Optimising postoperative care: Same-day discharge after transurethral resection of the prostate.

INTRODUCTION: This study aims to assess the feasibility and safety of same-day discharge after transurethral resection of the prostate. MATERIALS AND METHODS: Five years of records were retrospectively analysed. Length of stay categorised patients into Groups 1 (same-day discharge) and 2 (standard-length discharge). Logistic regression analysis was performed, controlling for clinicodemographic factors. Student's t-test compared continuous bladder irrigation and catheter dwell times. RESULTS: A total of 459 patients were identified between 2016 and 2021, 280 in Group 1 and 179 in Group 2, with median ages of 71.0 (interquartile range 36-92) and 72.0 (interquartile range 47-101) years (p = 0.067), respectively. Same-day discharge rates notably increased post-2018 (p = 0.025). Median prostate tissue resected in Group 2 was 7.1g (3.4-12.4g) and in Group 1 was 4.9g (2.4-10.2g; p = 0.034). While continuous bladder irrigation >1 hour was significantly lower in Group 1 than Group 2 (96.8% versus 27.4%; p = 0.0001), catheter dwell times were comparable (70.1 and 70.8 hours, respectively). Control-adjusted results showed a 40% reduction in emergency department representation odds for Group 1 compared with Group 2 (odds ratio = 0.60; 95% confidence interval = 0.37-0.99; p = 0.04). Length of stay was not significantly associated with hospital readmissions (p = 0.11). Continuous bladder irrigation for <1 hour in Group 1 was associated with a reduced emergency department representation (odds ratio = 0.43; 95% confidence interval = 0.197-0.980) but not readmission (odds ratio = 0.413; 95% confidence interval = 0.166-1.104). CONCLUSIONS: Same-day discharge post-transurethral resection of the prostate may be a viable and safe option for carefully selected patients.

Characterizing the Genomic Landscape of the Micropapillary Subtype of Urothelial Carcinoma of the Bladder Harboring Activating Extracellular Mutations of ERBB2.

The micropapillary subtype of urothelial carcinoma (MPUC) of the bladder is a very aggressive histological variant of urothelial bladder cancer (UBC). A high frequency of MPUC contains activating mutations in the extracellular domain (ECD) of ERBB2. We sought to further characterize ERBB2 ECD-mutated MPUC to identify additional genomic alterations that have been associated with tumor progression and therapeutic response. In total, 5,485 cases of archived formalin-fixed, paraffin-embedded UBC underwent comprehensive genomic profiling to identify ERBB2 ECD-mutated MPUC and evaluate the frequencies of genomic co-alterations. We identified 219 cases of UBC with ERBB2 ECD mutations (74% S310F and 26% S310Y), of which 63 (28.8%) were MPUC. Genomic analysis revealed that TERT, TP53, and ARID1A were the most common co-altered genes in ERBB2-mutant MPUC (82.5%, 58.7%, and 39.7%, respectively) and did not differ from ERBB2-mutant non-MPUC (86.5%, 51.9%, and 35.3%). The main differences between ERBB2 ECD-mutated MPUC compared with non-MPUC were KMT2D, RB1, and MTAP alterations. KMT2D and RB1 are tumor-suppressor genes. KMT2D frequency was significantly decreased in ERBB2 ECD-mutated MPUC (6.3%) in contrast to non-MPUC (27.6%; P < .001). RB1 mutations were more frequent in ERBB2 ECD-mutated MPUC (33.3%) than in non-MPUC (17.3%; P = .012). Finally, MTAP loss, an emerging biomarker for new synthetic lethality-based anticancer drugs, was less frequent in ERBB2 ECD-mutated MPUC (11.1%) than in non-MPUC (26.9%; P = .018). Characterizing the genomic landscape of MPUC may not only improve our fundamental knowledge about this aggressive morphological variant of UBC but also has the potential to identify possible prognostic and predictive biomarkers that may drive tumor progression and dictate treatment response to therapeutic approaches.

