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Description of additional methods and procedures used in the study. Also includes Supplementary References.

Although alterations in xenobiotic metabolism are considered causal in the development of bladder cancer, the precise mechanisms involved are poorly understood. In this study, we used high-throughput mass spectrometry to measure over 2,000 compounds in 58 clinical specimens, identifying 35 metabolites which exhibited significant changes in bladder cancer. This metabolic signature distinguished both normal and benign bladder from bladder cancer. Exploratory analyses of this metabolomic signature in urine showed promise in distinguishing bladder cancer from controls and also nonmuscle from muscle-invasive bladder cancer. Subsequent enrichment-based bioprocess mapping revealed alterations in phase I/II metabolism and suggested a possible role for DNA methylation in perturbing xenobiotic metabolism in bladder cancer. In particular, we validated tumor-associated hypermethylation in the cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) promoters of bladder cancer tissues by bisulfite sequence analysis and methylation-specific PCR and also by in vitro treatment of T-24 bladder cancer cell line with the DNA demethylating agent 5-aza-2′-deoxycytidine. Furthermore, we showed that expression of CYP1A1 and CYP1B1 was reduced significantly in an independent cohort of bladder cancer specimens compared with matched benign adjacent tissues. In summary, our findings identified candidate diagnostic and prognostic markers and highlighted mechanisms associated with the silencing of xenobiotic metabolism. The metabolomic signature we describe offers potential as a urinary biomarker for early detection and staging of bladder cancer, highlighting the utility of evaluating metabolomic profiles of cancer to gain insights into bioprocesses perturbed during tumor development and progression. Cancer Res; 71(24); 7376–86. ©2011 AACR.

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Penile squamous cell carcinoma (PeSCCA) is a rare malignancy for which there are limited treatment options due to a poor understanding of the molecular alterations underlying disease development and progression. Therefore, we performed comprehensive, targeted next-generation sequencing to identify relevant somatic genomic alterations in a retrospective cohort of 60 fixed tumor samples from 43 PeSCCA cases (including 14 matched primary/metastasis pairs). We identified a median of two relevant somatic mutations and one high-level copy-number alteration per sample (range, 0–5 and 0–6, respectively). Expression of HPV and p16 was detectable in 12% and 28% of patients, respectively. Furthermore, advanced clinical stage, lack of p16 expression, and MYC and CCND1 amplifications were significantly associated with shorter time to progression or PeSCCA-specific survival. Notably, four cases harbored EGFR amplifications and one demonstrated CDK4 amplification, genes for which approved and investigational targeted therapies are available. Importantly, although paired primary tumors and lymph node metastases were largely homogeneous for relevant somatic mutations, we identified heterogeneous EGFR amplification in primary tumor/lymph node metastases in 4 of 14 cases, despite uniform EGFR protein overexpression. Likewise, activating HRAS mutations occurred in 8 of 43 cases. Taken together, we provide the first comprehensive molecular PeSCCA analysis, which offers new insight into potential precision medicine approaches for this disease, including strategies targeting EGFR. Cancer Res; 75(24); 5219–27. ©2015 AACR.

Sanger sequencing validation of next generation sequencing (NGS) variant calls ; Alternative view of integrative molecular profiling heatmap ; p16 expression via immunohistochemistry ; Kaplan-Meier analysis of histologic subtypes of PeSCCA ; Comparison of prioritized molecular alterations in penile (PN) squamous cell carcinomas (SCCA) compared to other SCCAs .

Supplementary Figure 1 from Development of a Multiplex Quantitative PCR Signature to Predict Progression in Non–Muscle-Invasive Bladder Cancer

Supplementary Methods, Figures 1-7 from Development of a Multiplex Quantitative PCR Signature to Predict Progression in Non–Muscle-Invasive Bladder Cancer

