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Context: Dramatic gains in our understanding of the molecular biology of clear cell renal cell carcinoma (ccRCC) have created a foundation for clinical translation to improve patient care., Objective: To review and contextualize clinically impactful data surrounding genomic biomarkers in ccRCC., Evidence Acquisition: A systematic literature search was conducted focusing on genomic-based biomarkers with an emphasis on studies assessing clinical outcomes., Evidence Synthesis: The advancement of tumor sequencing techniques has led to a rapid increase in the knowledge of the molecular underpinnings of ccRCC and with that the discovery of multiple candidate genomic biomarkers. These include somatic gene mutations such as VHL, PBRM1, SETD2, and BAP1; copy number variations; transcriptomic multigene signatures; and specific immune cell populations. Many of these biomarkers have been assessed for their association with survival and a smaller number as potential predictors of a response to systemic therapy. In this scoping review, we discuss many of these biomarkers in detail. Further studies are needed to continue to refine and validate these molecular tools for risk stratification, with the ultimate goal of improving clinical decision-making and patient outcomes., Conclusions: While no tissue or blood-based biomarkers for ccRCC have been incorporated into routine clinical practice to date, the field continues to expand rapidly. There remains a critical need to develop and validate these tools in order to improve the care for patients with kidney cancer., Patient Summary: Genomic biomarkers have the potential to better predict outcome and select the most appropriate treatment for patients with kidney cancer; however, further research is needed before any of these currently developed biomarkers are adopted into clinical practice., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the complementary value of urinary MyProstateScore (MPS) testing and multiparametric MRI (mpMRI) and assess outcomes in patients with equivocal mpMRI., Materials and Methods: Included patients underwent mpMRI followed by urine collection and prostate biopsy at the University of Michigan between 2015 -2019. MPS values were calculated from urine specimens using the validated model based on serum PSA, urinary PCA3, and urinary TMPRSS2:ERG. In the PI-RADS 3 population, the discriminative accuracy of PSA, PSAD, and MPS for GG≥2 cancer was quantified by the AUC curve. Decision curve analysis was used to assess net benefit of MPS relative to PSAD., Results: There were 540 patients that underwent mpMRI and biopsy with MPS available. The prevalence of GG≥2 cancer was 13% for PI-RADS 3, 56% for PI-RADS 4, and 87% for PI-RADS 5. MPS was significantly higher in men with GG≥2 cancer [median 44.9, IQR (29.4 -57.5)] than those with negative or GG1 biopsy [median 29.2, IQR (14.8 -44.2); P <.001] in the overall population and when stratified by PI-RADS score. In the PI-RADS 3 population (n = 121), the AUC for predicting GG≥2 cancer was 0.55 for PSA, 0.62 for PSAD, and 0.73 for MPS. MPS provided the highest net clinical benefit across all pertinent threshold probabilities., Conclusion: In patients that underwent mpMRI and biopsy, MPS was significantly associated with GG≥2 cancer across all PI-RADS scores. In the PI-RADS 3 population, MPS significantly outperformed PSAD in ruling out GG≥2 cancer. These findings suggest a complementary role of MPS testing in patients that have undergone mpMRI., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To morphometrically measure to muscle mass which may reflect physical components of frailty. Hence, we evaluated the association between L4 total psoas area (TPA) and operative outcome after radical cystectomy (RC) for bladder cancer., Methods: In a retrospective single-center study, bladder cancer patients who underwent RC and urinary diversion between 2007 and 2012 were enrolled. TPA was evaluated in the cross-sectional imaging. The psoas muscles were normalized with the height. Male patients with a psoas mass index ≤7.4 cm 2 /m 2 and female patients with a psoas mass index ≤5.2 cm 2 /m 2 were classified as sarcopenic. Outcome measures were 30- and 90-day readmission and complications, and survival. Multivariable logistic and Cox proportional-hazards regression models were used to determine relevant predictors., Results: The median age of the 441 participants and follow up time was 68 years (IQR 59-75) and 1.2 years (IQR 0.5-1.9), respectively. One hundred forty-three patients (32.4%) were sarcopenic. The 30-day readmission and the complication rates were 13.8% and 44.7%, respectively. The 90-day readmission and complication rates were 23.9% and 53.1%, respectively. The 1-year mortality rate was 11.6% (95%CI 8.7-15.4). Multivariable logistic regression analysis revealed an association between increased TPA and lower odds of 