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Opinion Statement: Urothelial carcinoma is the predominant cancer of the urinary tract but when divergent and subtype histology (non-urothelial) are identified at time of pathologic diagnosis, therapeutic and diagnostic challenges transpire. To this end, pathologic review to confirm any non-urothelial histology is key since these subtypes can often be overlooked. Few prospective trials are dedicated to understanding these non-urothelial histologic types; however, current, and past trials did allow patients with these non-urothelial histologic types to enroll, and inferences can be made about treatment efficacy and survival. Existing treatment regimens for non-urothelial bladder cancers are akin to standard urothelial cancer regimens using surgical approaches for localized disease and platinum-based chemotherapy for advanced disease. The reported clinical trials, that will be discussed, center on non-urothelial histologic types. These studies, albeit limited, provide critical insight into tumor biology and response to standard platinum-based chemotherapy, immune checkpoint inhibitors, and antibody drug conjugates. The inclusion of non-urothelial histologic types will be essential for clinical trials in development to provide further therapeutic advances and provide essential efficacy data. [ABSTRACT FROM AUTHOR]

Background: Alternative splicing events (ASEs) are vital causes of tumor heterogeneity in genitourinary tumors and many other cancers. However, the clinicopathological relevance of ASEs in cancers has not yet been comprehensively characterized. Methods: By analyzing splicing data from the TCGA SpliceSeq database and phenotype data for all TCGA samples from the UCSC Xena database, we identified differential clinical feature-related ASEs in 33 tumors. CIBERSORT immune cell infiltration data from the TIMER2.0 database were used for differential clinical feature-related immune cell infiltration analysis. Gene function enrichment analysis was used to analyze the gene function of ASEs related to different clinical features in tumors. To reveal the regulatory mechanisms of ASEs, we integrated race-related ASEs and splicing quantitative trait loci (sQTLs) data in kidney renal clear cell carcinoma (KIRC) to comprehensively assess the impact of SNPs on ASEs. In addition, we predicted regulatory RNA binding proteins in bladder urothelial carcinoma (BLCA) based on the enrichment of motifs around alternative exons for ASEs. Results: Alternative splicing differences were systematically analyzed between different groups of 58 clinical features in 33 cancers, and 30 clinical features in 24 cancer types were identified to be associated with more than 50 ASEs individually. The types of immune cell infiltration were found to be significantly different between subgroups of primary diagnosis and disease type. After integrating ASEs with sQTLs data, we found that 63 (58.9%) of the race-related ASEs were significantly SNP-correlated ASEs in KIRC. Gene function enrichment analyses showed that metastasis-related ASEs in KIRC mainly enriched Rho GTPase signaling pathways. Among those ASEs associated with metastasis, alternative splicing of GIT2 and TUBB3 might play key roles in tumor metastasis in KIRC patients. Finally, we identified several RNA binding proteins such as PCBP2, SNRNP70, and HuR, which might contribute to splicing differences between different groups of neoplasm grade in BLCA. Conclusion: We demonstrated the significant clinical relevance of ASEs in multiple cancer types. Furthermore, we identified and validated alternative splicing of TUBB3 and RNA binding proteins such as PCBP2 as critical regulators in the progression of urogenital cancers. [ABSTRACT FROM AUTHOR]

