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Purpose: Intratumoral heterogeneity (ITH) challenges the molecular characterization of clear cell renal cell carcinoma (ccRCC) and is a confounding factor for therapy selection. Most approaches to evaluate ITH are limited by two-dimensional ex vivo tissue analyses. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can noninvasively assess the spatial landscape of entire tumors in their natural milieu. To assess the potential of DCE-MRI, we developed a vertically integrated radiogenomics colocalization approach for multi-region tissue acquisition and analyses. We investigated the potential of spatial imaging features to predict molecular subtypes using histopathologic and transcriptome correlatives. Experimental Design: We report the results of a prospective study of 49 patients with ccRCC who underwent DCE-MRI prior to nephrectomy. Surgical specimens were sectioned to match the MRI acquisition plane. RNA sequencing data from multi-region tumor sampling (80 samples) were correlated with percent enhancement on DCE-MRI in spatially colocalized regions of the tumor. Independently, we evaluated clinical applicability of our findings in 19 patients with metastatic RCC (39 metastases) treated with first-line antiangiogenic drugs or checkpoint inhibitors. Results: DCE-MRI identified tumor features associated with angiogenesis and inflammation, which differed within and across tumors, and likely contribute to the efficacy of antiangiogenic drugs and immunotherapies. Our vertically integrated analyses show that angiogenesis and inflammation frequently coexist and spatially anti-correlate in the same tumor. Furthermore, MRI contrast enhancement identifies phenotypes with better response to antiangiogenic therapy among patients with metastatic RCC. Conclusions: These findings have important implications for decision models based on biopsy samples and highlight the potential of more comprehensive imaging-based approaches.

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.

BACKGROUND The objective of this study was to determine whether standardized treatment of germ cell tumors (GCTs) could overcome sociodemographic factors limiting patient care. METHODS The records of all patients undergoing primary treatment for GCTs at both a public safety net hospital and an academic tertiary care center in the same metropolitan area were analyzed. Both institutions were managed by the same group of physicians in the context of multidisciplinary cancer care. Patients were grouped by care center; clinicopathologic features and outcomes were analyzed. RESULTS Between 2006 and 2018, 106 and 95 patients underwent initial treatment for GCTs at the safety net hospital and the tertiary care center, respectively. Safety net patients were younger (29 vs 33 years; P = .005) and were more likely to be Hispanic (79% vs 11%), to be uninsured (80% vs 12%; P

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.

IntroductionPatients with advanced germ cell tumors (GCT) receiving cisplatin-based chemotherapy have high rates of thromboembolic events (TEE) which can negatively affect their overall survival. While primary TEE prophylaxis during chemotherapy may prevent these events, it is unclear which patients will benefit in this setting.Materials and MethodsA review of PubMed/Medline was conducted in December 2020 and all pertinent articles were evaluated for relevancy and quality of data for inclusion in the review.ResultsStudies on patients receiving initial cisplatin-based chemotherapy for advanced GCT have reported up to a 19% rate of TEE. This high rate may be associated with multiple factors including retroperitoneal lymphadenopathy, advanced clinical stage, high risk Khorana scores and presence of a central line. Large phase III clinical trials have demonstrated the benefit of low-molecular-weight-heparin and direct oral anticoagulants for primary prophylaxis and against recurrent TEE. However, primary prophylaxis is currently underutilized with GCT patients starting chemotherapy.ConclusionPrecise models to predict TEE risk and consideration of anticoagulation are difficult to develop owing to the relatively uncommon nature of GCT and lack of representation in primary TEE prophylaxis clinical trials. Despite these limitations, we believe that the benefits of prophylactic anticoagulation outweigh the risk of major bleeding in select GCT patients with higher risk of TEE. We have developed a simple algorithm to help guide TEE prophylaxis selection based on patient factors and route of chemotherapy administration. Given the high rate of TEE in GCT patients, we believe better utilization of primary prophylaxis in patient starting cisplatin-based chemotherapy will have clinical benefit.