In bladder cancer, clinical grade and stage fail to capture outcome. We developed a clinically applicable quantitative PCR (QPCR) gene signature to predict progression in non–muscle-invasive bladder cancer. Comparative metaprofiling of 12 DNA microarray data sets (comprising 631 samples and 241,298 probe sets) identified 96 genes, which showed differential expression in seven clinical outcome categories, or were identified as outliers, historic markers, or housekeeping genes. QPCR was done to determine mRNA expression from 96 bladder tumors. Fifty-seven genes differentiated T2 from non-T2 tumors (P < 0.05). Principal components analysis and Cox regression models were used to predict probability of T2 progression for non-T2 patients, placing them into high- and low-risk groups based on their gene expression. At 2 years, high-risk patients exhibited greater T2 progression (45% for high-risk patients versus 12% for low-risk patients; P = 0.003, log-rank test). This difference remained significant within T1 tumors (61% for high-risk patients versus 22% for low-risk patients; P = 0.02) and Ta tumors (29% for high-risk patients versus 0% for low-risk patients; P = 0.03). The best multivariate Cox model included stage and gender, and this signature provided predictive improvement over both (P = 0.002, likelihood ratio test). Immunohistochemistry was done for two genes in the signature not previously described in bladder cancer, ACTN1 and CDC25B, corroborating their up-regulation at the protein level with disease progression. Thus, we identified a 57-gene QPCR panel to help predict progression of non–muscle-invasive bladder cancers and delineate a systematic, generalizable approach to converting microarray data into a multiplex assay for cancer progression. [Cancer Res 2009;69(9):3810–8]

Supplementary Figure 2 from Development of a Multiplex Quantitative PCR Signature to Predict Progression in Non–Muscle-Invasive Bladder Cancer

Clinicopathologic data for all profiled penile squamous cell carcinoma (PeSCCA) samples ; Sequencing data for all profiled penile squamous cell carcinoma (PeSCCA) samples ; Detailed somatic variant information from PeSCCA profiled by next generation sequenicng ; PeSCCA HPV genotyping and p16 immunohistochemistry (IHC) results .

We identified urothelial tract biopsy and resection specimens with keratinizing squamous metaplasia (KSM), nonkeratinizing squamous metaplasia (NKSM), and urothelial and squamous carcinomas over a 20-yr period, focusing on cases with neurogenic lower urinary tract dysfunction (NLUTD) and/or those with spatial or temporal variation in sampling. TERT promoter mutations as assessed via allele-specific polymerase chain reaction were surprisingly common in our testing cohort, identified not only in 15 (94%) invasive cancer foci but also in 13 (68%) examples of KSM and seven (70%) examples of NKSM. TERT promoter mutations were present in 23 foci from NLUTD specimens and 11 foci from bladder diverticula, including in foci of KSM, NKSM, and unremarkable urothelium from cases with no clinical association with previous, concurrent, or subsequent cancer. Our demonstration of temporally and spatially persistent TERT promoter mutation in examples of KSM and NKSM in cases of bladder cancer and in morphologically benign cases with neurogenic dysfunction suggests a molecular mechanism by which such pre-neoplastic lesions can potentially progress and develop into overt carcinoma. Given the interest in TERT promoter mutations as a potential biomarker for the development of bladder cancer, these findings possibly explain the association between conditions with chronic urinary bladder injury (such as the natural history of NLUTD) and higher risk of bladder cancer. TERT promoter mutations may represent an early event in bladder cancer tumorogenesis, and our findings expand on the clinical ramifications and predictive value of TERT promoter mutations in this context. Patient summary Mutations in the TERT gene are the most common genetic changes in bladder cancer. We found that these mutations are also sometimes present in patients with chronic bladder irritation such as neurogenic bladder dysfunction and changes to the lining of the bladder that pathologists would consider “benign.” This finding might explain why such conditions are associated with the development of bladder cancer.

Objective To evaluate MUSIC-KIDNEY's adherence to the American Urological Association (AUA) guidelines regarding the initial evaluation of patient's with clinical T1 (cT1) renal masses. Methods We reviewed MUSIC-KIDNEY registry data for patients with newly diagnosed cT1 renal masses to assess for adherence with the 2017 AUA guideline statements regarding recommendations to obtain (1) CMP, (2) CBC, (3) UA, (4) abdominal cross-sectional imaging, and (5) chest imaging. An evaluation consisting of all 5 guideline measures was considered “complete compliance.” Variation with guideline adherence was assessed by contributing practice, management strategy, and renal mass size. Results We identified 1808 patients with cT1 renal masses in the MUSIC-KIDNEY registry, of which 30% met the definition of complete compliance. Most patients received care that was compliant with recommendations to obtain laboratory testing with 1448 (80%), 1545 (85%), and 1472 (81%) patients obtaining a CMP, CBC, and UA respectively. Only 862 (48%) patients underwent chest imaging. Significant variation exists in complete guideline compliance for contributing practices, ranging from 0% to 45% as well as for patients which underwent immediate intervention compared with initial observation (37% vs 23%) and patients with cT1b masses compared with cT1a masses (36% vs 28%). Conclusion Complete guideline compliance in the initial evaluation of patients with cT1 renal masses is poor, which is mainly driven by omission of chest imaging. Significant variation in guideline adherence is seen across practices, as well as patients undergoing an intervention vs observation, and cT1a vs cT1b masses. There are ample quality improvement opportunities to increase adherence and decrease variability with guideline recommendations.