• The Meet-URO 23/I-RARE study is a retrospective and prospective study on rare genitourinary cancer. • We enrolled 37 patients with collecting duct carcinoma (CDC), male:female ratio: 3:1. • Seven patients were metastatic at diagnosis. 33 patients received first-line therapy, 4 only nephrectomy. • We confirmed the dismal prognosis of CDC, with a median overall survival (OS) of 22.1 months. • The median relapse-free survival was 3.7 months, while median progression-free survival (PFS) was 3.3 months. • PFS appeared to be longer in female and in patients with a good performance status (PS). • A better OS was reported in female patients and in patients with a good PS. Rare genitourinary tumors are lacking of randomized and observational data. We aimed to describe the clinical characteristics and outcomes of patients with collecting duct carcinoma (CDC) through the Meet-URO 23/I-RARE database. We performed a multicentric retrospective-prospective study within the Meet-URO network, enrolling patients from March 2021 (retrospectively up from 2011) until March 2023. The primary objective was to describe the clinical characteristics of patients with CDC, the secondary objectives were to assess the oncological outcomes in terms of relapse-free survival (RFS), progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) to treatment. 37 patients with CDC were enrolled. Four patients underwent only surgery, 33 received first-line systemic therapy. Median OS was 22.1 months (95% CI, 8.9-31.9). Median RFS for patients with localized disease at onset (n = 30) was 3.7 months (95% CI, 1.9-12.8), median PFS for first-line treatment was 3.3 months (95% CI, 2.7-9.9), with an ORR of 27%. Female sex and good performance status (PS) were associated with longer PFS (P =.072 and P <.01, respectively) and OS (P =.030 and P =.141, respectively). Patients with CDC had dismal prognosis, with scarce benefit from the available treatments. Female sex and good PS seemed to be associated with better prognosis. The Meet-URO 23/I-RARE is a retrospective-prospective study on rare genitourinary cancer. This analysis described the characteristics and outcomes of 37 patients with collecting duct carcinoma. Median overall survival (OS) was 22.1 months and median progression-free survival (PFS) for first-line treatment was 3.3 months. Female sex and good performance status seemed associated to longer OS (p =.030) and PFS (p <.01), respectively. [ABSTRACT FROM AUTHOR]

The objective of this review was to summarize published radiomics studies dealing with infradiaphragmatic cancers, blood malignancies, melanoma, and musculoskeletal cancers, and assess their quality. PubMed database was searched from January 1990 to February 2022 for articles performing radiomics on PET imaging of at least 1 specified tumor type. Exclusion criteria includd: non-oncological studies; supradiaphragmatic tumors; reviews, comments, cases reports; phantom or animal studies; technical articles without a clinically oriented question; studies including <30 patients in the training cohort. The review database contained PMID, first author, year of publication, cancer type, number of patients, study design, independent validation cohort and objective. This database was completed twice by the same person; discrepant results were resolved by a third reading of the articles. A total of 162 studies met inclusion criteria; 61 (37.7%) studies included >100 patients, 13 (8.0%) were prospective and 61 (37.7%) used an independent validation set. The most represented cancers were esophagus, lymphoma, and cervical cancer (n = 24, n = 24 and n = 19 articles, respectively). Most studies focused on 18F-FDG, and prognostic and response to treatment objectives. Although radiomics and artificial intelligence are technically challenging, new contributions and guidelines help improving research quality over the years and pave the way toward personalized medicine. [ABSTRACT FROM AUTHOR]

Purpose of Review: Our goal was to summarize current literature related to imaging of intra-abdominal genitourinary tumors diagnosed in the prenatal or neonatal period. Our specific interests included modalities used, diagnoses made, changing incidence of tumor detection, and proposed future uses of these imaging modalities. Recent Findings: Fetal and neonatal MRI have been used as an adjunct to ultrasound for better characterization and assessment of congenital mesoblastic nephroma, juvenile granulosa cell tumor, and other tumors. Despite recent literature describing fetal and neonatal MRI, it is not yet possible to determine whether its use is changing the incidence of tumor detection. Summary: Improvements in imaging technology, specifically the use of fetal MRI, have allowed for earlier identification of genitourinary masses with improved capability for diagnosis, surveillance, surgical planning, and sometimes prenatal treatment of the malignancy and related diagnoses, with a goal of preventing pregnancy and delivery complications. [ABSTRACT FROM AUTHOR]

The objective of this review was to summarize published radiomics studies dealing with infradiaphragmatic cancers, blood malignancies, melanoma, and musculoskeletal cancers, and assess their quality. PubMed database was searched from January 1990 to February 2022 for articles performing radiomics on PET imaging of at least 1 specified tumor type. Exclusion criteria includd: non-oncological studies; supradiaphragmatic tumors; reviews, comments, cases reports; phantom or animal studies; technical articles without a clinically oriented question; studies including 100 patients, 13 (8.0%) were prospective and 61 (37.7%) used an independent validation set. The most represented cancers were esophagus, lymphoma, and cervical cancer (n = 24, n = 24 and n = 19 articles, respectively). Most studies focused on 18F-FDG, and prognostic and response to treatment objectives. Although radiomics and artificial intelligence are technically challenging, new contributions and guidelines help improving research quality over the years and pave the way toward personalized medicine.