Evolution of the HIF targeted therapy in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, affecting hundreds of thousands of people worldwide and can affect people of any age. The pathogenesis of ccRCC is most commonly due to biallelic loss of the tumor suppressor gene VHL. VHL is the recognition subunit of an E3-ubiquitin-ligase-complex essential for degradation of the hypoxia-inducible factors (HIF) 1α and 2α. Dysfunctional degradation of HIF results in overaccumulation, which is particularly concerning with the HIF2α subunit. This leads to nuclear translocation, dimerization, and transactivation of numerous HIF-regulated genes responsible for cell survival and proliferation in ccRCC. FDA-approved therapies for RCC have primarily focused on targeting downstream effectors of HIF, then incorporated immunotherapeutics, and now, novel approaches are moving back to HIF with a focus on interfering with upstream targets. This review summarizes the role of HIF in the pathogenesis of ccRCC, novel HIF2α-focused therapeutic approaches, and opportunities for ccRCC treatment.

Clinical features of patients with MTAP-deleted bladder cancer.

Advanced urothelial carcinoma continues to have a dismal prognosis despite several new therapies in the last 5 years. FGFR2 and FGFR3 mutations and fusions, PD-L1 expression, tumor mutational burden, and microsatellite instability are established predictive biomarkers in advanced urothelial carcinoma. Novel biomarkers can optimize the sequencing of available treatments and improve outcomes. We describe herein the clinical and pathologic features of patients with an emerging subtype of bladder cancer characterized by deletion of the gene MTAP encoding the enzyme S-Methyl-5'-thioadenosine phosphatase, a potential biomarker of response to pemetrexed. We performed a retrospective analysis of 61 patients with advanced urothelial carcinoma for whom demographics, pathologic specimens, next generation sequencing, and clinical outcomes were available. We compared the frequency of histology variants, upper tract location, pathogenic gene variants, tumor response, progression free survival (PFS) and overall survival (OS) between patients with tumors harboring MTAP deletion (MTAP-del) and wild type tumors (MTAP-WT). A propensity score matching of 5 covariates (age, gender, presence of variant histology, prior surgery, and prior non-muscle invasive bladder cancer) was calculated to compensate for disparity when comparing survival in these subgroups. Non-supervised clustering analysis of differentially expressed genes between MTAP-del and MTAP-WT urothelial carcinomas was performed. MTAP-del occurred in 19 patients (31%). Tumors with MTAP-del were characterized by higher prevalence of squamous differentiation (47.4 vs 11.9%), bone metastases (52.6 vs 23.5%) and lower frequency of upper urinary tract location (5.2% vs 26.1%). Pathway gene set enrichment analysis showed that among the genes upregulated in the MTAP-del cohort, at least 5 were linked to keratinization (FOXN1, KRT33A/B, KRT84, RPTN) possibly contributing to the higher prevalence of squamous differentiation. Alterations in the PIK3 and MAPK pathways were more frequent when MTAP was deleted. There was a trend to inferior response to chemotherapy among MTAP-del tumors, but no difference in the response to immune checkpoint inhibitors or enfortumab. Median progression free survival after first line therapy (PFS1) was 5.5 months for patients with MTAP-WT and 4.5 months for patients with MTAP-del (HR = 1.30; 95% CI, 0.64-2.63; P = 0.471). There was no difference in the time from metastatic diagnosis to death (P = 0.6346). Median OS from diagnosis of localized or de novo metastatic disease was 16 months (range 1.5-60, IQR 8-26) for patients with MTAP-del and 24.5 months (range 3-156, IQR 16-48) for patients with MTAP-WT (P = 0.0218), suggesting that time to progression to metastatic disease is shorter in MTAP-del patients. Covariates did not impact significantly overall survival on propensity score matching. In conclusion, MTAP -del occurs in approximately 30% of patients with advanced urothelial carcinoma and defines a subgroup of patients with aggressive features, such as squamous differentiation, frequent bone metastases, poor response to chemotherapy, and shorter time to progression to metastatic disease.

Targeting Bladder Urothelial Carcinoma with pHLIP-ICG and Inhibition of Urothelial Cancer Cell Proliferation by pHLIP-amanitin.