Objective : Circulating microRNAs have clear potential for improving malignant germ-cell-tumor (MGCT) diagnosis. Here, we address the central issue of whether measurement of a single microRNA is sufficient for detecting testicular MGCTs, or whether there is added benefit in quantifying other members of the four-microRNA panel previously identified (miR-371a-3p/miR-372-3p/miR-373-3p and miR-367-3p). Patients/Methods : We performed a pooled analysis of available published data where all four panel miRNAs had been assessed using pre-amplification PCR technology (four studies; total 329 patients). Two studies using identical methodology (and identical normalization using endogenous miR-30b-5p) were used in the discovery phase (n=51 patients: 17 MGCT, 34 controls). The two other studies (n=278 patients: 140 MGCT, 138 controls), which assessed the same test panel but with different normalization approaches (endogenous miR-93-5p, exogenous cel-miR-39-3p), were used for the validation phase. We derived sensitivity, specificity, positive- and negative-predictive-values (PPV/NPV) for the detection thresholds that maximised the Youden Index (YI). Results : In the discovery-phase, the YI was 0.97 for miR-371a-3p (sensitivity=1, specificity=0.97), 0.71 (miR-367-3p), 0.68 (miR-372-3p), and 0.50 (miR-373-3p). These findings were confirmed in the validation-phase, with YI of 0.75 for miR-371a-3p (sensitivity=0.90, specificity 0.85), 0.55 (miR-367-3p), 0.47 (miR-372-3p), and 0.51 (miR-373-3p). Importantly, no combination of markers added additional diagnostic benefit to miR-371a-3p alone, in either the discovery or the validation phase. Conclusion : Quantifying circulating miR-371a-3p alone is sufficient for testicular MGCT diagnosis. PCR measurement of this single miRNA marker will be more cost-effective and easier to interpret, facilitating future incorporation into routine clinical practice. MicroAbstract Circulating microRNA testing is likely to transform future management for testicular cancer patients. Here, we undertook a pooled analysis (329 patients) to test whether measurement of a single microRNA is sufficient for detecting testicular cancer, or whether it is necessary to quantify other members of the four microRNA panel previously identified (miR-371a-3p/miR-372-3p/miR-373-3p/miR-367-3p). We show that quantifying circulating miR-371a-3p alone is sufficient for testicular cancer diagnosis.

INTRODUCTION AND OBJECTIVE: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 blad...

INTRODUCTION AND OBJECTIVE:Previous studies have demonstrated the benefit of blue light flexible cystoscopy (BLFC) in clinical practice though detection of additional cancers missed with white ligh...

INTRODUCTION AND OBJECTIVE:While open retroperitoneal lymph node dissection (O-RPLND) has been the gold standard of treatment for germ cell tumors (GCT), robotic RPLND (R-RPLND) is gaining populari...

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.

BACKGROUND Using a large, nationally representative, population-based cancer registry, this study systematically evaluated the impact of the location and burden of extranodal testicular germ cell tumor (TGCT) metastases on survival. METHODS Men with stage III TGCTs captured by the Surveillance, Epidemiology, and End Results registry from 2010 to 2015 with distant extranodal metastases were identified. Clinicopathologic information was collected, and patients were subdivided according to the specific organ site or sites of metastatic involvement (lung, liver, bone, and/or brain). Kaplan-Meier analysis and multivariable Cox regression were used to evaluate cancer-specific survival (CSS), and model performance was assessed with Harrell's C statistic. RESULTS Nine hundred sixty-nine patients with stage III TGCTs were included with predominantly nonseminomatous histology (84%). Most patients (91%) had pulmonary metastases, whereas 20%, 10%, and 10% had liver, bone, and brain metastases, respectively. Over a median follow-up of 21 months, 19% of these men died of TGCTs. When they were grouped by the primary site of metastasis, patients with more than 1 extrapulmonary metastasis exhibited the worst CSS (hazard ratio [HR] vs isolated pulmonary involvement, 4.27; 95% confidence interval [CI], 2.60-7.00; P