30-day complications after RC (OR 0.95, 95%CI 0.92-0.99, P = .02); similarly, an increase in TPA was of prognostic value, although not statistically significant in the multivariable model (P = .05) once adjusting for other patient factors., Conclusion: Sarcopenia predicted early complications and showed an informative trend for overall survival after RC, and thus may inform models predicting postsurgical outcomes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The potential for low-grade (grade group 1 [GG1]) prostate cancer (PCa) to progress to high-grade disease remains unclear., Objective: To interrogate the molecular and biological features of low-grade PCa serially over time., Design, Setting, and Participants: Nested longitudinal cohort study in an academic active surveillance (AS) program. Men were on AS for GG1 PCa from 2012 to 2017., Intervention: Electronic tracking and resampling of PCa using magnetic resonance imaging/ultrasound fusion biopsy., Outcome Measurements and Statistical Analysis: ERG immunohistochemistry (IHC) and targeted DNA/RNA next-generation sequencing were performed on initial and repeat biopsies. Tumor clonality was assessed. Molecular data were compared between men who upgraded and those who did not upgrade to GG ≥ 2 cancer., Results and Limitations: Sixty-six men with median age 64 yr (interquartile range [IQR], 59-69) and prostate-specific antigen 4.9 ng/mL (IQR, 3.3-6.4) underwent repeat sampling of a tracked tumor focus (median interval, 11 mo; IQR, 6-13). IHC-based ERG fusion status was concordant at initial and repeat biopsies in 63 men (95% vs expected 50%, p <  0.001), and RNAseq-based fusion and isoform expression were concordant in nine of 13 (69%) ERG + patients, supporting focal resampling. Among 15 men who upgraded with complete data at both time points, integrated DNA/RNAseq analysis provided evidence of shared clonality in at least five cases. Such cases could reflect initial undersampling, but also support the possibility of clonal temporal progression of low-grade cancer. Our assessment was limited by sample size and use of targeted sequencing., Conclusions: Repeat molecular assessment of low-grade tumors suggests that clonal progression could be one mechanism of upgrading. These data underscore the importance of serial tumor assessment in men pursuing AS of low-grade PCa., Patient Summary: We performed targeted rebiopsy and molecular testing of low-grade tumors on active surveillance. Our findings highlight the importance of periodic biopsy as a component of monitoring for cancer upgrading during surveillance., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Intermediate clinical endpoints (ICEs) prognostic for overall survival (OS) are needed for men receiving postprostatectomy radiation therapy (PORT) to improve clinical trial design., Objective: To identify a potential ICE for men receiving PORT., Design, Setting, and Participants: We performed an institutional review board-approved multi-institutional retrospective study of 566 men consecutively treated with PORT at tertiary care centers from 1986 to 2013. The median follow-up was 8.2 yr., Outcome Measurements and Statistical Analysis: Biochemical failure (BF), distant metastases (DM), and castrate-resistant prostate cancer (CRPC) were evaluated for correlation with OS and assessed as time-dependent variables in a multivariable Cox proportional hazards model and in landmark analyses at 1, 3, 5, and 7 yr after PORT. Cross-validated concordance (c) indices were used to assess model discrimination., Results and Limitations: OS at 1, 3, 5, and 7 yr after PORT was 98%, 95%, 90%, and 82%, respectively. In a time-varying model controlling for clinical and pathologic variables, BF (hazard ratio [HR] 2.32, 95% confidence interval [CI] 1.45-3.71; p<0.001), DM (HR 6.52, 95% CI 4.20-10.1; p<0.001), and CRPC (HR 2.47, 95% CI 1.56-3.92; p<0.001) were associated with OS. In landmark analyses, 5-yr DM had the highest c index when adjusting for baseline covariates (0.78), with 5-yr DM also providing the greatest increase in discriminatory power over a model only including baseline covariates. These findings require validation in prospective randomized data., Conclusions: While limited by the retrospective nature of the data, 5-yr DM is associated with lower OS following PORT, outperforming the prognostic capability of BF and CRPC at 1, 3, 5, or 7 yr after treatment. Confirmation of this ICE as a surrogate for OS is needed from randomized trial data so that it can be incorporated into future clinical trial design., Patient Summary: We assessed potential intermediate clinical endpoints prognostic for overall survival in a cohort of men receiving radiotherapy after prostatectomy. We identified the development of metastatic disease within 5 yr after treatment as the strongest predictor of overall survival., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate whether incidental