Acidity is a useful biomarker for the targeting of metabolically active-cells in tumors. pH Low Insertion Peptides (pHLIPs) sense the pH at the surfaces of tumor cells and can facilitate intracellular delivery of cell-permeable and cell-impermeable cargo molecules. In this study we have shown the targeting of malignant lesions in human bladders by fluorescent pHLIP agents, intracellular delivery of amanitin toxin by pHLIP for the inhibition of urothelial cancer cell proliferation, and enhanced potency of pHLIP-amanitin for cancer cells with 17p loss, a mutation frequently present in urothelial cancers. Twenty-eight ex-vivo bladder specimens, from patients undergoing robotic assisted laparoscopic radical cystectomy for bladder cancer, were treated via intravesical incubation for 15-60 minutes with pHLIP conjugated to indocyanine green (ICG) or IR-800 near infrared fluorescent (NIRF) dyes at concentrations of 4-8 µM. White light cystoscopy identified 47/58 (81%) and NIRF pHLIP cystoscopy identified 57/58 (98.3%) of malignant lesions of different subtypes and stages selected for histopathological processing. pHLIP NIRF imaging improved diagnosis by 17.3% (p < 0.05). All carcinoma-in-situ cases missed by white light cystoscopy were targeted by pHLIP agents and were diagnosed by NIRF imaging. We also investigated the interactions of pHLIP-amanitin with urothelial cancer cells of different grades. pHLIP-amanitin produced concentration- and pH-dependent inhibition of the proliferation of urothelial cancer cells treated for 2 hrs at concentrations up to 4 µM. A 3-4x enhanced cytotoxicity of pHLIP-amanitin was observed for cells with a 17p loss after 2 hrs of treatment at pH6. Potentially, pHLIP technology may improve the management of urothelial cancers, including imaging of malignant lesions using pHLIP-ICG for diagnosis and surgery, and the use of pHLIP-amanitin for treatment of superficial bladder cancers via intravesical instillation.

Intravesical docetaxel for high-risk non-muscle invasive bladder cancer after Bacillus Calmette-Guérin failure.

BACKGROUND: There are limited bladder-preserving therapeutic options for patients with high-risk non-muscle invasive bladder cancer (NMIBC) after failed Bacillus Calmette-Guérin (BCG) therapy. Salvage intravesical docetaxel therapy was described in 2006 but has not been validated outside of the original institution. In this study, we presented the first external report on the oncologic outcomes of intravesical docetaxel. MATERIALS AND METHODS: We identified 13 patients with high-risk NMIBC treated with ≥1 course of intravesical BCG who received salvage intravesical docetaxel. Recurrence-free survival (RFS) was estimated using the Kaplan-Meier method. Associations of clinicopathologic features with RFS were evaluated using Cox regression. RESULTS: Median age was 75.2 years, and 46.2% of patients were male. Of the patients 92.3% had a prior diagnosis of high-grade T1 disease, 38.5% had a prior diagnosis of carcinoma in situ, and 46.2% had received ≥2 courses of BCG. Only 1 (7.7%) patient experienced docetaxel-related toxicity. Nine (69.2%) patients had a complete response at initial post-docetaxel cystoscopy. During a median follow-up of 12.0 (interquartile range 5.0-18.1) months, a total of 7 (53.8%) patients developed recurrence. Median time to recurrence was 10.1 (interquartile range 4.8-11.6) months. Estimated RFS at 6-, 12-, 18-, and 24-months was 75%, 50%, 50%, and 25%. Three (23.1%) patients ultimately underwent cystectomy. On univariable analysis, multiple courses of induction BCG were associated with decreased RFS, although this did not reach statistical significance (hazard ratio 4.69, p = 0.08). CONCLUSIONS: In this first external validation study, intravesical docetaxel was associated with excellent response rates and intermediate-term RFS among patients with high-risk NMIBC after failed BCG therapy.

Direct Oral Anticoagulants for Venous Thromboembolism Prophylaxis Following Robot-assisted Radical Cystectomy: A Retrospective Feasibility Study at a Single Academic Medical Center.

