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Mobile health technology and integration of patient-reported outcome measures into clinical interventions have the potential to transform patient care. Though patient-reported outcome measure management has been shown to improve outcomes in ambulatory care settings, few studies have examined remote patient-reported outcome measure assessment after major cancer surgery.A multiphased feasibility and usability study was designed. A mobile app-based postoperative symptom intervention tool was developed and evaluated by a focus group of bladder cancer patients and caregivers. Patients were prospectively accrued prior to cystectomy and asked to complete the daily mobile postoperative symptom intervention tool and wear biometric monitoring devices for 30 days post discharge. Retention, postoperative symptom intervention tool completion, and usability were assessed. Exploratory analysis of daily symptoms and patient-generated health information correlated signals with postsurgical complications and hospital readmission.Fifteen patients with a median age of 72 years completed 78% of daily surveys over the 30-day recovery period. Average time to complete the postoperative symptom intervention tool was 152 seconds. All patients agreed that the daily survey was easy to use, and most reported it would be a better way to communicate with the care team about symptoms than calling the clinic. Frequency and severity of patient-reported symptoms appeared to cluster prior to or at the time of complication or unplanned health care encounters on visual-analogue mapping.Using smartphone and wearable technology to capture patient-reported symptoms and biometric data is feasible and rated as highly usable by bladder cancer patients after cystectomy. Symptom scores may signal developing complications and help clinicians identify postsurgical patients who may benefit from intervention.

Patients with muscle invasive bladder cancer (MIBC) of variant histology have a poor prognosis. It is unclear if neoadjuvant chemotherapy prior to radical cystectomy is associated with pathological downstaging or improved overall survival (OS) for patients with variant histology. Our objective was to assess for associations between receipt of neoadjuvant chemotherapy, pathological downstaging and OS for patients with variant histology MIBC.Patients were identified in the National Cancer Database from 2004 to 2017 with MIBC, without metastases, who underwent radical cystectomy. Patients were stratified by histological subgroup, and receipt or nonreceipt of neoadjuvant chemotherapy. Pathological downstaging was defined as pT0N0 or pT ≤1N0, and OS from the time of diagnosis to date of death or censoring at last followup. Multivariable logistic regression analysis determined associations between neoadjuvant chemotherapy and pathological downstaging. Multivariable Cox regression analysis determined associations between neoadjuvant chemotherapy and OS.A total of 31,218 patients were included in the final study population (urothelial carcinoma [UC]: 27,779; sarcomatoid UC: 501; micropapillary UC: 418; squamous cell carcinoma: 1,141; neuroendocrine carcinoma: 629; adenocarcinoma: 750). Neoadjuvant chemotherapy was associated with pathological downstaging to pT0N0 in all histological subgroups (UC: OR 5.1 [4.6-5.6]; sarcomatoid UC: OR 13.8 [5.5-39.0]; micropapillary UC: OR 9.7 [2.8-46.8]; squamous cell carcinoma: OR 7.4 [2.1-24.5]; neuroendocrine: OR 4.7 [2.6-9.2]; adenocarcinoma: OR 23.3 [8.0-74.2]). Neoadjuvant chemotherapy was associated with improved OS for UC (HR 0.8 [0.77-0.84]), sarcomatoid UC (HR 0.64 [0.44-0.91]) and neuroendocrine carcinoma (HR 0.55 [0.43-0.70]).Neoadjuvant chemotherapy was associated with pathological downstaging for all MIBC histological variants, with improved OS for patients with UC, sarcomatoid variant UC and neuroendocrine carcinoma.

BACKGROUND: To assess predictors, indicators and medical necessity of readmissions after neoadjuvant chemotherapy (NAC) and radical cystectomy in order to identify opportunities for reducing readmission rates. METHODS: Records for patients treated with cisplatin-based NAC followed by radical cystectomy between 2007 and 2017 were reviewed for 90-day complications and readmission. Readmissions were classified as necessary vs. discretionary based on independent clinician review. The association between postoperative complications and necessary or discretionary readmission were examined with adjusted regression models. RESULTS: Among a total of 250 patients, 76 patients (30.4%) were readmitted within 90 days of surgery (19 discretionary and 57 necessary). Age, insurance coverage, and comorbidity were similar between readmitted and non-readmitted patients. Readmission was more likely after neobladder than ileal conduit (39% vs. 23%, p=0.02). Major (grade ≥ 3) complications within 90-day of surgery including index admission and post-discharge period were significantly more common among re-admitted patients compared to patients who were not readmitted (40% in necessary, 21% in discretionary, 3% in none, p

INTRODUCTION AND OBJECTIVE:Limited data are available to evaluate the prognostic value of primary tumor and metastatic tumor response to preoperative systemic therapy (PST) for metastatic RCC follo...