Contains fulltext : 245130.pdf (Publisher’s version ) (Open Access) BACKGROUND: In patients with haematuria, a fast, noninvasive test with high sensitivity (SN) and negative predictive value (NPV), which is able to detect or exclude bladder cancer (BC), is needed. A newly developed urine assay, Xpert Bladder Cancer Detection (Xpert), measures five mRNA targets (ABL1, CRH, IGF2, UPK1B, and ANXA10) that are frequently overexpressed in BC. OBJECTIVE: To validate the performance of Xpert in patients with haematuria. DESIGN, SETTING, AND PARTICIPANTS: Voided precystoscopy urine specimens were prospectively collected at 22 sites from patients without prior BC undergoing cystoscopy for haematuria. Xpert, cytology, and UroVysion procedures were performed. Technical validation was performed and specificity (SP) was determined in patients without BC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Test characteristics were calculated based on cystoscopy and histology results, and compared between Xpert, cytology, and UroVysion. RESULTS AND LIMITATIONS: We included 828 patients (mean age 64.5 yr, 467 males, 401 never smoked). Xpert had an SN of 78% (95% confidence interval [CI]: 66-87) overall and 90% (95% CI: 76-96) for high-grade (HG) tumours. The NPV was 98% (95% CI: 97-99) overall. The SP was 84% (95% CI: 81-86). In patients with microhaematuria, only one HG patient was missed (NPV 99%). Xpert had higher SN and NPV than cytology and UroVysion. Cytology had the highest SP (97%). In a separate SP study, Xpert had an SP of 89% in patients with benign prostate hypertrophy and 92% in prostate cancer patients. CONCLUSIONS: Xpert is an easy-to-use, noninvasive test with improved SN and NPV compared with cytology and UroVysion, representing a promising tool for identifying haematuric patients with a low likelihood of BC who might not need to undergo cystoscopy. PATIENT SUMMARY: Xpert is an easy-to-perform urine test with good performance compared with standard urine tests. It should help identify (micro)haematuria patients with a very low likelihood to have bladder cancer.

Renal cell carcinoma (RCC) presenting with cough is a rare phenomenon, which is likely an immune-mediated paraneoplastic syndrome. To our knowledge, there are a few individual case reports and one case series in the literature. We report our experience with chronic cough as the presenting symptom for RCC. A retrospective chart review was performed on cases presenting with RCC and cough at two institutions. A recent case at a third institution was also included. The literature was reviewed via an Ovid MEDLINE search to reveal fourteen previously reported cases. Eight new cases were identified of patients presenting with a cough and subsequently being diagnosed with RCC. All cases of RCC were identified incidentally due to imaging obtained during a workup for chronic cough. Average age at presentation was 66.5 years old (range 54–79). Renal tumor size ranged from 3.8 to 10 cm. Final pathology was clear cell renal cell carcinoma in all patients, with one patient having Xp11 translocation. Six of the patients had resolution of the cough after resection of the primary tumor despite one patient with metastatic disease. One other patient reported a significant improvement. The final patient had transient improvement in her cough after cytoreductive nephrectomy. Chronic cough is a rare presentation of RCC. Treatment of the primary tumor with resection or embolization may lead to resolution of the cough, even in some patients with metastatic disease.

