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Context.—: In prostate cancer, "tertiary" higher-grade patterns (TPs) have been associated with biochemical recurrence after radical prostatectomy., Objective.—: To determine variation regarding definition and application of TPs., Design.—: Online survey regarding TPs in a range of grading scenarios circulated to 105 experienced urologic pathologists., Results.—: Among 95 respondents, 40 of 95 (42%) defined TPs as "third most common pattern" and 55 (58%) as "minor pattern/less than 5% of tumor." In a tumor with pattern 3 and less than 5% pattern 4, of the 95 respondents, 35 (37%) assigned 3 + 3 = 6 with TP4, while 56 (59%) assigned 3 + 4 = 7. In a tumor with pattern 4 and less than 5% pattern 5, of the 95 respondents, 51 (54%) assigned 4 + 4 = 8 with TP5, while 43 (45%) assigned 4 + 5 = 9. Six scenarios were presented in which the order of most common patterns was 3, 4, and 5 (Group 1) or 4, 3, and 5 (Group 2) with varying percentages. In both groups, when pattern 5 was less than 5%, we found that 98% and 93% of respondents would assign 3 + 4 = 7 or 4 + 3 = 7 with TP5. In scenarios with 15% or 25% pattern 5, most respondents (70% and 80%, respectively) would include pattern 5 as the secondary grade, that is, 3 + 5 = 8 (Group 1) or 4 + 5 = 9 (Group 2). For 85 of 95 (89%), a TP would not impact Grade Group assignment., Conclusions.—: This survey highlights substantial variation in practice patterns regarding definition and application of "tertiary" grading in radical prostatectomy specimens. High consistency was observed in 3 + 4 = 7/4 + 3 = 7 scenarios with truly minor pattern 5. These findings should inform future studies assessing the standardization and predictive value of "tertiary" patterns.

Purpose: Few groups have investigated the combined effects of PTEN loss and ERG expression on the outcomes of metastasis of or death from prostate cancer in surgically treated patients. We examined the association of PTEN/ERG status with lethal prostate cancer in patients treated with radical prostatectomy., Materials and Methods: Included in analysis were 791 patients with clinically localized prostate cancer treated with radical prostatectomy at a single institution. Genetically validated immunohistochemistry assays for PTEN and ERG were performed on tissue microarrays. Multivariable Cox proportional hazard models were used to assess the association of PTEN/ERG status with lethal prostate cancer (defined as metastasis or prostate cancer specific death), adjusting for patient age, race, pathological grade and stage, and surgical margin status., Results: Median followup in the cohort was 12.8 years. Of 791 cases 203 (25%) demonstrated PTEN loss and 330 of 776 (43%) were ERG positive. On multivariable analysis PTEN loss (HR 1.9, 95% CI 1.2-3.0, p=0.012) but not ERG expression (HR 0.6, 95% CI 0.4-1.1, p=0.11) was associated with an increased risk of lethal prostate cancer. The association of PTEN loss with lethal disease only remained among men with ERG negative tumors (HR 2.3, 95% CI 1.3-4.1, p=0.005) and not ERG positive tumors (HR 1.1, 95% CI 0.6-2.1, p=0.81)., Conclusions: PTEN loss is associated with an increased risk of lethal prostate cancer after radical prostatectomy and this risk is most pronounced in the subgroup of patients with ERG negative tumors. This work corroborates the use of PTEN and ERG status for risk stratification in surgically treated patients.