OBJECTIVE To evaluate the prognostic significance of lymph node count (LNC) at post-chemotherapy retroperitoneal lymphadenectomy (PC-RPLND) in metastatic non-seminomatous germ cell tumour (NSGCT) using the Surveillance, Epidemiology, and End Results (SEER) database and National Cancer Database (NCDB). PATIENTS AND METHODS SEER (2000-2013, n = 572) and NCDB (2004-2013, n = 731) identified patients undergoing PC-RPLND for Stage II and III NSGCT. Correlation between linear or categorial variables and LNC was conducted using Spearman's rank correlation or Kruskal-Wallis test by ranks. Patients were stratified by ≤20, 21-40, and >40 LNs for Kaplan-Meier analysis. Cox proportional hazards models evaluated the association of LNC at PC-RPLND with overall mortality (OM) in the NCDB and cancer-specific mortality (CSM) in the SEER database. The relationship between LNC and OM or CSM was also modelled as a non-linear function to determine a threshold for survival benefit. RESULTS Amongst all patients, the median (interquartile range) LNC was 17 (3-26) LNs in the NCDB, and 18 (6-31) LNs in the SEER database. More recent diagnosis year, higher hospital volume, higher median income, private insurance status, and positive LNC were associated with greater total LNC in one or both databases (P 40 LNs was associated with 5-year cancer-specific survival (CSS) of 99% and overall survival (OS) of 96%, whereas ≤20 LNs had a 5-year CSS of 91% and OS of 78% (CSS, P = 0.04; OS, P

Background Programmed death-ligand 1 (PD-L1) expression in metastatic renal cell carcinoma (RCC) correlates with a worse prognosis, but whether it also predicts responsiveness to anti-PD-1/PD-L1 therapy remains unclear. Most studies of PD-L1 are limited by evaluation in primary rather than metastatic sites, and in biopsy samples, which may not be representative. These limitations may be overcome with immuno–positron emission tomography (iPET), an emerging tool allowing the detection of cell surface proteins with radiolabeled antibodies. Here, we report iPET studies of PD-L1 in a preclinical tumorgraft model of clear cell RCC (ccRCC) from a patient who had a favorable response to anti-PD-1 therapy. Case presentation A 49-year-old man underwent a cytoreductive nephrectomy in 2017 of a right kidney tumor invading into the adrenal gland that was metastatic to the lungs and a rib. Histological analyses revealed a ccRCC of ISUP grade 4 with extensive sarcomatoid features. IMDC risk group was poor. Within two hours of surgery, a tumor sample was implanted orthotopically into NOD/SCID mice. Consistent with an aggressive tumor, a renal mass was detected 18 days post-implantation. Histologically, the tumorgraft showed sarcomatoid differentiation and high levels of PD-L1, similar to the patient’s tumor. PD-L1 was evaluated in subsequently transplanted mice using iPET and the results were compared to control mice implanted with a PD-L1-negative tumor. We labeled atezolizumab, an anti-PD-L1 antibody with a mutant Fc, with zirconium-89. iPET revealed significantly higher 89Zr-atezolizumab uptake in index than control tumorgrafts. The patient was treated with high-dose IL2 initially, and subsequently with pazopanib, with rapidly progressive disease, but had a durable response with nivolumab. Conclusions To our knowledge, this is the first report of non-invasive detection of PD-L1 in renal cancer using molecular imaging. This study supports clinical evaluation of iPET to identify RCC patients with tumors deploying the PD-L1 checkpoint pathway who may be most likely to benefit from PD-1/PD-L1 disrupting drugs.

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.

Introduction Nationwide cancer registries such as the National Cancer Database and Surveillance, Epidemiology, and End Results rely on accurate data from tumor registries to formulate hypotheses and report outcomes and treatment patterns. We evaluated the accuracy of our institutional registry for testicular germ cell tumors by comparing data abstracted by urologists with data abstracted by registry. Methods We performed a retrospective review of patients receiving initial diagnosis and treatment for germ cell tumors at our hospital system from 2005 to 2016. We compared coding for American Joint Committee on Cancer TNMS staging, overall composite stage, and first-line treatment between urologists and tumor registry at the time of diagnosis. Results Paired staging from registry and urologist was available for 80 patients. T, N, M, and S-staging were accurate for 90%, 81%, 94%, and 54% of records, respectively. Composite staging and first-line treatment were concordant for 39% and 90% of patients, respectively. A separate review of 33 Stage IS patients per registry for composite staging revealed 15% concordance. Conclusion Our institutional tumor registry had substantial inconsistencies in accurately staging N stage, S stage, and thus, composite stage for testicular cancer. An educational intervention to improve abstraction by registry led to increased concordance. Assuming similar discrepancies may exist at other institutions and for other cancer types, caution should be used when interpreting staging data in nationwide cancer registries. This sheds light on the need for improved clarification of staging guidelines, dynamic institutional internal auditing, and training reform within cancer registries.

