Local and Regional Recurrences of Clinically Localized Renal Cell Carcinoma after Nephrectomy: A 15 Year Institutional Experience with Prognostic Features and Oncologic Outcomes.

OBJECTIVE: To evaluate outcomes for patients with local recurrence (LR) of clinically localized renal cell carcinoma (RCC) without concurrent systemic metastasis from our institution, an event that occurs rarely (1%-3%) after surgery. LR may be a harbinger of poor outcomes, and the best management of these patients is unclear. MATERIALS/METHODS: We retrospectively reviewed patients surgically treated for clinically localized RCC (cT1-2N0M0) with subsequent LR (in the partial or radical nephrectomy bed) and/or regional recurrence (RR; in the abdomen distant from the direct site of surgery) without concurrent metastasis from our institutional database (2004-2018). Comparative and survival analyses were performed. RESULTS: Out of 3038 total patients, 1895 had clinically localized RCC, with 30 patients (1.6%) having isolated LR/RR. Median time to recurrence was 26.5 months (IQR:16-35). Of 26 patients treated with local therapy, 14 (53.8%) recurred over a median follow-up time of 29.5 months (IQR:12-45). The 1-year and 2-year secondary recurrence-free survival rates are 60.7% and 49.7%, respectively. Two or more sites of locoregional recurrence significantly predicted secondary recurrence/metastasis after local therapy for local recurrence (hazard ratio: 2.22, P= .04). CONCLUSION: Our results suggest local therapy is appropriate for select patients with LR/RR, with almost 50% of patients undergoing a second local therapy remaining alive with "local cure" and no secondary recurrence. The number of sites of recurrence can be used to better select patients that will benefit from local therapy or systemic/combination therapy. This work provides a framework onto which further studies regarding local therapy and locoregional recurrence of RCC can be performed.

Circulating Tumor Cell and Circulating Tumor DNA Assays Reveal Complementary Information for Patients with Metastatic Urothelial Cancer.

Despite considerable advances in the management of urothelial carcinoma (UC), better risk stratification and enhanced detection of minimal residual disease are still urgent priorities to prolong survival while avoiding the morbidity of overtreatment. Circulating tumor cells and DNA (CTCs, ctDNA) are two biologically distinct "liquid biopsies" that may potentially address this need, although they have been understudied in UC to date and their relative utility is unknown. To this end, matched CTC and ctDNA samples were collected for a head-to-head comparison in a pilot study of 16 patients with metastatic UC. CTCs were defined as cytokeratin- and/or EpCAM-positive using the RareCyte direct imaging platform. ctDNA was assayed using the PlasmaSelect64 probe-capture assay. 75% of patients had detectable CTCs, and 73% had detectable somatic mutations, with no correlation between CTC count and ctDNA. 91% of patients had tissue confirmation of at least one plasma mutation and, importantly, several clinically actionable mutations were detected in plasma that were not found in the matching tumor. A ctDNA fraction of >2% was significantly associated with worse overall survival (p=0.039) whereas CTC detection was not (p=0.46). Notably, using a predefined gene panel for ctDNA detection had a high but not complete detection rate in metastatic UC, similar to what has been described for a custom tissue-personalized assay approach. In sum, both liquid biopsies show promise in UC and deserve further investigation. PATIENT SUMMARY: New "liquid biopsy" blood tests are emerging for urothelial cancer aimed at early detection and avoiding overtreatment. Our results suggest that two such tests provide complementary information: circulating tumor cells may be best for studying the biological features of a person's cancer, whereas circulating tumor DNA may be better for early detection.

Understanding Psychosocial and Sexual Health Concerns Among Women With Bladder Cancer Undergoing Radical Cystectomy.

