Ayman S. Moussa

Prostate biopsy clinical and pathological variables that predict significant grading changes in patients with intermediate and high grade prostate cancer

To identify the clinical and pathological variables that predict pathological changes in the significant proportion of men with prostate cancer who have an intermediate‐ or high‐grade biopsy Gleason score (GS) of ≥7 and who are upgraded or downgraded on interpretation of radical prostatectomy (RP) pathological specimens, as GS is critical in treatment decisions.

Importance of Additional “Extreme” Anterior Apical Needle Biopsies in the Initial Detection of Prostate Cancer

OBJECTIVES To describe our experience of adding extreme apical cores in men undergoing initial biopsy. Prostate cancer detection efforts have focused on increasing the number of cores. A more significant factor, however, may be their location. Laterally directed and apical cores have been associated with the highest cancer detection rate, especially the apical cores for men undergoing repeated biopsies. METHODS A prospective trial was conducted between September 2007 and April 2009. A total of 181 men with increased prostate-specific antigen (PSA) or abnormal digital rectal examination (DRE), or both, underwent an initial transrectal ultrasound-guided biopsy (TRUS-BX). All patients underwent a standard 12-core biopsy scheme plus 2 additional cores taken from the extreme anterior apex, defined as the site immediately lateral to the junction of apex and urethra. Each core was marked by a special colored ink for identification. Site-specific detection and tumor characteristics were reported. RESULTS Prostate cancer was detected in 86 patients (47.5%). The apical cores (3 on each side) achieved the highest cancer detection rate (73.6% of all cancers), and the additional extreme anterior apical cores (1 on each side) achieved the highest rate of unique cancer detection (P = .011). CONCLUSIONS From our experience, the apical cores, especially the extreme apical cores, increase prostate cancer detection on initial TRUS-BX and minimize the potential for misdiagnosis and need for repeat biopsy.

Office based transrectal saturation biopsy improves prostate cancer detection compared to extended biopsy in the repeat biopsy population.

PURPOSE Multiple studies have shown significant prostate cancer detection for repeat biopsy. However, the best approach regarding core number and location remains controversial. Transrectal saturation biopsy is believed to increase cancer detection but to our knowledge no studies comparing it to 12 to 14-core extended biopsy have been published. We compared saturation and extended repeat biopsy protocols after initially negative biopsy. MATERIALS AND METHODS A total of 1,056 men underwent prostate biopsy after initially negative biopsy. The extended biopsy group included 393 men with 12 to 14-core repeat biopsy. The saturation biopsy group included 663 men with 20 to 24-core repeat biopsy. We analyzed demographics and prostate cancer between the 2 groups. We compared prostate cancer detection in patients with previous atypical small acinar proliferation and/or high grade prostatic intraepithelial neoplasia as well as the risk of detecting clinically insignificant tumors. RESULTS Prostate cancer was detected in 315 of the 1,056 patients (29.8%). Saturation biopsy detected almost a third more cancers (32.7% vs 24.9%, p=0.0075). In patients with a benign initial biopsy saturation biopsy achieved significantly greater prostate cancer detection (33.3% vs 25.6%, p=0.027). For previous atypical small acinar proliferation and/or high grade prostatic intraepithelial neoplasia there was a trend toward higher prostate cancer detection rate in the saturation group but it did not attain statistical significance (31.2% vs 23.3%, p=0.13). Of 315 positive biopsies 119 (37.8%) revealed clinically insignificant cancer (40.1% vs 32.6%, p=0.2). CONCLUSIONS Compared to extended biopsy, office based saturation biopsy significantly increases cancer detection on repeat biopsy. The potential for increased detection of clinically insignificant cancer should be weighed against missing significant cases.

Morbidity Of Prostate Biopsy After Simplified Versus Complex Preparation Protocols: Assessment of Risk Factors

OBJECTIVE To determine whether prostate biopsy complications were affected by 2 varying prebiospy protocols implemented at our institution. Although transrectal ultrasound (TRUS) guided prostate biopsy is considered generally safe, it is associated with significant complications. METHODS We retrospectively evaluated a total of 1438 TRUS-guided prostate biopsies between January 2001 and June 2008. In group A, 931 men had only one dose of a quinolone antibiotic immediately before the procedure, and no enema was performed. In group B, 507 men who underwent a prebiopsy enema and were given oral antibiotics starting the day before the procedure for 3 days. We analyzed demographics and biopsy complications between the 2 groups. RESULTS The overall complication rates were categorized as infection (2.2%), urine retention (0.8%), hematuria (4.4%), rectal bleeding (1.5%), sepsis (0.2%). There was no significant statistical difference in the incidence of infection or sepsis between the 2 groups (2.7% vs 1.4%, P = .157 and 0.1% vs 0.4%, P = .285 respectively, for group A vs B). Both hematuria and hematospermia were more common in group B (2.5% vs 7.9%, P < .001 and 0.2% vs 2%, P < .001 respectively, for group A vs B). Prostate size was a significant risk for both hematuria (odds ratio = 1.7, 95% confidence interval = 1.2-2.44, P = .003) and acute urinary retention (odds ratio = 4.45, 95% confidence interval = 2.01-9.84, P < .001). CONCLUSIONS This study demonstrates that a single antibiotic dose before prostate biopsy may be sufficient. In addition, use of prebiopsy enemas is unnecessary to decrease overall complication rates.