INTRODUCTION AND OBJECTIVE:As compared to targeted therapy (TT), clinical trials have shown an overall survival (OS) benefit for first-line immunotherapy (IT) and combination TT/IT regimens in meta...

Because the optimal number of cycles of neoadjuvant gemcitabine and cisplatin chemotherapy (GC) is unclear, we aimed to compare disease response and survival outcomes of patients receiving either 3 or 4 cycles of neoadjuvant GC for muscle-invasive bladder cancer (MIBC).A total of 166 patients who were treated with neoadjuvant GC and radical cystectomy for clinical stage T2-4N0M0 were identified. Response and effectiveness of different cycle counts were assessed using downstaging (complete pathologic and partial pathologic response), cancer-specific survival (CSS), and overall survival (OS). Response and survival outcomes were examined with adjusted logistic regression and Cox regression models. Statistical significance was defined as P0.05.Of 166 patients who received neoadjuvant GC, 107 (64.5%) received 3 cycles and 59 (35.5%) received 4 cycles. Age, insurance, comorbidity, tumor histology (pure urothelial carcinoma, urothelial with divergent differentiation, variant histology), and tumor stage were similar between the 2 treatment groups. Rates of complete response or any downstaging were similar between groups (21.5% and 40.2% in the 3-cycle group and 20.3% and 44.1% in the 4-cycle group, respectively). While disease response was similar (OR 1.03, 95% CI 0.43-2.45), both cancer-specific survival (HR 1.69, 95% CI 0.87-3.26) and overall survival (HR:1.88, 95% CI:1.02-3.48) were more favorable among patients managed with 4 cycles of neoadjuvant chemotherapy compared to those who received 3 cycles in adjusted models.Our analysis demonstrated that survival outcomes tended to be better among patients who received 4 cycle of neoadjuvant GC compared to those treated with 3 cycles. Although potential benefits of omission of fourth cycle may include expedited time to surgery, reduced chemotherapy-associated toxicity, and lower treatment costs, continuation of treatment with a fourth cycle of neoadjuvant GC chemotherapy may benefit patients with muscle-invasive bladder cancer and further improve disease outcomes.

Cancer-associated fibroblasts (CAF) are highly prevalent cells in the tumor microenvironment in clear cell renal cell carcinoma (ccRCC). CAFs exhibit a pro-tumor effect in vitro and have been implicated in tumor cell proliferation, metastasis, and treatment resistance. Our objective is to analyze the geospatial distribution of CAFs with proliferating and apoptotic tumor cells in the ccRCC tumor microenvironment and determine associations with survival and systemic treatment. Pre-treatment primary tumor samples were collected from 96 patients with metastatic ccRCC. Three adjacent slices were obtained from 2 tumor-core regions of interest (ROI) per patient, and immunohistochemistry (IHC) staining was performed for αSMA, Ki-67, and caspase-3 to detect CAFs, proliferating cells, and apoptotic cells, respectively. H-scores and cellular density were generated for each marker. ROIs were aligned, and spatial point patterns were generated, which were then used to perform spatial analyses using a normalized Ripley’s K function at a radius of 25 μm (nK(25)). The survival analyses used an optimal cut-point method, maximizing the log-rank statistic, to stratify the IHC-derived metrics into high and low groups. Multivariable Cox regression analyses were performed accounting for age and International Metastatic RCC Database Consortium (IMDC) risk category. Survival outcomes included overall survival (OS) from the date of diagnosis, OS from the date of immunotherapy initiation (OS-IT), and OS from the date of targeted therapy initiation (OS-TT). Therapy resistance was defined as progression-free survival (PFS) &lt, 6 months, and therapy response was defined as PFS &gt, 9 months. CAFs exhibited higher cellular clustering with Ki-67+ cells than with caspase-3+ cells (nK(25): Ki-67 1.19, caspase-3 1.05, p = 0.04). The median nearest neighbor (NN) distance from CAFs to Ki-67+ cells was shorter compared to caspase-3+ cells (15 μm vs. 37 μm, respectively, p &lt, 0.001). Multivariable Cox regression analyses demonstrated that both high Ki-67+ density and H-score were associated with worse OS, OS-IT, and OS-TT. Regarding αSMA+CAFs, only a high H-score was associated with worse OS, OS-IT, and OS-TT. For caspase-3+, high H-score and density were associated with worse OS and OS-TT. Patients whose tumors were resistant to targeted therapy (TT) had higher Ki-67 density and H-scores than those who had TT responses. Overall, this ex vivo geospatial analysis of CAF distribution suggests that close proximity clustering of tumor cells and CAFs potentiates tumor cell proliferation, resulting in worse OS and resistance to TT in metastatic ccRCC.

