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Objectives To report surgical outcomes, palliative durability, and quality of life (QOL) after palliative robotic cystectomy (RC) for symptomatic advanced prostate cancer (PC). Methods Retrospective review of patients who underwent RC (n=10) at our institution from 2013-2018. European Organization for Research and Treatment of Cancer (EORTC) Functional Assessment of Cancer Therapy – Bladder Cystectomy (FACT-BL-CYS) questionnaire was administered to assess QOL. Patient characteristics, peri-operative outcomes, changes in pre-operative symptoms, and FACT-BL-CYS scores were assessed post-operatively. Results Mean age was 70 years (IQR, 64-72), and median follow up was 505 days. Five patients (50%) had prior radiation therapy (RT). Rates of perioperative and delayed complications were 30% and 30%, respectively. There were no cases of rectal injury. At latest follow up, there were no cases of urinary obstruction, hematuria, or pelvic pain, and 80% of patients remained symptom free. Six of ten patients responded to the questionnaire and completed the FACT-BL-CYS. Individual sub-domain scores (physical, social, functional, emotional, bladder specific) and overall scores were similar to post-operative radical cystectomy populations in other studies. 100% of responding patients would repeat RC. Conclusion RC appears to be a safe and effective option for advanced PC refractory to other interventions. The majority of patients would repeat the procedure. However, given the differences in goals of care for patients undergoing surgery for curative intent vs for palliation, we lack the ability to make true inferences regarding measurable improvements in quality of life; this highlights the need for high quality multi-institutional studies to better understand the impact of RC on QOL.

OBJECTIVES To determine whether utilisation of a serum microRNA (miRNA) test could improve treatment appropriateness and cost-effectiveness for patients with Stage I non-seminomatous germ cell tumours (NSGCTs). PATIENTS AND METHODS A decision tree model was built to investigate treatment course, clinical and cost outcomes for patients with Stage IA (T1N0M0S0) and IB (T2-4N0M0S0) NSGCT. The model compared outcomes and cost of standard approach using histopathology, conventional serum tumour markers and radiographic staging (standard model) to a miRNA-based approach using the standard model + post-orchidectomy serum miR-371a-3p (marker model). Probabilities of expected treatment and outcomes were based on presence/absence of cancer upon entering into the model. Overtreatment was defined as adjuvant chemotherapy or primary retroperitoneal lymph node dissection in a patient without cancer. Undertreatment was defined as initial surveillance for a patient with cancer. RESULTS Utilising the miRNA marker-based approach, 26% of patients avoid overtreatment and 8% avoid undertreatment in Stage IA NSGCT; 27% avoid overtreatment and 23% avoid undertreatment in Stage IB disease. Appropriate treatment decision-making increased from 65% to 94% and 50% to 92% for Stage IA and IB, respectively. The miRNA-based approach remained cost-effective over a wide range of performance characteristics with savings of ~$1400 (American dollars)/patient for both Stage IA and IB disease. CONCLUSION A miRNA-based approach may potentially select patients with Stage I NSGCT for correct treatment in a cost-effective manner. Identification of residual teratoma-only remains an issue. Prospective studies are necessary to validate these findings.

Objective To determine feasibility and safety of robotic excision of local ipsilateral recurrences after nephrectomy for renal cell carcinoma (RCC). Surgical resection is an option for treatment of low burden locally recurrent RCC, potentially delaying the use of systemic therapy. This has historically been performed by open technique, which can impart significant morbidity. We present our experience with robotic excision. Methods We reviewed our institutional experience of patients with surgically excised RCC who underwent robotic excision of ipsilateral retroperitoneal recurrence in 2015-2018. Demographics and clinicopathological variables, including operative and postoperative outcomes, were examined. Results Twelve robotic excisions of ipsilateral local recurrences were performed in our hospital in 2015-2018. Mean age was 65.48 years (± standard deviation, SD: 9.51), 10 patients were male, and mean BMI 34.75 kg/m2 (± 6.71). Nine patients recurred after radical nephrectomy, and 3 after partial nephrectomy. Mean size of recurrence was 2.97 cm (±1.69). Mean anesthesia time, EBL, and LOS were 213 minutes (± 38.92), 152 mL (± 130.75), and 43 hours (± 12.64), respectively. All surgical margins were negative. No surgical complications were reported. Median follow-up was 19.0 months [interquartile range, IQR 12.7-30.0]. Five patients out of 12 recurred following robotic excision, these were treated with either systemic therapy, radiation, or palliative surgeries. Mean time for subsequent recurrence was 26.5 months. Conclusion In this small case series, robotic excision of ipsilateral RCC retroperitoneal recurrence appears safe, technically feasible, and oncologically sound in expert hands and carefully selected patients.

Testicular germ cell tumor (GCT) is the most common malignancy in 18- to 40-year-old men. Unlike most other cancers, GCT is frequently curable even when metastatic. These tumors can be classified histologically into seminoma and non-seminoma, which determines treatment. Therefore, successful treatment requires accurate diagnosis, classification, and monitoring. Serum tumor markers, including lactate dehydrogenase, α-fetoprotein, and β-human chorionic gonadotropin, aid in the classification and staging of GCTs. These markers therefore play a critical role in the decision-making process when managing GCT patients. However, there exist many scenarios in which these markers fail to perform adequately. This is particularly true in the case of seminoma, where only 10% to 15% will have elevated serum tumor markers. Non-specific elevation of these markers is also a common occurrence, complicating the interpretation of borderline positive results, particularly in follow-up. To bridge this gap in performance, next generation biomarkers are being investigated. In this review, we consider the role of conventional serum tumor markers in GCT management and discuss recent advances in the next generation of biomarkers, with a focus on circulating microRNAs. We discuss the value that circulating microRNAs could bring as an addition to currently used markers, as well as potential weaknesses, in GCT management.

Objectives To evaluate the utility of blue-light flexible cystoscopy (BLFC) for surveillance of non-muscle-invasive bladder cancer (NMIBC). Patients and methods Prospective cohort of consecutive patients who underwent office-based BLFC for NMIBC. Clinical information was collected including cystoscopic findings and pathological data. Results A total of 322 cases were performed on 190 patients. The mean age was 71 years and 83% were men. The highest stage prior to BLFC was Ta, carcinoma in situ (CIS), T1, and T2 in 45.3%, 18.4%, 30% and 2%, respectively. Prior to BLFC, 16.8%, 60.5%, and 16.8% were low grade (LG), high grade (HG), and CIS, respectively. Intravesical bacille Calmette-Guerin and intravesical chemotherapy were used in 54.2% and 18.4%, respectively. White-light cystoscopy (WLC) and BLFC were both normal in 173 (53.7%) of cases. WLC was normal and BLFC was abnormal in 26 (8%) cases. Of these, 15 had office-based biopsy and cancer was detected in 13 (87%; six CIS, four HG Ta, three LG Ta). Both WLC and BLFC were positive in 83 (25.8%) cases and 33% had additional tumours found. Cancer was found in 27 (75%) of WLC+/BLFC+ who underwent office-based biopsy including 19 LG Ta, six HG Ta, and two CIS. Conclusions Incorporation of BLFC in clinical practice has potential advantages of finding cancer in cases with normal WLC. BLFC detected additional cancers in 33% of patients with positive WLC and BLFC, which can improve surveillance and performance of office-based biopsy. Further research is needed to determine cost-effectiveness and impact on recurrence rates.

Management of patients with early-stage germ cell tumors is nuanced and complex as the aim is to maintain excellent cure rates while minimizing treatment-related morbidity. Comparison of the American Urological Association and European Association of Urology testicular cancer guidelines highlight opportunities to optimize care.

There are several treatment approaches for stage II germ cell tumors (GCTs), and a thorough understanding of the staging classification and histologic differences in tumor biology and therapeutic responsiveness is critical to determine an effective, multimodal management strategy that involves urologists, medical oncologists, and radiation oncologists. This article discusses contemporary management strategies for stage II GCTs, including chemotherapy, radiotherapy, retroperitoneal lymph node dissection (RPLND), and surveillance. Patient selection, histology, and extent of lymphadenopathy drive management, and, as both treatment and detection strategies continue to emerge and be refined, the management of patients with stage II GCT continues to evolve.