The objective of the present study is to characterize genitourinary tumors (GU) metastatic to the head and neck and to determine long-term prognoses. Using a retrospective chart review of 734 patients treated between January 1995 and May 2005 with an ICD-9 code pertaining to a metastatic head and neck cancer, we found 37 patients with primary GU tumors. There were 24 cases of prostate cancer, 10 cases of renal cell carcinoma, and 4 cases of transitional cell carcinoma. Sixteen of 24 patients (67%) with prostate cancer had a cranial metastasis while 6 of 9 (67%) patients with renal cell carcinoma had cerebral metastasis. We concluded that prolonged survival is possible in prostate cancer patients treated aggressively with radiation and chemotherapy, indicating that early detection and aggressive screening are important in these patients.

Context An oligometastatic state is an early event during tumor metastatic spread and is rarely reported in patients with genitourinary tumors. In this condition, the primary tumor has low capacity for distal dissemination because its aggressiveness has not yet reached a maximum. Objective To review recent findings on the diagnosis and treatment of oligometastatic disease in patients with genitourinary tumors. Evidence acquisition To identify relevant studies, we reviewed articles in PubMed from January 1966 to September 2017. The search was conducted by combining the words “oligometastasis” or “oligometastatic disease” with “bladder cancer”, “genitourinary tumor”, “prostate cancer”, and “renal cancer”. Evidence synthesis In renal cell carcinoma (RCC), tumors from patients with multiple metastases showed a different gene signature compared to oligometastatic RCC. In addition, an oligometastatic state was an independent prognostic factor for overall survival (OS). Otherwise, the characteristics of oligometastases from bladder cancer remain unclear, as do the clinical and prognostic significance of metastasectomy in this setting. However, patients with oligometastatic prostate cancer have longer recurrence-free survival and OS and seem to benefit from local metastasis-directed therapies. Conclusions Early detection of oligometastatic disease in patients with genitourinary tumors is fundamental in improving outcomes by identifying patients who would benefit from local approaches with potentially curative rather than palliative intent. [ABSTRACT FROM AUTHOR]

Background: Alternative splicing events (ASEs) are vital causes of tumor heterogeneity in genitourinary tumors and many other cancers. However, the clinicopathological relevance of ASEs in cancers has not yet been comprehensively characterized., Methods: By analyzing splicing data from the TCGA SpliceSeq database and phenotype data for all TCGA samples from the UCSC Xena database, we identified differential clinical feature-related ASEs in 33 tumors. CIBERSORT immune cell infiltration data from the TIMER2.0 database were used for differential clinical feature-related immune cell infiltration analysis. Gene function enrichment analysis was used to analyze the gene function of ASEs related to different clinical features in tumors. To reveal the regulatory mechanisms of ASEs, we integrated race-related ASEs and splicing quantitative trait loci (sQTLs) data in kidney renal clear cell carcinoma (KIRC) to comprehensively assess the impact of SNPs on ASEs. In addition, we predicted regulatory RNA binding proteins in bladder urothelial carcinoma (BLCA) based on the enrichment of motifs around alternative exons for ASEs., Results: Alternative splicing differences were systematically analyzed between different groups of 58 clinical features in 33 cancers, and 30 clinical features in 24 cancer types were identified to be associated with more than 50 ASEs individually. The types of immune cell infiltration were found to be significantly different between subgroups of primary diagnosis and disease type. After integrating ASEs with sQTLs data, we found that 63 (58.9%) of the race-related ASEs were significantly SNP-correlated ASEs in KIRC. Gene function enrichment analyses showed that metastasis-related ASEs in KIRC mainly enriched Rho GTPase signaling pathways. Among those ASEs associated with metastasis, alternative splicing of GIT2 and TUBB3 might play key roles in tumor metastasis in KIRC patients. Finally, we identified several RNA binding proteins such as PCBP2, SNRNP70, and HuR, which might contribute to splicing differences between different groups of neoplasm grade in BLCA., Conclusion: We demonstrated the significant clinical relevance of ASEs in multiple cancer types. Furthermore, we identified and validated alternative splicing of TUBB3 and RNA binding proteins such as PCBP2 as critical regulators in the progression of urogenital cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Duan, Zhang, Li, Liu, Yao, Wu, Li, Mao, Wu, Liu, Zeng, Li, Gong, Hu and Xu.)