pathologic T3a (pT3a) upstaging after partial nephrectomy (PN) for clinical T1 disease results in inferior oncologic outcomes compared to pT1a-b disease., Materials and Methods: Retrospective chart review was completed at the University of Michigan and Moffitt Cancer Center to identify patients undergoing PN for clinical T1 masses between 1995 and 2015. A total of 1955 patients were identified, of which 95 had pT3a upstaging. Median follow-up was 38.2 months. Patients with pT3a disease were individually matched by clinicopathologic features with patients undergoing PN with pT1a-b disease in a 1:2 ratio. Kaplan-Meier analysis and univariate and multivariable Cox proportional hazards regression analysis were performed. Primary endpoint was recurrence-free survival (RFS). Secondary endpoints were all-cause mortality, cancer-specific survival (CSS), and rates of local and distant recurrence., Results: Recurrence rates were significantly higher in pT3a disease compared to pT1a-b controls (P <.01). In those patients with pT3a upstaging, 3- and 5-year RFS were 81% and 58%, compared to 86% and 75% in pT1a-b controls (P = .01). CSS at 3 and 5 years were 91% and 90% in pT3a disease and 100% and 97% in pT1a-b controls (P <.01). All-cause mortality at 3 and 5 years were 82% and 71% in pT3a disease and 93% and 80% in pT1a-b controls (P = .04). Univariate and multivariable analysis of pT3a disease demonstrated no association between demographic or pathologic characteristics and RCC recurrence., Conclusion: Patients with pT3a upstaging following PN experience a significantly reduced RFS and CSS when compared to pT1 disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To investigate whether shortened inpatient length of stay (LOS) after radical cystectomy (RC) is associated with increased complication rates after hospital discharge., Materials and Methods: The analytic cohort comprised 484 consecutive patients with 90-day follow-up who underwent RC at our institution from 2005 to 2012 and with LOS ≤9 days. Patients were categorized according to LOS as short (s-LOS; ≤5 days) or routine (r-LOS; 6-9 days). The primary outcome was major complications (Clavien-Dindo grades 3-5) occurring within 90 days after discharge. A Cox proportional hazards model was used to determine the association between LOS and post-discharge major complications. Hospital readmission was a secondary outcome., Results: Patients in the s-LOS cohort had fewer comorbidities (P < .01), less frequently received neoadjuvant chemotherapy (P = .02), and more often underwent robotic RC (P < .01). Major outpatient complications occurred in 18.1% of s-LOS patients vs 11.2% of r-LOS patients, and s-LOS was associated with a significant independent increase in the risk of major outpatient complications (hazard ratio 1.91, 95% confidence interval 1.03-3.56, P = .04). There was also a statistically significant association between s-LOS and readmission (hazard ratio 1.60, 95% confidence interval 1.01-2.44, P = .048)., Conclusion: Early discharge post RC appears to be associated with an increased risk of major outpatient complications, suggesting that attempts to reduce LOS may need to be supplemented by additional outpatient services to diminish this effect. Further attention should be given to understanding how to better support patients discharged after a short LOS., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To review our clinical T1a renal mass active surveillance (AS) cohort to determine whether renal mass biopsy was associated with maintenance of AS., Materials and Methods: From our prospectively maintained database we identified patients starting AS from June 2009 to December 2011 who had at least 5 months of radiologic follow-up, unless limited by unexpected death or delayed intervention. The primary outcome was delayed intervention. Clinical, radiologic, and pathologic variables were compared. We constructed Kaplan-Meier survival curves for maintenance of AS. Cox multivariable regression analysis was performed to assess predictors of delayed intervention., Results: We identified 118 patients who met criteria for inclusion with a median radiologic follow-up of 29.5 months. The delayed intervention group had greater initial mass size and faster growth rate compared to those who continued AS. Rate of renal mass biopsy was similar between the 2 groups. In the multivariable analysis, size >2 cm (hazard ratio [HR] 3.65, 95% confidence interval [CI] 1.28-10.38, P = .015), growth rate (continuous by mm/year: HR 1.26, 95% CI 1.12-1.41, P < .001), but not renal biopsy (HR 1.52, 95% CI 0.70-3.30, P = .29), were associated with increased risk of delayed intervention. Time-to-event curves also showed that size was closely associated with delayed intervention whereas renal mass biopsy was not., Conclusion: At our institution, growth rate and initial tumor size appear to be more influential than renal mass biopsy results