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Introduction: Our goal was to determine whether zonal origin of anterior dominant prostate cancers is associated with clinical outcome among patients treated with radical prostatectomy., Methods: We investigated the clinical outcomes of 197 patients with previously well-characterized anterior dominant prostatic tumors on radical prostatectomy. Univariable Cox proportional hazards models were used to test for an association between anterior peripheral zone (PZ) or transition zone (TZ) tumor location and clinical outcomes., Results: Zonal origin of anterior dominant tumors: 97/197 (49%) anterior PZ, 70 (36%) TZ, 14 (7%) both zones and 16 (8%) indeterminate zone. Comparing anterior PZ and TZ tumors, there were no significant differences in Grade group, incidence of extraprostatic extension or surgical margin positivity rate. Overall, 19 (9.6%) patients experienced biochemical recurrence (BCR), including 10 with anterior PZ origin and 5 with TZ origin. Median followup time among those without BCR was 9.5 years (IQR 7.2, 12.7). BCR-free survival at 5 and 10 years was 91% and 89% for anterior PZ tumors, and 94% and 92% for TZ tumors, respectively. On univariate analysis, there was no evidence of a difference in time to BCR between anterior PZ and TZ tumor zone of origin (p=0.5)., Conclusions: In this anatomically well-characterized cohort of anterior dominant prostate cancers, long-term BCR-free survival was not significantly associated with zone of origin. Future studies utilizing zone of origin as a parameter should consider separating anterior and posterior PZ localization, as outcomes may differ.

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: To our knowledge the ideal methodology of quantifying secondary Gleason pattern 4 in men with Grade Group 2/Gleason score 3 + 4 = 7 on biopsy remains unknown. We compared various methods of Gleason pattern 4 quantification and evaluated associations with adverse pathology findings at radical prostatectomy., Materials and Methods: A total of 457 men with Grade Group 2 prostate cancer on biopsy subsequently underwent radical prostatectomy at our institution. Only patients with 12 or more reviewed cores were included in analysis. We evaluated 3 methods of quantifying Gleason pattern 4, including the maximum percent of Gleason pattern 4 in any single core, the overall percent of Gleason pattern 4 (Gleason pattern 4 mm/total cancer mm) and the total length of Gleason pattern 4 in mm across all cores. Adverse pathology features at radical prostatectomy were defined as Gleason score 4 + 3 = 7 or greater (Grade Group 3 or greater), and any extraprostatic extension, seminal vesical invasion and/or lymph node metastasis. A training/test set approach and multivariable logistic regression were used to determine whether Gleason pattern 4 quantification methods could aid in predicting adverse pathology., Results: On multivariable analysis all Gleason pattern 4 quantification methods were significantly associated with an increased risk of adverse pathology (p <0.0001) and an increased AUC beyond the base model. The largest AUC increase was 0.044 for the total length of Gleason pattern 4 (AUC 0.728, 95% CI 0.663-0.793). Decision curve analysis demonstrated an increased clinical net benefit with the addition of Gleason pattern 4 quantification to the base model. The total length of Gleason pattern 4 clearly provided the largest net benefit., Conclusions: Our findings support the inclusion of Gleason pattern 4 quantification in the pathology reports and risk prediction models of patients with Grade Group 2/Gleason score 3 + 4 = 7 prostate cancer. The total length of Gleason pattern 4 across all cores provided the strongest benefit to predict adverse pathology features.

