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In the recent decade, analysis of circulating tumor DNA (ctDNA) has improved cancer care by allowing for rapid detection of actionable molecular targets. A new generation of circulating DNA tests is now becoming available commercially. These tests are characterized by a superior limit of detection of 0.01% vaF or better, allowing for the detection of radiologically occult molecular residual disease (MRD). MRD tests have the potential to revolutionize neoadjuvant and adjuvant treatment. In addition, these tests can be used as tumor markers to assess disease response. We reviewed the current evidence for the use of high-sensitivity MRD assays with particular focus on the genitourinary tumors. Multiple studies have now been reported in urothelial, renal, and recently testicular carcinoma. We find that the sensitivity varies across tumor types in the adjuvant setting and may reach a high of 100% in urothelial cancer. Specificity in tumor-informed MRD appears to be preserved across tumor types (98%-100%). Several trials are now prospectively validating MRD testing in biomarker integral studies, mainly in urothelial carcinoma., (© The Author(s) 2024. Published by Oxford University Press.)

Purpose: Cabozantinib and nivolumab (CaboNivo) alone or with ipilimumab (CaboNivoIpi) have shown promising efficacy and safety in patients with metastatic urothelial carcinoma (mUC), metastatic renal cell carcinoma (mRCC), and rare genitourinary (GU) tumors in a dose-escalation phase I study. We report the final data analysis of the safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the phase I patients and seven expansion cohorts., Methods: This is an investigator-initiated, multicenter, phase I trial. CaboNivo doublet expansion cohorts included (1) mUC, (2) mRCC, and (3) adenocarcinoma of the bladder/urachal; CaboNivoIpi triplet expansion cohorts included (1) mUC, (2) mRCC, (3) penile cancer, and (4) squamous cell carcinoma of the bladder and other rare GU tumors (ClinicalTrials.gov identifier: NCT02496208)., Results: The study enrolled 120 patients treated with CaboNivo (n = 64) or CaboNivoIpi (n = 56), with a median follow-up of 49.2 months. In 108 evaluable patients (CaboNivo n = 59; CaboNivoIpi n = 49), the ORR was 38% (complete response rate 11%) and the median duration of response was 20 months. The ORR was 42.4% for mUC, 62.5% for mRCC (n = 16), 85.7% for squamous cell carcinoma of the bladder (n = 7), 44.4% for penile cancer (n = 9), and 50.0% for renal medullary carcinoma (n = 2). Grade ≥ 3 treatment-related adverse events occurred in 84% of CaboNivo patients and 80% of CaboNivoIpi patients., Conclusion: CaboNivo and CaboNivoIpi demonstrated clinical activity and safety in patients with multiple GU malignancies, especially clear cell RCC, urothelial carcinoma, and rare GU tumors such as squamous cell carcinoma of the bladder, small cell carcinoma of the bladder, adenocarcinoma of the bladder, renal medullary carcinoma, and penile cancer.

Urine cytology is a noninvasive, widely used diagnostic tool for screening and surveillance of genitourinary tract neoplasms. However, the absence of unified terminology and clear objective morphological criteria limits the clinical benefit of urine cytology. The Paris System for Reporting Urine Cytology (TPS) was developed with the goal of standardizing reporting and improving urine cytology performance in detecting high-grade malignancy (HGM). We aimed to evaluate potential effects of TPS on improving urine cytology diagnostic performance and clinical utility by conducting a systematic review and meta-analysis. We searched six electronic databases to identify cross-sectional and cohort studies written in English assessing the accuracy of urine cytology in detecting genitourinary tract malignancies of patients under surveillance or with clinical suspicion of malignancy from January 2004 to December 2022. We extracted relevant data from eligible studies to calculate relative distribution of cytology diagnostic categories; ratio of atypical to HGM cytology diagnosis; and risk of HGM (ROHGM) and HGM likelihood ratio (HGM-LR) associated with cytology diagnostic categories. We used a generalized linear mixed model with logit transformation to combine proportions and multilevel mixed-effect logistic regression to pool diagnostic accuracy measurements. We performed meta-regression to evaluate any significant difference between TPS and non-TPS cohorts. We included 64 studies for 99,796 combined total cytology samples, across 31 TPS and 49 non-TPS cohorts. Pooled relative distribution [95% confidence interval (CI)] of negative for high-grade urothelial carcinoma (NHGUC)/negative for malignancy (NM); atypical urothelial cells (AUC); suspicious for high-grade urothelial carcinoma (SHGUC)/suspicious for malignancy (SM); low-grade urothelial neoplasm (LGUN); and HGM categories among satisfactory cytology cases were 83.8% (80.3%-86.9%), 8.0% (6.0%-10.6%), 2.2% (1.4%-3.3%), 0.01% (0.0%-0.1%), and 4.2% (3.2%-5.5%) in TPS versus 80.8% (76.8-2.7%), 11.3% (8.6%-14.7%), 1.8% (1.2%-2.7%), 0.01% (0.0%-0.1%), and 3.3% (2.5%-4.3%) in non-TPS cohorts. Adopting TPS classification resulted in a significant increase in the frequency of NHGUC and a reduction in AUC cytology diagnoses, respectively. The AUC/HGM ratio in TPS cohort was 2.0, which showed a statistically significant difference from the atypical/HGM ratio of 4.1 in non-TPS cohort (p-value: 0.01). Moreover, the summary rate (95% CI) of LGUN called AUC on cytology significantly decreased to 20.8% (14.9%-28.3%) in the TPS compared with 34.1% (26.4%-42.8%) in non-TPS cohorts. The pooled ROHGM (95% CI) was 20.4% (6.2%-50.0%) in nondiagnostic (NDX), 15.5% (9.6%-24.2%) in NHGUC, 40.2% (30.9%-50.2%) in AUC, 80.8% (72.9%-86.8%) in SHGUC, 15.1% (5.7%-34.3%) in LGUN, and 91.4% (87.3%-94.3%) in HGM categories in TPS studies. NHGUC, AUC, SHGUC, and HGM categories were associated with HGM-LR (95% CI) of 0.2 (0.1-0.3), 0.9 (0.6-1.3), 6.9 (2.4-19.9), and 16.8 (8.3-33.8). Our results suggest that TPS 1.0 has reduced the relative frequency of AUC diagnosis, AUC/HGM ratio, and the frequency of LGUNs diagnosed as AUC on cytology. Adopting this classification has improved the clinical utility of SHGUC and HGM cytology diagnoses in ruling in high-grade lesions. However, an NHGUC diagnosis does not reliably rule out the presence of a high-grade lesion., (© 2024 John Wiley & Sons Ltd.)

Context.—: Urinary and Male Genital Tumours is the 8th volume of the World Health Organization Classification of Tumours series, 5th edition. Released in hard copy in September 2022, it presents an update to the classification of male genital and urinary tumors in the molecular age. Building upon previous volumes in this series, significant effort has been made to harmonize terminology across organ systems for biologically similar tumors (eg, neuroendocrine tumors). Genomic terminology has been standardized and genetic syndromes covered more comprehensively. This review presents a concise summary of this volume, highlighting new entities, notable modifications relative to the 4th edition, and elements of relevance to routine clinical practice., Objective.—: To provide a comprehensive update on the World Health Organization classification of urinary and male genital tumors, highlighting updated diagnostic criteria and terminology., Data Sources.—: The 4th and 5th editions of the World Health Organization Classification of Tumours: Urinary and Male Genital Tumours., Conclusions.—: The World Health Organization has made several changes in the 5th edition of the update on urinary and male genital tumors that pathologists need to be aware of for up-to-date clinical practice., (© 2024 College of American Pathologists.)