Purpose of review Understanding the molecular basis underlying testicular germ cell tumors (TGCTs) may help improve patient outcomes, particularly for patients with poorer risk or chemoresistant disease. Here, we review the major contemporary advances in elucidating TGCT genetics by discussing patterns of TGCT inheritance, recent genomic and transcriptomic discoveries in TGCT, and the role of genetics in predicting therapeutic resistance and in guiding treatment. Recent findings In the absence of a major high-penetrance TGCT susceptibility gene, inheritance is likely driven by a complex polygenic model with considerable variation. The most common genomic alterations found in TGCTs include gains in chromosome 12p and mutations in KIT, KRAS, and NRAS, particularly in seminomas. Sensitivity to cisplatin-based chemotherapy likely relies on intact TP53, reciprocal loss of heterozygosity, and high mitochondrial priming. Targetable mutations are uncommon in TGCTs, however, posing a challenge for the development of effective personalized therapies. Consistent with the characteristically low tumor mutational burden, immune checkpoint inhibitors do not appear to be effective for most TGCTs. Summary Refinements in next-generation sequencing techniques over the last few years have enabled considerable advances in elucidating the genomic, transcriptomic, and epigenetic landscape of TGCTs. Future efforts focused on developing novel treatment modalities are needed.

Objectives To determine the implications of different prostate sampling schemes on the diagnosis of clinically significant prostate cancer (csPCA, ISUP group 2–5) and clinically insignificant prostate cancer (ciPCA, ISUP group 1) in men with abnormal multiparametric magnetic resonance imaging (mpMRI) undergoing MRI-transrectal ulrasound fusion targeted biopsies. Materials and Methods This is a retrospective analysis of a cohort including all men who had a single lesion on mpMRI of the prostate performed between January 2016 and June 2017. All men underwent an MRI-transrectal ulrasound fusion biopsy and systematic (SBx) sampling of the prostate, which combined and were considered the standard of reference. The hypothetical 3 biopsy sampling schemes were defined as follows: Targeted biopsy only (TBx), TBx + ipsilateral SBx (ipsi-SBx) and TBx + contralateral SBx (contra-SBx) and were evaluated for the detection of csPCA and ciPCA. Sensitivity and 95% intervals were calculated, McNemar test was used to compare sensitivities between the various sampling schemes. Results TBx + SBx detected csPCa in 47% (55 of 116) of the 116 men who met eligibility criteria. Sensitivity and 95% confidence intervals for csPCa detection was 85.5% (73.3%–93.5%), 96.4% (87.5%–99.6%), and 92.7 (82.4%–98%) for TBx alone, TBx + ipsi-SBx and TBx + contra-SBx, respectively. csPCa detection rates were higher for both TBx + ipsi-SBx and TBx + contra-SBx compared to TBx alone. Clinically insignificant cancers alone were detected in 7.7% (9 of 116), 10.3% (12 of 116), and 14.6% (17 of 116) of the cohort by TBx only and TBx + ipsi-SBx, and TBx + contra-SBx, respectively. Conclusions TBx + ipsi-SBx may increase the detection of csPCa while limiting overdiagnosis of indolent cancers.

OBJECTIVES To perform a comparative analysis of perioperative outcomes and hospitalisation cost between open (OSP) and robot-assisted simple prostatectomy (RASP) for treatment of benign prostatic hyperplasia (BPH) using the National Inpatient Sample (NIS) in the contemporary robotic era. MATERIALS AND METHODS The NIS was queried for cases of OSP and RASP for the treatment of BPH between 2013 and 2016. Perioperative complications, unadjusted hospital cost and length of stay (LOS) were compared between RASP and OSP. Smoothed linear regression curves comparing hospitalisation cost by increasing LOS was stratified by surgical approach to identify point of cost equivalency between RASP and OSP. Multivariable linear regression analysis was used to construct a hospitalisation cost model to examine the contribution of the robotic approach and LOS to hospitalisation cost. RESULTS The total analytical cohort included 2551 OSP and 704 RASP procedures. Patients undergoing RASP were younger, at a median (interquartile range [IQR]) age of 68 (63-73) vs 71 (65-77) years, and with less comorbidity (76.8% vs 86.5%, P < 0.01). RASP was associated with fewer total complications (11.1% vs 29.2%, P < 0.01) and a greater likelihood of routine discharge to home rather than another facility (88.9% vs 76.7%, P < 0.01). While LOS was shorter with RASP (median [IQR], 2 [1-3] vs 4 [3-6] days, P < 0.01), total unadjusted hospitalisation cost (in United States dollars) was greater (median [IQR], $10 855 [$7965-$15 675] vs $13 467 [$10 572-$17 722], P < 0.01). Presence of any complication increased both LOS and hospitalisation cost (P < 0.01). Linear regression modelling determined the point of cost equivalence between RASP staying a median of 2 days was an OSP case staying between 5 and 6 days. On multivariable regression analysis, the robotic approach contributed an additional $6175 (P < 0.01) to the cost model, whereas each additional day of hospitalisation contributed $1687 (P < 0.01), suggesting LOS would need to be 3-4 days shorter with RASP to offset surgical costs of the robot. CONCLUSIONS While RASP appears to have significantly better perioperative complication rates with shorter LOS and likely discharge to home, total hospitalisation cost remained greater, likely related to upfront operative costs. While this retrospective study is limited by selection bias for patients undergoing RASP, the benefits of improved convalescence, discharge to home, and lower rate of perioperative complications appear to justify performance of RASP in an experienced pelvic robotic centre despite relatively greater hospitalisation cost if referral to an experienced holmium laser enucleation of the prostate centre is not feasible.

Current serum tumor markers for testicular germ cell tumor are limited by low sensitivity. Growing evidence supports the use of circulating miR-371a-3p as a superior marker for malignant (viable) germ cell tumor management. We evaluated the real-world application of serum miR-371a-3p levels in detecting viable germ cell tumor among patients undergoing partial or radical orchiectomy.Serum samples were collected from 69 consecutive patients before orchiectomy. Performance characteristics of serum miR-371a-3p were compared with conventional serum tumor markers (⍺-fetoproteinFor detecting viable germ cell tumor, combined conventional serum tumor markers had a specificity of 100%, sensitivity of 58% and AUC of 0.79. The miR-371a-3p test showed a specificity of 100%, sensitivity of 93% and AUC of 0.978. Median relative expression of miR-371a-3p in viable germ cell tumor cases was more than 6,800-fold higher than in those lacking viable germ cell tumor. miR-371a-3p levels correlated with composite stage (p=0.006) and, among composite stage I cases, independently associated with embryonal carcinoma percentage (p=0.0012) and tumor diameter (p0.0001). Six patients underwent orchiectomy after chemotherapy and were correctly predicted to have presence or absence of viable germ cell tumor by the miR-371a-3p test.If validated, the miR-371a-3p test can be used in conjunction with conventional serum tumor markers to aid clinical decision making. A positive miR-371a-3p test in patients after preoperative chemotherapy or with solitary testes could potentially guide subsequent orchiectomy or observation.

To compare perioperative outcomes and perform the first cost analysis between open retroperitoneal lymph node dissection (O-RPLND) and Robotic-RPLND (R-RPLND) using a national all-payer inpatient care database. Nationwide Inpatient Sample (NIS) was queried between 2013–2016 for primary RPLND and germ cell tumor. We compared cost, length of stay (LOS), and complications between O-RPLND and R-RPLND. Linear regression plots identified point of cost equivalence between R-RPLND and O-RPLND. A multivariable linear regression model was generated to analyze predictors of cost. 44 cases of R-RPLND and 319 cases of O-RPLND were identified. R-RPLND was associated with lower rate of complications (0% vs. 16.6%, p

Background Owing to surgical complexity and controversy regarding indications, there are wide practice variations in the use of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). Objective To evaluate patterns of PC-RPLND use in the USA and evaluate the association between PC-RPLND and survival in advanced nonseminomatous germ cell tumors (NSGCTs). Design, setting, and participants A retrospective, observational study using National Cancer Data Base (NCDB) data from 2004–2014 for 5062 men diagnosed with stage II/III NSGCT. Outcome measurements and statistical analysis In a comparative analysis based on receipt of PC-RPLND, the primary outcome of interest was factors associated with omission of PC-RPLND as explored via logistic regression. As a secondary outcome, we evaluated the association between PC-RPLND and overall survival (OS) via multivariable Cox regression and propensity score matching (PSM). Results and limitations Patients undergoing PC-RPLND were more likely to be younger, white, privately insured, and reside in more educated/wealthier regions (p Conclusions PC-RPLND represents a critical part of the multidisciplinary management of NSGCT. Patients with non-private insurance are less likely to undergo PC-RPLND, and omission of PC-RPLND is associated with lower OS. Patient summary We evaluated the practice patterns for advanced testicular cancer management and found that patients who did not undergo a postchemotherapy retroperitoneal lymph node dissection were more likely to have worse survival outcomes. Patients with unfavorable insurance were less likely to receive this surgical treatment.