Multifocal High Grade Prostatic Intraepithelial Neoplasia is a Risk Factor for Subsequent Prostate Cancer

PURPOSE The risk of under diagnosed or development of subsequent prostate cancer and the treatment of patients diagnosed with high grade prostatic intraepithelial neoplasia remain controversial. We evaluated the relationship between high grade prostatic intraepithelial neoplasia on initial biopsy and the future presence of prostate cancer. MATERIALS AND METHODS From December 1997 to February 2008 a total of 328 men underwent a second prostate biopsy after being initially diagnosed with high grade prostatic intraepithelial neoplasia. Men with prostate cancer or atypia on initial biopsy were excluded from study. Another 335 men without high grade prostatic intraepithelial neoplasia, prostate cancer or atypia underwent a second prostate biopsy based on clinical suspicion alone. A Cox proportional hazards model was used to estimate the effect of high grade prostatic intraepithelial neoplasia on the subsequent diagnosis of prostate cancer after adjustment for prostate specific antigen, age, presence of inflammation, abnormal digital rectal examination and number of cores obtained at biopsy. High grade prostatic intraepithelial neoplasia was also stratified into multifocal disease and laterality. Adjusted Kaplan-Meier plots were generated to estimate the rates of prostate cancer. RESULTS High grade prostatic intraepithelial neoplasia alone on initial prostate biopsy had a significant effect on the subsequent diagnosis of prostate cancer (HR 1.89; 95% CI 1.39, 2.55; p <0.0001). Stratifying high grade prostatic intraepithelial neoplasia into multifocal and bilateral disease significantly increased the hazard ratios to 2.56 (95% CI 1.83, 3.60) and 2.20 (95% CI 1.51, 3.21), respectively, resulting in estimated 3-year cancer rates of 29.0% and 37.0% compared to 12.5% and 18.9%, respectively, following benign biopsy. CONCLUSIONS Multifocal and bilateral disease are adverse features of high grade prostatic intraepithelial neoplasia that significantly increase the risk of prostate cancer despite adjusting for other clinical indicators such as prostate specific antigen and abnormal digital rectal examination.

A nomogram for predicting upgrading in patients with low‐ and intermediate‐grade prostate cancer in the era of extended prostate sampling

Study Type – Diagnostic (exploratory cohort)
Level of Evidence 2b

DOES TRANSRECTAL ULTRASOUND PROBE CONFIGURATION REALLY MATTER? END-FIRE VERSUS SIDE-FIRE PROBE PROSTATE CANCER DETECTION RATES

PURPOSE We compared prostate cancer detection rates for the 2 most commonly used transrectal ultrasound prostate biopsy probes, end fire and side fire, to determine whether the probe configuration affects detection rates. MATERIALS AND METHODS We evaluated 2,674 patients who underwent initial prostate biopsy between 2000 and 2008 with respect to prostate specific antigen, biopsy technique and pathological findings. Patients were divided into 1,124 in whom biopsies were performed with an end fire probe and 1,550 in whom biopsies were performed with a side fire probe. RESULTS There was a significant difference in the overall cancer detection rate in the end vs side fire arms (45.8% vs 38.5%, p <0.001). In the subsets of patients with prostate specific antigen greater than 4 to 10 ng/ml or less and greater than 10 ng/ml a significant difference persisted (46.4% vs 38.9% and 61.7% vs 49.1%, p <0.004 and <0.015, respectively). There was also a significant difference in detection rates between probes in those who underwent 8 to 19 biopsy cores (p <0.009). Biopsies of greater than 20 cores failed to attain statistical significance (p >0.105). We also found that prostate volume, patient age, prostate specific antigen and hypoechoic findings were independent variables for predicting cancer detection on multivariate analysis (p <0.001). CONCLUSIONS The type of probe significantly affects the overall prostate cancer detection rate, particularly in patients with prostate specific antigen greater than 4 ng/ml and/or nonsaturation (8 to 19 cores) prostate biopsy. This may be because the end fire probe allows better mechanical sampling of the lateral and apical regions of the peripheral zone, where cancer is most likely to reside. We set the stage for a randomized, controlled trial to confirm our observations.