Objective: To clarify how popularly the minimally invasive surgeries for urological tumors are currently conducted in Japan and to predict future trends. Methods: A nation-wide survey was performed by the Japanese Association for Minimum-Incision Endoscopic Surgery under the support of the Japanese Urological Association (JUA). A questionnaire was sent to 1186 JUA-certified educational institutions asking about surgical practices for representative urological tumors performed in 2005 and those to be performed in the near future. Surgical modalities were categorized into open, laparoscopic and minimized-incision surgeries, defined as that the operator considers the incision to be minimal and including minimum-incision endoscopic surgery but not limited. Results: 506 of the 1186 institutions (43%) responded and 20 193 surgical procedures were reported with radical prostatectomy being most frequently performed. Overall 20% and 6% of the procedures were performed with laparoscopic and minimized-incision surgeries, respectively. More than 20% of the respondents performed open surgery with reduced incision size than before. Surgical procedures without inserting fingers or hand were reported in 5–11% of the open surgeries and 33–45% of the minimized-incision surgeries. Endoscopy was utilized in 4–14% of the open surgeries and 24–59% of the minimized-incision surgeries. There was no difference in the incidence of complications among the surgical modalities. 40% and 27% of the respondents are aiming at laparoscopic surgery and at minimized-incision surgery, respectively. Conclusions: The results of this nation-wide survey indicate that minimally invasive surgeries, currently performed in 26% of urological tumor surgeries, are aimed at by the majority of the survey respondents. [ABSTRACT FROM AUTHOR]

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Introduction: The acquisition of resistance to VEGF-inhibiting therapies has prompted research toward immunotherapy for the treatment of metastatic renal cell carcinoma (mRCC). Among several, checkpoint inhibitors including PD-1 and PD-L1 inhibitors are the most promising approach., Areas Covered: This review addresses the clinical efficacy of the anti-PD-1 monoclonal antibody pembrolizumab in first- and second-line treatment for mRCC regarding the most recent and significant published and ongoing studies. Attention is also given to its pharmacological characteristics as well as adverse events and its impact on patients' quality of life., Expert Opinion: Immunotherapy has become the backbone for the treatment of advanced RCC. With the approval of several therapeutic options, research needs now to focus on defining the appropriate therapy for each patient. Axitinib plus pembrolizumab belongs to the combinations of tyrosine kinase inhibitors (TKI) plus immune checkpoint inhibitors for the first-line treatment of metastatic RCC. New combinations of pembrolizumab plus TKI for the evaluation in first- and second-line treatment of mRCC available. However, studies directly comparing the various treatment regimens using predictive biomarkers and long-term endpoints, including treatment-free survival, are lacking.