in determining delayed intervention after a period of AS. Further analysis is required to determine the role of renal biopsy in the management of patients being considered for AS., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To compare the accuracies of renal mass biopsy (RMB) and R.E.N.A.L. nephrometry score (RNS) nomograms for predicting benign vs malignant disease, and low- vs high-risk renal tumors., Materials and Methods: We included 281 renal masses in 277 patients who had complete RNS, preoperative RMB, and final pathology from renal surgery for clinically localized renal tumors. RMB and final pathology were determined to be benign or malignant, and malignancies were classified as low-risk (Fuhrman grade I/II) or high-risk (Fuhrman grade III/IV) (benign included in low-risk group). Previously published RNS nomograms were used to determine probabilities of any cancer and high-risk cancer. The gamma statistic was used to assess strength of association between RMB or RNS with final pathology., Results: Of the 281 masses, 13 (5%) and 268 (95%) were confirmed benign and malignant, respectively, and 155 (55%) and 126 (45%) were confirmed low-risk and high-risk, respectively, on final pathology. The areas under the curve of the RNS nomograms for benign vs malignant disease and for low-risk vs high-risk renal tumors were 0.56 and 0.64, respectively. Concordances for predicting benign vs malignant disease were 99% for RMB (P < .01, gamma 0.99) and 29% for RNS nomogram (P = .16, gamma 0.38). Concordances for predicting low-risk vs high-risk renal tumors were 67% for RMB (P < .01, gamma 0.97) and 61% for RNS nomogram (P < .01, gamma 0.47), respectively., Conclusion: Although RNS nomograms are useful for discriminating between benign vs malignant renal masses, and low-risk vs high-risk renal tumors, they are outperformed by RMB., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Limited data exist to guide the use of androgen deprivation therapy (ADT) for men treated with radiation therapy (RT) after radical prostatectomy (RP). The optimal duration of ADT in this setting is unknown., Objective: To determine if the duration of ADT influences clinical outcomes for men receiving post-RP RT., Design, Setting, and Participants: A total of 680 men who received adjuvant radiation therapy (n=105) or salvage radiation therapy (n=575) between 1986 and 2010 at a single tertiary care institution were reviewed retrospectively. Median follow-up post-RT was 57.8 mo., Intervention: RT was delivered using three-dimensional conformal or intensity-modulated RT in 1.8-Gy fractions. For patients treated with ADT, >80% were treated with a gonadotropin-releasing hormone agonist with or without a nonsteroidal antiandrogen., Outcome Measurements and Statistical Analysis: Biochemical failure (BF), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall mortality were assessed using Kaplan-Meier analysis and propensity score analysis., Results and Limitations: Overall, 144 patients (21%) received ADT with post-RP RT, most of whom had high-risk disease features such as Gleason score 8-10, seminal vesicle invasion, or pre-RT prostate-specific antigen >1 ng/ml. Median ADT duration was 12 mo (interquartile range: 6.0-23.7). Patients who received <12 mo of ADT had an association with increased BF (hazard ratio [HR]: 2.27; p=0.003) and DM (HR: 2.48; p=0.03) compared with patients receiving ≥12 mo of ADT. The 5-yr rates of DM were 6.0% and 23% for ≥12 and <12 mo of ADT, respectively. On propensity score analysis controlling for pretreatment and treatment-related factors, each month of ADT was associated with a decreased risk for BF (HR: 0.95; p=0.0004), DM (HR: 0.88; p=0.0004), and PCSM (HR: 0.90; p=0.037). These findings are limited by the retrospective nature of our analysis., Conclusions: For men with high-risk disease features receiving ADT with post-RP RT, the duration of ADT is associated with clinical outcomes. Our findings suggest that for these men an extended course of ADT ≥12 mo may be preferable. Validation of our findings is needed., Patient Summary: We evaluated outcomes for men with high-risk disease features treated with androgen deprivation therapy (ADT) and radiotherapy after radical prostatectomy. Longer durations of ADT resulted in improved patient outcomes., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To determine the relationship between prostate gland and tumor volume in men undergoing radical prostatectomy (RP) for prostate cancer. We hypothesized that larger tumors within smaller prostate glands are associated with more aggressive disease characteristics., Methods: Records of patients undergoing RP from 2000-2008 at a single institution were reviewed retrospectively. The dominant nodule was considered to be the largest focus of cancer within the prostate, and the dominant nodule-to-prostate volume ratio (DNVR) was calculated according to the ratio of the dominant