Key Points Question What is the comparative effectiveness of first-line targeted therapy, immunotherapy, and combination therapy in a real-world cohort of patients with metastatic clear cell renal cell carcinoma? Findings In this propensity-matched cohort study of 5872 patients treated in real-world clinical practice, first-line immunotherapy and combination therapy were associated with improved overall survival compared with first-line targeted therapy. Meaning This study suggests that clinical trial findings demonstrating an overall survival benefit associated with first-line immunotherapy-based regimens compared with targeted therapy are generalizable to a broader population of patients., Importance Clinical trials have shown an overall survival (OS) benefit associated with first-line immunotherapy (IT) and combination targeted therapy (TT) and IT regimens compared with TT among patients with metastatic clear cell renal cell carcinoma (RCC). Generalizability of these findings in a real-world cohort outside of a clinical trial setting is unclear. Objective To assess the association of first-line TT, IT, and combination TT and IT regimens with OS in a real-world cohort of patients with metastatic clear cell RCC. Design, Setting, and Participants This retrospective propensity-matched cohort study identified 5872 patients with metastatic clear cell RCC in the National Cancer Database from January 1, 2015, to December 31, 2017, who received first-line TT, IT, or combination TT and IT and were not treated on a clinical trial protocol. Patients were stratified by first-line systemic treatment. Statistical analysis was conducted from October 1 to December 1, 2020. Main Outcomes and Measures The primary outcome was OS from the date of diagnosis to death or censoring at last follow-up. After 1:1:1 nearest-neighbor caliper matching of propensity scores, survival analyses were conducted using Cox proportional hazards regression and Kaplan-Meier estimates. Results The final study population included 5872 patients (TT group: n = 4755 [81%]; 3332 men [70%]; median age, 64 years [interquartile range, 57-71 years]; IT group: n = 638 [11%]; 475 men [74%]; median age, 61 years [interquartile range, 54-69 years]; and combination TT and IT group: n = 479 [8%]; 321 men [67%]; median age, 62 years [interquartile range, 55-69 years]), and the matched cohort included 1437 patients (479 per treatment group). Patients in the IT and combination TT and IT groups were younger than those in the TT group, had fewer comorbid conditions (Charlson-Deyo score of 0, 480 of 638 [75%] in the TT group, 356 of 479 [74%] in the IT group, and 3273 of 4755 [69%] in the combination TT and IT group), and were more often treated at academic centers (315 of 638 [49%], 216 of 479 [45%], and 1935 of 4755 [41%], respectively). Both first-line IT and combination TT and IT were associated with improved OS compared with first-line TT for patients with metastatic clear cell RCC (IT group: hazard ratio [HR], 0.60 [95% CI, 0.48-0.75]; P, This cohort study assesses the association of first-line targeted therapy, immunotherapy, and combination targeted therapy and immunotherapy regimens with overall survival in a real-world cohort of patients with metastatic clear cell renal cell carcinoma (ccRCC).

Clinical trials have not shown a significant overall survival (OS) difference between chemotherapy and immunotherapy as first-line agents in metastatic urothelial carcinoma (UC). However, the generalizability of these findings in a real-world setting has not yet been evaluated in comparative effectiveness studies.To assess the effectiveness of first-line immunotherapy compared with chemotherapy regimens on OS in patients with metastatic UC of the bladder.This retrospective propensity-matched study identified metastatic bladder UC patients in the National Cancer Database from 2014 to 2017 who received either first-line immunotherapy-monotherapy or multi-agent chemotherapy, and who were not treated on a clinical trial protocol.The primary outcome was OS from the date of diagnosis to date of death or censoring at last follow-up. Patients were stratified into first-line immunotherapy and chemotherapy treatment groups. After 1:1 nearest-neighbor caliper-matching of propensity scores, the survival analysis was conducted using Cox regression modeling and Kaplan-Meier estimates.A total of 2,796 patients were included in the final study population, and 960 in the matched cohort (480 per treatment group). Utilization of immunotherapy increased over the time period studied as chemotherapy decreased (Immunotherapy: 3%-37%; Chemotherapy: 97%-63%; P0.001). In the overall cohort, patients who received first-line immunotherapy were older and more comorbid than those who received first-line chemotherapy (Age: 73 v. 67, respectively, P0.001; Charlson-Deyo score ≥2: 17% v. 11.5%, respectively, P0.001). In the matched cohort, patients who were treated with first-line immunotherapy had similar OS to those who were treated with first-line chemotherapy (HR: 0.91, 95CI 0.72-1.15). Due to the retrospective nature of the study, interpretation is limited by potential selection bias from unmeasured confounding.Metastatic bladder UC patients who received first-line immunotherapy had similar OS to those who received first-line chemotherapy.

