Correlating Immune Cell Infiltration Patterns with Recurrent Somatic Mutations in Advanced Clear Cell Renal Cell Carcinoma.

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

Geospatial Cellular Distribution of Cancer-Associated Fibroblasts Significantly Impacts Clinical Outcomes in Metastatic Clear Cell Renal Cell Carcinoma.

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

Spatial clustering of CD68+ tumor associated macrophages with tumor cells is associated with worse overall survival in metastatic clear cell renal cell carcinoma.

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

Retroperitoneal Lymph Node Dissection Versus Surveillance for Adult Early Stage Pure Testicular Teratoma: A Nationwide Analysis.

PURPOSE: Following radical orchiectomy, surveillance and primary retroperitoneal lymph node dissection (RPLND) are acceptable options for the management of early stage pure testicular teratoma in adult patients; however, there is no uniform consensus. The aim of this study was to investigate survival outcomes of adults with early stage pure testicular teratoma based on management strategy. METHODS: Data was extracted from the National Cancer Database (NCDB) from testicular cancer patients diagnosed with clinical stage (CS) I pure teratoma (pT1-4N0M0S0) between 2004 and 2014. Kaplan-Meier and Cox regression analyses were used to assess clinical outcomes based on management strategy. RESULTS: Of the 61,167 patients diagnosed with testicular cancer, 692 (1.1%) had pure teratoma. Only individuals with CS I disease were considered (n = 237). The median age was 28 (23-35) years. Overall, 43 (18%) patients underwent RPLND and 194 (82%) patients were managed with surveillance. There was an increase in surveillance for CS I teratoma during the study period. Increasing distance from residence to treatment facility was an unadjusted predictor for undergoing primary RPLND (p < 0.001). Median follow-up was 54 months and there was no significant difference in overall survival between CS I teratoma patients managed with RPLND and those managed with surveillance (p = 0.13). CONCLUSIONS: There has been a trend toward increasing adoption of surveillance for the management of early stage pure testicular teratoma in adults. Our findings suggest that surveillance provides comparable survival outcomes to primary retroperitoneal lymph node dissection in this setting.

Pathological and Survival Outcomes Associated with Variant Histology Bladder Cancers Managed by Cystectomy with or without Neoadjuvant Chemotherapy.

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

Topical chemotherapy for penile carcinoma in situ: Contemporary outcomes and reported toxicity.

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

Systemic and intravesical adoptive cell therapy of tumor-reactive T cells can decrease bladder tumor growth in vivo.

BACKGROUND: The therapeutic armamentarium of bladder cancer has been recently enriched with the introduction of new therapies including immune checkpoint inhibitors, receptor tyrosine kinase inhibitors and antibody drug conjugates, however treatment responses and duration of responses are still less than expected. Adoptive cellular therapy (ACT) using tumor-infiltrating lymphocytes (TILs) has potential to treat bladder cancer, as previously demonstrated by successful expansion of tumor reactive T cells from human bladder tumors. METHODS: A model system using OT-I T cells and an ovalbumin expressing MB49 tumor cell line (MB49OVA) was developed to study ACT in bladder cancer. Systemic ACT-treated mice were given T cells intravenously after lymphodepleting chemotherapy and followed by interleukin (IL)-2 administration. Intravesical ACT treated mice were given T cells directly into the bladder, without chemotherapy or IL-2. TILs were isolated from MB49 orthotopic tumors and expanded ex vivo in IL-2. Immune cell infiltrates were analyzed by flow cytometry. T cell infiltration was studied using a CXCR3 blocking antibody. RESULTS: Systemic ACT-treated mice had a decrease in tumor growth, increase in T cell infiltration and long-term immune protection compared with control-treated mice. OT-I T cells delivered intravesically were able to control tumor growth without lymphodepleting chemotherapy or IL-2 in MB49OVA orthotopic tumors. Intravesical delivery of TIL expanded from MB49 tumors was also able to decrease tumor growth in mice with MB49 orthotopic tumors. Blocking CXCR3 on OT-I T cells prior to intravesical delivery decreased T cell infiltration into the tumor and prevented the control of tumor growth. CONCLUSIONS: This study demonstrates how TIL therapy can be used in treating different stages of bladder cancer.