nodule volume to the gland weight. Cox regression was performed to assess the relationship between DNVR and both pathologic outcomes (Cancer of the Prostate Risk Assessment post-Surgical score) and biochemical recurrence (BCR)., Results: At a median follow-up of 3.7 years, 174 patients (7.2%) suffered BCR. There was no linear correlation between tumor volume and gland size (R = -0.09). DNVR above the median (≥0.033 cc/gm) was closely associated with high clinicopathologic risk as measured by Cancer of the Prostate Risk Assessment post-Surgical score (hazard ratio, 35.53; 95% confidence interval, 14.42-87.55 for high- vs low-risk groups). In the univariable analysis, both tumor diameter and DNVR were associated with increased risk of BCR. However, in the multivariable model, only tumor diameter remained a significant predictor of BCR (hazard ratio, 2.02; 95% confidence interval, 1.04-3.91)., Conclusion: Increased DNVR appears to be a characteristic of aggressive prostate tumors, although it did not predict BCR in the present study. However, these data support the association between tumor diameter and BCR after RP for prostate cancer independent of other key clinicopathologic features., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Urothelial tumors that invade the lamina propria but not the muscularis propria are a particularly problematic clinical entity. The aim of the present study was to assess the pathologic features and clinical outcomes of patients with clinical T1 grade 3 urothelial cell bladder carcinoma (UCBC) treated with radical cystectomy., Methods: We reviewed the records of 958 consecutive patients who underwent radical cystectomy and pelvic lymphadenectomy for bladder cancer at three U.S. academic centers. Of these patients, 167 (median age, 66.7 years) underwent radical cystectomy for clinical stage T1 grade 3 UCBC., Results: The median follow-up was 33.8 months (mean +/- standard deviation: 45.9 +/- 39.2 months, range, 0.4 to 177.1) for patients alive at last follow-up. Disease recurred in 48 of 167 of patients (29.4%) and 30 of 162 patients (18.5%) died from bladder cancer. A total of 29 of 166 patients (17.5%) had lymph nodal metastases. Of 167 patients, 84 (50%) were pathologically upstaged and 167 (27.5%) had extravesical disease. Patients with disease upstaging had poorer survival (P <0.001). A greater than 3-month delay between cystectomy and last transurethral resection showed a trend toward upstaging (P = 0.06). Presence of carcinoma in situ (CIS) was the only precystecomy factor that predicted disease recurrence (hazard ratio [HR]: 2.13, 95% confidence interval [CI]: 1.14 to 3.98) and mortality (HR: 2.75, 95% CI: 1.17 to 6.46)., Conclusions: A large proportion of patients undergoing cystectomy for clinical T1 grade 3 disease have adverse pathological features. The recurrence and survival outcomes in this group are suboptimal. Presence of CIS precystectomy predicts outcomes. Better markers are needed to identify patients at high risk for adverse outcomes.

Objectives: The finding of bladder cancer invading the detrusor muscle on transurethral resection (TUR) is one of the clearest indications for radical cystectomy. To the extent that detrusor invasion is, in practical effect, a binary variable, the variety of outcomes after radical cystectomy in these patients belies the simplicity of this approach. In this context, we assessed bladder cancer recurrence-free survival among patients noted to have muscle-invasive urothelial carcinoma (transitional cell cancer [TCC]) on staging TUR subsequently found to have non-muscle-invasive TCC at radical cystectomy (downstaged)., Methods: The records of 248 consecutive patients who underwent radical cystectomy for TCC at a single academic institution from 1994 to 2002 were retrospectively reviewed. Of these patients, 112 (45%) had documented muscle-invasive disease by TUR and were clear of gross residual tumor on cystoscopy before radical cystectomy., Results: Of the 112 patients, 25 (22.3%) were downstaged to non-muscle-invasive disease (Stage pT1 or less) at cystectomy and 87 (77.7%) had persistent muscle-invasive disease (Stage pT2 or greater) at cystectomy. Recurrence occurred in 4 downstaged patients (16.0%) compared with 29 patients (33.3%) who were not downstaged (P = 0.094). Kaplan-Meier analysis demonstrated a statistically significant improvement in recurrence-free survival with downstaging (log-rank P = 0.008). Multivariate analysis demonstrated a threefold reduction in recurrence risk with tumor downstaging (hazard ratio 0.33, 95% confidence interval 0.10 to 1.12) that approached statistical significance (P = 0.075). Nodal status was the strongest predictor of RFS., Conclusions: Downstaging from muscle-invasive TCC on TUR to non-muscle-invasive TCC at radical cystectomy can be associated with a reduced risk of recurrence even after adjusting for lymph node status and adjuvant chemotherapy.