The presence of tertiary lymphoid structures (TLSs) associated with distinct treatment efficacy and clinical prognosis has been identified in various cancer types. However, the mechanistic roles and clinical implications of TLSs in genitourinary (GU) cancers remain incompletely explored. Despite their potential role as predictive markers described in numerous studies, it is essential to comprehensively evaluate the characteristics of TLSs, including drivers of formation, structural foundation, cellular compositions, maturation stages, molecular features, and specific functionality to maximize their positive impacts on tumor-specific immunity. The unique contributions of these structures to cancer progression and biology have fueled interest in these structures as mediators of antitumor immunity. Emerging data are trying to explore the effects of therapeutic interventions targeting TLSs. Therefore, a better understanding of the molecular and phenotypic heterogeneity of TLSs may facilitate the development of TLSs-targeting therapeutic strategies to obtain optimal clinical benefits for GU cancers in the setting of immunotherapy. In this review, the authors focus on the phenotypic and functional heterogeneity of TLSs in cancer progression, current therapeutic interventions targeting TLSs and the clinical implications and therapeutic potential of TLSs in GU cancers., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Demonstrating the safety and efficacy of percutaneous irreversible electroporation (IRE) for the treatment of lymph node metastases., Materials and Methods: An IRB-approved, single-center retrospective review was performed on patients with lymph node metastases gastrointestinal, and genitourinary primary cancers. Primary objective safety was evaluated by assessing complications graded according to the Clavien-Dindo Classification, and efficacy was determined by tumor response on follow-up imaging and local progression-free survival (LPFS). Secondary outcome measures were technical success (complete ablation with an adequate ablative margin > 5 mm), length of hospital stay and distant progression-free survival (DPFS)., Results: Nineteen patients underwent percutaneous IRE between June 2018 and February 2023 for lymph node metastases, close to critical structures, such as vasculature, bowel, or nerves. The technical success was achieved in all cases. Complications occurred in four patients (21.1%), including two self-limiting grade 1 hematomas, a grade 1 abdominal pain, and grade 2 nerve pain treated with medication. Seventeen patients were hospitalized overnight, one patient stayed two nights and another patient stayed fourteen nights. Median follow-up was 25.5 months. Median time to local progression was 24.1 months (95% CI: 0-52.8) with 1-, 2-, and 5-year LPFS of 57.9%, 57.9% and 20.7%, respectively. Median time to distant progression was 4.3 months (95% CI: 0.3-8.3) with 1-, 2-, and 5-year DPFS of 31.6%, 13.2% and 13.2%, respectively., Conclusion: IRE is a safe and effective minimally-invasive treatment for lymph node metastases in locations, where temperature dependent ablation may be contraindicated. Care should be taken when employing IRE near nerves., (© 2024. The Author(s).)

Purpose: To apply natural language processing (NLP) to a large volume of structured radiology reports in the investigation of CT imaging features of new liver metastases from primary genitourinary cancers., Methods: In this retrospective study, a previously reported NLP model was applied to consecutive structured CT reports from 2016 to 2022 to predict those patients with primary genitourinary cancer who developed liver metastasis. Pathology or imaging follow-up served as the reference standard for validating NLP predictions. Subsequently, diagnostic CTs of the identified patients were qualitatively assessed by two radiologists, whereby several imaging features of new liver metastasis were assessed. Proportions of the assessed imaging features were compared between primary genitourinary cancers using the Chi-square or Fisher's exact test., Results: In 112 patients (mean age = 72 years; 83 males), the majority of new liver metastases were hypovascular (73.2%), well defined (76.6%), homogenous (66.9%), and without necrotic/cystic component (73.2%). There was a higher proportion of iso- to hyperdense liver metastases for primary kidney cancer vs other primary genitourinary cancers (42.5% in kidney cancer; 2.3% in ureter/bladder cancer, 8% in prostate cancer, and 0% in testicular cancer; p < 0.05) and a higher proportion of new liver metastases with ill-defined margin for primary prostate cancer vs other primary genitourinary cancers (44.0% in prostate cancer, 15.0% in kidney cancer, 18.6% in ureter/bladder cancer, and 25.0% in testicular cancer; p < 0.05)., Conclusion: New liver metastases from primary genitourinary cancers tend to be hypovascular and show several distinct imaging features between different primary genitourinary cancers., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

With the high incidence of urogenital tumors worldwide, urinary system tumors are among the top 10 most common tumors in men, with prostate cancer ranking first and bladder cancer fourth. Patients with resistant urogenital tumors often have poor prognosis. In recent years, researchers have discovered numerous specific cancer antigens, which has led to the development of several new anti-cancer drugs. Using protein analysis techniques, researchers developed immune checkpoint inhibitors (ICIs) and antibody-conjugated drugs (ADCs) for the treatment of advanced urogenital tumors. However, tumor resistance often leads to the failure of monotherapy. Therefore, clinical trials of the combination of ICIs and ADCs have been carried out in numerous centers around the world. This article reviewed phase 2 and 3 clinical studies of ICIs, ADCs, and their combination in the treatment of urogenital tumors to highlight safe and effective methods for selecting individualized therapeutic strategies for patients. ICIs activate the immune system, whereas ADCs link monoclonal antibodies to toxins, which can achieve a synergistic effect when the two drugs are combined. This synergistic effect provides multiple advantages for the treatment of urogenital tumors., (© 2024. The Author(s).)