Overcoming sociodemographic factors in the care of patients with testicular cancer at a safety net hospital.

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 < .001), to present via the emergency department (76% vs 8%; P < .001), and to have metastatic (stage II/III) disease (42% vs 26%; P = .025). In a multivariable analysis, an absence of lymphovascular invasion (odds ratio [OR], 0.30; P = .008) and an embryonal carcinoma component (OR, 0.36; P = .02) were associated with decreased use of adjuvant treatment for stage I patients; hospital setting was not (OR, 0.67; P = .55). For patients with stage II/III nonseminomatous GCTs, there was no difference in the performance of postchemotherapy retroperitoneal lymph node dissection between the safety net hospital and the tertiary care center (52% vs 64%; P = .53). No difference in recurrence rates was observed between the cohorts (5% vs 6%; P = .76). CONCLUSIONS: Sociodemographic factors are often associated with adverse clinical outcomes in the treatment of GCTs; they may be overcome with integrated, standardized management of testicular cancer.

Current management and management controversies in early- and intermediate-stage of nonseminoma germ cell tumors.

Early stage nonseminomatous germ cell tumor (NSGCT) remains a treatable disease, with stage I cancer specific survival exceeding 95%. Using a risk-adapted approach; active surveillance (AS), adjuvant chemotherapy, and retroperitoneal lymph node dissection (RPLND) all options for treatment; with surveillance being increasingly used. With persistently elevated markers (stage IS), chemotherapy remains the hallmark of treatment. Management of stage II NSGCT varies based on status of tumor markers. With negative markers, both induction chemotherapy and upfront RPLND remain options. Management of a residual mass <1 cm after chemotherapy remains controversial, with AS and nerve-sparing RPLND considered options. The development of miR-371a-3p microRNA shows promise a novel biomarker for testicular cancer (GCT). Despite controversies in management, cures for NSGCT are achievable in 95-99% of patients.

Therapeutic strategies for uncommon testis cancer histologies: teratoma with malignant transformation and malignant testicular sex cord stromal tumors.

Testicular cancer is the most common solid malignancy in male adolescents and young adults, with germ cell derived seminomas and non-seminomas being by far the most common histologies. Teratoma with somatic-type malignancy is a rare chemo-resistant phenotype of testis cancer associated with poor prognosis in patients with advanced stage disease. Malignant gonadal-stromal tumors comprise 5% of testicular neoplasms and approximately 10% are malignant and considered chemo-radiation resistant. Prognostic factors and treatment strategies for these uncommon histologies are lacking.

Systematic Review and Meta-Analysis-Is there a Benefit in Using Neoadjuvant Systemic Chemotherapy for Locally Advanced Penile Squamous Cell Carcinoma?

PURPOSE: Neoadjuvant chemotherapy is a recommended treatment for patients with penile cancer with bulky inguinal lymphadenopathy or unresectable primary tumors, although there is no evidence of its benefit from randomized trials. MATERIALS AND METHODS: We conducted a systematic search in Embase® and MEDLINE® for studies reporting on patients who received preoperative neoadjuvant chemotherapy for locally advanced penile squamous cell carcinoma. Objective response rate, pathological complete response, grade 3 or greater toxicity and overall mortality were evaluated in terms of neoadjuvant chemotherapy type, which was dichotomized as nontaxane-platinum and taxane-platinum regimens. RESULTS: Overall 10 studies met the inclusion criteria, enrolling a total of 182 patients, with 66 (36.3%) and 116 (63.7%) treated with nontaxane-platinum and taxane-platinum regimens, respectively. The pooled results demonstrated an objective response rate of 53% (95% CI 42-64), pathological complete response rate of 16%, grade 3 or greater toxicity rate of 40% (95% CI 19-64) and overall mortality of 55% (95% CI 40-70) in patients treated with neoadjuvant chemotherapy. Stratified subanalysis revealed an objective response rate of 55% and 49%, a pathological complete response of 9% and 20%, a toxicity rate of 26% and 49%, and an overall mortality of 54% and 58% for nontaxane-platinum vs taxane-platinum regimens, respectively. CONCLUSIONS: The pooled findings in this study suggest that approximately 50% of the patients with bulky regional lymph node metastases from penile cancer respond to platinum based neoadjuvant chemotherapy and approximately 16% of patients achieve a pathological complete response. Nontaxane based regimens appear to be better tolerated than taxane regimens based on reported grade 3 or greater adverse events (26% vs 49%). Ultimately the robustness of these observations should be interpreted with an awareness of the inherent limitations of deriving data from a collection of small, heterogeneous series.