OBJECTIVE: To better understand the physical and psychosocial components of female sexual dysfunction (FSD) among women undergoing radical cystectomy (RC) for bladder cancer (BCa). METHODS: We conducted semistructured individual interviews and a focus group with pre- and post-RC female patients and their partners regarding the impact of RC on sexual health and psychosocial wellbeing. Themes were inductively identified by 2 independent coders and subsequently organized into themes and subthemes using qualitative description and constant comparison. RESULTS: In the preoperative cohort, 6 women and 1 partner participated (50% contact rate, 75% participation rate). In the postoperative cohort, 16 women and 2 partners participated (61% contact rate, 64% participation rate). Major themes that emerged in interviews with both cohorts included concerns about changes to body image, the psychological impact of BCa diagnosis and treatment, concerns about the impact of RC on sexual function, and inadequacies in provider-led sexual health counseling. Participants varied in the importance they placed on sexual function, with factors such as age, relationship status, and oncologic concerns impacting prioritization, although both younger and older patients expressed a desire to retain the option of sexual function. CONCLUSION: Female patients with BCa undergoing RC experience changes in body image, psychological distress, physical disruptions in sexual function, and inadequacies in sexual health counseling and education. Future efforts should be directed towards improving sexual health counseling and psychosocial support resources for women with BCa.

Clinical Restaging and Tumor Sequencing are Inaccurate Indicators of Response to Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer.

BACKGROUND: Standard of care for patients with muscle-invasive bladder cancer (MIBC) includes neoadjuvant cisplatin-based chemotherapy (NAC) followed by consolidative therapy with either chemoradiation or radical cystectomy (RC). Some patients experience robust pathologic responses to NAC, and these have been reported to associate with somatic mutations in specific gene pathways including DNA damage response genes. OBJECTIVE: To evaluate the ability of post-NAC clinical restaging, with or without tumor sequencing, to predict final RC pathologic staging. DESIGN, SETTING, AND PARTICIPANTS: We reviewed our institutional review board-approved institutional database to identify patients with MIBC who underwent NAC followed by RC from 2003 to 2016. Following NAC prior to RC, cystoscopy was performed routinely, with resection of residual visible tumor and/or tumor base (transurethral resection [TUR]). For patients with pre-NAC tumor tissue available, tumor sequencing was performed. Outcome measurements and statistical analysis: Clinical restaging and tumor sequencing were evaluated for their ability to predict the final pathologic stage accurately at RC using chi-square or Fisher's exact test. RESULTS AND LIMITATIONS: A total of 114 patients underwent restaging TUR following NAC and prior to RC. The diagnostic accuracy of post-NAC clinical restaging including TUR was poor, with 32% of patients being downstaged falsely when compared with their final RC pathology. Forty-nine patients had sequencing of pre-NAC tumor tissue, of whom 32 showed at least one mutation of interest. However, NAC responses and rates of false downstaging did not differ significantly according to tumor mutation status. CONCLUSIONS: This study highlights the inaccuracy of post-NAC clinical restaging TUR with or without adjunctive tumor mutation analysis, to assess pathologic residual disease accurately. Caution must be taken when performing post-NAC restaging, especially when considering conservative management strategies such as active surveillance on this basis. Patient summary: Several groups are evaluating whether certain patients, whose bladder cancer responds well to upfront chemotherapy, may be able to forego cystectomy safely. We demonstrate that currently available staging tools and tumor DNA sequencing cannot identify such patients reliably and accurately.

High-dimensional Cytometry (ExCYT) and Mass Spectrometry of Myeloid Infiltrate in Clinically Localized Clear Cell Renal Cell Carcinoma Identifies Novel Potential Myeloid Targets for Immunotherapy.