Testicular germ cell tumor (GCT) is the most common malignancy in young men [1]. Through a multidisciplinary approach involving surgery, chemotherapy, and radiation, GCTs have cure rates approachin...

Existing tumor markers for testicular germ cell tumor (TGCT) cannot detect the presence of pure teratoma. Serum miRNAs have strong performance detecting other subtypes of TGCT. Previous reports suggest high levels of miR-375 expression in teratoma tissue. The purpose of this study was to explore the role of serum miRNA, including miR-375, in detecting the presence of teratoma at postchemotherapy retroperitoneal lymph node dissection (PC-RPLND).We prospectively collected presurgical serum from 40 TGCT patients undergoing PC-RPLND (21 with teratoma at RPLND and 19 with no evidence of disease). We examined the utility of serum miR-375-3p and miR-375-5p by quantitative polymerase chain reaction, and searched for other putative serum miRNAs with small RNA sequencing. The area under the receiver operating characteristic curve (AUC) and univariate analyses were utilized to evaluate test characteristics and predictors of teratoma.Both serum miR-375-3p and miR-375-5p exhibited poor performance (miR-375-3p: 86% sensitivity, 32% specificity, AUC: 0.506; miR-375-5p: 55% sensitivity, 67% specificity, AUC: 0.556). Teratoma at orchiectomy was the only predictor of PC-RPLND teratoma. Small RNA sequencing identified three potentially discriminatory miRNAs, but further validation demonstrated no utility. Our results confirm prior reports that serum miR-375 cannot predict teratoma, and suggest that there may not exist a predictive serum miRNA for teratoma. Patient summary: We found that serum miR-375 cannot detect the presence of teratoma at postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). We are also unable to find any other serum miRNAs predictive of pure teratoma at PC-RPLND. Hence, the lack of a reliable circulating marker of teratoma remains a critical clinical need.

Purpose To assess the effects of variable adoption of Medicaid Expansion (ME) of the Affordable Care Act among different states on urologic malignancies using a new variable that defines ME status of patient's residence in a nationwide cancer registry. Basic procedures The National Cancer Database was queried for urologic malignancies (bladder, prostate, kidney and testis) from 2011 to 2016, spanning the period surrounding the primary ME which took place in 2014. Trends in insurance status at time of diagnosis and effects on stage at presentation and survival after ME were evaluated using a difference-in-differences estimator and stratified Cox proportional hazards regression model. Main findings The percentage of patients with Medicaid coverage at the time of diagnosis increased significantly after adoption of ME in ME states across all urologic malignancies. Concurrently, there was a significant decrease in percentage of uninsured patients diagnosed with testis cancer, but not other urologic malignancies, in ME states. A change in the stage at presentation was not observed across all urologic malignancies for patients in ME states after adoption of ME. No difference in overall survival was noted among patients living in a ME state compared to non-ME states with adoption of ME in 2014. Principal conclusions Despite increases in the proportion of patients with Medicaid coverage after 2014 in states that enrolled in ME, there was not an associated change in stage at presentation or survival for patients with genitourinary malignancy.