Prognostic significance of BAP1 expression in high-grade upper tract urothelial carcinoma: a multi-institutional study.

PURPOSE: 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. METHODS: 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 < 1. Clinicopathologic characteristics and oncologic outcomes [recurrencefree (RFS), cancer-specific (CSS), and overall survival (OS)] were stratified by BAP1 status. The prognostic role of BAP1 was assessed using Kaplan-Meier (KM) and Cox regression analysis. Significance was defined as p < 0.05. RESULTS: 348 patients were included for analysis and 173 (49.7%) showed BAP1 loss. Median follow-up was 36.0 months. BAP1 loss was associated with papillary architecture and absence of tumor necrosis or CIS. On univariable analysis, BAP1 loss was associated with improved RFS (HR 0.60, p = 0.013) and CSS (HR 0.55, p = 0.007), although significance was lost on multivariable analysis (HR 0.71, p = 0.115 and HR 0.65, p = 0.071; respectively) after adjusting for other significant parameters. BAP1 expression was not significantly associated with OS. CONCLUSIONS: BAP1 loss was associated with favorable pathologic features and better oncologic outcomes in univariate but not multivariate analysis in patients with high-grade UTUC. In contrast to renal cell carcinoma, loss of BAP1 expression appears to confer a better prognosis in high-grade UTUC. The role of the BAP1 pathway in UTUC pathogenesis remains to be further elucidated.

Multi-institutional evaluation of the prognostic significance of EZH2 expression in high-grade upper tract urothelial carcinoma.

PURPOSE: 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. METHODS: 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 as>20% 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 P<0.05. RESULTS: 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, P<0.001). 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. CONCLUSION: 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.

Evaluation of Deceased Kidney Donors for Renal Stone Disease: Is Computed Tomography Needed?

OBJECTIVE: To investigate the clinical consequences of neglected risk of urolithiasis in deceased kidney donors in routine clinical practice, this study focused on different management options for transplanted allograft stones, and tried to find new solutions for more accurate detection of urolithiasis in deceased kidney donors prior to renal transplantation. METHODS AND RESULTS: The overall prevalence of stone disease in endemic countries is between 7 and 29%. Because of the increased risk for stone disease in epidemic countries, screening renal grafts from deceased donors necessitates more sensitive imaging tests. Despite well established procedures on preoperative living related renal donor evaluation, there is no consensus on a preoperative imaging tool in cadaveric renal donor evaluation. The most commonly used imaging modality in deceased renal donors is ultrasonography. The overall sensitivity and specificity of ultrasonography for kidney stones are 45 and 88%, respectively. Use of a computed tomography scan for renal diseases, especially for urinary stones is now almost a routine test in clinical practice. Its sensitivity for renal stones < 3 mm is 85%, whereas for renal stones > 3 mm it is 100%. CONCLUSION: The use of radiological modalities i.e. computed tomography with higher sensitivity in deceased donors prior to renal transplantation seems reasonable in urinary stone epidemic countries.

Practice Patterns and Impact of Postchemotherapy Retroperitoneal Lymph Node Dissection on Testicular Cancer Outcomes.

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 < 0.001). Insurance status was independently associated with receipt of PC-RPLND; compared to patients with private insurance, those without insurance were significantly less likely to receive PC-RPLND (odds ratio 0.49; p < 0.001). After multivariate adjustment, age, comorbidity, non-private insurance, distance from hospital, clinical stage, and risk group were independently associated with all-cause mortality. In addition, omission of PC-RPLND remained associated with all-cause mortality (hazard ratio 1.98; p < 0.001). After PSM, the 5-yr OS was significantly lower among those not undergoing PC-RPLND (72% vs 77%; p = 0.007). 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.

Differences at Presentation and Treatment of Testicular Cancer in Hispanic Men: Institutional and National Hospital-based Analyses.

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.