Background Clear cell renal cell carcinoma (ccRCC) tumors have low frequencies of genetic alterations compared with other malignancies, but very high levels of immune cell infiltration and favorable response rates to immunotherapy. Currently, the interplay between specific ccRCC somatic mutations and immune infiltration pattern is unclear. Objective To analyze the associations between common ccRCC somatic mutations and immune cell infiltration patterns within the tumor immune microenvironment (TIME). Design, setting, and participants The study included tumor samples (24 primary and 24 metastatic) from 48 patients with stage IV ccRCC. Targeted sequencing was performed for well-characterized recurrent somatic mutations in ccRCC, with the analysis focusing on the six most common ones: VHL, BAP1, PBRM1, SETD2, TP53, and KDM5C. For each sample, multiplex immunofluorescence (IF) was performed in lymphoid and myeloid panels, for seven regions of interest in three zones (tumor core, stroma, and tumor-stroma interface). IF-derived cellular densities were compared across patients, stratified by their somatic mutation status, using a linear mixed-model analysis. External validation was pursued using RNA-seq enrichment scoring from three large external data sources. Results and limitations Tumors with SETD2 mutations demonstrated significantly decreased levels of FOXP3+ T cells in the tumor core, stroma, and tumor-stroma interface. PBRM1 mutations were associated with decreased FOXP3+ T cells in the tumor core. Primary KDM5C mutations were associated with significantly increased CD206+ macrophage tumor infiltration in the tumor core. A computational method estimating immune cell types in the TIME using bulk RNA-seq data, xCell scoring, failed to validate associations from the IF analysis in large external data sets. A major limitation of the study is the relatively small patient population studied. Conclusions This study provides evidence that common somatic mutations in ccRCC, such as SETD2, PBRM1, and KDM5C, are associated with distinct immune infiltration patterns within the TIME. Patient summary In this study, we analyzed tumor samples from patients with metastatic kidney cancer to determine whether common genetic mutations that arise from the cancer cells are associated with the density of immune cells found within those tumors. We found several distinct immune cell patterns that were associated with specific genetic mutations. These findings provide insight into the interaction between cancer genetics and the immune system in kidney cancer.

BackgroundIt is highly contested whether cytoreductive nephrectomy for treating advanced renal cell carcinoma (RCC) with sarcomatoid features (sRCC) benefits overall survival. Patients with sRCC are known to have a poor prognosis, and these tumors have a more aggressive biology than those without sarcomatoid features.MethodsPatients with clear cell RCC or non–clear cell RCC underwent cytoreductive nephrectomy in efforts to improve overall survival (OS). Patients were stratified by presence or absence of histologic sarcomatoid features within tumor samples.ResultsOf 167 patients who underwent cytoreductive nephrectomy, 127 had clear cell RCC, of whom 14 had sarcomatoid features, and 40 had non–clear cell RCC, of whom 13 had sarcomatoid features. Median age of the cohort was 62 years (range, 56.5–69 years). The cohort included 119 male (71.3%) and 48 (28.7%) female patients. Among all patients with advanced RCC, having sRCC had a significantly worse OS after cytoreductive nephrectomy (30 vs 8 months; hazard ratio [HR], 2.88; P P =0.00016). For patients with clear cell RCC, having sRCC conferred a significantly poorer survival (30 vs 9 months; HR, 2.82; P=0.0035). Patients with non–clear cell sRCC also had significantly worse outcomes compared to patients whose tumors did not have sarcomatoid features (30 vs 6.5 months; HR, 3; P =0.009). When patients with sRCC were stratified by whether there was >10% or ≤10% sarcomatoid features present within the sample, there was no significant difference in OS (8 vs 8.5 months; P =0.32).ConclusionsSarcomatoid features within tumor histology confer significantly poor prognosis. Patients with sRCC, regardless of clear cell vs non–clear cell histology, have significantly shorter OS. Even among patients with 10% or less sarcomatoid features, there was no OS benefit to cytoreductive nephrectomy. Based on our findings, there appears to be a limited to no role of cytoreductive nephrectomy if sRCC is identified on pretreatment biopsy. The role of radiomics and pre-operative biopsies may confer significant benefit in this patient population.

