed.• Of 298 patients diagnosed with Gleason 6 tumour on biopsy, 201 (67.4%) were upgraded to Gleason 7 or higher on fi nal 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 signifi cantly 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 fi nal pathology to 4 + 3 were signifi cantly 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% confi dence interval 0.96 -0.99, P < 0.001) and larger total tumour volume (hazard ratio 1.87, 95% confi dence 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% confi dence interval 1.01 -9.3, P = 0.048) was a signifi cant predictor of upgrading on multivariate analysis. CONCLUSIONS• Under-graded tumours are signifi cantly smaller than tumours concordant for the higher grade, indicating that incomplete tumour sampling plays a signifi cant role in Gleason score assignment error.
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