Renal Cell Carcinoma (RCC) is one of the most commonly diagnosed cancers worldwide with research efforts dramatically improving understanding of the biology of the disease. To investigate the role of the immune system in treatment-naïve clear cell Renal Cell Carcinoma (ccRCC), we interrogated the immune infiltrate in patient-matched ccRCC tumor samples, benign normal adjacent tissue (NAT) and peripheral blood mononuclear cells (PBMCs isolated from whole blood, focusing our attention on the myeloid cell infiltrate. Using flow cytometric, MS, and ExCYT analysis, we discovered unique myeloid populations in PBMCs across patient samples. Furthermore, normal adjacent tissues and ccRCC tissues contained numerous myeloid populations with a unique signature for both tissues. Enrichment of the immune cell (CD45+) fraction and subsequent gene expression analysis revealed a number of myeloid-related genes that were differentially expressed. These data provide evidence, for the first time, of an immunosuppressive and pro-tumorigenic role of myeloid cells in early, clinically localized ccRCC. The identification of a number of immune proteins for therapeutic targeting provides a rationale for investigation into the potential efficacy of earlier intervention with single-agent or combination immunotherapy for ccRCC.

Effect of Pharmacologic Prophylaxis on Venous Thromboembolism After Radical Prostatectomy: The PREVENTER Randomized Clinical Trial.

BACKGROUND: Direct high-quality evidence is lacking evaluating perioperative pharmacologic prophylaxis (PP) after radical prostatectomy (RP) to prevent venous thromboembolism (VTE) leading to significant practice variation. OBJECTIVE: To study the impact of in-hospital PP on symptomatic VTE incidence and adverse events after RP at 30 d, with the secondary objective of evaluating overall VTE in a screening subcohort. DESIGN, SETTING, AND PARTICIPANTS: A prospective, phase 4, single-center, randomized trial of men with prostate cancer undergoing open or robotic-assisted laparoscopic RP was conducted (July 2017-November 2018). INTERVENTION: PP (subcutaneous heparin) plus routine care versus routine care alone. The screening subcohort was offered lower extremity duplex ultrasound at 30 d. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: The primary efficacy outcome was symptomatic VTE incidence (pulmonary embolism [PE] or deep venous thrombosis [DVT]). Primary safety outcomes included the incidence of symptomatic lymphocele, hematoma, or bleeding after surgery. Secondary outcomes were overall VTE, estimated blood loss, total surgical drain output, complications, and surveillance imaging bias. Fisher's exact test and modified Poisson regression were performed. RESULTS AND LIMITATIONS: A total of 501 patients (75% robotic) were randomized and >99% (500/501) completed follow-up. At second interim analysis (N = 445), the symptomatic VTE rate was 2.3% (four PE + DVT and one DVT) for routine care versus 0.9% (one PE + DVT and one DVT) for PP (relative risk 0.40 [95% confidence interval 0.08-2.03], p = 0.3) meeting a futility threshold for early stopping. In the screening subcohort, the overall VTE rate was 3.3% versus 2.4% (p = 0.7). Results were similar at the final analysis (symptomatic VTE: 2.0% vs 0.8%, p = 0.3; overall VTE: 2.9% vs 2.8%, p = 1). No differences were observed in safety or secondary outcomes. All VTE events (seven symptomatic and three asymptomatic) occurred in patients undergoing pelvic lymph node dissection. CONCLUSIONS: This study was not able to demonstrate a statistically significant reduction in symptomatic VTE associated with PP. There was no increase in the development of symptomatic lymphoceles, bleeding, or other adverse events. Given that the event rate was lower than powered for, further research is needed among high-risk patients (Caprini score ≥8) or patients receiving pelvic lymph node dissection. PATIENT SUMMARY: In this report, we randomized patients undergoing radical prostatectomy to perioperative pharmacologic prophylaxis or routine care alone. We found that pharmacologic prophylaxis did not reduce postoperative symptomatic venous thromboembolism significantly for men at routine risk. Importantly, pharmacologic prophylaxis did not increase adverse events, such as formation of lymphoceles or bleeding, and can safely be implemented when indicated for patients with risk factors undergoing radical prostatectomy.

Transcriptional profiling of tumor associated macrophages in human renal cell carcinoma reveals significant heterogeneity and opportunity for immunomodulation.