Genitourinary tumors are groups of tumors with high complexity and heterogeneity. For long-term monitoring, biomarkers that can be used in detection, grading and treatment response assessment are needed. With rapid development in imaging technology and cancer genomics, radiogenomics, the combination of "radiology" and "genomics", has emerged as a powerful tool in oncology practice in recent years because imaging can provide some information that genomic test cannot as gene expression and mutation status are usually evaluated on a small portion of the tumor and are usually not powerful enough to reflect tumor heterogeneity. Radiogenomics investigates the correlations between imaging features and gene expression of a disease, especially in oncologic diseases. It aims to detect the disease's mutation status and supplement genomic analysis based on imaging analysis, providing additional findings for diagnosis, treatment decisions, evaluation of treatment response and prognosis prediction of the disease. Recent years have seen an increase in the number of studies investigating the application of radiogenomics in genitourinary tumors. Many studies have shown promising results. However, there still exist limitations and challenges. In this review, we will summarize recent applications of radiogenomics in genitourinary tumors and discuss limitiations, challenges and future directions of radiogenomics., Competing Interests: None., (AJCR Copyright © 2021.)

Few molecular prognostic and predictive biomarkers have been identified so far in genitourinary tumors. We started from a literature search to explore the status of the art of molecular pathology tests as diagnostic, prognostic, predictive biomarkers in genitourinary cancers. Next generation sequencing approaches now provide mind-changing information in the fields of kidney cancer diagnosis, predictive oncology of urothelial cancer, understanding the causes of testicular and penile cancer, and the comprehension of the drivers of prostate cancer progression beyond androgen regulation. The classification of kidney cancer will be based soon on molecular changes. The causes of non-HPV related penile cancer are largely unknown. The emerging high incidence of testicular cancer could be explained only on the basis of molecular changes. The response to novel therapeutic agents in prostatic and urothelial cancer will require thorough molecular tumor characterization. The hereditary risk of patients with early onset prostate cancer and their potential treatment with targeted therapy requires germline and somatic genetic assays. The implementation of effective biomarkers for the response to immune check-point inhibitors in genitourinary cancer is based on the assessment of inflammatory expression profiles and the tumor mutational burden. This review deals with the current tests and provides a tentative foresee of the future molecular biomarkers of genitourinary cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tau-20-1185). The series “Update on Molecular Classification and Individualized Treatments of Genitourinary Tumors” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2021 Translational Andrology and Urology. 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.

Genitourinary tumors are heterogeneous groups of tumors with high morbidity and mortality rates. Confronted with existing problems in the management of genitourinary tumors, a personalized imaging method called radiomics shows great potential in areas including detection, grading, and treatment response assessment. Radiomics is characterized by extraction of quantitative imaging features which are not visible to the naked eye from conventional imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT), followed by data analysis and model building. It outperforms other invasive methods in terms of non-invasiveness, low cost and high efficiency. Recently, a number of studies have evaluated the application of radiomics in patients with genitourinary tumors with promising data. The combination of radiomics and clinical/laboratory factors provides added value in many studies. Despite this, there are limitations and challenges to be overcome before a more extensive clinical application in the future. In this article, we will introduce the concept, significance and workflow of radiomics, review their current applications in patients with genitourinary tumors and discuss limitations and future directions of radiomics. It would help multidisciplinary team involved in the treatment of patients with genitourinary tumors to achieve a better understanding of the results of radiomics study toward a personalized medicine., Competing Interests: None., (AJCR Copyright © 2020.)