OBJECTIVES: To evaluate the use of direct oral anticoagulants following radical cystectomy for venous thromboembolism prophylaxis. We compared the experience of those who received venous thromboembolism prophylaxis following a robot-assisted radical cystectomy with either a direct oral anticoagulant or enoxaparin. METHODS: Medical records of 66 patients who underwent robot-assisted radical cystectomy between July 2017 and May 2020 at a single academic institution were reviewed retrospectively. Patients received extended prophylaxis with either a direct oral anticoagulant or enoxaparin before or following surgical discharge. Venous thromboembolic events and complications resulting in emergency department visits and readmissions were reviewed over a 90-day postoperative period. RESULTS: A total of 4 venous thromboembolic events within 90 days of surgery were observed. Among patients taking enoxaparin, 5% (2/37) developed a deep vein thrombosis and 3% (1/37) developed a pulmonary embolism. Among patients taking direct oral anticoagulants, 3% (1/29) developed a deep vein thrombosis. Zero patients in the enoxaparin group and 3% (1/29) of patients in the direct oral anticoagulant group experienced bleeding that required an emergency department visit. CONCLUSION: Direct oral anticoagulants performed comparably to enoxaparin in this feasibility study following robot-assisted radical cystectomy in 66 patients. No significant differences in the number of venous thromboembolisms or bleeding complications were observed. These data encourage future studies and support the prospect of direct oral anticoagulants as a potentially suitable oral alternative to injectable low molecular weight heparins for venous thromboembolism prophylaxis following radical cystectomy.

p53 Expression, Programmed Death Ligand 1, and Risk Factors in Urinary Tract Small Cell Carcinoma.

Introduction: Small cell carcinoma of the urinary tract (SCCUT) is a rare finding with poor clinical course. This study sheds light on the molecular subtype and identifies risk factors in patients diagnosed with SCCUT. Methods: Immunohistochemical expression of immunotherapy target programmed death ligand 1 (PD-L1) and luminal (GATA3), basal (p63), and p53 markers are assessed in patients diagnosed with SCCUT. Univariate analysis identified risk factors. Overall survival (OS) is computed using the Kaplan-Meier method. Results: Tissue was available for 70.2% (33/47). All showed a high PD-L1 expression phenotype. p53 is seen in 93.9% (31/33), mostly as overexpression, GATA3 in 45.5% (15/33), and p63 in 57.6% (19/33). For the entire cohort (n = 47), 1-year survival was 59.6%, and the median OS was 17 months. Univariate analysis shows that chemotherapy [hazard ratio (HR) = 0.29, 95% confidence interval (CI) = 0.14-0.61, p = 0.001], radical surgery (HR = 0.37, 95% CI = 0.18-0.76, p = 0.007), and diagnosis of non-pure SCCUT (HR = 0.44, 95% CI = 0.22-0.86, p = 0.02) are favorable prognostic features. Metastasis had negative associations with survival (HR = 2.1, 95% CI = 1.1-4.2, p = 0.03). Conclusions: In this series, pure and mixed SCCUT are characterized by p53 overexpression and a high PD-L1 phenotype. Histology of non-pure SCCUT is a positive prognosticator, and radical cystectomy or chemotherapy can improve OS. These findings demonstrate that SCCUT may be eligible for PD-L1 immunotherapy.

Development of a Deep Learning Algorithm for the Histopathologic Diagnosis and Gleason Grading of Prostate Cancer Biopsies: A Pilot Study.

BACKGROUND: The pathologic diagnosis and Gleason grading of prostate cancer are time-consuming, error-prone, and subject to interobserver variability. Machine learning offers opportunities to improve the diagnosis, risk stratification, and prognostication of prostate cancer. OBJECTIVE: To develop a state-of-the-art deep learning algorithm for the histopathologic diagnosis and Gleason grading of prostate biopsy specimens. DESIGN, SETTING, AND PARTICIPANTS: A total of 85 prostate core biopsy specimens from 25 patients were digitized at 20× magnification and annotated for Gleason 3, 4, and 5 prostate adenocarcinoma by a urologic pathologist. From these virtual slides, we sampled 14803 image patches of 256×256 pixels, approximately balanced for malignancy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We trained and tested a deep residual convolutional neural network to classify each patch at two levels: (1) coarse (benign vs malignant) and (2) fine (benign vs Gleason 3 vs 4 vs 5). Model performance was evaluated using fivefold cross-validation. Randomization tests were used for hypothesis testing of model performance versus chance. RESULTS AND LIMITATIONS: The model demonstrated 91.5% accuracy (p<0.001) at coarse-level classification of image patches as benign versus malignant (0.93 sensitivity, 0.90 specificity, and 0.95 average precision). The model demonstrated 85.4% accuracy (p<0.001) at fine-level classification of image patches as benign versus Gleason 3 versus Gleason 4 versus Gleason 5 (0.83 sensitivity, 0.94 specificity, and 0.83 average precision), with the greatest number of confusions in distinguishing between Gleason 3 and 4, and between Gleason 4 and 5. Limitations include the small sample size and the need for external validation. CONCLUSIONS: In this study, a deep learning-based computer vision algorithm demonstrated excellent performance for the histopathologic diagnosis and Gleason grading of prostate cancer. PATIENT SUMMARY: We developed a deep learning algorithm that demonstrated excellent performance for the diagnosis and grading of prostate cancer.