Neuroendocrine carcinoma (NEC) is a rare yet potentially perilous neoplasm. The objective of this study was to develop prognostic models for the survival of NEC patients in the genitourinary system and subsequently validate these models. A total of 7125 neuroendocrine neoplasm (NEN) patients were extracted. Comparison of survival in patients with different types of NEN before and after propensity score-matching (PSM). A total of 3057 patients with NEC, whose information was complete, were extracted. The NEC influencing factors were chosen through the utilization of the least absolute shrinkage and selection operator regression model (LASSO) and the Fine & Gary model (FGM). Furthermore, nomograms were built. To validate the accuracy of the prediction, the efficiency was verified using bootstrap self-sampling techniques and receiver operating characteristic curves. LASSO and FGM were utilized to construct three models. Confirmation of validation was achieved by conducting analyses of the area under the curve and decision curve. Moreover, the FGS (DSS analysis using FGM) model produced higher net benefits. To maximize the advantages for patients, the FGS model disregarded the influence of additional occurrences. Patients are expected to experience advantages in terms of treatment options and survival assessment through the utilization of these models., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Niu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Context: Lymphadenectomy during surgery for genitourinary malignancies has varying benefits., Objective: To review contemporary evidence on lymph node dissection in genitourinary cancers., Evidence Acquisition: We performed a collaborative review to summarize current evidence supporting lymph node dissection in urothelial, prostate, kidney, penile, and testis cancers. We present the evidence on patient selection and recommended dissection templates, and highlight knowledge gaps and ongoing areas of investigation., Evidence Synthesis: Lymph node dissection remains the reference standard for lymph node staging. Pathologic nodal stage informs prognosis and guides adjuvant treatment. Appropriate template and patient selection are paramount to optimize outcomes and capitalize on the selective therapeutic benefits., Conclusions: Accurate staging with lymphadenectomy is contingent on appropriate template selection. The cumulative benefit will depend on judicious patient selection., Patient Summary: We performed a collaborative review by a diverse group of experts in urology. We reviewed current evidence on lymph node dissection., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Opinion Statement: The treatment of oligometastatic genitourinary cancers is a rapidly advancing field with ablative radiotherapy as one of the critical treatment components. The oligometastatic disease state, which can be defined as 1-5 metastatic sites with a controlled primary, represents a distinct clinical state where comprehensive ablative local therapies may provide improved outcomes. Enhanced imaging has increased the number of patients identified with oligometastatic disease. Evidence for improved outcomes with metastasis-directed therapy (MDT) in oligometastatic genitourinary cancers is increasing, and previously published outcome data continues to mature with an increasing body of prospective data to inform the role of MDT in histology-specific settings or in the context of systemic therapy. In select patients, MDT can offer benefits beyond improved local control and allow for time off of systemic therapy, prolonged time until next therapy, or even the hope of cure. However, treatment decisions for locally ablative therapy must be balanced with consideration towards safety. There are exciting advances in technologies to target and adapt treatment in real-time which have expanded options for safer delivery and dose escalation to metastatic targets near critical organs at risk. The role of systemic therapies in conjunction with MDT and incorporation of tumor genetic information to further refine prognostication and treatment decision-making in the oligometastatic setting is actively being investigated. These developments highlight the evolving field of treatment of oligometastatic disease. Future prospective studies combining MDT with enhanced imaging and integrating MDT with evolving systemic therapies will enable the optimal selection of patients most likely to benefit from this "all-or-none" approach and reveal settings in which a combination of therapies could result in synergistic outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Solitary fibrous tumour (SFT) is a mesenchymal neoplasm with variable behaviour, very rarely involving the genitourinary (GU) tract. Most reported cases correspond to isolated case reports. STAT6 immunohistochemistry is a more recent and reliable diagnostic marker. The pathology database of two tertiary institutes was searched for SFTs involving the GU tract. STAT6 strong diffuse nuclear staining confirmed the diagnosis in all four cases, and the NAB2::STAT6 fusion was demonstrated by NGS in one case. Two cases were diagnosed in needle biopsy, one involving the prostate and the other involving the seminal vesicle. One case corresponded to a pelvic mass inseparable from and infiltrating the prostate and bladder. The remainder represented an exceedingly rare involvement of the spermatic cord. Involvement by a SFT should be considered in the differential diagnosis of spindle cell lesions involving GU organs. STAT6 strong diffuse nuclear staining is an important ancillary tool, particularly in a biopsy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose of Review: Genitourinary (GU) malignancies are a real burden in global health worldwide. Each model has its own clinical challenges, and the early screening and/or detection of occult cancer in follow-up is transversal to all of them. MicroRNAs (miRNAs) have been proposed as minimally invasive liquid biopsy cancer biomarkers, due to their stability and low degradation., Recent Findings: The different GU tumor models are in different stages concerning miRNAs as biomarkers for cancer detection. Testicular germ cell tumors (TGCTs) already have a specific defined target, miR-371a-3p, that has shown high sensitivity and specificity in different clinical settings, and is now in final stages of preanalytical testing before entering the clinic. The other GU malignancies are in a different stage, with many liquid biopsy studies (both in urine and plasma/serum) being currently performed, but there is not an agreeable miRNA or set of miRNAs that is ready to follow the footsteps of miR-371a-3p in TGCTs., Summary: Further studies with proper molecular characterization of miRNA profiles of GU malignancies and standardization of sampling, biobanking and formal analysis may aid in the advance and choosing of specific target sets to be used for occult cancer detection., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Context.—: The morphologic features of different entities in genitourinary pathology overlap, presenting a diagnostic challenge, especially when diagnostic materials are limited. Immunohistochemical markers are valuable when morphologic features alone are insufficient for definitive diagnosis. The World Health Organization classification of urinary and male genital tumors has been updated for 2022. An updated review of immunohistochemical markers for newly classified genitourinary neoplasms and their differential diagnosis is needed., Objective.—: To review immunohistochemical markers used in the diagnosis of genitourinary lesions in the kidney, bladder, prostate, and testis. We particularly emphasized difficult differential diagnosis and pitfalls in immunohistochemistry application and interpretation. New markers and new entities in the 2022 World Health Organization classifications of genitourinary tumors are reviewed. Recommended staining panels for commonly encountered difficult differential diagnoses and potential pitfalls are discussed., Data Sources.—: Review of current literature and our own experience., Conclusions.—: Immunohistochemistry is a valuable tool in the diagnosis of problematic lesions of the genitourinary tract. However, the immunostains must be carefully interpreted in the context of morphologic findings with a thorough knowledge of pitfalls and limitations., (© 2024 College of American Pathologists.)

Objective: To outline our experimental gonadal tissue cryopreservation (GTC) protocol that does not disrupt the standard of care in medically-indicated gonadectomy for patients with differences of sex development, including highlighting the multidisciplinary collaborative protocol for when neoplasm is discovered in these cases., Methods: Two patients with complete gonadal dysgenesis who were undergoing medically-indicated prophylactic bilateral gonadectomy elected to pursue GTC. Both were found to have germ cell neoplasia in situ on initial pathologic analysis, requiring recall of the gonadal tissue, which had been cryopreserved., Results: Cryopreserved gonadal tissue was successfully thawed and transferred to pathology for complete analysis. No germ cells were identified in either patient nor were found to have malignancy, so further treatment beyond gonadectomy was not indicated. Pathologic information was communicated to each family, including that long-term GTC was no longer possible., Conclusion: Organizational planning and coordination between the clinical care teams, GTC laboratory, and pathology were key to handling these cases with neoplasia. Processes that anticipated the possibility of discovering neoplasia within tissue sent to pathology and the potential need to recall GTC tissue to complete staging included (1) documenting the orientation and anatomical position of tissue processed for GTC, (2) defining parameters in which tissue will be recalled, (3) efficiently thawing and transferring GTC tissue to pathology, and (4) coordinating release of pathology results with verbal communication from the clinician to provide context. GTC is desired by many families and at the time of gonadectomy and is (1) feasible for patients with DSD, and (2) did not inhibit patient care in 2 patients with GCNIS., Competing Interests: DECLARATION OF COMPETING INTEREST Authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Drug resistance presents a major obstacle in the treatment of genitourinary cancers. Exosomes as the medium of intercellular communication serve important biological functions and play essential roles in pathological processes, including drug response. Through the transfer of bioactive cargoes, exosomes can modulate drug resistance via multiple mechanisms. This review attempts to elucidate the mechanisms of exosomal cargoes with reference to tumor drug resistance, their role in genitourinary cancers, and their potential clinical applications as candidate biomarkers in liquid biopsy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Embryonal rhabdomyosarcoma (ERMS) is the most common subtype of rhabdomyosarcoma (RMS). Among RMS subtypes, ERMS is associated with a favorable outcome with an overall survival of 70% at 5 years for localized disease. The molecular profile of ERMS is heterogeneous, including mostly point mutations in various genes. Therapeutic strategies have remained relatively consistent irrespective of the molecular abnormalities. In this study, we focus on a homogeneous RAS/RAF mutated ERMS subset and correlate with clinicopathologic findings. Twenty-six cases (16 males and 10 females) were identified from screening 98 ERMS, either by targeted DNA sequencing (MSK-IMPACT) or by Sanger sequencing. Fourteen (54%) cases had NRAS mutations, 6 (23%) had KRAS mutations, 5 (19%) had HRAS mutations, and 1 case (4%) had BRAF mutation. Median age at diagnosis was 8 years (range 1-70) with two-thirds occurring in the children. Tumor sites varied with H&N and GU sites accounting for 62% of cases. RAS isoform hot spot mutations predominated: NRAS p.Q61K (57%), KRAS p.G12D (67%), and HRAS (codons 12, 14, and 61). Additional genetic abnormalities were identified in 85% of the RAS-mutated cases. At last follow-up, 29% of patients died of disease and 23% were alive with disease. The 3-year and 5-year survival rates were 75% and 61% respectively. In conclusion, RAS mutations occur in 27% of ERMS, with NRAS mutations encompassing half of the cases. Overall RAS-mutant RMS does not correlate with age or site, but most tumors show an undifferentiated and spindle cell morphology., (© 2021 Wiley Periodicals LLC.)

Introduction: Introducing new drugs for clinical application is a very difficult, long, drawn-out, and costly process, which is why drug repositioning is increasingly gaining in importance. The aim of this study was to analyze the cytotoxic properties of ciprofloxacin and levofloxacin on bladder and prostate cell lines in vitro., Methods: Bladder and prostate cancer cell lines together with their non-malignant counterparts were used in this study. In order to evaluate the cytotoxic effect of both drugs on tested cell lines, MTT assay, real-time cell growth analysis, apoptosis detection, cell cycle changes, molecular analysis, and 3D cultures were examined., Results: Both fluoroquinolones exhibited a toxic effect on all of the tested cell lines. In the case of non-malignant cell lines, the cytotoxic effect was weaker, which was especially pronounced in the bladder cell line. A comparison of both fluoroquinolones showed the advantage of ciprofloxacin (lower doses of drug caused a stronger cytotoxic effect). Both fluoroquinolones led to an increase in late apoptotic cells and an inhibition of cell cycle mainly in the S phase. Molecular analysis showed changes in BAX , BCL2 , TP53 , and CDKN1 expression in tested cell lines following incubation with ciprofloxacin and levofloxacin. The downregulation of topoisomerase II genes ( TOP2A and TOP2B ) was noticed. Three-dimensional (3D) cell culture analysis confirmed the higher cytotoxic effect of tested fluoroquinolone against cancer cell lines., Conclusions: Our results suggest that both ciprofloxacin and levofloxacin may have great potential, especially in the supportive therapy of bladder cancer treatment. Taking into account the low costs of such therapy, fluoroquinolones seem to be ideal candidates for repositioning into bladder cancer therapeutics.