Immune infiltration is typically quantified using cellular density, not accounting for cellular clustering. Tumor-associated macrophages (TAM) activate oncogenic signaling through paracrine interactions with tumor cells, which may be better reflected by local cellular clustering than global density metrics. Using multiplex immunohistochemistry and digital pathologic analysis we quantified cellular density and cellular clustering for myeloid cell markers in 129 regions of interest from 55 samples from 35 patients with metastatic ccRCC. CD68+ cells were found to be clustered with tumor cells and dispersed from stromal cells, while CD163+ and CD206+ cells were found to be clustered with stromal cells and dispersed from tumor cells. CD68+ density was not associated with OS, while high tumor/CD68+ cell clustering was associated with significantly worse OS. These novel findings would not have been identified if immune infiltrate was assessed using cellular density alone, highlighting the importance of including spatial analysis in studies of immune cell infiltration of tumors.SIGNIFICANCEIncreased clustering of CD68+ TAMs and tumor cells was associated with worse overall survival for patients with metastatic ccRCC. This effect would not have been identified if immune infiltrate was assessed using cell density alone, highlighting the importance of including spatial analysis in studies of immune cell infiltration of tumors.

Background Emerging evidence from studies in sarcoma and melanoma immune checkpoint blockade(ICB) trials demonstrated enhanced efficacy in tumors harbouring tertiary lymphoid structures(TLS)1–3 - lymph node like aggregates in the tumor microenvironment postulated to recruit lymphocyte infiltration and coordinate tumor antigen presentation and lymphocyte priming. Previously, our group described a 12-chemokine metagene signature that reflects strong intratumoral chemotactic signalling and accurately predicts the presence of TLS in colorectal carcinoma.4 Grounded in these works, we attempted to correlate high 12CK signature with TLS formation in the context of muscle invasive bladder cancer(MIBC), and then sought to define its prognostic implications and its ability to predict response to ICB. Methods A total of 130 MIBC samples were arrayed on Affymetrix microarrays and 12CK scores were assessed. Scores were normalized using 12CK>1 to denote 12CK-High(n=24). We then investigated the the presence of TLS with the associated immune cellular infiltration evaluated by immunohistochemistry and gene signature deconvolution method (xCell).5 12CK scores were also correlated with survival in our institutional cohort and validated using data from TCGA. Finally, 12CK scores were extracted from the IMVIGOR210 study to examine its ability to predict response to ICB.6 Results Type III TLS, consisting of germinal center-like structures and discrete T-cell zones were found in 7/22 12CK-High vs. 0/21 12CK-Low tumors (p=0.009) (figure 1a). Additionally, a more robust immuno-environment was seen in 12CK-High tumors, consisting of increased infiltration of CD4+ T lymphocytes (p=0.1), CD8+ T lymphocytes (p=0.02), activated dendritic cells (p=0.047), and B lymphocytes (p=0.006) on immunohistochemistry (figure 1b). Furthermore, on xCell deconvolution, M1 macrophage, NK cells, CD8+ Tem, CD4+ Tem, and memory B cells were enriched in 12CK-High tumors, suggesting both a heightened innate and adaptive immune response (figure 1c, d). Kaplan-Meier survival analyses of our internal cohort revealed improved PFS (HR 0.25, p=0.003 ), CSS (HR 0.25, p=0.003), and OS (HR 0.55, p=0.03) amongst 12CK-High patients (figure 2a-c). From the TCGA, similar improvements were found in PFS (HR 0.55, p=0.007), CSS (HR 0.40, p=0.002), and OS (HR 0.59, p=0.01) in 12CK-High patients (figure 2d-f). From the IMVIGOR 210 study, complete responders exhibited significantly higher 12-CK scores than all other groups (figure 2g). Strikingly, the 12CK-High signature conferred a median overall survival benefit of almost 1 year in the atezolizumab-treated patients (figure 2h). Conclusions In muslce invasive bladder cancer, 12CK-High scores corresponded with formation of TLS in the TME; favourable prognosis in surgically treated MIBC patients; and CR in atezolizumab-treated patients. References Cabrita R, Lauss M, Sanna A, et al. Tertiary lymphoid structures improve immunotherapy and survival in melanoma. Nature 2020;577(7791):561–565. Helmink BA, Reddy SM, Gao J, et al. B cells and tertiary lymphoid structures promote immunotherapy response. Nature 2020;577(7791):549–555. Petitprez F, de Reynies A, Keung EZ, et al. B cells are associated with survival and immunotherapy response in sarcoma. Nature 2020;577(7791):556–560. Aran D, Hu Z, Butte AJ. xCell: digitally portraying the tissue cellular heterogeneity landscape. Genome biology 2017;18(1):220. Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet (London, England). 2016;387(10031):1909–1920.