Among the more notable immunotherapies are checkpoint inhibitors, which prevent suppressive signaling on T cells, thereby (re)activating them to kill tumor cells. Despite remarkable treatment responses to immune checkpoint blockade, with a subset of patients achieving complete responses, a large population have little-to-no response, dictating the necessity of further research in this field. Myeloid derived cells heavily infiltrate the tumor microenvironment (TME) of many cancers and are believed to have a number of potent anti-inflammatory effects. Here we use primary non-metastatic renal cell carcinoma to interrogate the gene expression profiles of M2-tumor associated macrophages (M2-TAMs). We performed Fluorescent Activated Cell (FACS) sorting on monocytes from the peripheral blood and tumors of fresh clear cell renal cell carcinoma (ccRCC) samples obtained after patients underwent a partial (7 patients-87.5%) or radical (1 patient-12.5%) nephrectomy. We then utilized NanoString gene expression profiling to show that TAMs express a heterogeneous transcriptional profile that does not cleanly fit into the traditional M1-M2 TAM paradigm. We identified expression of M1 associated costimulatory molecules, a multitude of diverse chemokines, canonical M2 associated molecules, as well as factors involved in the Complement system and checkpoint receptors. Our data are in agreement with other published literature investigating TAMs in various non-ccRCC TMEs, and support the growing literature concerning expression of Complement factors and checkpoint receptors on TAMs.

Stage-specific conditional survival in renal cell carcinoma after nephrectomy.

OBJECTIVES: Conditional survival (CS) represents the probability that a cancer patient will survive some additional number of years, given that the patient has already survived for a certain period of time. CS estimates, therefore, serve as better measures of survival probability compared to standard estimates as they incorporate patient survivorship. Stage-specific CS has not been widely investigated in the context of renal cell carcinoma (RCC) after nephrectomy. We aimed to examine this phenomenon. MATERIALS AND METHODS: We analyzed retrospective data on a population-based cohort of 87,225 surgically-treated RCC patients extracted from the Surveillance, Epidemiology, and End Results database (2004-2015) and on a similar validation cohort of 1,642 patients from our institution (1995-2015). 5-year cancer-specific CS estimates stratified by stage were obtained using the Kaplan-Meier method. Multivariable Cox regression analyses were performed to evaluate the possible variation in risk of cancer-specific mortality by stage at nephrectomy and with increasing postoperative survivorship. RESULTS: 5-year cancer-specific survival rates at time of nephrectomy for stage I, II, III, and IV patients in the population-based cohort were 97.4%, 89.9%, 77.9%, and 26.7%, respectively. Improvement in 5-year CS was mainly observed in surviving patients with advanced-stage disease; given 1, 2, 3, 4, and 5 years of survivorship after nephrectomy, the subsequent 5-year cancer-specific survival rates were, respectively, 79.3% (+1.8% increase over previous survival probability), 81.3% (+2.5%), 83.3% (+2.5%), 84.3% (+1.2%), and 85.1% (+1.0%) for stage III, and 34.6% (+29.6%), 42.5% (+22.8%), 49.0% (+15.3%), 55.7% (+13.7%), and 58.6% (+5.2%) for stage IV. A similar trend was established in the validation cohort. Findings were confirmed upon multivariable analyses. CONCLUSIONS: CS after nephrectomy for RCC varies dramatically by stage of disease. Gains in CS over time occur primarily among patients with advanced-stage disease. Stage-specific CS estimates can help urologists better plan postoperative surveillance for RCC patients.

The incidence, predictors, and survival of disappearing small renal masses on active surveillance.