Environmental and/or occupational exposure to metals such as Arsenic (As), Cadmium (Cd), and Chromium (Cr) have been shown to induce carcinogenesis in various organs, including the urogenital system. However, the mechanisms responsible for metal-induced carcinogenesis remain elusive. We and others have shown that metals are potent inducers of autophagy, which has been suggested to be an adaptive stress response to allow metal-exposed cells to survive in hostile environments. Albeit few, recent experimental studies have shown that As and Cd promote tumorigenesis via autophagy and that inhibition of autophagic signaling suppressed metal-induced carcinogenesis. In light of the newly emerging role of autophagic involvement in metal-induced carcinogenesis, the present review focuses explicitly on the mechanistic role of autophagy and potential signaling pathways involved in As-, Cd-, and Cr-induced urogenital carcinogenesis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Context.—: Lesions in the genitourinary (GU) organs, both benign and malignant, can demonstrate overlapping morphology, and practicing surgical pathologists should be aware of these potential pitfalls and consider a broad differential diagnosis for each specific type of lesion involving the GU organs. The following summary of the contents presented at the 6th Annual Chinese American Pathologists Association (CAPA) Diagnostic Course (October 10-11, 2020), supplemented with relevant literature review, exemplifies the common diagnostic challenges and pitfalls for mass lesions of the GU system of adults, including adrenal gland, with emphasis on immunohistochemical and molecular updates when relevant., Objective.—: To describe the common mass lesions in the GU system of adults, including adrenal gland, with emphasis on the diagnostic challenges and pitfalls that may arise in the pathologic assessment, and to highlight immunohistochemical workups and emerging molecular findings when relevant., Data Sources.—: The contents presented at the course and literature search comprise our data sources., Conclusions.—: The diagnostic challenges and pitfalls that arise in the pathologic assessment of the mass lesions in the GU system of adults, including adrenal gland, are common. We summarize the contents presented at the course, supplemented with relevant literature review, and hope to provide a diagnostic framework to evaluate these lesions in routine clinical practice.

Objective: To examine the risk of urogenital, colorectal, and neurological cancers after a first diagnosis of acute urinary retention., Design: Nationwide population based cohort study., Setting: All hospitals in Denmark., Participants: 75 983 patients aged 50 years or older with a first hospital admission for acute urinary retention during 1995-2017., Main Outcome Measures: Absolute risk of urogenital, colorectal, and neurological cancer and excess risk of these cancers among patients with acute urinary retention compared with the general population., Results: The absolute risk of prostate cancer after a first diagnosis of acute urinary retention was 5.1% (n=3198) at three months, 6.7% (n=4233) at one year, and 8.5% (n=5217) at five years. Within three months of follow-up, 218 excess cases of prostate cancer per 1000 person years were detected. An additional 21 excess cases per 1000 person years were detected during three to less than 12 months of follow-up, but beyond 12 months the excess risk was negligible. Within three months of follow-up the excess risk for urinary tract cancer was 56 per 1000 person years, for genital cancer in women was 24 per 1000 person years, for colorectal cancer was 12 per 1000 person years, and for neurological cancer was 2 per 1000 person years. For most of the studied cancers, the excess risk was confined to within three months of follow-up, but the risk of prostate and urinary tract cancer remained increased during three to less than 12 months of follow-up. In women, an excess risk of invasive bladder cancer persisted for several years., Conclusions: Acute urinary retention might be a clinical marker for occult urogenital, colorectal, and neurological cancers. Occult cancer should possibly be considered in patients aged 50 years or older presenting with acute urinary retention and no obvious underlying cause., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/. and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The prognostic significance of programmed cell death-ligand 1 (PD-L1) expression on circulating tumor cells (CTCs) has been explored but is still in controversy. We performed, for the first time, a meta-analysis to systematically evaluate its prognostic value in human cancers., Methods: Literature databases were searched for eligible studies prior to June 30, 2021. The pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated for the associations of pre-treatment and post-treatment PD-L1 + CTCs with progression-free survival (PFS) and overall survival (OS). Subgroup analyses with regards to cancer type, treatment, CTC enrichment method, PD-L1 detection method, cut-off, and specifically the comparison model were performed., Results: We included 30 eligible studies (32 cohorts, 1419 cancer patients) in our analysis. Pre-treatment PD-L1 + CTCs detected by immunofluorescence (IF) tended to predict better PFS (HR = 0.55, 95% CI 0.28-1.08, p = 0.084) and OS (HR = 0.61, 95% CI 0.36-1.04, p = 0.067) for immune checkpoint inhibitor (ICI) treatment, but were significantly associated with unfavorable survival for non-ICI therapies (PFS: HR = 1.85, 95% CI 1.21-2.85, p = 0.005; OS: HR = 2.44, 95% CI 1.69-3.51, p < 0.001). Post-treatment PD-L1 + CTCs predicted markedly worse PFS and OS. The prognostic value was obviously modulated by comparison models. Among patients with detectable CTCs, PD-L1 + individuals had comparable survival to PD-L1 - individuals, except ICI treatment for which PD-L1 + may predict better PFS (HR = 0.42, 95% CI 0.17-1.06, p = 0.067). Patients with PD-L1 + CTCs had worse survival prognosis compared to those without PD-L1 + CTCs in overall analysis (PFS: HR = 2.10, 95% CI 1.59-2.77, p < 0.001; OS: HR = 2.55, 95% CI 1.70-3.81, p < 0.001) and in most subgroups., Conclusions: Our analysis demonstrated that PD-L1 positive expression on CTCs predicted better survival prognosis for ICI treatment but worse survival for other therapies, which thus can be potentially used as a prognostic marker of malignant tumor treatment. However, the prognostic value of PD-L1 + CTCs for ICI treatment needs validation by more large-scale studies in the future., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Centralization of specialized care for rare cancers can improve patient outcomes. Inguinal lymph node evaluation is the most important clinical aspect of penile cancer care and is often neglected in a decentralized setting. Centralization of care may reduce system delays, improve guideline adherence, provide access to a wider team of specialists, and improve prognosis, albeit with some inconveniences for patients. PATIENT SUMMARY: We reviewed evidence for the centralization of care for penile cancer. Patients may have to travel greater distances to receive specialized care in expert centers. However, centralization means that rare cancers can be treated by more experienced surgeons, which can yield better outcomes in terms of survival and penis-preserving or reconstruction surgery., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

OBJECTIVE. Organ-specific nonregional and regional lymph nodes vary considerably among tumors. Nonregional lymph node involvement equals metastasis, which is critical to detect to ensure correct tumor staging, management, and prognosis. Knowledge of nodal nomenclature and anatomy is therefore essential in every cross-sectional imaging study. CONCLUSION. This article reviews the most important changes and highlights of the N category of the American Joint Committee on Cancer 8th edition of the TNM classification for urogenital cancers.