Summary A clearer understanding of the tumor immune microenvironment (TIME) in metastatic clear cell renal cell carcinoma (ccRCC) may help to inform precision treatment strategies. We sought to identify clinically meaningful TIME signatures in ccRCC. We studied tumors from 39 patients with metastatic ccRCC using quantitative multiplexed immunofluorescence and relevant immune marker panels. Cell densities were analyzed in three regions of interest (ROIs): tumor core, tumor–stroma interface and stroma. Patients were stratified into low- and high-marker density groups using median values as thresholds. Log-rank and Cox regression analyses while controlling for clinical variables were used to compare survival outcomes to patterns of immune cell distributions. There were significant associations with increased macrophage (CD68+CD163+CD206+) density and poor outcomes across multiple ROIs in primary and metastatic tumors. In primary tumors, T-bet+ T helper type 1 (Th1) cell density was highest at the tumor–stromal interface (P = 0·0021), and increased co-expression of CD3 and T-bet was associated with improved overall survival (P = 0·015) and survival after immunotherapy (P = 0·014). In metastatic tumor samples, decreased forkhead box protein 3 (FoxP3)+ T regulatory cell density correlated with improved survival after immunotherapy (P = 0·016). Increased macrophage markers and decreased Th1 T cell markers within the TIME correlated with poor overall survival and treatment outcomes. Immune markers such as FoxP3 showed consistent levels across the TIME, whereas others, such as T-bet, demonstrated significant variance across the distinct ROIs. These findings suggest that TIME profiling outside the tumor core may identify clinically relevant associations for patients with metastatic ccRCC.

PURPOSE: Although neoadjuvant chemotherapy is associated with a survival advantage in pure urothelial, muscle invasive bladder cancer, the role of neoadjuvant chemotherapy is less clear in variant histology or urothelial carcinoma with divergent differentiation. We compared chemotherapy response and survival outcomes of patients with nonpure urothelial carcinoma histology who were managed with neoadjuvant chemotherapy followed by cystectomy vs cystectomy alone. MATERIALS AND METHODS: We analyzed 768 patients with clinical muscle invasive bladder cancer (cT2–4N0M0) who were treated with cystectomy at a tertiary care center from 2007 to 2017. Patients were stratified by histology and treatment strategy. Adjusted logistic and Cox regression models were used to evaluate pathological downstaging, cancer specific survival and overall survival. RESULTS: The cohort consisted of 410 patients (53%) with pure urothelial carcinoma, 185 (24%) with urothelial carcinoma with divergent differentiation and 173 (23%) with variant histology. Overall, 314 patients (41%) received neoadjuvant chemotherapy prior to cystectomy. There were similar rates of complete (18% to 30%) and partial (37% to 46%) pathological downstaging with neoadjuvant chemotherapy across all histological subgroups (p=0.30 and p=0.40, respectively). However, while patients with pure urothelial carcinoma experienced an overall survival benefit (HR 0.71, 95% CI 0.51–0.98, p=0.0013) and those with variant histology experienced a cancer specific survival benefit (HR 0.55, 95% CI 0.30–0.99, p=0.0495) with neoadjuvant chemotherapy, patients with urothelial carcinoma with divergent differentiation did not experience overall or cancer specific survival benefits with the use of neoadjuvant chemotherapy prior to cystectomy. CONCLUSIONS: Among patients with muscle invasive bladder cancer those with nonpure urothelial carcinoma histology with variant histology achieved nearly equivalent response rates and survival benefits with the use of neoadjuvant chemotherapy as those with pure urothelial carcinoma, while patients with urothelial carcinoma with divergent differentiation experienced significantly worse survival outcomes regardless of the use of neoadjuvant chemotherapy prior to cystectomy.