Purpose: We evaluated whether the prediction of biochemical recurrence after radical prostatectomy is enhanced by any of 6 parameters, including prostate volume, total tumor volume, high grade total tumor volume, the ratio of high grade total tumor volume to total tumor volume, the ratio of total tumor volume to prostate volume and/or the ratio of high grade total tumor volume to prostate volume., Materials and Methods: A total of 1,261 patients who underwent radical prostatectomy during a 3-year period had tumor maps constructed with the Gleason pattern denoted as low-3 or high-4 or 5 and volumetric data generated using commercially available software. Univariate Cox regression models were used to assess whether each volume related parameter was associated with biochemical recurrence after radical prostatectomy. A multivariable Cox regression base model (age, prostate specific antigen, Gleason score/grade group, pathological stage and margin status) was compared with 6 additional models (base model plus each volume related parameter) to evaluate enhancement in predictive accuracy. Decision curve analysis was performed to determine the clinical utility of parameters that enhanced predictive accuracy., Results: On univariate analysis each parameter was significantly associated with biochemical recurrence except prostate volume. Predictive accuracy of the multivariable base model was high (c-index = 0.861). Adding volume related parameters marginally enhanced discrimination. Decision curve analysis failed to show added benefit even for high grade total tumor volume/total tumor volume, which was the parameter with the highest discriminative improvement., Conclusions: Tumor volume related parameters are significantly associated with radical prostatectomy but do not add important discrimination to standard clinicopathological variables for radical prostatectomy prediction or provide benefit across a range of clinically relevant decision thresholds. Volume related measurement is not warranted in routine pathological evaluation and reporting.

Purpose: We evaluated the relationship of progression to positive surgical margin linear length and Gleason grade at a positive surgical margin., Materials and Methods: We studied 2,150 prostatectomies done for pT2 or pT3a disease to determine grade, stage and surgical margin status. In patients with positive surgical margins we recorded the location, number, positive margin linear length and highest Gleason grade at a positive margin. The Kaplan-Meier method and log rank test were used to determine differences in progression-free probability among positive margin features. The concordance index was used to discriminate the accuracy of grouping surgical margin status as negative/positive vs positive margin linear length/highest Gleason grade., Results: A total of 207 cases (10%) showed positive surgical margins, including 93 (45%) that were pT2+ and 114 (55%) that were pT3a. Patients with pT3a and positive margins had greater prostate specific antigen and tumor volume, and Gleason score 7 or greater than those with pT2+. A total of 45 patients with positive margins progressed. We then subcategorized positive margins. Of the patients 164 (79%) had 1 positive margin. Positive margin linear length was 1 mm or less, 1.1 to 3 and greater than 3 in 104 (50%), 55 (27%) and 48 cases (23%), respectively. Two-year progression-free probability was 95%, 91%, 83% and 47% in patients with negative margins and the 3 positive margin linear length groups, respectively (p <0.001). Gleason grade at a positive margin was 3 and 4/5 in 154 (74%) and 53 patients (26%), respectively. The latter group was significantly more likely to progress (p <0.001). The overall margin status concordance index was 0.636. It was not considerably enhanced by categorizing by positive surgical margin linear length/highest Gleason grade at positive margins., Conclusions: The linear extent of and highest Gleason grade at a positive surgical margin are associated with progression. However, subcategorization does not importantly add to predictive models using margin status only. More robust markers are needed in patients with positive surgical margins to warrant routine reporting and identify those at risk for biochemical recurrence., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Aggressive screening and prostate needle biopsy protocols have been successful in early detection of low-volume posterior tumors. Consequently, we have observed an increased incidence of anterior-predominant prostate cancers. However, the zones of origin, patterns of spread, and patterns of extraprostatic extension of this group of tumors have not been well studied. Of 1312 radical prostatectomies performed at our institution over a span of 4.5 years, 197 had predominant (largest) tumors anterior to the urethra in whole-mounted radical prostatectomy specimens. Detailed histopathologic analysis of this cohort was undertaken emphasizing the variability in anterior prostatic anatomy from apex through base to determine zone of origin and pathologic staging. Using this approach, 97/197 (49.2%) anterior-predominant tumors (ATs) were assigned to the anterior peripheral zone (APZ), 70 (35.5%) to the transition zone (TZ), 16 (8.1%) were of indeterminate zone, and 14 (7.1%) were of both zones. Comparing APZ and TZ tumors, there were no significant differences in Gleason scores, incidence of extraprostatic extension, overall surgical margin positivity rate, or laterality. Involvement of the anterior fibromuscular stroma was significantly more likely in tumors of TZ origin (P< or =0.01), yet was observed in 50.5% of APZ tumors. Conversely, APZ tumors were more commonly localized within the apical one third of the prostate. Most of the prostates (91.4%) also showed additional PZ tumors, which were occasionally stage determining (7/197; 3.9%). In conclusion, ATs of APZ origin are more prevalent than those arising from the TZ. Contrary to previous reports comparing TZ tumors to all PZ tumors, ATs of both zones exhibit similar grading and staging parameters in this series. Given these similarities, long-term clinical outcomes and future molecular analyses will be necessary to assess whether true differences in biology and behavior exist between tumors of TZ and APZ origin.