Embryonal rhabdomyosarcoma (ERMS) of the uterus has recently been shown to frequently harbor DICER1 mutations. Interestingly, only rare cases of extrauterine DICER1-associated ERMS, mostly located in the genitourinary tract, have been reported to date. Our goal was to study clinicopathologic and molecular profiles of DICER1-mutant (DICER1-mut) and DICER1-wild type (DICER1-wt) ERMS in a cohort of genitourinary tumors. We collected a cohort of 17 ERMS including nine uterine (four uterine corpus and five cervix), one vaginal, and seven urinary tract tumors. DNA sequencing revealed mutations of DICER1 in 9/9 uterine ERMS. All other ERMS of our cohort were DICER1-wt. The median age at diagnosis of patients with DICER1-mut and DICER1-wt ERMS was 36 years and 5 years, respectively. Limited follow-up data (available for 15/17 patients) suggested that DICER1-mut ERMS might show a less aggressive clinical course than DICER1-wt ERMS. Histological features only observed in DICER1-mut ERMS were cartilaginous nodules (6/9 DICER1-mut ERMS), in one case accompanied by foci of ossification. Recurrent mutations identified in both DICER1-mut and DICER1-wt ERMS affected KRAS, NRAS, and TP53. Copy number analysis revealed similar structural variations with frequent gains on chromosomes 2, 3, and 8, independent of DICER1 mutation status. Unsupervised hierarchical clustering of array-based whole-genome DNA methylation data of our study cohort together with an extended methylation data set including different RMS subtypes from genitourinary and extra-genitourinary locations (n = 102), revealed a distinct cluster for DICER1-mut ERMS. Such tumors clearly segregated from the clusters of DICER1-wt ERMS, alveolar RMS, and MYOD1-mutant spindle cell and sclerosing RMS. Only one tumor, previously diagnosed as ERMS arising in the maxilla of a 6-year-old boy clustered with DICER1-mut ERMS of the uterus. Subsequent sequencing analysis identified two DICER1 mutations in the latter case. Our results suggest that DICER1-mut ERMS might qualify as a distinct subtype in future classifications of RMS., (© 2021. The Author(s).)

Purpose: Several immune checkpoint inhibitors (ICIs) are FDA approved for treatment of genitourinary (GU) malignancies. We aim to determine demographic and clinicopathologic characteristics that significantly affect clinical outcomes in patients with advanced stage GU malignancies treated with ICIs., Materials and Methods: We performed a single-center, consecutive, retrospective cohort analysis on patients with metastatic or unresectable GU malignancies who were treated with ICIs at the University of Michigan. Immune-related adverse events (irAEs), putative immune-mediated allergies, and overall response rates (ORR) were assessed. Comorbidity index scores were calculated. Survival analysis was performed to evaluate progression-free survival (PFS) and overall survival (OS), stratifying and controlling for a variety of clinicopathologic baseline factors including site of metastases., Results: A total of 160 patients were identified with advanced renal cell carcinoma (RCC) or urothelial carcinoma. Median PFS and OS were 5.0 and 23.6 months for RCC, and 2.8 and 9.6 months for urothelial carcinoma, respectively. Patients who experienced increased frequency and higher grade irAEs had better ICI treatment response (P < 0.0001). Presence of liver metastases was associated with poor response to ICI therapy (P = 0.001). Multivariable modeling demonstrates that patients with urothelial carcinoma and liver metastases had statistically worse PFS and OS compared to patients with RCC or other sites of metastases, respectively., Conclusion: Greater frequency and higher grades of irAEs are associated with better treatment response in patients with RCC and urothelial malignancy receiving ICI therapy. The presence of liver metastases denotes a negative predictive marker for immunotherapy efficacy., Summary: Immune checkpoint inhibitors (ICI) are increasingly used to treat genitourinary (GU) malignancies. However, clinical data regarding patients with advanced-stage GU malignancies treated with ICI is lacking. Thus, we performed a single-center, retrospective cohort study on patients with metastatic and unresectable renal cell carcinoma (RCC) and urothelial carcinoma who were treated with ICIs at the University of Michigan to provide demographic and clinicopathologic data regarding this population. We specifically focused on immune-related adverse events (irAEs), immune-mediated allergies, and the associated overall response rates (ORR). To better assess performance status, we calculated comorbidity scores for all patients. Finally, survival analyses for progression-free survival (PFS) and overall survival (OS) were performed using Kaplan-Meier analysis and Cox proportional hazards modeling, stratifying and controlling for clinicopathologic baseline factors, including sites of metastases, in our multivariable analysis. A total of 160 patients were identified with advanced RCC or urothelial carcinoma. We found decreased PFS (2.8 vs. 5.0 months) and decreased OS (9.8 vs. 23.6 months) for urothelial carcinoma compared to RCC patients. We noted that patients who experienced increased frequency and higher grades of irAEs had better treatment ORR with ICI therapy (P ≤ 0.0001). The presence of liver metastases was associated with worse ORR (P = 0.001), PFS (P = 0.0014), and OS (P = 0.0028) compared to other sites of metastases including lymph node, lung, and CNS/bone. The poor PFS and OS associated with urothelial carcinoma and liver metastases were preserved in our multivariable modeling after controlling for pertinent clinical factors. We conclude that greater frequency and higher grades of irAEs are associated with better treatment response in GU malignancy patients receiving ICI, a finding that is consistent with published studies in other cancers. The presence of liver metastases represents a significantly poor predictive marker in GU malignancy treated with ICI. Our findings contribute to the growing body of literature that seeks to understand the clinicopathologic variables and outcomes associated with ICI therapy., Competing Interests: Declaration of competing interest Dr. Ajjai Alva serves as a consultant for Merck, AstraZeneca, Bristol-Myers Squibb, and Pfizer/EMD Serono. Dr. Ajjai Alva receives research funding through the University of Michigan from Merck, Genentech, Prometheus Laboratories, Mirati Therapeutics, Roche, Bayer, Progenics, Astellas Pharma, Arcus Biosciences, AstraZeneca, Bristol-Myers Squibb, and Clovis Oncology. Dr. Jeremy Taylor serves as a consultant for Sarepta. Dr. Vincent Ma, Dr. Christopher Su, Miriam Hu, Stephanie Daignault-Newton, Olesia Kellezi, Megan Dal, Miloni Sha, Stephanie Erickson, Jessica Lora, Reema Hamasha, Alicia Ali, Sabrina Yancey, Leah Kiros, Hannah Balicki, Daniel Winfield, and Dr. Michael Green have no conflict of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Importance: Health insurance coverage is associated with improved outcomes in patients with cancer. However, it is unknown whether Medicaid expansion through the Patient Protection and Affordable Care Act (ACA) was associated with improvements in the diagnosis and treatment of patients with genitourinary cancer., Objective: To assess the association of Medicaid expansion with health insurance status, stage at diagnosis, and receipt of treatment among nonelderly patients with newly diagnosed kidney, bladder, or prostate cancer., Design, Setting, and Participants: This case-control study included adults aged 18 to 64 years with a new primary diagnosis of kidney, bladder, or prostate cancer, selected from the National Cancer Database from January 1, 2011, to December 31, 2016. Patients in states that expanded Medicaid were the case group, and patients in nonexpansion states were the control group. Data were analyzed from January 2020 to March 2021., Exposures: State Medicaid expansion status., Main Outcomes and Measures: Insurance status, stage at diagnosis, and receipt of cancer and stage-specific treatments. Cases and controls were compared with difference-in-difference analyses., Results: Among a total of 340 552 patients with newly diagnosed genitourinary cancers, 94 033 (27.6%) had kidney cancer, 25 770 (7.6%) had bladder cancer, and 220 749 (64.8%) had prostate cancer. Medicaid expansion was associated with a net decrease in uninsured rate of 1.1 (95% CI, -1.4 to -0.8) percentage points across all incomes and a net decrease in the low-income population of 4.4 (95% CI, -5.7 to -3.0) percentage points compared with nonexpansion states. Expansion was also associated with a significant shift toward early-stage diagnosis in kidney cancer across all income levels (difference-in-difference, 1.4 [95% CI, 0.1 to 2.6] percentage points) and among individuals with low income (difference-in-difference, 4.6 [95% CI, 0.3 to 9.0] percentage points) and in prostate cancer among individuals with low income (difference-in-difference, 3.0 [95% CI, 0.3 to 5.7] percentage points). Additionally, there was a net increase associated with expansion compared with nonexpansion in receipt of active surveillance for low-risk prostate cancer of 4.1 (95% CI, 2.9 to 5.3) percentage points across incomes and 4.5 (95% CI, 0 to 9.0) percentage points among patients in low-income areas., Conclusions and Relevance: These findings suggest that Medicaid expansion was associated with decreases in uninsured status, increases in the proportion of kidney and prostate cancer diagnosed in an early stage, and higher rates of active surveillance in the appropriate, low-risk prostate cancer population. Associations were concentrated in population residing in low-income areas and reinforce the importance of improving access to care to all patients with cancer.