Performance of Prostate Cancer Prevention Trial Risk Calculator in a Contemporary Cohort Screened for Prostate Cancer and Diagnosed by Extended Prostate Biopsy

PURPOSE Statistical models such as the Prostate Cancer Prevention Trial risk calculator have been developed to estimate the cancer risk in an individual and help determine indications for biopsy. We assessed risk calculator performance in a large contemporary cohort of patients sampled by extended biopsy schemes. MATERIALS AND METHODS The validation cohort comprised 3,482 men who underwent a total of 4,515 prostate biopsies. Calculator performance was evaluated by ROC AUC and calibration plots. A multivariate regression model was fitted to address important predictor variables in the validation data set. Prediction error was calculated as the response variable in another multivariate regression model. RESULTS Using an average of 13 cores per biopsy prostate cancer was detected in 1,862 patients. The calculator showed an AUC of 0.57 to predict all cancers and 0.60 for high grade cancer. Multivariate analysis of the predictive ability of various clinical factors revealed that race and the number of biopsy cores did not predict overall or high grade cancer at biopsy. Prior negative biopsy, patient age and free prostate specific antigen were significantly associated with prediction error for overall and high grade cancer. Race and family history had a significant association with prediction error only for high grade disease. CONCLUSIONS To our knowledge our external validation of the Prostate Cancer Prevention Trial risk calculator was done in the largest cohort of men screened for prostate cancer to date. Results suggest that the current calculator remains predictive but does not maintain initial accuracy in contemporary patients sampled by more extensive biopsy schemes. Data suggest that the predictive ability of the calculator in current clinical practice may be improved by modeling contemporary data and/or incorporating additional prognostic variables.

Development of Improved Nomogram for Prediction of Outcome of Initial Prostate Biopsy Using Readily Available Clinical Information

OBJECTIVES To construct a nomogram that can be used to estimate the risk of prostate cancer (PCa) and high-grade PCa using readily available clinical information for men undergoing initial extended prostate biopsy (PBx). Many nomograms have been developed to predict the outcome of initial PBx. However, most require information not available at the decision to biopsy. METHODS From March 2000 to April 2010, 1551 men with a prostate-specific antigen (PSA) of ≤10 ng/mL who underwent initial extended PBx were included in the present study. The nomogram predictor variables were patient age, race, prostate-specific antigen (PSA) level, percent free PSA, family history of PCa, and the digital rectal examination findings. The area under the receiver operating characteristic curve was calculated as a measure of discrimination. The calibration was assessed graphically. RESULTS Of the 1551 men, 606 (39.1%) had PCa on biopsy. The mean value for age, PSA, and percent free PSA was 63.4 years, 5.1 ng/mL, and 21.4%, respectively. Also, 25.1% and 7.8% of patients with positive PBx findings had digital rectal examination abnormalities and a positive family history, respectively. The univariate and multivariate analyses suggested that all 6 risk factors were predictors of PCa in the study cohort (P < .05). The area under the curve for all factors in a model predicting PCa was 0.73 (95% confidence interval 0.71-0.76). The area under the curve for predicting high-grade PCa was 0.71 (95% confidence interval 0.69-0.74). CONCLUSIONS The present predictive model allows an assessment of the risk of PCa and high-grade PCa for men undergoing initial extended PBx using readily available, noninvasively obtained clinical data.

Risk of Prostate Cancer After Diagnosis of Atypical Glands Suspicious for Carcinoma on Saturation and Traditional Biopsies

PURPOSE Prostatic glandular atypia is present in approximately 5% of traditional template biopsy specimens. Prior reports suggest this finding carries a 40% risk of prostate cancer on subsequent biopsy. We determined the risk of malignancy in patients with atypia diagnosed on saturation biopsy. MATERIALS AND METHODS We identified 57 patients with a diagnosis of atypia who underwent repeat biopsy between January 2001 and August 2007. Charts were reviewed for clinical and pathological information. RESULTS Median patient age was 62 years (range 46 to 79). Of the 57 patients 19 (33%) had atypia diagnosed on saturation biopsy (20 cores or greater) (group 1), whereas 38 (67%) had atypia diagnosed with a more traditional biopsy technique (12 cores or fewer) (group 2). All patients subsequently underwent saturation repeat biopsy a median of 5 months after the original biopsy. Eight group 1 patients (42%) were found to have cancer on rebiopsy compared to 15 (39.5%) in group 2 (p = 1.00). Whereas only 1 of the 8 patients (12.5%) with cancer in group 1 had a Gleason score of 7 or greater, this was found in 5 of the 15 (33%) in group 2 (p = 0.37). Interestingly patients with cancer were less likely to have inflammation on initial biopsy (p = 0.05). CONCLUSIONS The finding of atypia on prostate biopsy is associated with a high likelihood of underlying malignancy regardless of the number of cores taken on initial biopsy. Inflammation in the initial biopsy may create a false-positive finding of atypia.