Nephrogenic adenomas are uncommon benign lesions that are typically cytologically bland, but degenerative and reactive changes may make it difficult to distinguish these lesions from malignant entities, such as urothelial carcinoma and prostatic adenocarcinoma. In this study, we explored whether napsin A, a sensitive marker for lung adenocarcinoma, may also have a role in distinguishing nephrogenic adenoma from other genitourinary lesions. Immunohistochemically, napsin A was expressed in all 43 nephrogenic adenomas (bladder: 38, prostatic urethra: 4, and ureter: 1; mean positive tumor cells: 72%, median: 80%, range: 15-100%) and showed regional variability in its expression pattern with a bias toward surface architectures (flat, papillary) compared with stromal architectures (tubular/glandular, microcystic). We also compared napsin A with other markers including PAX8, GATA3, p63, and 34BE12. Although napsin A matched PAX8 in terms of its sensitivity for nephrogenic adenoma (100%), napsin A stained a lower percentage of tumor cells than PAX8 (72% vs 99%, respectively, P = 1.0 × 10 -5 ). P63 was negative in all nephrogenic adenomas, whereas GATA3 showed variable staining in 25 cases (58%). All 43 nephrogenic adenomas showed variable 34BE12 staining. Finally, we profiled napsin A expression among 401 genitourinary tumors on tissue microarrays (n = 308) and full tissue blocks (N = 93) and observed napsin A positivity in 37 tumors (9%), which included urothelial carcinomas with the glandular/microcystic component differentiation (in the glandular/microcystic component in 4/6), bladder adenocarcinomas (primary: 4/4 and metastatic: 3/3), urinary tract clear-cell carcinomas (primary: 8/9, metastatic uterine primary: 1/1), and some renal tumors (17/174). All 81 pure urothelial carcinomas and 53 prostatic acinar adenocarcinomas were negative for napsin A. Our study indicates that napsin A is a highly sensitive marker for nephrogenic adenoma and can serve as a useful addition in immunohistochemical panels seeking to distinguish it from pure urothelial carcinoma and prostatic acinar adenocarcinoma but not clear-cell carcinoma or urothelial carcinoma with glandular differentiation., Competing Interests: Conflict of Interest Statement No conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The multidisciplinary management of oncologic patients is identified as the bottom line element of quality in tumor care., Methods: In 2015, 7 Italian scientific societies representing the specialists involved in the diagnosis and treatment of genitourinary tumors joined efforts in the Italian uro-oncologic multidisciplinary teams (MDTs) project. The aims were to promote the reorganization of genitourinary cancer care, switching to a multidisciplinary approach, reach a consensus on the core elements for the setup of MDTs in genitourinary oncology, and support health policy makers and managers in remodeling of the assistance and care of uro-oncologic patients on a national level., Results: The first activity was the setup of 5 working groups, given the task of exploring selected topics: general principles, organization of MDTs, minimal requirements, economic evaluation, and relations with authorities. The groups participated in the writing of a document that was approved by the scientific societies and published on their web sites. Moreover, a few items summarizing the extensive document were approved in the first MDT Consensus Conference held in Milan in December 2015., Conclusions: The experience of this initial phase led to the opening of the team to other professionals and societies, in line with a correct management of patients with genitourinary tumors, which need a multidisciplinary as well as a multiprofessional approach with emerging techniques and procedures, and with a new project work package on genitourinary paths of care and indicators.

Background: Extra-adrenal paragangliomas (PGLs) are infrequent, benign, and neuroendocrine tumors arising from chromaffin cells of the autonomic nervous system. Most PGLs are sporadic, but up to 32% are associated with inherited syndromes such as neurofibromatosis type 1, von Hippel-Lindau disease, and familial PGL. Although most PGLs develop above the umbilicus, they have been reported in the genitourinary (GU) tract. Owing to the paucity of literature on the rates of GU PGL, the objective of our study is to describe the demographic, pathologic, and clinical characteristics of GU PGL, and compare them to non-GU sites of PGL using the surveillance, epidemiology, and end results (SEER) database.Methods: The SEER 18 database was used to identify all cases of PGL from 2000 to 2012. Demographic, pathologic, and clinical characteristics were described using chi-square and t-test for categorical and continuous variables, respectively. The Kaplan-Meier method was used to compare overall survival (OS) between GU and non-GU PGL. Statistical significance was defined as P<0.05. All analyses were performed using excel and SAS/Stat version 9.4.Results: A total of 299 cases of PGL were retrieved from SEER, and 20 (6.7%) of the total PGL arose from the GU tract. The mean age at diagnosis was higher in non-GU than GU PGL (50.4±17.2 vs. 40.8±15.6, P = 0.026). Furthermore, 75% of GU PGLs developed in the bladder, followed by the kidneys/renal pelvis, and spermatic cord (20%). Non-GU PGL developed most frequently within the endocrine system (43%). PGL, overall, was more common in men than in women, and it was more common in whites than all other races. Although 55.5% of GU PGLs were organ confined, only 22.2% of non-GU PGLs were localized at diagnosis. All cases of PGL were treated with surgery. There were 2 cause-specific deaths in the GU PGL groups between 2000 and 2012. The 5-year OS was 93.3% for GU PGL vs. 65.5% in non-GU PGL (P = 0.062).Conclusions: GU PGL remains rare with low incidence (6.7% of all PGL cases) in the US population between 2000 and 2012. Bladder PGL represents just 5% of all PGL. Moreover, GU PGL had better OS compared to PGL developing outside of the GU tract although the P-value only approached statistical significance. The bladder represents the most common site of involvement, and surgery is the mainstay of treatment for GU PGL. Clearer prognostic factors, including tumor grade and stage, are needed to better elucidate PGL management in the future; thus, pooled studies from various institutions with detailed clinical information are needed to delineate these prognostic factors. [ABSTRACT FROM AUTHOR]