Introduction: The artificial urinary sphincter (AUS) is the most effective treatment option for incontinence after prostate cancer treatment. However, patients with a “fragile urethra” (defined as prior radiotherapy, previous failed AUS, or previous urethroplasty) are at increased risk of AUS failure. The aim of this study was to evaluate outcomes using standard and transcorporal cuff placement in this group of patients. Methods: A retrospective review was performed on patients with a fragile urethra who underwent AUS insertion between 2004 and 2017. The primary outcome was the need for AUS revision. Secondary outcome measures included change in pad use, patient satisfaction, continence (≤1 pad/day), improvement (≥50% change in pad use) and cuff erosion rates. Results: Seventy-six patients met the criteria for inclusion, with a mean age of 71.6 years and a mean followup of 37.9 months. A total of 42.1% had prior radiotherapy, 56.6% had a history of failed AUS, and 19.7% had previous urethroplasty. Transcorporal cuff placement was performed in 31.6% (n=24). These patients had lower revision (20.8% vs. 36.5%; p=0.05) and erosion rates (8.3% vs. 17.3%; p=0.09). There was no significant difference in functional outcomes such as continence (66.7% vs. 73.1%; p=0.57), improvement (100% vs. 90.4%;p=0.17), or satisfaction (82.6% vs. 69.4%; p=0.26), nor for 90-day complications (4.2% vs. 9.6%; p=0.41). Conclusions: AUS insertion is an effective treatment option for post-prostatectomy incontinence in the setting of a fragile urethra. Transcorporal cuff placement in this subset of patients may be recommended, as it is associated with lower revision and erosion rates compared to standard cuff placement.

Purpose The toxicity of topical chemotherapeutics has been well-characterized in extra-genital squamous cell carcinoma; however, there is limited data regarding the use of topical agents for penile squamous cell carcinoma in situ (CIS). We aim to describe the clinical outcomes and toxicities associated with the use of topical fluorouracil and imiquimod for penile CIS. Materials and Methods We performed an observational analysis of penile CIS cases treated with topical chemotherapy from 2009 to 2019 at a tertiary cancer center. Results Twenty patients with penile CIS received fluorouracil (n= 17, 85%) or imiquimod (n = 3, 15%). The median age was 66 years. The median follow-up was 18 months. Complete response (CR) was achieved in 65% (n= 13/20), partial response in 25% (n = 5/20), and no response in 10% (n = 2/20). Overall, 50% required additional alternative treatments due to lack of CR or relapse. The median recurrence-free survival was 14 months. Fifty percent of patients reported Common Terminology Criteria for Adverse Events v5.0 grade 1 to 2 acute toxicities, including local skin irritation (40%), pain (35%), dysuria (5%), or nausea (5%). Only 65% completed the full course of treatment. Nonadherence was associated with a diminished CR rate of 28.6%. Conclusions Topical chemotherapy is a reasonable first-line therapy for penile CIS. A substantial proportion of patients experience acute toxicity and are unable to complete the full course of therapy. We recommend that patients with penile CIS be monitored regularly in order to promptly address issues with adherence and toxicity associated with topical treatment.

INTRODUCTION AND OBJECTIVE:The recent success of anti-PD1 therapeutics is known to be associated with an upregulated Th1 gene signature and an immunogenic tumor microenvironment (TME). There remain...

INTRODUCTION AND OBJECTIVE:Optimal selection of metastatic renal cell carcinoma (mRCC) for cytoreductive nephrectomy (CN) is challenging because outcomes vary significantly and patients who survive...

INTRODUCTION AND OBJECTIVE:Complications and readmissions are common after radical cystectomy (RC) and urinary diversion and have been subject to extensive examination in efforts to improve recover...

INTRODUCTION AND OBJECTIVE:Pure testicular teratoma accounts for less than 5% of testicular neoplasms in adults and is considered less aggressive and less likely to metastasize than other non-semin...

Purpose: We examined radiographic predictors of intervention for blunt renal trauma independent of AAST-OIS (American Association for the Surgery of Trauma-Organ Injury Scale).Materials and Methods...

INTRODUCTION AND OBJECTIVE:Adaptive anti-tumor immunity can be orchestrated by lymph node-like immune cell aggregates within the tumor microenvironment (TME) called tertiary lymphoid structures (TL...