Personal Protective Equipment for Common Urologic Procedures Before and During the United States COVID-19 Pandemic: A Single Institution Study.

OBJECTIVE: To evaluate the personal protective equipment (PPE) utilized in common urologic procedures before and during the COVID-19 outbreak in the United States. As elective urologic procedures are being reduced to conserve resources, we sought to quantify the PPE used per case to determine the impact on potentially limited resources needed for protecting healthcare providers treating COVID-19 patients. METHODS: An IRB approved retrospective analysis of all urologic procedures in March 2019 and March 2020 was performed. Additionally, all urologic procedures performed by vascular interventional radiology (VIR) in May 2019 and March 2020 were included in the analysis. Case length, surgical and operating room staff present and number of articles of PPE were quantified. Articles of PPE were defined as surgical bonnet/hat and mask, and disposable or reusable gown with 1 pair of surgical gloves. RESULTS: Four hundred and thirty-seven urologic and VIR procedures were included in the analysis. The mean PPE per case varied significantly between endoscopic and robotic categories. Robotic assisted laparoscopic cystectomy required the most hats and masks (14.5 per case in March 2019) whereas percutaneous nephrostomy tube placement by VIR required the fewest (3.1 in May 2019 and March 2020). CONCLUSION: PPE consumption varied significantly across urologic procedures. Robotic-assisted cases require the most PPE and percutaneous nephrostomy placement by VIR requires the fewest. While PPE shortages are currently being addressed national and internationally, our results provide a baseline benchmark for articles of PPE required should another pandemic or global disaster requiring careful attention to resource allocation occur in the future.

Emulating Target Clinical Trials of Radical Nephrectomy With or Without Lymph Node Dissection for Renal Cell Carcinoma.

OBJECTIVE: To emulate two target clinical trials of radical nephrectomy (RN) with lymph node dissection (LND) vs radical nephrectomy alone. METHODS: Using the National Cancer Database, we separately emulated an index trial of patients with cT1-3cN0cM0 renal cell carcinoma (RCC), designed to resemble EORTC 30881 ("index trial emulation"), and a hypothetical trial of patients at increased risk for lymph node metastases with cT1-4cN0-1cM0 RCC ("high-risk trial emulation"). A propensity score for LND was estimated using preoperative features (Model 1) or preoperative and pathologic features (Model 2). The associations of LND with overall survival (OS) were estimated using Cox regression with stabilized inverse probability weights. RESULTS: A total of 67,388 patients were included in the index trial emulation. Median follow-up was 49.2 (interquartile range 27.2-74.3) months. LND was not associated with improved OS when adjusting using either Model 1 (hazard ratio [HR] 1.26; 95% confidence interval [CI] 1.20-1.33; P <.0001) or Model 2 (HR 1.13; 95% CI 1.07-1.20; P <.0001). A total of 69,477 patients were included in the high-risk trial emulation. Median follow-up was 48.6 (interquartile range 26.6-73.8) months. LND was not associated with improved OS when adjusting using either Model 1 (HR 1.24; 95% CI 1.18-1.30; P <.0001) or Model 2 (HR 1.09; 95% CI 1.04-1.16; P = .001). In sensitivity analyses, LND was not associated with improved OS across cN stage, pT stage, tumor grade, histologic subtype, or probability of pN1 disease. CONCLUSION: In observational analyses, that emulate target trials representing EORTC 30881 and a trial of LND in high-risk RCC, LND was not associated with improved OS.

SpaceOAR Hydrogel Present 32 Weeks After Instillation Prevents Neobladder Creation in Patient Undergoing Robot-Assisted Laparoscopic Radical Cystoprostatectomy.