OBJECTIVE: To evaluate the incidence, predictors, and survival for those small renal masses (SRM, solid mass ≤4 cm suspicious for a clinical T1a renal cell carcinoma) that disappear on imaging while undergoing active surveillance (AS). SUBJECTS/PATIENTS AND METHODS: The Delayed Intervention and Surveillance for SRM registry prospectively enrolled 739 patients with SRMs. Patients having at least 1 image showing no lesion were considered to have a "disappearing" SRM. Logistic regression assessed predictors of having a disappearing SRM and Kaplan-Meier estimates illustrated relative survival. RESULTS: Of 374 patients enrolled in AS, 22 (5.9%) experienced a disappearing SRM. Mean time to tumor disappearance was 2.0 years (SD = 1.9) and 50.0% reappeared on subsequent CT imaging. SRM disappearance, most commonly encountered on ultrasound imaging surveillance, was independently associated with tumors <1 cm on multivariable analysis (OR = 10.6 (95% CI: 1.1-100.3), P = 0.04). Furthermore, patients with disappearing SRMs were healthier than other patients on AS with no compromise in overall survival during follow-up (5-year survival = 100% vs. 73.2%, P = 0.06). CONCLUSIONS: Approximately 5% of SRM on AS will disappear during follow-up on surveillance imaging. Most of these represent artifacts of heterogeneous imaging modalities, including ultrasound, and the SRM will reappear on subsequent imaging. Given the indolent nature of these lesions, disappearance events do not require reflex repeat imaging and patients should continue AS with their original surveillance schedule intact. A smaller percentage of patients undergoing AS for a SRM may have a mass the permanently disappears.

Urothelial carcinoma within the prostatic utricle of an adult with hypospadias and Fanconi anemia.

Prostatic utricles are rare in the general population and are often otherwise unremarkable anatomic variants. These structures are contiguous with the prostatic urethra and are nevertheless susceptible to urothelial carcinoma. This case report discusses the first reported patient with Fanconi anemia with urothelial carcinoma within an enlarged prostatic utricle.

Surgical removal of renal tumors with low metastatic potential based on clinical radiographic size: A systematic review of the literature.

INTRODUCTION: Many patients with small renal masses (SRM) undergo surgical resection of benign and potentially indolent renal masses. We review the available literature to quantify the proportion of renal tumors that are low-risk based on clinical radiographic size, and quantify the number of low-risk masses surgically removed in the United States. METHODS: We systematically reviewed the literature for studies including pathologic findings after excision of renal masses. Inclusion criteria required studies capture both benign and malignant histology at surgical pathology, tumor grade, and stratification by radiographic tumor size. We queried our institutional database using the same parameters. Meta-analysis results were applied to SEER incidence and management data for renal masses. Very-low-risk tumors were defined as benign or grade 1 cT1a, and low-risk tumors as benign, grade 1, or grade 2 cT1a. RESULTS: A total of 733 titles were reviewed at title screening with 6 full text articles and our institutional database included for meta-analysis. Pooled estimates of benign, very-low-risk, and low-risk tumors were stratified by tumor size: ≤2 cm (25.5%, 40.1%, and 89.3%), 2 to 3 cm (21.2%, 34.1%, and 84.5%), 3 to 4 cm (16.1%, 26.6%, and 77.1%), 4 to 6 cm (11.9%, 23.8%, and 66.4%), and >6 cm (7.2%, 12.6%, and 50.3%). An estimated 3,300 benign, 5,400 very-low-risk, and 13,600 low-risk SRMs were resected in 2014 in the United States. CONCLUSION: A substantial portion of patients with SRM are undergoing surgical excision despite harboring tumors of low metastatic potential. The rate of high-grade histology increased with increasing clinical radiographic size, which can be used in counseling and decision-making regarding placement on active surveillance. The number of low-risk SRM removed annually in the United States increased from 8,500 in 2000 to 13,600 in 2014 with stabilization in recent years.

Selecting Patients with Small Renal Masses for Active Surveillance: A Domain Based Score from a Prospective Cohort Study.