The study of DNA damage repair response (DDR) in prostate cancer is restricted by the limited number of prostate cancer cell lines and lack of surrogates for heterogeneity in clinical samples. Here, we sought to leverage our experience with patient derived explants (PDEs) cultured ex vivo to study dynamics of DDR in primary tumors following application of clinically relevant doses of ionizing radiation (IR) to tumor cells in their native 3-dimensional microenvironment. We compared DDR dynamics between prostate cancer cell lines, PDEs and xenograft derived explants (XDEs) following treatment with IR (2Gy) either alone or in combination with pharmacological modulators of DDR. We have shown that following treatment with 2Gy, DDR can be consistently detected in PDEs from multiple solid tumors, including prostate, kidney, testes, lung and breast, as evidenced by γ-H2AX, 53BP1, phospho-ATM and phospho-DNA-PKcs foci. By examining kinetics of resolution of IR-induced foci, we have shown that DDR in prostate PDEs (complete resolution in 8 h) is much faster than in prostate cancer cell lines (, Highlights • IR induces distinct DNA damage repair kinetics in prostate cancer PDEs and cell lines. • IR induces a distinct transcriptional program in prostate cancer PDE and cell lines. • DNA-PKcs inhibition blocks IR-induced DDR in prostate cancer PDE. • Inhibition of AR impairs NHEJ in prostate cancer PDEs.

Background Despite the significant societal burden of human papillomavirus (HPV)-associated cancers, clinical screening interventions for HPV-associated noncervical cancers are not available. Blood-based biomarkers may help close this gap in care. Methods Five databases were searched, 5687 articles were identified, and 3631 unique candidate titles and abstracts were independently reviewed by 2 authors; 702 articles underwent a full-text review. Eligibility criteria included the assessment of a blood-based biomarker within a cohort or case-control study. Results One hundred thirty-seven studies were included. Among all biomarkers assessed, HPV-16 E seropositivity and circulating HPV DNA were most significantly correlated with HPV-associated cancers in comparison with cancer-free controls. In most scenarios, HPV-16 E6 seropositivity varied nonsignificantly according to tumor type, specimen collection timing, and anatomic site (crude odds ratio [cOR] for p16+ or HPV+ oropharyngeal cancer [OPC], 133.10; 95% confidence interval [CI], 59.40-298.21; cOR for HPV-unspecified OPC, 25.41; 95% CI, 8.71-74.06; cOR for prediagnostic HPV-unspecified OPC, 59.00; 95% CI, 15.39-226.25; cOR for HPV-unspecified cervical cancer, 12.05; 95% CI, 3.23-44.97; cOR for HPV-unspecified anal cancer, 73.60; 95% CI, 19.68-275.33; cOR for HPV-unspecified penile cancer, 16.25; 95% CI, 2.83-93.48). Circulating HPV-16 DNA was a valid biomarker for cervical cancer (cOR, 15.72; 95% CI, 3.41-72.57). In 3 cervical cancer case-control studies, cases exhibited unique microRNA expression profiles in comparison with controls. Other assessed biomarker candidates were not valid. Conclusions HPV-16 E6 antibodies and circulating HPV-16 DNA are the most robustly analyzed and most promising blood-based biomarkers for HPV-associated cancers to date. Comparative validity analyses are warranted. Variations in tumor type-specific, high-risk HPV DNA prevalence according to anatomic site and world region highlight the need for biomarkers targeting more high-risk HPV types. Further investigation of blood-based microRNA expression profiling appears indicated.

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.

Optimization of cell culture protocol for a given cell line is critical for the proper conduct of in vitro experiments. Because germ cell tumors can be so heterogeneous, optimal culture conditions can vary widely between cell lines. Here, we describe our experience in routine culture and cryopreservation of germ cell tumor cell culture. Additionally, methods for measuring cell viability and proliferation validated on these lines are provided.

PURPOSE Although primary germ cell tumors (GCTs) have been extensively characterized, molecular analysis of metastatic sites has been limited. We performed whole-exome sequencing and targeted next-generation sequencing on paired primary and metastatic GCT samples in a patient cohort enriched for cisplatin-resistant disease. PATIENTS AND METHODS Tissue sequencing was performed on 100 tumor specimens from 50 patients with metastatic GCT, and sequencing of plasma cell-free DNA was performed for a subset of patients. RESULTS The mutational landscape of primary and metastatic pairs from GCT patients was highly discordant (68% of all somatic mutations were discordant). Whereas genome duplication was common and highly concordant between primary and metastatic samples, only 25% of primary-metastasis pairs had ≥ 50% concordance at the level of DNA copy number alterations (CNAs). Evolutionary-based analyses revealed that most mutations arose after CNAs at the respective loci in both primary and metastatic samples, with oncogenic mutations enriched in the set of early-occurring mutations versus variants of unknown significance (VUSs). TP53 pathway alterations were identified in nine cisplatin-resistant patients and had the highest degree of concordance in primary and metastatic specimens, consistent with their association with this treatment-resistant phenotype. CONCLUSION Analysis of paired primary and metastatic GCT specimens revealed significant molecular heterogeneity for both CNAs and somatic mutations. Among loci demonstrating serial genetic evolution, most somatic mutations arose after CNAs, but oncogenic mutations were enriched in the set of early-occurring mutations as compared with VUSs. Alterations in TP53 were clonal when present and shared among primary-metastasis pairs.