Background: The injection of hydrogel in between the anterior rectal wall and prostate protects the rectum from the radiation field in men undergoing radiotherapy for prostate cancer. Multicenter prospective trials have demonstrated safety of the material, and that liquefication and reabsorption of the material occur roughly 12 weeks after injection. Other studies have noted the presence of the hydrogel up to 24 weeks after injection and documented significant complications with its use. In this study we discuss a patient in whom hydrogel was discovered in the anterior rectal wall who was undergoing radical cystoprostatectomy 32 weeks after injection, and how this precluded creation of a neobladder. Case Presentation: A 64-year-old Caucasian man with a history of diabetes mellitus and hypertension was diagnosed with unfavorable intermediate risk prostate cancer. He underwent injection of hydrogel followed by radiotherapy. He subsequently developed hematuria and carcinoma in situ and high grade T1 nonmuscle invasive bladder cancer were diagnosed. Thirty-two weeks later, he underwent robot-assisted radical cystoprostatectomy. The patient was originally planned for neobladder creation but intraoperative findings of persistent hydrogel in between rectum and prostate precluded this reconstruction and necessitated construction of an ileal conduit. Conclusion: Urologists should be aware of the fact that SpaceOAR hydrogel can persist beyond the expected 12- to 24-week dissolution period. In a patient who requires a radical cystectomy, the persistent presence of that gel may preclude the creation of a neobladder. Preoperative imaging to identify persistence vs dissolution of the gel would facilitate better preoperative patient counseling.

Ex-vivo Imaging of Upper Tract Urothelial Carcinoma Using Novel pH Low Insertion Peptide (Variant 3), a Molecular Imaging Probe.

OBJECTIVE: To improve visualization of upper tract urothelial carcinomas. Previous studies using the novel pH low insertion peptide (pHLIP) variant 3 (Var3) conjugated to indocyanine green (ICG) have demonstrated high sensitivity and specificity for imaging of bladder urothelial carcinoma. Here, we describe a novel approach for the imaging of upper tract urothelial carcinomas using ICG-Var3 pHLIP. METHODS: Twelve ex-vivo upper urinary tract specimens were irrigated with ICG-Var 3 pHLIP for 15 minutes and then examined using a white light laparoscopic camera followed by near infrared fluorescent (NIRF) imaging using a Stryker 1588 AIM imaging system. Standard histopathologic evaluation was performed and findings were correlated with white light and ICG-Var3 NIRF imaging. One patient who underwent radical nephrectomy for renal cell carcinoma was used as a negative control. RESULTS: Nineteen lesions were identified on histopathologic evaluation in 10 patients, including 82% high-grade urothelial carcinoma and 18% low-grade urothelial carcinoma. Nineteen (100%) malignant lesions were identified using NIRF imaging, while 15 (78.9%) lesions were identified using conventional white light examination. The sensitivity of ICG-Var3 pHLIP NIRF imaging was 100% compared to 78.9% white light examination. Both modalities are 100% specific. Benign collecting systems and ureters did not show uptake of the pHLIP construct. CONCLUSION: In this feasibility study, the ICG-Var3 pHLIP imaging agent demonstrated superior diagnostic performance compared to conventional white light examination. While additional studies are required for validation and in-vivo translation, pHLIP-based imaging represents a promising tool to improve the evaluation and management of upper tract urothelial carcinoma.

Outcomes of upper tract urothelial carcinoma with isolated lymph node involvement following surgical resection: implications for multi-modal management.

BACKGROUND: There are limited data on the oncologic outcomes of upper tract urothelial carcinoma with isolated lymph node (LN) involvement (pN+ M0) following surgical resection. We examined pN+ M0 UTUC in a large, nationwide oncology dataset to characterize its natural history, describe trends in utilization of perioperative chemotherapy, and identify clinicopathologic features associated with survival. METHODS: We identified 794 patients aged 18-89 years who underwent radical nephroureterectomy with lymph node dissection for pN+ M0 UTUC from 2006 to 2013 in the National Cancer Database. The associations of clinicopathologic features with overall survival (OS) were evaluated using Cox regression models, and a simplified risk score was created. RESULTS: Median follow-up among survivors was 39.5 months, during which time 555 (70%) patients died. Over the study period, neoadjuvant chemotherapy utilization increased from 6.7 to 14.2% (p = 0.002), while adjuvant chemotherapy utilization remained stable (42.7 to 44.3%; p = 0.86). One-, 5-, and 8-year OS rates were 63.7%, 24.2%, and 18.7%, respectively. On multivariable analysis, older age, larger tumor size, higher pT stage, positive surgical margins, number of positive LNs, and non-receipt of adjuvant chemotherapy were independently associated with worse OS. A simplified risk score consisting of age, tumor size, pT stage, number of positive LNs, and margin status was created with predicted 5-year OS ranging from 12 to 44%. CONCLUSIONS: In this large, contemporary cohort, pN+ M0 UTUC was associated with a 5-year OS of only 24%. Clinicopathologic predictors of survival after surgical resection may improve risk-stratification, counseling, and selection of patients for multimodal management.