PURPOSE: We sought to identify predictors of active surveillance in a prospective cohort study of patients with a small renal mass demonstrating favorable outcomes. We generated a summary score to discriminate patients selected for active surveillance or primary intervention. MATERIALS AND METHODS: We analyzed the records of 751 patients from 2009 to 2018 who were enrolled in the DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) Registry to compare active surveillance and primary intervention in the domains of demographics, tumor characteristics, comorbidity and patient reported quality of life. Regression models were created to assess univariable and multivariable model discrimination by the AUC and quality by the AIC (Akaike information criterion). The DISSRM score was based on the most predictive combination of variables and validated for its association with overall survival by Kaplan-Meier survival curves and a Cox proportional hazards regression model. RESULTS: Of the patients 410 (55%) elected active surveillance and 341 (45%) elected primary intervention. Of the domains patient age, the Charlson comorbidity index, tumor diameter and the SF-12® Physical Component Score had the greatest discrimination for clinical selection into active surveillance. These domains made up the DISSRM score (AUC 0.801). The maximum DISSRM score was 7. The average score for active surveillance was 4.19 (median 4, IQR 2-6) and 72% of scores were 4 or greater. The average score for primary intervention was 3.03 (median 3, IQR 1-5) and 63% of scores were 3 or less. A higher DISSRM score was associated with worse overall survival, for example a score of 6-7 had a HR of 10.45 (95% CI 1.25-87.49, p = 0.03). CONCLUSIONS: The DISSRM score represents a measure of oncologic and competing risks of death in various important domains in patients with a small renal mass. It could be used to guide the management selection. Patients with intermediate scores that express illness uncertainty may require additional workup, such as confirmatory biopsy, to reach a treatment decision.

Access to Urological Care and Internet Connectivity in the United States: A Geospatial Analysis.

INTRODUCTION: Telemedicine video visits have been suggested as a mechanism to improve access to urological care in geographically isolated communities. However, Internet availability is not consistent across the United States. This study aims to better understand the interplay of broadband Internet, urologist density and county demographics to inform the strategic deployment of urological telemedicine. METHODS: A geospatial analysis was conducted to assess associations between broadband Internet and urologist density. Adequate broadband Internet availability was determined to be greater than 50% county coverage. Data were obtained from 2015 Federal Communications Commission filings. Physician density in 2015 was obtained from 2016-2017 Area Health Resources Files. A univariate regression was performed to estimate the associations of county demographics with broadband availability and urologist density. RESULTS: More than 10.9 million Americans lack access to local urology care and broadband Internet. Overall 31.7 million Americans lack access to a urologist but have reliable broadband Internet coverage. Counties with no urologists were associated with having less accessibility to broadband Internet and greater distance to the nearest county with a urologist. Counties without Internet availability or urologists were more likely to be rural (OR 9.93) and be designated as a whole county health professional shortage area (OR 10.05). CONCLUSIONS: A quarter of communities that lack access to local urologists also lack access to broadband Internet. Telemedicine cannot address poor access to urology care in communities without high-speed Internet. Future studies are needed to establish whether, pending expanded access to broadband Internet coverage, telemedicine will improve patient outcomes in geographically isolated communities.

Patient Decision-making and Predictors of Genital Satisfaction Associated With Testicular Prostheses After Radical Orchiectomy: A Questionnaire-based Study of Men With Germ Cell Tumors of the Testicle.

OBJECTIVE: To better understand patient decision-making and genital satisfaction associated with postorchiectomy testicular prosthesis (TP) implantation in patients with germ cell tumors of the testicle. MATERIALS AND METHODS: An electronic survey to assess TP decision-making and genital satisfaction was distributed to patients via an institutional database (n = 70) and social media outlets (n = 167). Statistical analyses were performed using chi-square tests for categorical variables, Wilcoxon-Mann-Whitney tests for continuous variables, and multivariate regression analyses to identify independent predictors of receiving a prosthesis, genital satisfaction, and prosthesis satisfaction. RESULTS: 24.9% of respondents elected to receive a TP, but 42% of men without a prosthesis reported never being offered one. Identifying as a heterosexual man (2.86) and receiving a TP (odds ratio = 3.29) were both positive predictors of overall genital satisfaction. Having the orchiectomy performed at an academic institution (odds ratio = 2.87) was a positive predictor of testicular prosthesis TP placement. 89.8% of TP recipients were satisfied with the look of their prosthetic, but only 59.3% of respondents were satisfied with prosthetic feel. CONCLUSION: There are high levels of genital satisfaction in those who elect to receive a TP postorchiectomy. Associations between TP placement, genital satisfaction, and sexuality merit further investigation. Our results also indicate that patients who pursue an orchiectomy at an academic institution are more likely to receive a TP. The use of social media to recruit study participants in urology should be explored further.