The COVID-19 pandemic-related constraints on healthcare access have raised concerns about adverse outcomes from delayed treatment, including the risk of cancer progression and other complications. Further, concerns were raised about a potentially significant backlog of patients in need of cancer care due to the pandemic-related delays in healthcare, further exacerbating any potential adverse outcomes. Delayed access to surgery is particularly relevant to urologic oncology since one-third of new cancers in men (20% overall) arise from the genitourinary (GU) tract and surgery is often the primary treatment. Herein, we summarize the prepandemic literature on deferred surgery for GU cancers and risk of disease progression. The aforementioned data on delayed surgery were gathered in the context of systemic delays present in certain healthcare systems, or occasionally, due to planned deferral in suboptimal surgical candidates. These data provide indirect, but sufficient insight to develop triage schemas for prioritization of uro-oncological cases. Herein, we outline the extent to which the pandemic-related triage guidelines had influenced urologic practice in various regions. To study the adverse outcomes in the pandemic-era, a survey of urologic oncologists was conducted regarding modifications in their initial management of urologic cancers and any delay-related adverse outcomes. While the adverse effects directly from COVID-19 related delays will become apparent in the coming years, the results showing short-term outcomes are quite instructive. Since cancer care was assigned a higher priority at most centers, this strategy may have avoided significant delays in care and limited the anticipated negative impact of pandemic-related constraints., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The non-coding RNA (ncRNA) are generally classified, based on length, into small ncRNAs less than 200 nucleotides, such as miRNA, and long ncRNA (lnRNA) with more than 200 nucleotides. The transcription of ncRNAs, similarly to genes that code for proteins, is highly deregulated in cancer. Their expression level can influence physiological processes, e.g. epigenetic regulation of gene expression, regulation of cell cycle and modification of chromatin. Recent studies on androgen receptor in oncology revealed that it exerts a pivotal role in genitourinary malignancies, in particular in prostate tumor was demonstrated that its deregulation takes part in all stages of carcinogenesis. Here, we discuss present learning of the main lnRNAs involvement on androgen signaling pathways in genitourinary neoplasms, highlighting lnRNAs potential in the regulating network comfortable to cancer onset and progression, and discuss the lnRNAs prognostic and diagnostic value in cancer management., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Abstract: Decision-making to stop cancer treatment in patients with advanced cancer is stressful, and it significantly influences subsequent end-of-life palliative treatment. However, little is known about the extent to which the patient's self-decisions influenced the prognostic period. This study focused on the patient's self-decision and investigated the impact of the self-decision to stop cancer treatment on their post-cancer treatment survival period and place of death.We retrospectively analyzed 167 cases of advanced genitourinary cancer patients (kidney cancer: 42; bladder cancer: 68; prostate cancer: 57) treated at the University of Fukui Hospital (UFH), who later died because of cancer. Of these, 100 patients decided to stop cancer treatment by themselves (self-decision group), while the families of the remaining 67 patients (family's decision group) decided to stop treatment on their behalf because the patient's decision-making ability was already impaired. Differences in the post-cancer-treatment survival period and place of death between the 2 groups were examined. The association between place of death and survival period was also analyzed.The median survival period after terminating cancer treatment was approximately 6 times longer in the self-decision group (145.5 days in self-decision group vs 23.0 days in family's decision group, P < .001). Proportions for places of death were as follows: among the self-decision group, 42.0% of patients died at UFH, 45.0% at other medical institutions, and 13.0% at home; among the family's decision group, 62.7% died at UFH, 32.8% at other medical institutions, and 4.5% at home. The proportion of patients who died at UFH was significantly higher among the family's decision group (P = .011). The median survival period was significantly shorter for patients who died at UFH (UFH: 30.0 days; other institutions/home: 161.0 days; P < .001).Significantly longer post-cancer-treatment survival period and higher home death rate were observed among patients whose cancer treatment was terminated based on their self-decision. Our results provide clinical evidence, especially in terms of prognostic period and place of death that support the importance of discussing bad news, such as stopping cancer treatment with patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Little research has been done on clinicopathological characteristics and human papillomavirus (HPV) status of anogenital and oropharyngeal squamous cell carcinomas (SCC) with a strong expression of programmed death ligand 1 (PD-L1) in tumor cells. Therefore, we conducted this meta-analysis., Methods: We performed a comprehensive research in PubMed, Embase and Cochrane databases up to 30 September 2020. The effect size was hazard ratio (HR) with 95% confidence interval (CI) for overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS). The pooled odds ratio (OR) with 95% CI were used to assess the association between PD-L1 expression and clinicopathological features along with HPV status., Results: A total of 2003 cases (944 anogenital and 1059 oropharynx SCC patients) were included. High PD-L1 expression in anogenital SCC cases were associated with advanced age (OR = 1.63, 95% CI: 1.04-2.58) and HPV negativity (OR = 0.47, 95% CI: 0.31-0.71). Besides, PD-L1 positive anogenital SCC cases held a significantly declined OS (HR = 2.18, 95% CI: 1.37-3.47) and CSS (HR = 2.45, 95% CI: 1.30-4.65). For oropharynx SCC, PD-L1 was more frequent in younger and HPV positive patients (OR = 0.60, 95% CI: 0.37-0.98; OR = 3.01, 95% CI: 1.78-5.09) and PD-L1 expression was relevant to better OS and DFS (HR = 0.76, 95% CI: 0.60-0.97; HR = 0.50, 95% CI: 0.33-0.75)., Conclusions: The meta-analysis demonstrated that in anogenital SCC, PD-L1 positivity had to do with a worse outcome, which might attribute to advanced age, higher tumor grade, lymph node metastasis and HPV negativity, while in oropharynx cancer, PD-L1 expression was related to better prognosis for the reason that PD-L1 was less frequent in the aged and negative HPV status., (© 2021 The Author(s).)

Purpose: Circulating tumor cells (CTC) are under investigation as a minimally invasive liquid biopsy that may improve risk stratification and treatment selection. CTCs uniquely allow for digital pathology of individual malignant cell morphology and marker expression. We compared CTC features and T-cell counts with survival endpoints in a cohort of patients with metastatic genitourinary cancer treated with combination immunotherapy., Experimental Design: Markers evaluated included pan-CK/CD45/PD-L1/DAPI for CTCs and CD4/CD8/Ki-67/DAPI for T cells. ANOVA was used to compare CTC burden and T-cell populations across timepoints. Differences in survival and disease progression were evaluated using the maximum log-rank test., Results: From December 2016 to January 2019, 183 samples from 81 patients were tested. CTCs were found in 75% of patients at baseline. CTC burden was associated with shorter overall survival (OS) at baseline ( P = 0.022), but not on-therapy. Five morphologic subtypes were detected, and the presence of two specific subtypes with unique cellular features at baseline and on-therapy was associated with worse OS (0.9-2.3 vs. 28.2 months; P < 0.0001-0.013). Increasing CTC heterogeneity on-therapy had a trend toward worse OS ( P = 0.045). PD-L1 + CTCs on-therapy were associated with worse OS ( P < 0.01, cycle 2). Low baseline and on-therapy CD4/CD8 counts were also associated with poor OS and response category., Conclusions: Shorter survival may be associated with high CTC counts at baseline, presence of specific CTC morphologic subtypes, PD-L1 + CTCs, and low %CD4/8 T cells in patients with metastatic genitourinary cancer. A future study is warranted to validate the prognostic utility of CTC heterogeneity and detection of specific CTC morphologies., (©2020 American Association for Cancer Research.)