Therapy for early stage testicular seminoma has changed radically over the past several decades. Given high cure rates and clinical trials supporting less active therapy in most cases, close observation after radical orchiectomy is now considered standard of care for clinical stage (CS) IA/IB seminoma, with either radiation therapy (RT) or chemotherapy salvage options possible. For CS IIA/IIB seminoma characterized by non-bulky retroperitoneal lymph node involvement (≤5 cm in greatest dimension), RT or combination chemotherapy are the standard of care. Given high comparable survival rates, preventing treatment-related toxicity and second malignancy, and limiting quality of life deficits associated with intense treatment has gained much greater importance. Clinical trials are currently testing the feasibility of retroperitoneal lymph node dissection (RPLND) for low volume CS IIA/IIB metastatic testicular seminoma to this end. Likewise, one cycle of chemotherapy is being evaluated as an adjuvant approach to reduce recurrence rates in CS I disease with unfavorable risk factors. Moreover, recent genomic and molecular studies have recently identified novel signatures and a potential biomarker for testicular seminoma. In this review, we first summarize the evolution of early stage seminoma management and discuss the effectiveness and drawbacks of contemporary treatment strategies. We further outline future perspectives and potential challenges in management of early stage testicular seminoma.

Penile squamous cell carcinoma is a rare condition that is associated with significant morbidity and mortality in its advanced stages. In today's rapidly evolving field of oncology, physicians and scientists are learning to harness the power of genomics to drive innovative targeted, immunotherapeutic, and multimodal strategies across different cancer types; however, there remains a pressing need for a deeper understanding of the molecular pathways of penile carcinogenesis in order to help direct individualized therapy for patients with this disease. In this article, we will review our current understanding of some of the biologic mechanisms, including virally and nonvirally based pathways, which are thought to drive the development and progression of penile cancer.

466 Background: Adaptive anti-tumor immunity can be orchestrated by lymph node-like immune cell aggregates within the tumor microenvironment (TME) called tertiary lymphoid structures (TLSs). TLSs are postulated to be the gateway of lymphocyte infiltration into the TME, and are privileged sites for coordinated tumor antigen presentation and lymphocyte priming, differentiation, and proliferation, leading to a robust tumor-specific immune response. A 12-chemokine metagene grouping (12-CK score) has previously been described that correlates with the presence of TLSs in other solid tumor types. In this study, we explored the prognostic implication of the 12-CK score in bladder cancer and its correlation with the presence of TLSs. Methods: Cystectomy specimens from 132 patients with bladder cancer were arrayed on Affymetrix microarrays. 12-CK scores were normalized with > 1 denoting high scores (12-CKHi). Immunohistochemistry (IHC) antibody staining was performed for DC-LAMP, CD20, CD4, and CD8. A GU pathologist scored TLSs into Types I-III, with type III representing fully developed TLSs. The Fisher’s exact test was used to test the associations between the 12-CK scores and the type of lymphoid aggregate. Overall survival was estimated using the Kaplan Meier method. Findings were validated using 12-CK scores extracted from TCGA transcriptome sequencing data and the IMvigor210CoreBiologies package. Results: Twenty-five (n = 25) patients had 12CK scores > 1 and were classified as 12CK-High. Pathologic review of 43 bladder tumor specimens confirmed higher levels of Type III TLS patients (33% vs. 9%, p = 0.03), B cells (p = 0.002), CD8 T cells (p = 0.01), and activated DC (p = 0.01) in 12-CKHi compared to 12-CKLo. 12-CKHi was found to have a progression-free survival (PFS, HR 0.29, p = 0.003, Fig1a), disease specific survival (DSS, HR 0.29, p = 0.004, Fig1b), and overall survival (OS, HR 0.55, p = 0.03, fig1c) advantage compared to 12-CKLo in the Moffitt patient cohort. These results were validated using the publically available RNA expression data from TCGA. TCGA patients with 12-CKHi (18%,n = 72) had improved PFS ( HR 0.55, p = 0.007, fig1d), DSS (HR = 0.40, p = 0.002, fig1e), and 0S (HR = 0.59, p = 0.01, fig1f). From the IMVIGOR-210 patient who were 12-CKHi were more likely to have a complete response (p < 0.05, fig1g) and have a 11.2mo OS benefit (fig1h) after treatment using atezolizumab. Conclusions: Three important findings emerged from the current study: 12CK-High scores corresponded with formation of TLS in the TME; favorable prognosis in surgically treated MIBC patients; and CR in atezolizumab-treated patients. The findings herein suggest the 12CK gene signature to be a clinically actable biomarker for predicting response to immune checkpoint blockade. We believe the 12CK signature may serve as an important tool to refine patient selection for immune checkpoint blockade treatment.