Use of delayed intervention for small renal masses initially managed with active surveillance.

INTRODUCTION: A number of patients who elect active surveillance of their small renal masses (≤4 cm) subsequently pursue delayed intervention (DI). The indications, timing, and rates of DI have not been well determined prospectively. MATERIALS AND METHODS: Data from Delayed Intervention and Surveillance for Small Renal Masses, a prospective, multi-institutional registry was utilized to evaluate factors associated with DI between 2009 and 2018. RESULTS: Of 371 patients enrolled in AS, 46 (12.4%) pursued DI. Patients who pursued DI spent a median 12 months on surveillance (interquartile range 5.5-23.6), had better functional status (P < 0.01), and had greater median growth rate vs. those who remained on surveillance (0.38 vs. 0.05, P < 0.001). Indications for intervention included growth rate >0.5 cm/y for 23 (50%) patients, patient preference for 22 (47.8%) patients, and qualification for renal transplant in 1 (2.2%) patient. Thirty-two patients (69.6%) underwent nephron-sparing surgery, 5 (10.9%) underwent radical nephrectomy, and 9 (19.6%) underwent percutaneous cryoablation. Renal mass biopsy was utilized in 37 (11.4%) and 15 (32.7%) patients in the AS and DI arms, respectively (P = 0.04). No patients experienced metastatic progression or died of kidney cancer. CONCLUSIONS: As nearly 50% of patients pursue DI secondary to anxiety in the absence of clinical progression, comprehensive counseling is essential to determine if patients are suitable for a surveillance protocol. AS remains a safe initial management option for many patients but may not be a durable strategy for patients who are acceptable surgical candidates with an extended life expectancy. DI does not compromise oncologic outcomes or limit treatment options.

Comparative effectiveness of management options for patients with small renal masses: a prospective cohort study.

OBJECTIVES: To explore the comparative effectiveness of partial nephrectomy (PN), radical nephrectomy (RN), ablative therapies (ablation) and active surveillance (AS) for small renal masses (SRMs; tumour diameter ≤4.0 cm) in the domains of survival, renal function and quality of life (QoL) using the prospectively maintained Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) Registry. PATIENTS AND METHODS: Estimated glomerular filtration rate (eGFR) was calculated from creatinine values to determine renal function. QoL was measured using the Short Form 12 (SF-12) questionnaire. The Kaplan-Meier method and Cox proportional hazards regression were used for survival analysis. The mixed-effects model was used for renal function and QoL analysis. RESULTS: Of 638 patients, 231 (36.2%) chose PN, 41 (6.4%) RN, 27 (4.2%) ablation and 339 (53.1%) AS. Cancer-specific survival at 7 years was 98.8% in PN patients and 100% in all other groups. Overall survival (OS) at 7 years was 87.9%, 90.2%, 83.5% and 66.1% in PN, RN, ablation and AS patients, respectively. The OS rate was significantly worse in the AS group than other groups and likely attributable to older age and increased comorbidities. The eGFR was lowest in RN patients but comparable in all other groups. QoL was lowest in AS patients due to lower physical health scores, but mental health scores were similar in all groups. CONCLUSIONS: With excellent oncological outcomes in all groups, nephron-sparing approaches, like PN and ablation, are preferred over RN when intervention is indicated for SRMs. AS is a reasonable option for select patients, given the comparable oncological and mental health outcomes.

Management of advanced adenocarcinoma in Indiana Pouch urinary diversion.