No data exist on time to recovery of patient-reported and performance-related measures of functional independence after radical cystectomy (open or robotic).To determine recovery of functional independence after radical cystectomy and whether robot-assisted radical cystectomy (RARC) is associated with any advantage over open procedures.Data for this secondary analysis from the RAZOR (Randomized Open vs Robotic Cystectomy) trial were used. RAZOR was a phase 3 multicenter noninferiority trial across 15 academic medical centers in the US from July 1, 2011, to November 18, 2014, with a median follow-up of 2 years. Participants included the per-protocol population (n = 302). Data were analyzed from February 1, 2017, to May 1, 2021.Robot-assisted radical cystectomy or open radical cystectomy (ORC).Patient-reported (activities of daily living [ADL] and independent ADL [iADL]) and performance-related (hand grip strength [HGS] and Timed UpGo walking test [TUGWT]) measures of independence were assessed. Patterns of postoperative recovery for the entire cohort and comparisons between RARC and ORC were performed. Exploratory analyses to assess measures of independence across diversion type and to determine whether baseline impairments were associated with 90-day complications or 1-year mortality were performed.Of the 302 patients included in the analysis (254 men [84.1%]; mean [SD] age at consent, 68.0 [9.7] years), 150 underwent RARC and 152 underwent ORC. Baseline characteristics were similar in both groups. For the entire cohort, ADL, iADL, and TUGWT recovered to baseline by 3 postoperative months, whereas HGS recovered by 6 months. There was no difference between RARC and ORC for ADL, iADL, TUGWT, or HGS scores at any time. Activities of daily living recovered 1 month after RARC (mean estimated score, 7.7 [95% CI, 7.3-8.0]) vs 3 months after ORC (mean estimated score, 7.5 [95% CI, 7.2-7.8]). Hand grip strength recovered by 3 months after RARC (mean estimated HGS, 29.0 [95% CI, 26.3-31.7] kg) vs 6 months after ORC (mean estimated HGS, 31.2 [95% CI, 28.8-34.2] kg). In the RARC group, 32 of 90 patients (35.6%) showed a recovery in HGS at 3 months vs 32 of 88 (36.4%) in the ORC group (P = .91), indicating a rejection of the primary study hypothesis for HGS. Independent ADL and TUGWT recovered in 3 months for both approaches. Hand grip strength showed earlier recovery in patients undergoing continent urinary diversion (mean HGS at 3 months, 31.3 [95% CI, 27.7-34.8] vs 33.9 [95% CI, 30.5-37.3] at baseline; P = .09) than noncontinent urinary diversion (mean HGS at 6 months, 27.4 [95% CI, 24.9-30.0] vs 29.5 [95% CI, 27.2-31.9] kg at baseline; P = .02), with no differences in other parameters. Baseline impairments in any parameter were not associated with 90-day complications or 1-year mortality.The results of this secondary analysis suggest that patients require 3 to 6 months to recover baseline levels after radical cystectomy irrespective of surgical approach. These data will be invaluable in patient counseling and preparation. Hand grip strength and ADL tended to recover to baseline earlier after RARC; however, there was no difference in the percentage of patients recovering when compared with ORC. Further study is needed to assess the clinical significance of these findings.ClinicalTrials.gov Identifier: NCT01157676.

We evaluated health related quality of life following robotic and open radical cystectomy as a treatment for bladder cancer.Using the Randomized Open versus Robotic Cystectomy (RAZOR) trial population we assessed health related quality of life by using the Functional Assessment of Cancer Therapy (FACT)-Vanderbilt Cystectomy Index and the Short Form 8 Health Survey (SF-8) at baseline, 3 and 6 months postoperatively. The primary objective was to assess the impact of surgical approach on health related quality of life. As an exploratory analysis we assessed the impact of urinary diversion type on health related quality of life.Analyses were performed in subsets of the per-protocol population of 302 patients. There was no statistically significant difference between the mean scores by surgical approach at any time point for any FACT-Vanderbilt Cystectomy Index subscale or composite score (p0.05). The emotional well-being score increased over time in both surgical arms. Patients in the open arm showed significantly better SF-8 sores in the physical and mental summary scores at 6 months compared to baseline (p0.05). Continent diversion (versus noncontinent) was associated with worse FACT-bladder-cystectomy score at 3 (p0.01) but not at 6 months, and the SF-8 physical component was better in continent-diversion patients at 6 months (p=0.019).Our data suggests lack of significant differences in the health related quality of life in robotic and open cystectomies. As robotic procedures become more widespread it is important to discuss this finding during counseling.