Background: Research of biomarkers in genitourinary tumors goes along with the development of complex emerging techniques ranging from next generation sequencing platforms, applied to archival pathology specimens, cytological samples, liquid biopsies, and to patient-derived tumor models., Methods: This contribution is an update on molecular biomarkers for diagnosis, prognosis and prediction of response to therapy in genitourinary tumors. The following major topics are dealt with: Immunological biomarkers, including the microbiome, and their potential role and caveats in renal cell carcinoma, bladder and prostate cancers and testicular germ cell tumors; Tissue biomarkers for imaging and therapy, with emphasis on Prostate-specific membrane antigen in prostate cancer; Liquid biomarkers in prostate cancer, including circulating tumor cell isolation and characterization in renal cell carcinoma, bladder cancer with emphasis on biomarkers detectable in the urine and testicular germ cell tumors; and Biomarkers and economic sustainability., Conclusion: The identification of effective biomarkers has become a major focus in cancer research, mainly due to the necessity of selecting potentially responsive patients in order to improve their outcomes, as well as to reduce the toxicity and costs related to ineffective treatments., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: GATA binding protein 3 (GATA3) is a transcription factor, which belongs to a distinct family of tumor suppressor genes. It is involved in human cancer cell growth and differentiation, and plays an important role in cell proliferation and apoptosis. Although, its expression has been reported in various cancers, there are limited data in genitourinary malignancies. Recent studies found GATA3 to be a sensitive marker for urothelial carcinoma (UC) and associated with prognostic pathologic features. Its level of expression was found to be an independent factor predicting cancer recurrence.Methods and Materials: In this article, immunohistochemical evaluation of GATA3 expression in genitourinary malignancies (invasive UC, renal cell carcinoma, and prostatic adenocarcinomas) was performed.Results: GATA3 was positive in 56/79 (70.8%) of invasive UC, and was negative in all renal cell carcinoma and prostatic adenocarcinomas. The pattern of GATA3 staining, when positive, was intensely nuclear within the clusters of malignant cells. No cytoplasmic staining was noted. Negative controls were all negative. High GATA3 expression was associated with larger tumor size in invasive UC (3.19cm vs. 1.65cm, P = 0.01). GATA3 expression did not correlate with other clinicopathologic parameters in UC.Conclusions: This data suggest that GATA3 is a sensitive marker in confirming invasive UC, and may be helpful in differentiating it from metastatic tumors of renal and prostatic origin. Furthermore, strong GATA3 expression was noted to have an effect on tumor size in patients with UC. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors have revolutionized the treatment of many malignancies with over a dozen new United States Food and Drug Administration (FDA) approvals in the past six years. Due to the combination of potent treatment success and potentially deadly adverse effects from immune checkpoint inhibitors, gathering prognostic and predictive information about FDA-indicated tumors is prudent., Method: PD-L1 expression is a poor prognostic factor and predictive of better responses from both PD-1 and PD-L1 inhibitors in a variety of tumor types including Renal Cell Carcinoma (RCC) and urothelial carcinoma. Each FDAapproved PD-1/PD-L1 drug is paired with a PD-L1 Immunohistochemistry (IHC) assay. The majority of PD-1/PDL1 inhibitor clinical trials use proprietary IHC antibodies with undefined validation data. Thus, there is need for improved knowledge and application of PD-1/PD-L1 IHC biomarkers. There is a wealth of recent publications using antibody clones to characterize tumor PD-1/PD-L1 expression profiles., Results: PD-1 is expressed on lymphocytes. PD-L1 is expressed on both tumor cells and immune cells. IHC staining appears in membranous fashion. A cutoff of at least 5% tumor cell PD-L1 staining for positivity has worked for most studies. Caution should be observed when employing tissue microarray techniques., Conclusion: RCC has been the most studied of the genitourinary malignancies for PD-L1 expression. The atezolizumab- approved IHC assay is unique in that only immune cell staining is quantified for the use of this assay in urothelial carcinoma. With familiarity of the current FDA guidelines, published medical literature, and general immunohistochemical considerations, the use of immune checkpoint biomarkers can continue to flourish., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The development of molecular and functional imaging with new imaging techniques such as computed tomography, magnetic resonance imaging, and positron emission tomography (PET) among others, has greatly improved the detection of tumors, tumor staging, and the detection of possible recurrences. Furthermore, the combination of these different imaging modalities and the continual development of radiotracers for PET have advanced our understanding and knowledge of the different pathophysiological processes in cancer, thereby helping to make treatment more efficacious, improving patients' quality of life, and increasing survival. PET is one of the imaging techniques that has attracted the most interest in recent years for its diagnostic capabilities. Its ability to anatomically locate pathologic foci of metabolic activity has revolutionized the detection and staging of many tumors, exponentially broadening its potential indications not only in oncology but also in other fields such as cardiology, neurology, and inflammatory and infectious diseases., (Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.)