We evaluated the discordance between ureteroscopic biopsy and surgical pathology findings for grading and staging upper tract urothelial carcinoma. We also sought to establish preoperative predictors of aggressive tumors.We retrospectively reviewed the records of 314 patients who underwent ureteroscopic biopsy followed by surgical management of upper tract urothelial carcinoma from 2000 to 2016 at a total of 3 institutions. Our primary outcomes were muscle invasive (pT2 or greater) disease at surgical pathology and upgrading of clinical low grade tumors to pathological high grade.At biopsy 61% of the patients had clinical high grade tumors and 21% had subepithelial connective tissue invasion (cT1+). On final pathology 79% of the patients had pathological high grade tumors and 45% had stage pT2 or greater. On multivariate analysis advanced patient age, clinical high grade and cT1+ were independently associated with pT2 or greater. The combined presence of clinical high grade and cT1+ had 86% positive predictive value for muscle invasion while the combined absence of clinical high grade and cT1+ had 80% negative predictive value. The likelihood of missing invasion on biopsy in patients with muscle invasive disease was increased when biopsy fragments were limited to 1 mm or less. Of clinical low grade cases on biopsy 51% were upgraded at surgery. The presence of positive urine cytology was associated with an increased risk of upgrading but this was not statistically significant.Clinical high grade, cT1+ on biopsy and advanced patient age are independent risk factors for muscle invasive upper tract urothelial carcinoma. There is a significant risk of upgrading in patients with clinical low grade tumors on biopsy, especially when urine cytology is positive. The predictive value of biopsy can likely be improved by more extensive ureteroscopic sampling.

Objective To describe epidemiologic patterns, stage at presentation, histology, and treatment differences associated with Hispanic men diagnosed with testicular germ cell tumor (TGCT). Hispanics are the fastest growing demographic in the United States and reports suggest that the incidence of TGCT is rising most rapidly in this demographic, yet little is known about TGCTs in Hispanic patients. Materials and Methods We compared patient factors, tumor characteristics, treatment patterns, and outcomes of non-Hispanic white (NHW) vs Hispanic patients at our own institution in North Texas from 2010 to 2016. The findings were corroborated by analyzing the National Cancer Database testicular cancer registry from 2004 to 2014. Results We identified 154 patients with TGCT at our institution, of which 89 were NHW (56.0%) and 65 were Hispanic (40.9%). A review of the National Cancer Database identified 49,607 NHW patients (81.5%) and 6724 Hispanic patients (11.0%) diagnosed with TGCT. At presentation, Hispanic patients were approximately 5 years younger than NHW patients, delay seeking care for testicular cancer, were more likely to have nonseminomatous histology, had a larger tumor size, and had a higher disease burden at presentation. Additionally, we identified differences in treatment patterns at the national level. Conclusion Differences in outcomes and treatment patterns of Hispanic and NHW patients with TGCT may represent underlying socioeconomic issues and access to care; however, discrepancies in age of onset and histology of TGCT between Hispanic and NHW patients may signify differences in tumor biology or risk factors. We suggest that this possibility be explored further as we embark upon the genomic classification of TGCT.

Purpose Metastasis-directed radiation therapy (MDRT) may improve oncologic and quality of life outcomes in patients with metastatic cancer, but data on its use in metastatic bladder cancer is severely limited. We sought to review our institutional experience with MDRT in patients with metastatic bladder cancer following radical cystectomy. Materials and Methods We reviewed records of patients who underwent radical cystectomy and subsequent MDRT at our institution between 2009 and 2020. Baseline demographic and clinical/pathologic factors were collected, as were details of treatment including systemic therapy and MDRT. Cases were categorized by treatment intent as consolidative (intended to prolong survival) and palliative (intended only to relieve symptoms). Response to treatment, survival, and toxicity outcomes were reviewed. Results A total of 52 patients underwent MDRT following radical cystectomy. MDRT was categorized as consolidative in 40% of cases and palliative in 60%. Toxicity (CTCAE Grade ≥ 2) was reported in 15% of patients, none of which exceeded Grade 3. Most patients undergoing consolidative MDRT were treated with SBRT techniques (76%) and a majority (67%) received concurrent treatment with an immuno-oncology agent. Among patients treated with consolidative intent, 2-year progression-free and overall survival were 19% and 60%, respectively. Conclusion MDRT is safe and well-tolerated by a majority of patients. A majority of patients treated with consolidative intent survived ≥ 2 years from treatment.

We report pathological, functional and oncologic outcomes in patients treated with radical nephroureterectomy following radical cystectomy.We identified patients who underwent radical cystectomy and then radical nephroureterectomy for metachronous urothelial recurrence at our institution between January 1995 and December 2014. Univariable Cox regression was used to assess the association between overall survival and age, grade, stage, lymph node metastasis and radiographic findings.Of the 3,173 patients treated with radical cystectomy 64 underwent subsequent radical nephroureterectomy for metachronous urothelial recurrence. Median age at radical cystectomy was 66 years (IQR 61-74). In the 64 patients who underwent radical nephroureterectomy median time from radical cystectomy to radical nephroureterectomy was 2.7 years (IQR 1.4-4.6). Among 37 patients who underwent ureteroscopy prior to radical nephroureterectomy 29 (78%) had a positive biopsy. Radical nephroureterectomy pathology findings revealed locally advanced disease (pT3/pT4) in 39% of cases and positive node status in 11% compared with locally advanced disease in 17% and positive node status in 6% on radical cystectomy pathology findings. The post-radical nephroureterectomy estimated glomerular filtration rate was less than 60 and less than 30 ml/minute/1.73 mThe prognosis is poor in patients with panurothelial carcinoma treated with nephroureterectomy following cystectomy with locally advanced disease in a large proportion. Renal function after these procedures diminished and almost all patients were ineligible for cisplatin based chemotherapy.

With recent advances in immunooncology and the introduction of checkpoint inhibitors into clinical practice for many cancers, the treatment landscape of urothelial carcinoma has changed dramatically and will continue to change further. Currently, a number of compounds and combinations are under investigation in numerous clinical trials and various clinical scenarios for bladder cancer. Areas covered: In this review, the authors provide an overview of the history and rationale for immunotherapy in bladder cancer. They also provide the currently available data evaluating checkpoint inhibitors for bladder cancer, and discuss ongoing trials and future perspectives for urothelial carcinoma treatment. Expert opinion: The introduction of checkpoint inhibitors into the management of bladder cancer marks a significant milestone for this disease. Checkpoint inhibitors have the potential to impact patients across multiple disease states from non-muscle-invasive disease to metastatic tumors refractory to conventional treatment. That being said, validated biomarkers, including genetic signatures, to accurately predict response, and the establishment of optimal sequencing and combination of these immunotherapeutic agents with chemo/radiotherapy are urgently needed.

Non-muscle-invasive bladder cancer (NMIBC) represents the vast majority of bladder cancer diagnoses, but this definition represents a spectrum of disease with a variable clinical course, notable for significant risk of recurrence and potential for progression. Management involves risk-adapted strategies of cystoscopic surveillance and intravesical therapy with the goal of bladder preservation when safe to do so. Multiple organizational guidelines exist to help practitioners manage this complicated disease process, but adherence to management principles among practising urologists is reportedly low. We review four major organizational guidelines on NMIBC: the American Urological Association (AUA)/Society of Urologic Oncology (SUO), European Association of Urology (EAU), National Comprehensive Cancer Network (NCCN), and National Institute for Health and Care Excellence (NICE) guidelines.