OBJECTIVE To better understand the financial implications of readmission after radical cystectomy, an expensive surgery coupled with a high readmission rate. Currently, whether hospitals benefit financially from readmissions after radical cystectomy remains unclear, and potentially obscures incentives to invest in readmission reduction efforts. MATERIALS AND METHODS Using a 20% sample of national Medicare beneficiaries, we identified 3544 patients undergoing radical cystectomy from January 2010 to November 2014. We compared price-standardized Medicare payments for index admissions and readmissions after surgery. We also examined the variable financial impact of length of stay and the proportion of Medicare payments coming from readmissions based on overall readmission rate. RESULTS Medicare patients readmitted after cystectomy had higher index hospitalization payments ($19,164 readmitted vs $18,146 non-readmitted, P = .03) and an average readmission payment of $7356. Adjusted average Medicare readmission payments and length of stay varied significantly across hospitals, ranging from $2854 to $15,605, and 2.0 to 17.1 days, respectively (both P

INTRODUCTION AND OBJECTIVE:Standard treatment for low-grade upper tract urothelial carcinoma (LG UTUC) involving the renal pelvis and calyces is radical nephroureterectomy (RNU), or nephron-sparing...

INTRODUCTION AND OBJECTIVE:Urothelial cancer is less common, but may be associated with poorer outcomes in women than in men. The literature on gender-based differences in low-grade upper tract uro...

Rationale and Objectives To evaluate whether a computed tomography (CT)-based computerized decision-support system for muscle-invasive bladder cancer treatment response assessment (CDSS-T) can improve identification of patients who have responded completely to neoadjuvant chemotherapy. Materials and Methods Following Institutional Review Board approval, pre-chemotherapy and post-chemotherapy CT scans of 123 subjects with 157 muscle-invasive bladder cancer foci were collected retrospectively. CT data were analyzed with a CDSS-T that uses a combination of deep-learning convolutional neural network and radiomic features to distinguish muscle-invasive bladder cancers that have fully responded to neoadjuvant treatment from those that have not. Leave-one-case-out cross-validation was used to minimize overfitting. Five attending abdominal radiologists, four diagnostic radiology residents, two attending oncologists, and one attending urologist estimated the likelihood of pathologic T0 disease (complete response) by viewing paired pre/post-treatment CT scans placed side-by-side on an internally-developed graphical user interface. The observers provided an estimate without use of CDSS-T and then were permitted to revise their estimate after a CDSS-T-derived likelihood score was displayed. Observer estimates were analyzed with multi-reader, multi-case receiver operating characteristic methodology. The area under the curve (AUC) and the statistical significance of the difference were estimated. Results The mean AUCs for assessment of pathologic T0 disease were 0.80 for CDSS-T alone, 0.74 for physicians not using CDSS-T, and 0.77 for physicians using CDSS-T. The increase in the physicians' performance was statistically significant (P Conclusion CDSS-T improves physician performance for identifying complete response of muscle-invasive bladder cancer to neoadjuvant chemotherapy.

Five percent of urothelial carcinoma occurs in the upper urinary tract (UUT), a challenging location to biopsy. We aim to evaluate concordance between biopsy, cytology, and resection specimens in a large upper tract urothelial carcinoma (UTUC) cohort. One hundred seventeen UTUC resections with UUT biopsy and/or cytology specimens from 2000 to 2016 were retrieved; pathologic material was re-reviewed, evaluated for concordance, and correlated with clinical information. Fourteen percent of preoperative biopsies, including 8 from the renal pelvis and 6 from the ureter, lacked neoplastic diagnoses. Seventy-seven percent of diagnostic biopsies included subepithelial tissue; 11% demonstrated reclassification of grade and 30% demonstrated reclassification of invasion status. Twenty-six percent of renal pelvis UTUC and 36% of ureter UTUC were invasive only on resection. Of 18 UTUCs reclassified from noninvasive high-grade papillary urothelial carcinoma to invasive high-grade papillary urothelial carcinoma, 39% had prior radical cystectomy (versus 8% invasive UTUC and 11% noninvasive UTUC with concordant biopsies). Most high-grade UTUC (88%) and some low-grade UTUC (58%) resections had abnormal cytology results. Biopsy-resection pairs with concordant invasion status and pairs with discordant invasion status showed similar rates of recurrence (38% versus 38%) and metastasis (25% versus 27%). Fourteen percent of UUT biopsies lacked diagnostic neoplastic material. Grade concordance between biopsy and resection was high (89%), but 30% of cases showed invasion only on resection. Subepithelial tissue was less commonly present in ureter biopsies, particularly from the midureter or proximal ureter. UTUC in patients with prior cystectomy were more likely to show invasion on resection but not biopsy.