Purpose: Incision of the anterior layer of Denonvilliers' fascia is commonly cited as a key step in successful dissection of the vasa deferentia and seminal vesicles from the posterior bladder neck during laparoscopic radical prostatectomy. However, anatomical descriptions do not support the presence of Denonvilliers' fascia anterior to the seminal vesicles. To address this inconsistency we performed a detailed anatomical study of tissue planes encountered during laparoscopic dissection of the posterior bladder neck., Materials and Methods: To grossly characterize the tissue planes encountered during laparoscopic posterior bladder neck dissection, ex vivo dissections were performed on 4 separate cystoprostatectomy specimens. Biopsies of the representative areas were obtained from 20 consecutive laparoscopic radical prostatectomy specimens by 2 dedicated uropathologists., Results: Following incision into the posterior bladder neck mucosa, longitudinally oriented fibers were readily visualized, extending from bladder neck to prostate base. Histologically this anatomical landmark represents the fusion of 2 separate tissue layers, that is an inner lamella composed of longitudinally disposed smooth muscle fibers in continuation with the longitudinal fascia of the bladder detrusor (medial fascicle of the detrusor running in between the ureters) and an outer lamella composed of fibroadipose tissue in continuation with the bladder adventitia., Conclusions: Our anatomical and histological analysis refutes the prevailing belief in the laparoscopic literature that the longitudinal muscle fibers identified during dissection of the posterior bladder neck represent the anterior layer of Denonvilliers' fascia. They correspond to the posterior longitudinal fascia of the detrusor muscle that is externally upholstered by the bladder adventitia.

Objective: To determine whether subclassification of positive surgical margins (PSMs) increases predictive ability for biochemical recurrence (BCR) and aids clinical decision‐making in patients undergoing radical prostatectomy. Patients and Methods: We studied 2147 patients with pT2 and pT3a prostate cancer with detailed surgical margin parameters and BCR status. We compared a base model, a linear predictor calculated from the Memorial Sloan Kettering Cancer Center postoperative nomogram (prostate‐specific antigen, pathological tumour grade and stage), with the addition of surgical margin status to five additional models (base model plus surgical margin subclassifications) to evaluate enhancement in predictive accuracy. Decision curve analysis (DCA) was performed to determine the clinical utility of parameters that enhanced predictive accuracy. Results: Among 2147 men, 205 had PSMs, and 231 developed BCR. Discrimination for the base model with addition of surgical margin status was high (c‐index = 0.801) and not meaningfully improved by adding surgical margin subclassification in the full cohort. In analyses considering only men with PSMs (N = 55 with BCR), adding surgical margin subclassification to the base model increased discrimination for total length of all PSMs – alone or with maximum Gleason grade at the margin (c‐index improvement = 0.717 to 0.752 and 0.753, respectively). DCA demonstrated a modest benefit to clinical utility with the addition of these parameters. Conclusions: Specific subclassification parameters add predictive accuracy for BCR and may aid clinical utility in decision‐making for patients with PSMs. These findings may be useful for patient counselling and future adjuvant therapy trial design. [ABSTRACT FROM AUTHOR]