Objective To evaluate the pathologic response, safety, and feasibility of nephrectomy following receipt of immune checkpoint inhibition (ICI) for renal cell carcinoma (RCC). Methods Patients who underwent nephrectomy for RCC after exposure to nivolumab monotherapy or combination ipilimumab/nivolumab were reviewed. Primary surgical outcomes included operative time (OT), estimated blood loss (EBL), length of stay (LOS), readmission rates, and complication rates. Pathologic response in the primary and metastatic sites constituted secondary outcomes. Results Eleven nephrectomies (10 radical, 1 partial) were performed in 10 patients after ICI with median postoperative follow-up 180 days. Six patients received 1 to 4 cycles of ipilimumab/nivolumab, while 5 received 2 to 12 infusions of nivolumab preoperatively. Five surgeries were performed laparoscopically, and 4 patients underwent concomitant thrombectomy. One patient exhibited complete response (pT0) to ICI, and 3/4 patients who underwent metastasectomy for hepatic, pulmonary, or adrenal lesions exhibited no detectable malignancy in any of the metastases resected. No patients experienced any major intraoperative complications, and all surgical margins were negative. Median OT, EBL, and LOS were 180 minutes, 100 ml, and 4 days, respectively. Four patients experienced a complication, including 3 that were addressed with interventional radiology procedures. One patient died of progressive disease >3 months after surgery, and 1 patient succumbed to pulmonary embolism complicated by sepsis. No complications or readmissions were noted in 6 patients. Conclusion Nephrectomy following ICI for RCC is safe and technically feasible with favorable surgical outcomes and pathologic response. Timing of the nephrectomy relative to checkpoint dosing did not seem to impact outcome. Biopsies of lesions responding radiographically to ICI may warrant attention prior to surgical excision.

Background Management strategies for advanced testicular cancer published from a few, high-volume clinical centers may not be generalizable. Objective To discern treatment patterns for stage II nonseminomatous germ cell tumor (NSGCT) in a nationwide cancer registry. Design, setting, and participants The National Cancer Database was queried for patients with a stage II NSGCT from 2004 to 2014. Patients were stratified by clinical nodal status: cN1/stage IIA, cN2/stage IIB, and cN3/stage IIIC. Outcomes measurements and statistical analysis Logistic regression was performed to determine factors independently associated with primary retroperitoneal lymph node dissection (RPLND), primary chemotherapy, and postchemotherapy RPLND (PC-RPLND). Results and limitations A total of 2203 patients (stages IIA, n = 1060; IIB, n = 869; and IIC, n = 274) met the inclusion criteria. Overall, 83% of patients underwent primary chemotherapy, while 17% underwent primary RPLND. Stratified by stage, use of primary chemotherapy was 78%, 88%, and 86% for stages IIA, IIB, and IIC, respectively. Overall, 24% of patients underwent PC-RPLND. Factors independently associated with a lower likelihood of undergoing primary RPLND were a more recent diagnosis and a higher clinical nodal stage. Conversely, patients treated at high-volume facilities were more likely to receive primary RPLND. Factors associated with a higher likelihood of undergoing PC-RPLND included a higher clinical nodal stage, treatment at a high-volume center, and a greater distance of patient travel. Associations based on serum tumor markers could not be assessed. Conclusions For clinical stage II NSGCT, nationwide utilization of primary chemotherapy is increasing compared with RPLND and is the preferred therapy for more advanced nodal disease. Primary RPLND may be underutilized in stage IIA disease. Utilization of PC-RPLND is driven by nodal stage as well as accessibility of a high-volume center. Patient summary The use of primary retroperitoneal lymph node dissection (RPLND) in early nodal disease is declining, while upfront chemotherapy is increasingly utilized. Primary RPLND may identify patients who are actually pN0 and would not benefit from systemic chemotherapy. Primary RPLND and postchemotherapy RPLND are performed more frequently at centers of excellence.

Purpose To identify preoperative risk factors for disease recurrence, following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), and to create a predictive nomogram. Materials and methods Based on a multicenter database, we identified patients who underwent RNU due to high grade UTUC. Urothelial carcinoma of the bladder or contralateral UTUC was not considered as recurrence. Cox regression model was used to determine the effect of different preoperative variables as predictors of recurrence. Results Two hundred and forty-five patients were included in the analysis. The 2 and 5 years recurrence rates were 16.3% and 19.2%, respectively. Factors associated with recurrence on univariable analysis were sessile architecture hazard ratio (HR) 3.16 (95% CI, 1.38–7.26, P = 0.006), ≥cT3 disease HR 2.30 (95% CI, 1.12–4.72, P= 0.023), age >65 HR 2.02 (95% CI, 1.00–4.05, P= 0.048), Eastern Cooperative Group > 0 HR 1.98 (95% CI, 1.09–3.57, P= 0.023), hydronephrosis HR 1.93 (95% CI, 1.04–3.57, P= 0.035). Higher hemoglobin levels HR 0.81 (95% CI, 0.69–0.96, P= 0.013) and preoperative estimated glomerular filtration rate ≥ 50 HR 0.48 (95% CI, 0.25–0.92, P = 0.028) were associated with lower probability for recurrence. Multivariable analysis identified sessile architecture as the only independent predictor of recurrence HR 2.52 (95% CI, 1.09–5.86, P= 0.0308). C-index of 0.71 was calculated for a predictive model including all variables in the multivariable analysis, indicating good predictive accuracy. A nomogram predicting 2 and 5 year recurrence free probability was developed accordingly. Conclusions Based on a multicenter database, we developed a nomogram with good predictive accuracy for recurrence following RNU. This may serve as an aid in decision-making regarding the use of neoadjuvant chemotherapy.

To evaluate the prognostic value of BRCA1-associated protein-1 (BAP1) expression in upper tract urothelial carcinoma (UTUC), as BAP1 mutations have been associated with prognostic implications in urologic and non-urologic malignancies. We reviewed a multi-institutional cohort of patients who underwent radical nephroureterectomy (RNU) for high-grade UTUC from 1990–2008. Immunohistochemistry (IHC) for BAP1 was performed on tissue microarrays. Staining intensity was graded from 0–3, with BAP1 loss defined as an average intensity of

Introduction Percutaneous renal mass biopsy results can accurately diagnose clear cell renal cell carcinoma (ccRCC); however, their reliability to determine nuclear grade in larger, heterogeneous tumors is limited. We assessed the ability of radiomics analyses of magnetic resonance imaging (MRI) to predict high-grade (HG) histology in ccRCC. Patients and Methods Seventy patients with a renal mass underwent 3 T MRI before surgery between August 2012 and August 2017. Tumor length, first-order statistics, and Haralick texture features were calculated on T2-weighted and dynamic contrast-enhanced (DCE) MRI after manual tumor segmentation. After a variable clustering algorithm was applied, tumor length, washout, and all cluster features were evaluated univariably by receiver operating characteristic curves. Three logistic regression models were constructed to assess the predictability of HG ccRCC and then cross-validated. Results At univariate analysis, area under the curve values of length, and DCE texture cluster 1 and cluster 3 for diagnosis of HG ccRCC were 0.7 (95% confidence interval [CI], 0.58-0.82, false discovery rate P = .008), 0.72 (95% CI, 0.59-0.84, false discovery rate P = .004), and 0.75 (95% CI, 0.63-0.87, false discovery rate P = .0009), respectively. At multivariable analysis, area under the curve for model 1 (tumor length only), model 2 (length + DCE clusters 3 and 4), and model 3 (DCE cluster 1 and 3) for diagnosis of HG ccRCC were 0.67 (95% CI, 0.54-0.79), 0.82 (95% CI, 0.71-0.92), and 0.81 (95% CI, 0.70-0.91), respectively. Conclusion Radiomics analysis of MRI images was superior to tumor size for the prediction of HG histology in ccRCC in our cohort.