Objective: Bladder cancer (BCa) is a disease of older persons, the incidence of which is expected to increase as the population ages. There is controversy, however, regarding the outcomes of radical cystectomy (RC), the gold standard treatment of high-risk BCa, in patients of advanced chronological age. The aim of our study was to assess the impact of patient age on pathological characteristics and recurrence-free and disease-specific survival following RC., Methods: The records of 888 consecutive patients who underwent RC for transitional cell carcinoma (TCC) were reviewed. Age at RC was analyzed both as a continuous (yr) and categorical (< or =60 yr old, n=240; 60.1-70 yr old, n=331; 70.1-80 yr old, n=266; >80 yr old, n=51) variable. Logistic regression and survival analyses were performed., Results: Higher age at RC, analyzed as a continuous or categorical variable, was associated with extravesical disease and pathological upstaging (all p<0.02). Older patients were less likely to receive postoperative chemotherapy (< or =60 yr: 32% vs. >80 yr: 14%, p=0.008). In both pre- and postoperative multivariate models, higher age at RC as a categorical variable was associated with BCa-specific survival (p<0.05). Patients >80 yr old had a significantly greater risk of disease recurrence than patients aged < or =60 yr (p<0.05)., Conclusion: Greater patient age at the time of RC for BCa is independently associated with adverse outcomes. Better understanding of factors associated with postoperative outcomes in this growing segment of the population is necessary. Prospective corroboration and further refinement of similar analyses in other large datasets is needed.

Objectives: We compared clinical and pathologic staging in a large, contemporary, consecutive series of patients who were treated with radical cystectomy and pelvic lymphadenectomy, and determined the effect of stage discrepancy on outcomes., Methods: We collected retrospective data from 778 consecutive patients with bladder transitional cell carcinoma who were treated with radical cystectomy and pelvic lymphadenectomy, and for whom the clinical and pathologic stage were available., Results: Pathologic upstaging occurred in 42% of patients, and pathologic downstaging occurred in 22%. Forty percent of patients with non-muscle-invasive clinical stage had muscle-invasive pathologic stage. Thirty-six percent of patients with organ-confined clinical stage had non-organ-confined pathologic stage (> or =pT3N0 or pTanyN-positive). Patients with higher clinical stage were more likely to be upstaged to non-organ-confined disease (p<0.001). Patients were stratified into three groups: pathologically upstaged, same clinical and pathologic stage, and pathologically downstaged. When adjusted for the effects of standard postoperative features, upstaged patients were at a significantly higher risk of disease recurrence and bladder cancer-specific death than patients who had the same pathologic and clinical stage, who in turn were at significantly higher risk than downstaged patients. This observation remained true within each clinical stage strata. Within each pathologic stage strata, clinical stage did not substratify into different risk groups., Conclusions: Clinical to pathologic stage discrepancy is a relatively common finding after extirpative surgery for bladder cancer. Clinical outcomes after radical cystectomy are largely driven by pathologic stage. Better clinical staging is necessary to improve patient evaluation and management.

Objectives: Carcinoma in situ (CIS) is a nonpapillary, high-grade, potentially aggressive, and unpredictable manifestation of transitional cell carcinoma (TCC) of the bladder. The aim of this study was to assess whether presence of concomitant CIS has a detrimental effect on cancer control after radical cystectomy., Methods: The records of 812 consecutive patients who underwent radical cystectomy and pelvic lymphadenectomy for bladder TCC at three US academic centres were reviewed. Ninety-nine of 812 (12%) patients had CIS only at radical cystectomy and were excluded from the analyses., Results: Three hundred thirty of the 713 (46.3%) patients had concomitant CIS at radical cystectomy. Patients with TCC involvement of the urethra were more likely to have concomitant CIS than not (61% vs. 40%, p=0.018). Concomitant CIS was significantly more common in patients with lower cystectomy stages and higher tumour grades. In univariate, but not multivariate, analysis, patients with concomitant CIS versus those without were at increased risk of disease recurrence (p=0.0371). In patients with organ-confined disease, concomitant CIS was an independent predictor of disease recurrence (p=0.048 and p=0.012, respectively) but not bladder cancer-specific mortality (p=0.160 and p=0.408, respectively) after adjusting for the effects of standard postoperative features., Conclusions: Concomitant CIS in the cystectomy specimen is common, and patients with concomitant CIS are at increased risk of urethral TCC involvement. The presence of concomitant CIS appears to confer a worse prognosis in patients with non-muscle-invasive TCC treated with radical cystectomy.