OBJECTIVE: To evaluate the effect of the minimally invasive approach on spending and perioperative outcomes for patients undergoing radical cystectomy for bladder cancer. In a randomized control trial conducted at high volume centers, robotic and open cystectomy were shown to have similar outcomes. However, because the majority of cystectomies are performed in low-volume centers, it is unknown whether these findings are broadly generalizable. MATERIALS AND METHODS: We identified Medicare patients who underwent radical cystectomy for bladder cancer between 2008 and 2015. We examined the length of stay, readmission rate, and 90-day spending after minimally invasive or open cystectomy. We used multiple regression to estimate the association between minimally invasive surgery and the outcomes, accounting for patient, hospital, and surgeon factors that may influence these outcomes. RESULTS: Of 4760 patients, 693 (14.6%) underwent minimally invasive cystectomy and 4,067 (85.4%) had an open approach. Minimally invasive cystectomy was associated with shorter length of stay (10.1 days v 11.9 days, P

Background The Paris System (TPS) introduced diagnostic criteria for urine cytology to improve reproducibility among pathologists. Thus far, most cytology studies have investigated application of TPS on lower urinary tract specimens. Also, it is unclear which cytologic features are most predictive of malignancy, particularly in the upper urinary tract. We evaluate concordance rates of preoperative upper urinary tract cytology specimens before and after application of TPS criteria with surgical resections and assess cytologic features associated with malignancy. Design 54 resections with high- and low-grade urothelial carcinoma (HGUC, LGUC) from 2000-2016 with available preoperative cytology (n = 61) were identified. Cytology was re-reviewed to evaluate cytologic features and provide diagnoses before and after TPS implementation. Results The most common cytologic features associated with HGUC were N:C ratios ≥0.7 (88%), hyperchromasia (83%), coarse chromatin distribution (67%), and nuclear pleomorphism in cell clusters (65%). Application of TPS criteria resulted in 10 diagnostic downgrades and 6 diagnostic upgrades. After TPS criteria were applied, the sensitivity of a positive diagnosis decreased from 29% to 19%. The morphologic feature most consistently associated with a downgrade from positive to suspicious was a lack of marked nuclear contour irregularities in atypical urothelial cells. Conclusion Using strict TPS criteria in upper urinary tract cytology specimens may decrease the frequency of positive diagnoses with a concurrent increase in suspicious diagnoses. These findings may indicate that different morphologic features, particularly markedly irregular nuclear contours, may have different predictive values for HGUC in upper urinary tract cytology specimens compared with those from the lower urinary tract.

Background Integrated molecular profiling has identified intrinsic expression-based bladder cancer molecular subtypes. Despite frequent histological diversity, robustness of subtypes in paired conventional (urothelial) and squamous components of the same bladder tumor has not been reported. Objective To assess the impact of histological heterogeneity on expression-based bladder cancer subtypes. Design, setting, and participants We performed clinically applicable, targeted DNA and/or RNA sequencing (multiplexed DNA and RNA sequencing [mxDNAseq and mxRNAseq, respectively]) on 112 formalin-fixed paraffin-embedded (FFPE) bladder cancer samples, including 12 cases with paired urothelial/squamous components and 21 bladder cancer cell lines. Outcome measurements and statistical analysis Unsupervised hierarchical and consensus clustering of target gene expression enabled derivation of basal/luminal molecular subtyping. Results and limitation Across 21 bladder cancer cell lines, our custom mxRNAseq panel was highly concordant with whole transcriptome sequencing, and assessed targets robustly determined expression-based basal/luminal subtypes from The Cancer Genome Atlas data (in silico) and internally sequenced FFPE tissues. Frequent deleterious TP53 (56%) and activating hotspot PIK3CA (30%) somatic mutations were seen across 69 high-quality tissue samples. Potentially targetable focal ERBB2 (6%) or EGFR (6%) amplifications were also identified, and a novel subgene copy-number detection approach is described. Combined DNA/RNA analysis showed that focally amplified samples exhibit outlier EGFR and ERBB2 expression distinct from subtype-intrinsic profiles. Critically, paired urothelial and squamous components showed divergent basal/luminal status in three of 12 cases (25%), despite identical putatively clonal prioritized somatic genomic alterations. Limitations include lack of profiled paired normal tissues for formal somatic alteration determination, and the need for formal analytical and clinical validation. Conclusions Our results support the feasibility of clinically relevant integrative bladder cancer profiling and challenge the intrinsic nature of expression subtypes in histologically diverse bladder cancers. Patient summary A targeted RNA sequencing assay is capable of assessing gene expression-based subtypes in individual components of clinical bladder cancer tissue specimens. Different histological components of the same tumor may yield divergent expression profiles, suggesting that expression-based subtypes should be interpreted with caution in heterogeneous cancers.