Purpose: Genomic characterization of radical nephroureterectomy specimens in patients with upper tract urothelial carcinoma may allow for thoughtful integration of systemic and targeted therapies. We sought to determine whether genomic alterations in upper tract urothelial carcinoma are associated with adverse pathological and clinical outcomes., Materials and Methods: Next generation exon capture sequencing of 300 cancer associated genes was performed in 83 patients with upper tract urothelial carcinoma. Genomic alterations were assessed individually and also grouped into core signal transduction pathways or canonical cell functions for association with clinicopathological outcomes. Binary outcomes, including grade (high vs low), T stage (pTa/T1/T2 vs pT3/T4) and organ confined status (pT2 or less and N0/Nx vs greater than pT2 or N+) were assessed with the Kruskal-Wallis and Fisher exact tests as appropriate. Associations between alterations and survival were estimated using the Kaplan-Meier method and Cox regression., Results: Of the 24 most commonly altered genes in 9 pathways TP53/MDM2 alterations and FGFR3 mutations were the only 2 alterations uniformly associated with high grade, advanced stage, nonorgan confined disease, and recurrence-free and cancer specific survival. TP53/MDM2 alterations were associated with adverse clinicopathological outcomes whereas FGFR3 mutations were associated with favorable outcomes. We created a risk score using TP53/MDM2 and FGFR3 status that was able to discriminate between adverse pathological and clinical outcomes, including in the subset of patients with high grade disease. The study is limited by small numbers and lack of validation., Conclusions: Our data indicate that specific genomic alterations in radical nephroureterectomy specimens correlate with tumor grade, stage and cancer specific survival outcomes., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We report cancer specific outcomes of micropapillary nonmuscle invasive bladder cancer., Materials and Methods: We retrospectively reviewed the records of 36 cases restaged within 3 months of the initial diagnosis of micropapillary nonmuscle invasive bladder cancer. Early radical cystectomy within a 3-month landmark after restaging transurethral bladder tumor resection or conservative treatment with intravesical bacillus Calmette-Guérin, surveillance or deferred radical cystectomy was offered according to surgeon and patient preference. The cumulative incidence of cancer specific mortality and metastasis was estimated using the Kaplan-Meier method. Differences in the cumulative incidence of cancer specific mortality and metastasis between the groups were tested using the log rank test., Results: Median patient age was 68 years (IQR 63-77). The male-to-female ratio was 3:1. At restaging all patients had cT1 disease or less. Early radical cystectomy was performed in 15 patients (42%) while 21 (58%) underwent conservative treatment. Median followup after landmark in cancer specific survivors was 3.1 years (IQR 1.1-5.9). The 5-year cumulative incidence of cancer specific mortality was 17% in the early radical cystectomy group and 25% in the conservative management group for an absolute difference of 7% (95% CI -26-41, p = 0.8). The 5-year cumulative incidence of metastasis was 21% and 34%, respectively, with an absolute difference of 13% (95% CI -23-49, p = 0.9). The extent of the micropapillary component was not significantly associated with cancer specific mortality (p = 0.4) or metastasis (p = 0.9)., Conclusions: Using proper selection criteria, including patient and pathological factors, certain patients in whom cT1 micropapillary urothelial carcinoma was managed conservatively did not have significantly worse outcomes than patients treated with early radical cystectomy., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

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.)

Purpose: Urachal carcinoma is a rare urological neoplasm that arises along the urachal remnant from umbilicus to bladder dome. To our knowledge no published study has examined the diagnostic accuracy of modern preoperative testing to differentiate urachal carcinoma from a benign urachal cyst and spare the resection of potentially benign urachal tissue. We determined whether a urachal mass could be safely diagnosed preoperatively., Materials and Methods: We reviewed the records of 104 patients with a urachal mass treated between 1979 and 2011. Study exclusion criteria were unresectable metastatic disease at presentation, no surgery and management by transurethral resection alone. Of the patients who remained only 65 had preoperative diagnostic testing as well as definitive pathological results available for analysis. Mean age was 51 years. Of the patients 86% were white and 65% were male. The accuracy of diagnosis based on preoperative tests was compared to that of final pathology (cancer or benign)., Results: A total of 57 tumors (87%) were malignant and 83% of the masses were adenocarcinoma. Compared to computerized tomography, cytology and exploration under anesthesia, transurethral resection of bladder tumor had the highest sensitivity (0.93), specificity (1) and positive predictive value (1) but low negative predictive value (0.5). Study limitations included small cohort size and few benign urachal masses for comparison., Conclusions: No test has a high enough negative predictive value to prevent urachal mass excision. With few treatment options for localized, advanced and metastatic urachal cancer, these data suggest that early excision remains the best treatment for a suspicious urachal mass., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We compared clinical outcomes, and identified predictors of cancer specific and overall survival after radical cystectomy in patients with urothelial carcinoma with squamous differentiation and those with pure squamous cell carcinoma., Materials and Methods: We reviewed data on 2,031 patients treated with radical cystectomy and pelvic lymph node dissection at a single high volume referral center. Of these patients 78 had squamous cell carcinoma and 67 had squamous differentiation. Survival estimates by histological subtype were described using Kaplan-Meier methods. Within histological subtypes pathological stage, nodal invasion, soft tissue margins, age and gender were evaluated as predictors of cancer specific survival and overall survival using univariate Cox regression., Results: Median followup was 44 months. Of 104 patient deaths 60 died of their disease. We did not find a statistically significant difference between survival curves of patients with squamous cell carcinoma and squamous differentiation (log rank overall survival p = 0.6, cancer specific survival p = 0.17). Positive soft tissue margins were associated with worse cancer specific survival (HR 6.92, 95% CI 2.98-16.10, p ≤0.0005) and overall survival (HR 3.68, 95% CI 1.84-7.35, p ≤0.0005) in patients with pure squamous cell carcinoma. Among patients with squamous differentiation, pelvic lymphadenopathy was associated with decreased overall survival (HR 2.52, 95% CI 1.33-4.77, p = 0.004) and cancer specific survival (HR 3.23, 95% CI 1.57-6.67, p = 0.002)., Conclusions: There appears to be no evidence of a difference in cancer specific survival or overall survival between patients with squamous cell carcinoma and those with squamous differentiation treated with radical cystectomy and pelvic lymph node dissection. Patients with squamous differentiation and tumor metastases to pelvic lymph nodes should be followed more closely, and adjuvant treatment should be considered to improve survival. Wide surgical resection is critical to achieve local tumor control and improve survival in patients with squamous cell carcinoma., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)