Background The American Joint Committee on Cancer 8th edition staging guidelines for testicular cancer established a 3 cm cutoff to subclassify stage T1 seminomas ( Methods We retrospectively reviewed patients with pT1 testicular seminoma in the National Cancer Database from 2004 to 2016. Receiver operating curves were used to determine the efficacy of the 3 cm tumor cutoff in identifying metastatic disease, and multivariable regression was used to compute the effect of tumor size on the rate of adjuvant therapy among Stage I patients. Results A total of 10,134 patients with pT1 seminoma were evaluated. The current size cutoff of 3 cm for subclassification did not exhibit high discrimination in identifying metastatic disease (area under receiver operating curve: 0.546). Surveillance has grown as the preferred treatment after orchiectomy −32.1% in 2004 to 81.2% in 2015. However, the rate of adjuvant therapy for pT1, Stage I seminomas associated positively with tumor size even with adjustment for year of diagnosis. For tumors above 3 cm, the odds ratio stabilized around 1.9. By using the 3 cm cutoff to guide adjuvant therapy, up to 85% of T1b patients may be overtreated. Conclusion The 3 cm cutoff for subclassification of Stage I seminoma does not predict metastatic recurrence but is associated with increased receipt of adjuvant therapy. A 3 cm cutoff and the pT1a/b classification may therefore contribute to overtreatment in many young patients with a long life expectancy for whom minimizing adverse effects should be prioritized.

Objective Whether pathologic stage at radical nephroureterectomy (RNU) can serve as an appropriate surrogate for oncologic outcomes in patients with high-grade (HG) upper tract urothelial carcinoma (UTUC) treated with neoadjuvant chemotherapy (NAC) is not defined. We sought to determine whether patients who achieve pathologically non-muscle-invasive (ypT0, ypTa, ypT1, ypTis) HG UTUC after receipt of NAC exhibit oncologic outcomes comparable to those who are inherently low stage without chemotherapy. Methods We identified 647 UTUC patients who underwent RNU among 3 institutions from 1993to2016. Patients with low or unknown grade, pathologic muscle invasion, or receipt of adjuvant chemotherapy were excluded. We compared clinicopathologic data and oncologic outcomes between pT0-1 and ypT0-1 patients. Kaplan-Meier analysis was used to assess overall (OS), cancer-specific (CSS), and systemic recurrence-free (RFS) survival. Predictors of these endpoints were identified using Cox regression. Results 234 (43 ypT0-1, 191 pT0-1) patients with HG UTUC were included. Two patients exhibited pathologic complete response after NAC. OS (P = 0.055), CSS (P = 0.152), and RFS (P = 0.098) were similar between ypT0-1 and pT0-1 patients. Predictors of worse outcomes included African-American race (RFS, CSS, and OS), Charlson score (OS), and systemic recurrence (OS and CSS). Conclusions Patients with HG UTUC who achieve ypT0-1 stage after NAC exhibit favorable oncologic outcomes comparable to those inherently non-muscle-invasive who do not receive chemotherapy. Improvements in clinical staging will play an important role in better defining candidacy for NAC in treating HG UTUC while minimizing overtreatment. Furthermore, pathologic stage may serve as an appropriate early surrogate for oncologic endpoints in designing clinical trials.

Purpose Single, postoperative instillation of prophylactic intravesical chemotherapy (pIVC) is effective in reducing bladder cancer recurrences following radical nephroureterectomy (RNU). Despite high level evidence, pIVC is underutilized. Intraoperative pIVC (I-pIVC) may be easier and safer to implement than postoperative pIVC (P-pIVC). We aimed to evaluate the efficacy of I-pIVC during RNU. Materials and methods Retrospective analysis of patients undergoing RNU and I-pIVC or postoperative pIVC (P-pVC) with 20 to 40 mg mitomycin-C or 1 to 2 g gemcitabine. Recurrence rates were evaluated using the Kaplan-Meier curves and log rank test. Cox regression was used for univariable and multivariable analysis. Results One hundred and thirty-seven patients were included in the final analysis. 81% (111/137) had I-pIVC and 19% (26/137) had P-pIVC. In the I-pIVC group higher rates of HG, muscle invasive disease and gemcitabine use were observed. Overall, 74% (101/137) and 26% (36/137) had mitomycin-C and gemcitabine instillations, respectively. Within 12 months 14% (19/137) of the patients experienced bladder recurrence. Median time to bladder recurrence was 7 months (range 3–27). Twelve months bladder recurrence-free survival rates were 82% for the I-pIVC group, and 72% for the P-pIVC group ((log rank P = 0.365). Conclusions I-pIVC during RNU may reduce bladder recurrence rates. Bladder recurrence rates are comparable to those reported using postoperative instillations. Intraoperative instillations may be easier to implement and may increase usage rates.

There is controversy regarding the benefit of a grossly complete transurethral resection of bladder tumor (TURBT) for muscle-invasive bladder cancer (MIBC) in patients prior to neoadjuvant chemotherapy (NAC). Advocates for this approach suggest a higher response rate to NAC, while others suggest this can increase the surgical risk for no clear benefit.We retrospectively reviewed our institutional radical cystectomy (RC) database from 2011 to 2018 for patients who received an adequate course of cisplatin-based NAC for nonmetastatic MIBC. Univariable and multivariable logistic regression analyses were performed to identify factors associated with complete response [ypT0] or no residual muscle invasive bladder cancer [ypT2] following NAC based on clinicopathologic characteristics and grossly complete or incomplete TURBT.A total of 167 patients received NAC followed by RC for MIBC during the study period and 100 patients were included in the analysis due to known status of the completeness of TURBT-of these 49 patients underwent complete resection while 51 patients underwent incomplete resection prior to NAC. There were no significant differences in baseline clinicopathologic characteristics between patients who had complete vs. incomplete TURBT. At the time of RC, the overall ypT0 rate was 24% (n = 24), while the overall rate of ypT2 was 45%. On logistic regression, there was no association between completeness of TURBT and ypT0 or ypT2. Age, histology, and organ-confined disease were not significantly associated with response to NAC. Only smoking status (current or prior history) was negatively associated with ypT0 on univariable and multivariable analysis (odds ratio = 0.36, 95% confidence interval: [0.14-0.91], P = 0.031).We found no association between response to cisplatin-based NAC and completeness of TURBT in a cohort of MIBC patients. The study is limited by its retrospective nature and lack of ability to predict response to NAC based on TURBT tissue evaluation.

OBJECTIVES: Despite immune checkpoint inhibitor (ICI) approval for metastatic renal cell carcinoma (mRCC) in 2015, cytoreductive nephrectomy (CN) is guided by extrapolation from earlier classes of therapy. We evaluated survival outcomes, timing, and safety of combining CN with modern immunotherapy (IO) for mRCC. METHODS: From 96,329 renal cancer cases reported to the NCDB between 2015–2016, we analyzed 391 surgical candidates diagnosed with clear cell mRCC treated with IO±CN and no other systemic therapies. Primary outcome was overall survival (OS) stratified by the per formance of CN (CN+IO vs. IO alone). Secondary outcomes included OS stratified by the timing of CN, pathologic findings, and perioperative outcomes. RESULTS: Of 391 patients, 221 (56.5%) received CN+IO and 170 (43.5%) received IO only. Across a median follow-up of 14.7 months, patients who underwent CN+IO had superior OS (median NR vs. 11.6 mos.; HR 0.23, p

Purpose of review We aim to give an overview of the epidemiology and treatment trends of testicular germ cell tumors (TGCTs), with an emphasis on recent trends. Recent findings The incidence of TGCT appears to be increasing, particularly in developed countries, although the reasons are not well understood. There is evidence of racial differences in predisposition to TGCT, with white men having highest risk and men of African or Asian descent having lower risk. In the United States, the incidence of TGCT among Hispanics appears to be rising most quickly. A recent genomic analysis indicates there is no highly penetrant major TGCT susceptibility gene. Incorporation of multidisciplinary care has led to excellent long-term cure rates; however, access to care and insurance remains barriers in young men. Recent treatment trends have centered on maximizing oncologic outcomes while minimizing long-term morbidity. Summary Emerging population-level data provide critical insight into the evolving demographics of TGCT, which may allow for elucidation of biologic and environmental determinants of TGCT. Further, identification of socioeconomic barriers to excellent clinical outcomes will allow for targeted interventions to patients with unique demographic and socioeconomic considerations. Treatment trend analyses suggest that the field is moving toward minimizing treatment-related morbidity.