Objective: To evaluate precystectomy prediction of pT and pN stages at cystectomy., Methods: Multivariate logistic regression analyses modelled variables of 726 evaluable patients treated with radical cystectomy and bilateral pelvic lymphadenectomy. The first set of models predicted pT(3-4) stage at cystectomy, and the second set predicted pN(1-3) stages at cystectomy. Transurethral resection (TUR) predictors consisted of 2002 T stage, 1973 WHO tumour grade, presence of carcinoma in situ, age, gender, and delivery of neo-adjuvant chemotherapy. The area under the ROC curve quantified nomogram accuracy. Two hundred bootstrap resamples were used to reduce overfit bias., Results: At TUR, 11% of patients were staged as pT(3-4) versus 42% at cystectomy. Lymph node metastases were found in 24% of patients at cystectomy (pN(1-3)). The multivariate pT(3-4) nomogram was 75.7% accurate versus 71.4% for TUR T stage. The multivariate pN(1-3) nomogram was 63.1% accurate versus 61.0% for TUR T stage., Conclusion: Multivariate nomograms are not perfect, but they do predict more accurately than TUR T stage alone.

Objectives: To describe the cancer-specific outcomes of patients with pathologic carcinoma in situ (CIS) only at radical cystectomy., Methods: The records of 812 consecutive patients who underwent radical cystectomy and pelvic lymphadenectomy for bladder transitional cell carcinoma at three U.S. academic centers were reviewed. Of the 812 patients, 99 (12%) had CIS only at radical cystectomy., Results: The distribution of clinical stage for the 99 patients with CIS only at radical cystectomy was as follows: 47% of patients had CIS only, 8% had cT1, 15% had cT1 plus CIS, 10% had cT2, 13% had cT2 plus CIS, 6% had cTa, and 1% had Ta plus CIS. Two patients had lymphovascular invasion in the radical cystectomy specimen, and three had metastases to the lymph nodes. The actuarial recurrence-free survival estimates were 89.8% (95% confidence interval [CI] 83.0% to 96.6%) at 3 years and 83.0% (95% CI 73.2% to 92.8%) at 5 and 7 years after radical cystectomy. Six patients (6%) had died of bladder cancer at analysis and 13 (13%) had died of other causes without evidence of disease recurrence. The actuarial disease-specific survival estimates were 95.8% (95% CI 91.2% to 99.9%) at 3 years, 90.7% (95% CI 82.4% to 98.9%) at 5 years, and 87.2% (95% CI 76.8% to 97.5%) at 7 years after surgery. On univariate Cox regression analyses, only metastasis to lymph nodes was associated with bladder cancer recurrence and death (P <0.001)., Conclusions: Disease control seemed durable for patients with pathologic CIS only at radical cystectomy in the absence of metastases to the lymph nodes, even in the case of failure after intravesical therapy.

CpG island hypermethylation may be one of the earliest somatic genome alterations to occur during the development of multiple cancers. Recently, aberrant methylation patterns for different tumors have been reported. We present a comprehensive review of the literature describing the role of CpG island hypermethylation of DNA from prostatic tissue and bodily fluids from men with prostate cancer. We reviewed the literature to evaluate CpG island hypermethylation in tissue and bodily fluids of men with primary and metastatic prostate cancer. Additionally, we reviewed the literature with respect to CpG island hypermethylation patterns in other urological malignancies. Using modern analytic methods, CpG island hypermethylation detection can be achieved. In men with prostate cancer, correlations between specific gene regulatory region hypermethylation analyses and Gleason score, pathologic stage and tumor recurrence have been demonstrated. CpG island hypermethylation may serve as a useful molecular biomarker for the detection and diagnosis of patients with prostate cancer.