Clinically node-positive (cN+) urothelial carcinoma of the bladder treated with chemotherapy and radical cystectomy: Clinical outcomes and development of a postoperative risk stratification model.

INTRODUCTION AND OBJECTIVE: Although node-positive (cN+) bladder cancer is considered Stage IV disease, a subset of patients is treated with chemotherapy and consolidative radical cystectomy (RC). We examined the clinical outcomes of such patients and developed a risk prediction model to facilitate risk-stratification and management. METHODS: We identified adult patients with cTany cN1-3 M0 urothelial carcinoma of the bladder treated with chemotherapy followed by RC from 2006 to 2013 in the NCDB. The associations of clinicopathologic features with overall survival (OS) were evaluated using Cox regression, and a simplified risk score was developed. RESULTS: A total of 491 patients received chemotherapy followed by RC. Median number of lymph nodes removed was 16 (interquartile range 9-25). At RC, 10% of patients were ypT0, and 35% were ypN0. Over a median follow-up of 18.7 months, 160 patients died of any cause. 1-, 5-, and 8-year OS were 69%, 34%, and 29%, respectively. On multivariable analysis, pT stage (hazard ratio [HR] 2.18; P = 0.003 for pT3, HR 2.65; P < 0.001 for pT4 vs.

The natural history of renal cell carcinoma with isolated lymph node metastases following surgical resection from 2006 to 2013.

INTRODUCTION: Renal cell carcinoma (RCC) with isolated lymph node (LN) involvement (pN1 M0 RCC) is a rare clinical entity associated with a poor prognosis. Prior studies comprised cohorts treated predominantly prior to the introduction of targeted systemic therapy. We therefore examined the natural history of pN1M0 RCC following surgical resection in a contemporary cohort, and evaluated clinicopathologic features associated with survival. PATIENTS AND METHODS: We identified patients aged 18 to 89 years who underwent radical or partial nephrectomy with LN dissection for pN1 M0 RCC from 2006 to 2013 in the National Cancer Database. The associations of clinicopathologic features with overall survival (OS) were evaluated using Cox regression models, and a simplified risk score was developed. RESULTS: A total of 2,679 patients were found to have pN1 M0 RCC after nephrectomy. Median follow-up was 19.2 (interquartile range 8.2, 39.8) months, during which time 1,782 patients died. One-, 5-, and 8-year OS rates were 68%, 28%, and 19%, respectively. On multivariable analysis, older age (HR 1.50; P< 0.001 for ≥70 vs, 18-<50 years old), rural location (HR 1.49; P= 0.01), larger tumor size (HR 1.29; P= 0.01 for 5-<10 cm; HR 1.34; P= 0.01 for 10-<15 cm; HR 1.43; P= 0.01 for ≥15 cm vs. <5 cm); higher pT stage (HR 1.25; P= 0.04 for pT3; HR 2.41; P< 0.001 for pT4 vs. pT1), positive surgical margins (HR 1.55; P< 0.001), number of positive LNs (HR 1.18; P= 0.01 for 2-3; HR 1.37; P< 0.001 for >3 vs. 1), and nonclear cell histologic subtype (HR 1.32; P< 0.001) were independently associated with decreased OS. A simplified risk score was developed based on the multivariable results. Five-year OS was 49%, 28%, 22%, and 10% for patients with scores of <4, 4 to 6, 7 to 9, and >9, respectively. CONCLUSIONS: In this large, contemporary cohort, pN1 M0 RCC was associated with a poor prognosis, with 5-year survival less than 30%. A simplified risk score was developed to facilitate postoperative risk-stratification and selection of patients for consideration of adjuvant therapy and clinical trial enrollment.