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

OBJECTIVE. The purpose of this article is to review the utility of 18F-fluciclovine PET/CT in the evaluation of recurrent prostate cancer. CONCLUSION. Fluorine-18-labeled fluciclovine PET/CT has shown promise in the evaluation of recurrent prostate cancer. Its performance has been superior to that of other imaging modalities. It has had good diagnostic accuracy, especially in the detection of extra-prostatic disease recurrence, and the findings have an impact on treatment planning. Gallium-68-labeled prostate-specific membrane antigen PET/CT has also had excellent performance in the detection of biochemically recurrent prostate cancer with detection rates superior to those of fluciclovine PET/CT.

Treatment paradigms for patients with upper tract urothelial carcinoma (UTUC) are typically extrapolated from studies of bladder cancer despite their distinct clinical and molecular characteristics. The advancement of UTUC research is hampered by the lack of disease-specific models. Here, we report the establishment of patient derived xenograft (PDX) and cell line models that reflect the genomic and biological heterogeneity of the human disease. Models demonstrate high genomic concordance with the corresponding patient tumors, with invasive tumors more likely to successfully engraft. Treatment of PDX models with chemotherapy recapitulates responses observed in patients. Analysis of a HER2 S310F-mutant PDX suggests that an antibody drug conjugate targeting HER2 would have superior efficacy versus selective HER2 kinase inhibitors. In sum, the biological and phenotypic concordance between patient and PDXs suggest that these models could facilitate studies of intrinsic and acquired resistance and the development of personalized medicine strategies for UTUC patients., The advancement of upper tract urothelial carcinoma (UTUC) research is hampered by the lack of disease-specific models. Here, the authors report patient derived xenograft and cell line models of UTUC, and show that these models retain the genomic and biological heterogeneity of human disease.

INTRODUCTION AND OBJECTIVE:Positive surgical margins (PSM) in men undergoing radical prostatectomy (RP) for prostate cancer (PCa) are an adverse surgical outcome associated with increased risk of r...

INTRODUCTION AND OBJECTIVE:Immune checkpoint inhibitors (ICI) were approved for treating metastatic renal cell carcinoma (mRCC) in 2015. Current use of cytoreductive nephrectomy (CN) is guided by e...

INTRODUCTION AND OBJECTIVE:Nested variant urothelial carcinoma (NVUC) is a historically aggressive variant of bladder cancer with management reliant on radical cystectomy given unclear effectivenes...

Gastric cancer (GC) is the sixth most common worldwide malignancy and the third leading cancer cause of death. Early diagnosis and effective after-surgical monitoring can significantly improve survival rates. Previous studies have revealed several serum biomarkers that are elevated in GC patients, including CEA, CA19-9, and CA72-4. However, sensitivity of these biomarkers is below 30%. Identification of more sensitive and specific to GC markers is critical for individualized therapy of this disease. Here we developed an approach for single-cell transcriptomic data analysis that identifies secretory proteins that are abundantly expressed in GC cells and that could be measurable in the blood. Using early GC scRNA-seq data, we identified 19 secretory proteins significantly overexpressed in GC cells. Notably, 4 proteins (IL32, KLK10, KLK7, OLFM4) have demonstrated more superior sensitivity in comparison to conventional serum markers in previous studies. Moreover, 2 proteins, F12 and CFD, were not previously associated with GC and were not utilized for serum-based testing of other malignancies. Proposed approach has a high potential to be used for serum marker identification in other types of cancers and presented here data could be a source for the development of more sensitive and specific diagnostic panel for early gastric cancer detection and patient post-treatment monitoring.