With the increasing adoption of targeted prostate biopsies, it becomes important to understand the strengths and shortcomings of the techniques available for targeting suspicious lesions.To compare clinically significant prostate cancer (csPCa) detection rate with magnetic resonance imaging-transrectal ultrasound (MRI-TRUS) fusion versus in-bore biopsy in men with abnormal multiparametric MRI (mpMRI).This single-center, retrospective analysis of prospectively generated data included all men with abnormal mpMRI and fusion or in-bore biopsy between May 2017 and April 2018. Grade group (GG) 2-5 cancers were considered csPCa.Detection of csPCa was adjusted according to patient- and lesion-related characteristics using propensity score weighting. Secondary endpoints included the detection of clinically insignificant tumors and the rate of GG upgrade from biopsy to prostatectomy specimen. Analyses were performed at patient and lesion levels.A total of 103 and 300 men were included in the in-bore and fusion cohorts, respectively. On a per-patient basis, in-bore biopsies detected a higher proportion of csPCa (61%, 63/103) than fusion plus systematic biopsies (47%, 141/300; adjusted odds ratio [OR]: 2.1, 95% confidence interval [CI]: 1.6-2.8, p0.0001). In-bore biopsies also detected fewer (11%, 11/103) clinically insignificant cancers than fusion biopsies (18%, 53/300; OR: 0.5, 95% CI: 0.3-0.8, p=0.001). Of those who had radical prostatectomy, GG upgrade after surgery was seen in 17% (4/24) of the men in the in-bore cohort and in 27% (22/82) of the men in the fusion cohort (p=0.55).MRI-guided in-bore biopsies detected more clinically significant and fewer insignificant prostate cancers than MRI-TRUS fusion targeted biopsies. Further cost-utility and patient outcome analyses are needed.In-bore biopsies (where the patient is on the magnetic resonance imaging [MRI] scanner itself) detected more aggressive cancers and fewer indolent cancers than fusion (where software blends MRI and ultrasound images) biopsies. These findings may help patients and physicians choose the best biopsy approach.

Enhancer of zeste homolog 2 is a methyltransferase encoded by the EZH2 gene, whose role in upper tract urothelial carcinoma (UTUC) is poorly understood. We sought to evaluate the prognostic value of EZH2 expression in UTUC.We reviewed a multi-institutional cohort of patients who underwent radical nephroureterectomy for high-grade UTUC from 1990 to 2008. Immunohistochemistry for EZH2 was performed on tissue microarrays. Percentage of staining was evaluated, and the discriminative value of EZH2 was tested, with EZH2 positivity defined as20% staining present. Clinicopathologic characteristics and oncologic outcomes (recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS)) were compared, stratified by EZH2 positivity. The prognostic role of EZH2 was assessed using Kaplan-Meier, univariate (UVA), and multivariate (MVA) Cox regression analyses. Significance was defined for P0.05.A total of 376 patients were included for analysis, with median follow-up 36.0 months. Overall, 78 (20.7%) were EZH2-positive. EZH2 expression was more often associated with ureteral location, lymphovascular invasion, sessile architecture, necrosis, and concomitant carcinoma in situ. On UVA, increased EZH2 expression was a significant predictor for inferior RFS (HR 1.63, P = 0.033), CSS (HR 2.03, P = 0.003), and OS (HR 2.11, P0.001). On MVA EZH2 remained a significant predictor of worse CSS (HR 1.99 [95% CI: 1.21-3.27], P = 0.007) and OS (HR 1.54 [95% CI: 1.06-2.24], P = 0.024), while significance was lost for RFS.Increased EZH2 expression is associated with adverse pathologic features and inferior oncologic outcomes in patients with high-grade UTUC. The role of EZH2 biology in UTUC pathogenesis remains to be further elucidated.

BACKGROUND: Radical nephrectomy with inferior vena cava thrombectomy (RN-IVCT) is a complicated procedure for which the impact of hospital case volume on overall survival (OS) is unknown. OBJECTIVE: To assess the degree to which renal cell carcinoma (RCC) with inferior vena cava tumor thrombus (IVC-TT) care is centralized and to evaluate the impact of hospital case volume on outcomes following RN-IVCT. DESIGN, SETTING, AND PARTICIPANTS: The National Cancer Data Base was queried for patients with pT3b–c RCC treated with RN-IVCT. Hospitals were classified by case volume percentile as low (95th percentile, >3 cases annually). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was OS. Secondary outcomes were short-term (30- and 90-d) mortality rates according to hospital case volume. Kaplan-Meier curves and Cox regression model were used to evaluate OS and the effect of covariables. RESULTS AND LIMITATIONS: There were 2664 cases of RN-IVCT for pT3b–c tumors reported by 573 institutions, of which 435, 108, and 30 were classified as low, intermediate, and high volume, accounting for 28.5%, 34.5%, and 37% of cases, respectively. Treatment at high-volume institutions was associated with better OS: the median OS was 42, 53, and 60 mo for low, intermediate and high-volume centers, respectively (p = 0.009). After multivariable adjustment, treatment at a high-volume institution was associated with a 24% relative risk reduction for all-cause mortality compared to treatment at a low-volume institution (hazard ratio 0.76, 95% confidence interval 0.65–0.89; p = 0.001). There was no significant difference in short-term mortality following RN-IVCT when stratified by hospital case volume. CONCLUSIONS: Higher hospital case volume was associated with better OS for patients undergoing RN-IVCT. These findings support efforts to centralize care for cases of advanced RCC. PATIENT SUMMARY: In this study we looked at the impact of hospital case volume on survival following surgery for renal cell carcinoma and inferior vena cava thrombectomy. Survival was significantly better in high-volume hospitals performing three or more procedures per year.

PURPOSE: To evaluate the impact of timing of blood transfusion in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). METHODS: Outcomes of consecutive patients with UTUC treated with RNU were analyzed. Clinicopathologic factors were compared using Fisher’s exact test or the Wilcoxon rank-sum test between patients that received any transfusion and no transfusion, and between patients receiving intraoperative transfusion only and patients receiving no transfusion. Cancer-specific and overall survival were estimated and multivariable analyses were performed to assess the impact of timing of transfusion on clinical outcomes. RESULTS: Among 402 patients included in this study, 71 (17.6%) patients received a transfusion at any point and 27 (6.7%) patients received an intraoperative blood transfusion. Transfusion at any time, patient comorbidity, high grade, advanced stage, positive surgical margins, low preoperative hemoglobin, longer operative duration, and increased blood loss were significantly associated with cancer-specific survival (DSS) on univariable analysis (HR 1.85, 95% CI 1.20–2.85, p

MicroRNAs are poised to radically change the way we care for patients with germ cell tumors (GCTs) across all disease states, from diagnosis to managing chemorefractory disease. miR-371a-3p is a promising candidate biomarker that may precisely individualize GCT treatment paradigms.

To assess the potential biologic impact of tumor location on oncological outcomes for patients with upper tract urothelial carcinoma (UTUC), we used prospectively collected molecular signatures of high-grade UTUC. Immunohistochemical staining for p21, p27, p53, cyclin E, and Ki-67 was prospectively performed on 96 UTUC specimens of patients with non-metastatic high-grade UTUC treated with extirpative surgery. Patients were grouped according to primary tumor location (pelvicalyceal vs. ureteral) where primary tumor was defined as the highest tumor stage and diameter. Primary outcome was assessment of differences in marker expression between groups. Secondary outcome was difference in survival according to marker status. Pelvicalyceal and ureteral tumors were found in 52.1 and 47.9 %, respectively, and 42.7 % of patients had non-organ-confined disease. Over a median follow-up of 22.0 months, 31.2 and 20.8 % of patients experienced disease recurrence and died of UTUC, respectively. The total number of altered markers stained for was 0–2 in 67.7 and 3–5 in 32.3 % of patients. The number of altered markers and alteration status of markers were not significantly different between patients with primary pelvicalyceal versus ureteral tumors when stratified by tumor stage and nodal status. There were no significant differences in survival outcomes between both groups when stratified by number of altered markers (0–2 and 3–5). The prospective assessment of selected cell cycle and proliferative markers suggests no molecular difference between UTUC of the pelvicalyceal system and that of the ureter. Our study is limited by its size and definition of location.