We evaluated whether a computerized decision support system for bladder cancer treatment response assessment (CDSS-T) can assist physicians from different institutions in identifying patients who have complete response after neoadjuvant chemotherapy. Pre- and post-chemotherapy CTU scans of 96 patients (114 pre- and post-treatment lesion pairs) were collected retrospectively. The pathological cancer stage after treatment was collected as the reference standard of response to treatment. 24% of the lesion pairs had T0 cancer stage (complete response) after chemotherapy. Our CDSST that combined DL-CNN and radiomics features was trained to distinguish between T0 and

Objectives To examine length of stay (LOS) and readmission rates for all minimally-invasive partial nephrectomy (MIPN) and MI radical nephrectomy (MIRN) performed for localized renal masses ≤7 cm in size (cT1RM) within 12 Michigan urology practices. Both RN and PN are commonly performed in treating cT1RM. Although technically more complex and associated with higher complication rates, Centers for Medicare & Medicaid Services considers MIPN an outpatient procedure and MIRN is inpatient. Methods We collected data for renal surgeries for cT1RM at MUSIC-KIDNEY practices between May 2017–February 2020. Data abstractors recorded clinical, radiographic, pathologic, surgical, and short-term follow-up data into the registry for cT1RM patients. Results Within MUSIC-KIDNEY, 807 patients underwent MI renal surgery at 12 practices. Median LOS for cT1RM patients after MIPN (n = 531, 66%) was 2 days and after MIRN (n = 276, 34%) was also 2 days. Among patients undergoing laparoscopic or robotic PN, 171 (32%), 230 (43%), and 130 (24%) stayed ≤1, 2, ≥3 days. Among patients undergoing laparoscopic or robotic RN, 81 (29%), 112 (41%), and 83 (30%) stayed ≤1, 2, ≥3 days. No significant difference was observed between MIPN and MIRN on LOS commensurate with outpatient surgery (≤1-day, OR = 0.97, P = 0.87). Conclusions Less than one-third of patients had a LOS ≤1-day and LOS was comparable for MIPN and MIRN. Centers for Medicare & Medicaid Services should be advised that MIPN is a more complex surgery than MIRN, most patients receiving a MIPN will require a ≥2-day hospital stay and it would be more appropriate to classify MIPN an inpatient procedure with MIRN.

PURPOSE: Utilization of neoadjuvant chemotherapy (NAC) for the management of muscle-invasive bladder cancer remains low. We sought to understand our practice of NAC use in order to design a quality improvement initiative geared towards optimizing medical oncology referral. MATERIALS AND METHODS: We identified 339 patients with ≥cT2 bladder cancer treated with radical cystectomy between 2012-2017 at our institution. We assessed the rate of referral to medical oncology, rate of NAC administration, as well as medical, patient and provider variables associated with NAC use. Bayesian logistic regression modeling identified variables associated with NAC use and chart review provided granular patient-level data. RESULTS: 85% (n=289) of patients were referred to medical oncology and 62.5% (n=212) received NAC. Renal insufficiency, hearing loss, and treating urologist were conclusively associated with lower odds of NAC use. 46 patients were not referred to medical oncology and 50% of these had medical contraindications to cisplatin cited as the reason for no referral. 38 patients met with medical oncology but did not receive NAC. 30 (79%) had comorbidities that impacted this decision with 15 (39%) ineligible based on impaired renal function. CONCLUSIONS: Despite the relatively high rates of medical oncology referral and NAC use in this cohort, there are still opportunities to improve the efficiency of this practice. Quality improvement initiatives could optimize the referral of patients with ≥T2 bladder cancer for consideration of cisplatin-based NAC and establish an important quality metric in the management of these patients.