Clear cell adenocarcinoma (CCA) is a rare tumor in the genitourinary tract with female predominance and few reports in men. We identified 15 cases of CCA in men evaluated at our institution. Five arose in the bladder, 7 in the prostate or prostatic urethra, 2 in the membranous urethra (1 multifocal in the prostatic and membranous urethra), 1 periprostatic (likely from an embryologic remnant), and 1 between rectum and bladder (likely in a prostatic utricle cyst). No cases showed associated Müllerian structures. One case showed separate foci of nephrogenic adenoma at diagnosis, and 1 case showed urothelial carcinoma in situ on a later follow-up biopsy. Four tumors extended into other organs (prostate to seminal vesicle and periprostatic soft tissue, periprostatic soft tissue to prostate, prostatic urethra to bladder and rectum, and prostate to bladder neck). One tumor showed extraprostatic extension alone. Four tumors metastasized to lymph nodes, with 3 also metastasizing to other sites (bladder, lung and adrenal, and right flank). Eleven patients underwent resection, including 3 transurethral resections. Seven underwent other treatments, including radiation (5 [1 for recurrence]), chemotherapy (3), hormonal therapy (3), immunotherapy with nivolumab (1), and targeted therapy with gefitinib (1). The mean follow-up was 35 months (range: 1 to 138 mo). At the last follow-up, 7 patients showed no evident disease and 3 were alive with disease. Four died with the cause of death unknown, with 2 cases having confirmed disease at the time of death and the remaining 2 dying less than a year after diagnosis. The mean time to death was 16 months (range: 6 to 39 mo). No follow-up was available on 1 patient. All patients who died in this series had CCA of the prostate or prostatic urethra. Pathologists need to be attuned to CCA occurring in males, given that the literature emphasizes its occurrence in females. In addition to established sites such as bladder and urethra, our series demonstrates that tumor may present in unusual adjacent sites, such as in periprostatic embryologic remnants or prostatic utricle., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patient-reported outcomes have been used to assess treatment effectiveness and actively engage patients in their disease management. This study was designed to describe the patient-reported performance status (PS) and the provider-reported PS., Methods: Patients with metastatic genitourinary cancers were recruited from a single cancer center before the initiation of a new line of treatment. PS (Eastern Cooperative Oncology Group [ECOG]), quality of life (Functional Assessment of Chronic Illness Therapy-General), and distress (Patient-Reported Outcomes Measurement Information System Anxiety and Depression) were self-reported by patients. Clinical data (eg, age, sex, diagnosis, and physician-reported ECOG PS) were extracted from medical records. Multivariate analysis was used to determine the association between PS, quality of life, and psychological symptoms., Results: One hundred forty-five patients were enrolled (76.6% male, 70.3% White, 81.4% married, and 76.6% well educated). The median age was 67 years; 66.9% were diagnosed with renal cell carcinoma, 20.0% were diagnosed with urothelial carcinoma, and 13.1% were diagnosed with prostate cancer. Clinicians more frequently classified patients' ECOG PS as 0 in comparison with the patients themselves (92.4% vs 64.1%; P = .001). Higher clinician-reported ECOG PS was associated with poorer physical and functional well-being and higher rates of depression (P < .01), whereas higher patient-reported ECOG PS was associated with worse psychosocial outcomes (P < .01)., Conclusions: Discrepancies were noted between the patient- and provider-reported ECOG PS, with clinicians overestimating the ECOG PS in comparison with the patients themselves. This study's findings suggest that patients incorporate their social and emotional well-being into their PS score in addition to their physical well-being. This information is not immediately accessible to most clinicians from just a standard patient interview and likely accounts for the overestimation of the patients' ECOG PS by the clinicians., (© 2020 American Cancer Society.)

Radiation therapy for malignant tumors of the female genital area, even with the use of modern radiotherapy equipment and dosimetric planning, causes the development of local radiation changes. An approach involving methodsof general and local exposure is used in their treatment. One of the most promising directions is the creation of optimal combinations of medicines (in the form of ointments, gels, aerosols, suppositories, etc.), which have a therapeutic effect on the inflammatory process. The article reflects the clinical course and stage of occurrence of late radiation reactions of the skin, vaginal/cervix mucosa, bladder, and intestines, as well as the features of their treatment.Literary data and own practical experience in the treatment of radiation complications are presented. Whenreviewing the topic under study, it could be concluded that the leading cause of the development of local radiationdamage is the errors in the planning and implementation of radiation therapy, when high absorbed doses thatexceed the tolerance of healthy tissues are used. Another reason for this is the poor accounting for dose distribution of ionizing radiation in tissues, the presence of concomitant diseases in patients, and the underestimation ofthe long-term effects of radiation., (O. M. Sukhina, K. V. Nemaltsova, O. V. Panov.)

Patients with advanced genitourinary cancers face many challenges throughout their disease trajectory, and many will experience clinically relevant psychosocial distress. Certain groups, including female gender, younger age (and older age for suicide), unmarried status, and non-clear cell histology, remain at a higher risk, and evidence suggests that those with kidney and bladder cancers may be at an increased risk of suicide. Routine psychosocial screening, with brief validated tools, has the ability to identify patients' unmet needs, assist the health care team in addressing such symptoms, and subsequently improve quality of life, adherence, and clinical outcomes. Effective supportive care modalities are available that address common patient needs in the context of incurable disease (eg, emotional and physical symptoms); however, challenges remain in terms of patient acceptance and access through insurance coverage. As a result, remote home-based interventions have emerged with the potential to mitigate emotional symptom burden and improve disease adjustment. In this study, we highlight studies reporting on the prevalence of psychosocial distress and associated risk factors in advanced genitourinary cancers, and review evidence-based interventions for the management of distress, including distress screening and psychosocial interventions. PATIENT SUMMARY: This mini-review reports the prevalence of psychosocial distress and associated risk factors among patients with advanced kidney, bladder, or prostate cancer. We found that patients with these types of advanced genitourinary cancers are at a great risk of distress, including suicide, with consequent impairments in quality of life. We recommend that a distress screening program be incorporated as the standard of care and that referrals to appropriate psychosocial interventions be available to assist patients in greatest need., (Copyright © 2019. Published by Elsevier B.V.)

The age of immuno-oncology has ushered in a rush within the biopharmaceutical industry. This intense focus has been characterized as a frenzy or overhyped, but represents a substantial investment in new products that hope to harness the immune system against cancer. Such agents include next-generation checkpoint antagonists, immune costimulatory agonists, and a diverse array of novel mechanisms of action and therapeutic modalities targeting immune cell types and the interplay of the host and tumor at the immune synapse. This article surveys the clinical development and investment activity with Immuno-Oncology, specifically prostate, kidney, and bladder cancers., Competing Interests: Disclosure CHBC works for many BioPharma companies developing immuno-oncology therapies on a project fee basis. Neither I nor the company has any financial stake in any of these clients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose of Review: Pathomics, the fusion of digitalized pathology and artificial intelligence, is currently changing the landscape of medical pathology and biologic disease classification. In this review, we give an overview of Pathomics and summarize its most relevant applications in urology., Recent Findings: There is a steady rise in the number of studies employing Pathomics, and especially deep learning, in urology. In prostate cancer, several algorithms have been developed for the automatic differentiation between benign and malignant lesions and to differentiate Gleason scores. Furthermore, several applications have been developed for the automatic cancer cell detection in urine and for tumor assessment in renal cancer. Despite the explosion in research, Pathomics is not fully ready yet for widespread clinical application., Summary: In prostate cancer and other urologic pathologies, Pathomics is avidly being researched with commercial applications on the close horizon. Pathomics is set to improve the accuracy, speed, reliability, cost-effectiveness and generalizability of pathology, especially in uro-oncology.

Background: Determining whether members follow guidelines, including guidelines prepared to help direct practice management during the coronavirus disease 2019 (COVID-19) pandemic, is an important goal for medical associations., Objective: To determine whether practice of urologists is in line with guidelines for the management of common urological conditions during the COVID-19 pandemic produced by leading (inter)national urological associations., Design, Setting, and Participants: Self-selected urologists completed a voluntary survey available online from March 27 to April 11, 2020 and distributed globally by the Société Internationale d'Urologie., Outcome Measurements and Statistical Analysis: Responses to two survey questions on the (1) management of 14 common urological procedures and (2) priority scoring of 10 common urological procedures were evaluated by practice setting and geographical region using chi-square and one-way analysis of variance analyses, respectively., Results and Limitations: There were 2494 respondents from 76 countries. Oncological conditions were prioritised over benign conditions, and benign conditions were deferred when feasible and safe. Oncological conditions with the greatest malignant potential were prioritised over less aggressive cancers. Respondents from Europe were least likely to postpone and most likely to prioritise conditions identified by guidelines as being of the highest priority. Respondents' priority scoring of urological procedures closely matched the priorities assigned by guidelines. The main limitation of this study is that respondents were self-selected, and access to the survey was limited by language and technology barriers., Conclusions: Prioritisation and management of urological procedures during the COVID-19 pandemic are in line with current guidelines. The greatest agreement was reported in Europe. Observed differences may be related to limited resources in some settings., Patient Summary: When deciding how best to treat patients during the coronavirus disease 2019 (COVID-19) pandemic, urologists are taking into account both expert recommendations and the availability of important local resources., (Copyright © 2020 European Association of Urology. All rights reserved.)