To characterize the presence of bland (nontumor) thrombus in advanced renal cell carcinoma and assess the impact of this finding on cancer-specific survival.A multi-institutional database of patients treated with nephrectomy with caval thrombectomy for locally-advanced renal tumors was assembled from 5 tertiary care medical centers. Using clinicopathologic variables including patient age, body mass index, Eastern Cooperative Oncology Group performance status, tumor stage, grade, nodal status and histology, and nearest-neighbor and multiple-matching propensity score matched cohorts of bland thrombus vs nonbland thrombus patients were assessed. Multivariable analysis for predictors of cancer-specific survival was performed.From an initial cohort of 579 patients, 446 met inclusion criteria (174 with bland thrombus, 272 without). At baseline, patients with bland thrombus had significantly worse performance status, higher tumor stage, higher prevalence of regional nodal metastases and higher nuclear grade (P .01 for all). In both nearest-neighbor and multiple-matching propensity score matched cohorts, the presence of bland thrombus presence was associated with inferior median cancer-specific survival (28.1 months vs 156.8 months, and 28.1 months vs 76.7 months, P .001 for both). The presence of bland thrombus remained independently associated with an increased risk of cancer-specific mortality on multivariable analysis (hazard ratio 4.33, 95% confidence interval 2.79-6.73, P .001).Presence of bland thrombus is associated with adverse survival outcomes in patients treated surgically for renal tumors with venous tumor thrombus. These findings may have important implications in patient counseling, selection for surgery and inclusion in clinical trials.

Urothelial carcinoma of the upper tract (UTUC) presents specific challenges regarding accurate staging and tumor sampling. We aimed to assess the feasibility of applying next-generation sequencing to biopsy specimens and gauged the concordance of their genetic profiles with matched radical nephroureterectomy (RNU) specimens. Of the 39 biopsy specimens collected, 36 (92%) had adequate material for sequencing using a hybridization-based exon capture assay (MSK-IMPACT). The most frequently altered genes across the patient cohort were consistent with the urothelial carcinoma-associated alterations identified in a cohort of 130 RNU specimens previously sequenced at our center, including mutations in the TERT promoter (64%), hotspot activating mutations in FGFR3 (64%), and frequent mutations in chromatin remodeling genes. For 12 patients, a matching tumor sample from a subsequent RNU was sequenced. We found a high level of concordance between matched biopsy and RNU specimens, up to 92% for the likely pathogenic alterations. PATIENT SUMMARY: We evaluated the feasibility of genomic characterization of tumor tissue collected at the time of ureteroscopic biopsy and found high concordance with subsequent radical nephroureterectomy specimens. Molecular characterization of urothelial carcinoma of the upper tract biopsies could guide treatment decision-making and identify high-risk patients who could benefit from neoadjuvant chemotherapy and low-risk patients who could benefit from conservative or organ-sparing strategies.

Background Postchemotherapy retroperitoneal lymph node dissection (pcRPLND) is indicated in testicular cancer patients with normalised or plateaued serum tumour markers and residual retroperitoneal lesions >1cm. Challenges remain in predicting postchemotherapy residual mass (pcRM) histology, which may lead to unnecessary surgery. Objective To develop an accurate model to predict pcRM histology in patients with nonseminomatous germ cell tumours (NSGCTs). Design, setting, and participants A retrospective review of 335 patients undergoing pcRPLND for metastatic NSGCTs to develop a model to predict benign histology in retroperitoneal pcRM. Our model was compared with others and externally validated. Intervention Chemotherapy and pcRPLND. Outcome measurements and statistical analysis Multivariable logistic regression to evaluate the presence of benign histology, and fractional polynomials to allow for a nonlinear association between continuous variables and the outcome. The final Princess Margaret model (PMM) was selected based on the number of variables used, reliability, and discriminative capacity to predict benign pcRM. Results and limitations PMM included the presence of teratoma in the orchiectomy, prechemotherapy α-fetoprotein, prechemotherapy mass size, and change in mass size during chemotherapy. Model specificity was 99.3%. Compared with Vergouwe et al's model, PMM had significantly better accuracy (C statistic 0.843 vs 0.783). PMM appropriately identified a larger number of patients for whom pcRPLND can safely be avoided (13.9% vs 0%). Validated in external cohorts, the model retained high discrimination (C statistic 0.88 and 0.80). Larger and prospective studies are needed to further validate this model. Conclusions Our clinical model, externally validated, showed improved discriminative ability in predicting pcRM histology when compared with other models. The higher accuracy and reduced number of variables make this a novel and appealing model to use for patient counselling and treatment strategies. Patient summary Princess Margaret model accurately predicted postchemotherapy benign histology. These results might have clinical impact by avoiding unnecessary retroperitoneal lymph node dissection and consequently changing the paradigm of advanced testicular cancer treatment.

Objectives To describe the natural history of prostate cancer in men who experience a second biochemical recurrence (BCR) after salvage radiotherapy (SRT) following prostatectomy. Subjects/Patients and Methods Following SRT at two institutions from 1986-2013, 286 patients developed second BCR, defined as two rises in PSA of ≥0.2 ng/mL above nadir. Event rates for distant metastasis (DM) or freedom from DM (FFDM), castration-resistant prostate cancer (CRPC), prostate cancer-specific survival (PCSS), and overall survival (OS) were estimated using the Kaplan-Meier method. Cox regression was used for comparative analyses. Results At a median 6.1 years following second BCR, rates of DM, CRPC, PCSS, and OS were 41%, 27%, 83%, and 73%, respectively. On multivariable analysis, interval to second BCR

Prostate cancer is a heterogeneous disease. Existing risk stratification tools based on standard clinlicopathologic variables (prostate specific antigen [PSA], Gleason score, and tumor stage) provide a modest degree of predictive ability. Advances in high-throughput sequencing has led to the development of several novel tissue-based biomarkers that can improve prognostication in prostate cancer management.The authors review commercially-available, tissue-based biomarker assays that improve upon existing risk-stratification tools in several areas of prostate cancer management, including the appropriateness of active surveillance and aiding in decision making regarding the use of adjuvant therapy. Additionally, some of the obstacles to the widespread adoption of these biomarkers and discuss several investigational sources of new biomarkers are discussed.Work is ongoing to answer pertinent clinical questions in prostate cancer management including which patients should undergo biopsy, active surveillance, receive adjuvant therapy, and what systemic therapy is best in the first-line. Incorporation into novel biomarkers may allow for the incorporation of a 'personalized' approach to management. Further validation will be required and questions of cost must be considered before wide scale adoption of these biomarkers. Tumor heterogeneity may impose a ceiling on the prognostic ability of biomarkers using currently available techniques.

Urothelial carcinoma is a highly heterogeneous disease that can arise throughout the entire urothelial lining from the renal pelvis to the proximal urethra. Upper tract urothelial carcinoma (UTUC) is rare, and while it shares many similarities with urothelial carcinoma of bladder (UCB), there are also significant differences between UTUC and UCB regarding clinical management and outcomes. No major advances have been made recently in the development of new systemic therapies for urothelial carcinoma, partly due to the lack of understanding of underlying molecular pathogenetic mechanisms. In the past decade, the emergence of next-generation sequencing has greatly enabled genomic characterization of tumor samples. Researchers are currently exploring a personalized approach to augment traditional clinical decision-making based on genetic alterations. In the present review, we summarize current genomic advances in UTUC and discuss the potential implications of these developments for developing prognostic and predictive biomarkers.