Adenocarcinoma is a rare finding following urinary diversion with gastrointestinal segments. This report describes an 80-year-old woman with a history of bladder cancer who subsequently developed a pT4 adenocarcinoma 8 years following her radical cystectomy and Indiana Pouch continent urinary diversion. An en bloc resection of the pouch and affected small bowel was performed and the patient underwent conversion to an ileal conduit diversion. We use this case to highlight a mechanism for possible pathogenesis and the management of adenocarcinoma in urinary diversions including the need for regular surveillance and the surgical approach.

Comparison of Pathological Stage in Patients Treated with and without Neoadjuvant Chemotherapy for High Risk Upper Tract Urothelial Carcinoma.

PURPOSE: High risk upper tract urothelial carcinoma has been associated with poor survival outcomes. Limited retrospective data support neoadjuvant chemotherapy prior to radical nephroureterectomy. To validate prior findings we evaluated differences in the pathological stage distribution in patients with high risk upper tract urothelial carcinoma based on the administration of neoadjuvant chemotherapy before radical nephroureterectomy. MATERIALS AND METHODS: We retrospectively analyzed the records of 240 patients with upper tract urothelial carcinoma at The Johns Hopkins Hospital from 2003 to 2017. Patients with biopsy proven high grade disease and a visible lesion on cross-sectional imaging were offered neoadjuvant chemotherapy prior to radical nephroureterectomy. A control group of a time matched cohort of patients with biopsy proven high grade disease underwent extirpative surgery alone. The chi-square and Fisher exact tests were used to evaluate clinical and pathological variables between the cohorts. RESULTS: There were 32 patients in the study group and 208 in the control group. Significantly lower pathological stage was noted in the study group than in the control group (p <0.001). Significantly fewer patients with pT2 disease or higher were treated with neoadjuvant chemotherapy (37.5% vs 59.6%, p = 0.02). There was a 46.5% reduction in the prevalence of pT3 disease or higher in study group patients without clinically node positive or low volume metastatic disease (25.9% vs 48.4%, p = 0.04). A 9.4% complete remission rate was observed in patients who underwent neoadjuvant chemotherapy. CONCLUSIONS: Patients with high risk upper tract urothelial carcinoma treated with neoadjuvant chemotherapy were noted to have a lower pathological stage distribution than patients treated with radical nephroureterectomy alone.

Growth Kinetics of Small Renal Masses on Active Surveillance: Variability and Results from the DISSRM Registry.

PURPOSE: Active surveillance is emerging as a safe and effective strategy for the management of small renal masses (4 cm or less). We characterized the growth rate and its pertinence to clinical outcomes in a prospective multi-institutional study of patients with small renal masses. MATERIALS AND METHODS: Since 2009, the DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) prospective, multi-institutional registry of patients with small renal masses has enrolled patients who elect primary intervention or active surveillance. Patients who elect active surveillance received regularly scheduled imaging and those with 3 or more followup images were included in the current study to evaluate growth rates. RESULTS: We evaluated 318 patients who elected active surveillance, of whom 271 (85.2%) had 3 or more followup images available with a median imaging followup of 1.83 years. The overall mean ± SD small renal mass growth rate was 0.09 ± 1.51 cm per year (median 0.09) with no variables demonstrating statistically significant associations. The growth rate and variability decreased with longer followup (0.54 and 0.07 cm per year at less than 6 months and greater than 1 year, respectively). No patients had metastatic disease or died of kidney cancer. No statistically significant difference was noted in the growth rate in patients with biopsy demonstrated renal cell carcinoma or in those who died. CONCLUSIONS: Small renal mass growth kinetics are highly variable early on active surveillance with growth rates and variability decreasing with time. Early in active surveillance, especially during the initial 6 to 12 months, the growth rate is variable and does not reliably predict death or adverse pathological features in the patient subset with available pathology findings. An elevated growth rate may indicate the need for further assessment with imaging or consideration of biopsy prior to progressing to treatment. Additional followup will inform the best clinical pathway for elevated growth rates.