Background The optimal timing of targeted therapy (TT) initiation for metastatic renal-cell carcinoma (mRCC) is not clear. We used a nationwide cancer registry to determine clinical and social factors associated with delayed TT and to evaluate the association of a delayed approach with overall survival (OS). Patients and Methods We performed a retrospective observational study utilizing the National Cancer Data Base from 2006 to 2012 for patients diagnosed with mRCC (clear-cell histology) treated with cytoreductive nephrectomy and TT. Time to initiation of TT was defined as early (within 2 months), moderately delayed (2-4 months), delayed (4-6 months), and late (> 6 months). Results Of the 2716 patients included in the analysis, the median (interquartile range) time from diagnosis to initiation of TT was 2.1 (1.3-3.23) months. A total of 1255 patients (46.2%) had early TT, 1072 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 initiation was not independently associated with OS in multivariable analysis. The time interval from diagnosis to TT initiation was not correlated with time from initiation of TT to death (r = 0.04, P = .08). Conclusion We found that delayed initiation of TT 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.

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.

Organ-confined muscle-invasive bladder cancer is treated with cystectomy or bladder preservation techniques, including radiation therapy. There are currently no biomarkers to inform management decisions and aid patient choice. Previously we showed high levels of MRE11 protein, assessed by immunohistochemistry (IHC), predicted outcome after radiation therapy, but not cystectomy. Therefore, we sought to develop the MRE11 IHC assay for clinical use and define its relationship to clinical outcome in samples from 2 major clinical trials.Samples from the BCON and BC2001 randomized controlled trials and a cystectomy cohort were stained using automated IHC methods and scored for MRE11 in 3 centers in the United Kingdom.Despite step-wise creation of scoring cards and standard operating procedures for staining and interpretation, there was poor intercenter scoring agreement (kappa, 0.32; 95% confidence interval, 0.17-0.47). No significant associations between MRE11 scores and cause-specific survival were identified in BCON (n = 132) and BC2001 (n = 221) samples. Reoptimized staining improved agreement between scores from BCON tissue microarrays (n = 116), but MRE11 expression was not prognostic for cause-specific survival.Manual IHC scoring of MRE11 was not validated as a reproducible biomarker of radiation-based bladder preservation success. There is a need for automated quantitative methods or a reassessment of how DNA-damage response relates to clinical outcomes.

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.

Purpose Oligoprogression, defined as limited sites of progression on systemic therapy, in patients with metastatic renal cell carcinoma (mRCC) is not uncommon, possibly because of inter- and intratumoral heterogeneity. We evaluated the effect of stereotactic ablative radiation therapy (SAbR) for longitudinal control of oligoprogressive mRCC. Methods and Materials Patients with extracranial mRCC were included in this retrospective analysis if they progressed in ≤3 sites on systemic therapy while demonstrating response/stability at other sites and received SAbR to all progressing sites without switching systemic therapy. Our primary endpoint was modified progression-free survival (mPFS), which we calculated from the start of SAbR to the start of a subsequent systemic therapy, death, or loss to follow-up. Results We identified 36 patients with a median follow-up of 20.4 months (interquartile range, 10.9-29.4). Forty-three sites were treated with SAbR with a median dose of 36 Gy (range, 18-50) in 3 fractions (range, 1-5). Median time to SAbR from the start of systemic therapy was 11.4 months (interquartile range, 6.1-17.1). Median mPFS was 9.2 months (95% confidence interval [CI], 5.9-13.2). Patients receiving SAbR while on immunotherapy exhibited a longer median mPFS (>28.4 months, log-rank P = .0001) than patients not on immunotherapy (9.2 months). Median overall survival from SAbR administration was 43.4 months (95% CI, 21.5-not Reached). The 1-year local control rate was 93% (95% CI, 78.7-97.5). Most SAbR-related toxicities were grade 1 to 2 (33% of patients), with one grade 5 hemoptysis event possibly related to SAbR or disease progression. Conclusions SAbR has the potential to extend the the duration of current systemic therapy for selected patients with mRCC, preserving subsequent therapies for later administration possibly enabling longer treatment duration.