Objectives To evaluate the usage of surgical staging of inguinal lymph nodes (SSILNs) in the United States for intermediate to high-risk, clinically localized penile squamous cell cancer (SCC), to explore patient and hospital factors associated with omission of this staging, and to evaluate the effect on survival. Patients and methods Retrospective, observational study using the National Cancer Database from 2004 to 2014 of 1,689 men diagnosed with pT1b–T3, cN0 penile SCC, who by current guidelines should receive SSILNs—either by inguinal lymph node (ILN) dissection or sentinel node biopsy. Binomial logistic regression analysis was performed to determine predictors of SSILNs. Multivariate Cox regression analysis was performed to determine the impact of SSILNs on survival in the overall and propensity-score matched patient populations. Results Only 25.3% of patients underwent SSILNs. Increasing patient age, higher comorbidity status, lower pathologic stage, Medicaid insurance, and treatment at a nonacademic facility were independent factors associated with the omission of SSILNs. Omission of SSILNs was an independent predictor of overall mortality, both in the overall patient population after multivariate adjustment, HR = 1.46 [(95% CI: 1.14–1.88), P = 0.003], and in the propensity-score matched adjusted population, HR = 1.59 [(95% CI: 1.20–2.13), P = 0.001]. Limitations include an inability to distinguish biopsy from ILN dissection and those inherent in observational study design. Conclusion Utilization of SSILN for penile SCC is low and has not changed significantly since the publication of guidelines in the United States. In particular, nonacademic institutions were less likely to adhere to recommendations for performance of SSILNs. We found the omission of SSILNs is associated with a significant increase in mortality.

586 Background: Targeted therapy (TT) is the first-line option for metastatic renal cell carcinoma (mRCC) however, it is not curative and associated with a high-cost and adverse events. Preliminary data suggests TT may be safely delayed in appropriately selected patient, however the utilization and impact of delayed TT has not been evaluated on larger-scale. Methods: The National Cancer Database (NCDB) was queried from 2006-2012 for patients with mRCC treated with cytoreductive nephrectomy and TT. Time to initiation of TT was defined as ‘early’ (within 2 months), ‘moderately delayed’ (2-4 months), and ‘delayed’ (4-6 months), and ‘late’ ( > 6 months) based on time from diagnosis to initiation of therapy. Multivariable logistic regression was performed to determine factors associated with delayed TT. The impact time to initiation of TT on OS was estimated by Kaplan-Meier and Cox multivariable survival analysis. Results: For2,716 patients in the analysis, the median (interquartile range [IQR]) follow-up was 18.8 (9.1-32.9) months, and 71.8% of patients had died at last follow-up. The median (IQR) time from diagnosis to initiation of TT was 2.1 (1.3-3.23) months, with the longest delay being 20.1 months. 1,255 patients (46.2%) had early TT, 1,072 patients (39.5%) had moderately delayed TT, 284 patients (10.5%) had delayed TT, and 105 patients (3.9%) had late TT. Delay in TT was not found to be a predictor of mortality in multivariable analysis; early TT (reference), moderately delayed TT (HR 0.98, p = 0.74), delayed TT (HR 0.95, p = 0.51), and late TT (HR 0.86, p = 0.20). Time from diagnosis to initiation of TT and time from initiation of TT to patient death were not correlated after control for covariates ( r= 0.04, p = 0.08). Conclusions: Delay in initiation of TT for mRCC was not an independent predictor of worse OS. Although this study is subject to limitations of observation study design and selection bias, the results are consistent with the notion that in carefully selected patients, outcomes might not be compromised with initial observation. Prospective, randomized evaluation is warranted.

Given the rarity of testicular germ cell tumors (TGCTs) and the complex aspects of management, we evaluate the effect of hospital TGCT case volume on overall survival outcomes and practice patterns.The National Cancer Database was queried for patients diagnosed with seminoma or nonseminomatous germ cell tumor (NSGCT). Hospitals were classified by case volume as high (99th percentile, ≥26.1 cases annually), high-intermediate (95-99th percentile, 14.6-26.0 cases annually), intermediate (75-95th percentile, 6.1-14.5 cases annually), low-intermediate (25-75th percentile, 1.8-6.0 cases annually), and low (25th percentile,1.8 cases annually). The median (interquartile range) number of TGCT cases per institution per year was 3.4 (1.8-6.1).A total of 33,417 patients with TGCT diagnosed from 1,239 institutions met inclusion criteria. Despite worse disease characteristics of patients treated at higher volume institutions, hospital volume was positively associated with survival outcomes in more advanced cases of TGCT. In the overall cohort, compared to the high-volume hospitals, patients treated at high-intermediate, intermediate, low-intermediate, and low volume hospitals the hazard ratio for overall mortality was 1.28, 1.45, 1.48, and 1.83, respectively (P0.05). The association between survival and hospital volume was not apparent for seminoma or stage I NSGCT. Patients treated at higher volume hospitals were more likely to undergo surveillance for stage I seminoma, primary retroperitoneal lymph node dissection (RPLND) for stage I NSGCT, and postchemotherapy RPLND for stage II/III NSGCT.Our analysis of a nationwide cancer registry demonstrated that increased hospital TGCT case volume was associated with significant differences in management strategies and improved survival outcomes, in particular for more advanced disease.

473 Background: Approximately 30% of patients with advanced germ cell tumor (aGCT) will progress after first-line chemotherapy. Nearly half of these patients will die of progressive GCT. We describe potentially actionable mutations in a cohort of patients with platinum-resistant aGCT through targeted sequencing. Methods: 76 patients with cisplatin-resistant (CR) disease were sequenced using the Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay that examines 341 cancer-related genes. Patients were categorized as CR if they met any of the following criteria: 1) incomplete response to first-line cisplatin-based chemotherapy; 2) nonteratomatous tumor progression after standard chemotherapy; 3) nonteratomatous GCT identified at postchemo surgery. We grouped all somatic mutations into core signal transduction pathways or canonical cell functions to identify potential precise targets for therapy. Results: The majority of patients had nonseminoma histology (n = 64, 84%). International Germ Cell Cancer Collaborative Group risk was good, intermediate, and poor in 34%, 13%, and 53% of patients. 17 patients died of disease. In total, 51 potentially actionable alterations were identified in 36/76 (47%) patients. In the TP53 pathway, 7 MDM2 amplifications and 4 MYCN amplifications that may sensitize to nutlin-3 inhibitors were identified. Within the receptor tyrosine kinase pathway, 3 KIT mutations, 1 KDR amplification, and 1 MET amplification were seen that may sensitize to tyrosine kinase inhibitors. Eleven KRAS mutations, 3 NRAS mutations, 3 BRAF mutations, and 2 RAC1 mutations were see among the RAS pathway with preclinical data suggesting efficacy towards respective inhibitors. Actionable targets were also among the PI3-K, WNT, and cell cycle pathways. Potential targets with chromatin modifying or tumor suppressor functions were also seen. Conclusions: We describe actionable alterations that may guide treatment selection in a significant proportion of patients with CR aGCT. Targeted sequencing of these patients may allow us to enrich future clinical trials with patients whose tumors harbor alterations in the drug target of interest.

Background The management of patients with renal cell carcinoma (RCC) with venous tumor thrombus (VTT) is challenging. We report our 15 year experience in the management of patients with RCC with VTT utilizing a multidisciplinary team approach, highlighting improved total and specifically Clavien III-V complication rates. Methods We reviewed the records of 146 consecutive patients who underwent radical nephrectomy with venous thrombectomy between 1998 and 2012. Data on patient history, staging, surgical techniques, morbidity, and survival were analyzed. Additionally, complication rates between two surgical eras, 1998–2006 and 2006–2012, were assessed. Results The study included 146 patients, 97 males (66 %), and a median age of 61 years (range, 24–83). Overall complications rate was 53 %, high grade complications (Clavien III -V) occurred in 10 % of patients. Most importantly, there was a lower incidence of overall and high grade complications (45 % and 8 %, respectively) in the last 6 years compared to the earlier surgeries included in the study (67 % and 13 % respectively) [p = .008 and .03, respectively). 30 day postoperative mortality was 2.7 %. 5 year overall survival (5Y- OS) and 5 year cancer specific survival (5Y- CSS) were 51 % and 40 %, respectively. Metastasis was the only independent predictor factor for CSS (HR 3.8, CI 1.9-7.6 and p