Long non-coding RNAs (lncRNAs), a kind of non-coding single-strand RNAs, play an important role as carcinogenic genes or tumor suppressors in the development of human cancer. Myocardial infarction-associated transcript (MIAT) was first identified as a lncRNA in 2006 and originally isolated as a candidate gene for myocardial infarction. Later, it was reported that MIAT exhibits regulatory effects on the human cell cycle. Since its discovery, MIAT has also been identified as a carcinogenic regulator in many malignant tumors. High expression of MIAT is related to the clinicopathological characteristics of cancer patients. It can also regulate cell proliferation, invasion, metastasis, and anti-apoptosis through a variety of mechanisms. Therefore, MIAT is considered a potential biomarker and therapeutic target in cancer. In this review, we summarize the biological function, mechanism, and potential clinical significance of MIAT during tumorigenesis., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Extrapulmonary small cell carcinoma is a rare malignancy with scarce data. Treatment paradigms extrapolate from pulmonary small cell carcinoma and single institution studies. We analyzed the epidemiology, patterns of care, prognostic factors, and overall survival (OS) of EPSCC patients., Methods: The cohort included EPSCC. Patients with <2 months follow-up, unknown demographic/treatment variables were excluded. Descriptive statistics were performed to characterize the cohort. Kaplan-Meier methods were used to estimate OS. Cox proportional hazard modeling was done to analyze the influence of prognostic variables on OS., Results: 5747 patients were included. Median OS was 1.2 years. Head and neck (HR: 0.60, 95% CI 0.53-0.67, p < 0.0001) and breast (HR: 0.69, 95% CI 0.53-0.89, p = .0046) were associated with improved OS; gastrointestinal (HR: 1.19, 95% CI 1.09-1.29, p < .0001) worse OS; and gynecologic (HR: 1.04, 95% CI 0.92-1.17, p = .5660) showing no difference, all compared to genitourinary (reference). Surgery was associated with improved overall survival (HR: 0.84, 95% CI 0.79-0.91, p=<.0001). Chemoradiation showed a decreased HR (HR: 0.91, 95% CI 0.83-0.99, p = .0363) when compared to chemotherapy alone (reference)., Conclusion: EPSCC occurs throughout the body with poor survival. Anatomic subsite was predictive for survival. Surgical resection may improve survival. Concurrent chemoradiation appears to improve survival over chemotherapy alone., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: The immune checkpoint inhibitors (ICI) programmed cell death protein and ligands 1 (PD1- and PD-L1) as well as cytotoxic T-lymphocyte-associated protein 4 have demonstrated clinical efficacy in genitourinary cancer. While different ICI exist, focus of the current study work was to evaluate the PD-L1 antibody avelumab within this framework of ICI., Areas Covered: The manuscript reviews the pharmacological characteristics and preclinical and clinical data of avelumab in the treatment for advanced or metastatic genitourinary cancers. It highlights its respective clinical relevance and special features in the context of the other available ICI., Expert Opinion: Avelumab has shown promising antitumor activity and a manageable safety profile in patients with mRCC and mUC as mono- and combination therapy. The approach of an avelumab maintenance therapy in mUC is promising and could become part of future clinical practice. Results of ICI used in the neoadjuvant or adjuvant setting are eagerly awaited. Avelumab's uniqueness is its capacity to enhance antibody-dependent cell-mediated cytotoxicity. Because of this, currently ongoing clinical trials investigate the combination of avelumab with other immune modulating agents like IL-12 and IL-15. Thereby, it can be assumed that avelumab will have an ongoing role in the treatment of patients with genitourinary tumors.

Ano-uro-genital (AUG) mucosal melanomas are rare cancers associated with poor outcomes and limited evidence-based management. The United Kingdom AUG mucosal melanoma guideline development group used an evidence-based systematic approach to make recommendations regarding the diagnosis, treatment and surveillance of patients diagnosed with AUG mucosal melanomas. The guidelines were sent for international peer review, and are accredited by The National Institute for Health and Clinical Excellence (NICE). A summary of the key recommendations is presented. The full documents are available on the Melanoma Focus website., Competing Interests: Conflict of interest statement None declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: This case-series is aimed to describe the natural history of epithelioid sarcoma (ES) and to provide insights into the differential clinical behaviour of its two variants ("classic-type" and "proximal-type"). The value of a subtype-adapted grading system based on pathological features is explored., Methods: Data from consecutive, primary, localised, INI1-deleted ES operated at three Italian sarcoma reference centres (1995-2015) were included. Centralised pathological review was performed. Classic-type ES was broken down into "high-grade" and "low-grade", according to number of mitoses, evidence of necrosis and nuclear atypia. Five- and 10-year overall survival (OS) and crude cumulative incidence (CCI) of local recurrence (LR) and distant metastasis (DM) were estimated., Results: Fifty-two patients were included. 5- and 10-year OS estimates were 70% and 47% in the whole series, 57% and 37% in patients with proximal-type ES, 77% and 54% in patients with classic-type ES (P = 0.02). In classic-type ES, 5- and 10-year OS was higher for low-grade (95% and 72%, respectively) than high-grade tumours (P = 0.002). 5- and 10-year CCI estimates for LR were 21% and 33% in the whole series. 5- and 10-year CCI estimates for DM were 35% and 39% in the whole series, both 28% in classic-type ES, 47% and 59% in proximal-type ES (P = 0.03)., Conclusions: Suffering from a proximal- or a classic-type is the stronger predictor of outcome in patients with localised ES, with proximal-type ES patients having lower survival due to a higher tendency toward metastatic spreading. However, the "high-grade" classic-type ES was associated with outcomes close to proximal-type ES., Competing Interests: Declaration of competing interest AMF received institutional clinical trials support from Amgen Dompé, AROG Bayer, Blueprint Medicines, Eli Lilly, Daiichi Sankyo Pharma, Epizyme, GlaxoSmithKline, Novartis, Pfizer, PharmaMar and travel grants from PharmaMar. GGB received travel grants and advisory honoraria from Pharmamar and Eli Lilly, advisory honoraria from Eisai. NS received institutional clinical trials support from Amgen Dompé, AROG Bayer, Blueprint Medicines, Eli Lilly, Daiichi Sankyo Pharma, Epizyme, GlaxoSmithKline, Novartis, Pfizer, PharmaMar. PGC has reported advisory roles for Deciphera Pharmaceuticals, Eisai, Eli Lilly, Nektar Therapeutics, speaker's honoraria from Eisai, Eli Lilly, Pfizer, PharmaMar, and conducted studies sponsored by Amgen Dompé, AROG Bayer, Blueprint Medicines, Eli Lilly, Daiichi Sankyo Pharma, Epizyme, GlaxoSmithKline, Novartis, Pfizer, PharmaMar. SSt has received honoraria from Eli Lilly, PharmaMar, Takeda; institutional research grants from Amgen Dompé, Advenchen, Bayer, Eli Lilly, Daiichi Sankyo Pharma, Epizyme Inc., Novartis, Pfizer and PharmaMar; travel grants from PharmaMar and has reported advisory/consultant roles for Bayer, Daiichi, Eli Lilly, Epizyme, Karyopharm, ImmuneDesign, Maxivax and PharmaMar. MS, SLV, FF, DC, DC, SP, AG, APDT, MG, MB, AP, LM have nothing to declare., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)