The STAT3 is often dysregulated in genitourinary tumors. In prostate cancer, STAT3 activation correlates with Gleason score and pathological stage and modulates cancer stem cells and epithelial-mesenchymal transition. In addition, STAT3 promotes the progression from carcinoma in situ to invasive bladder cancer and modulates renal cell carcinoma angiogenesis by increasing the expression of HIF1α and VEGF. STAT3 is also involved in the response to tyrosine kinase inhibitors sunitinib and axitinib, in patients with metastatic renal cell carcinoma, and to second-generation androgen receptor inhibitor enzalutamide in patients with advanced prostate cancer. In this review, we describe the role of STAT3 in genitourinary tumors, thus describing its potential for future therapeutic strategies., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

The development of targeted agents has completely revolutionized the therapeutic scenario of genitourinary tumors. However, no biomarkers of tumor response or patient tolerability have been validated so far, and the selection of patients who may benefit from these approaches is still empirical. Significant advances in genomic sequencing and molecular characterization of these tumors have allowed identification of complex genomic abnormalities, thus increasing our knowledge on cancer biological landscapes and paving the way to the development of personalized strategies based on the patient's genomic and cancer's molecular profiles. This review is an overview of recent findings and emerging individualized therapies in patients with prostate, renal and bladder cancer, focusing on the promises and limitations of this approach in this setting.

Many of the cellular abnormalities present in solid tumors are structural in nature and involve the proteins of the extracellular matrix (ECM). Periostin is a protein produced and secreted by the fibroblasts as a component of the ECM where it is involved in regulating intercellular adhesion. The expression of periostin has an important physiological role during embryogenesis and growth, namely at the level of bone, dental, and cardiac tissues. Many studies indicate that periostin plays an important role for tumor progression in various types of cancer, such as colon, lung, head and neck, breast, ovarian, and prostate. To the best of our knowledge, a limited number of studies have investigated periostin expression in urogenital cancer, such as prostate, bladder, penile, and renal cancer, and no studies were performed in testis cancer. In this review article, we summarize the most recent knowledge of periostin, its genetic and protein structure, and the role of the different isoforms identified and sequenced so far. In particular, we focus our attention on the role of this protein in genitourinary tumors, trying to emphasize the role not only as a possible prognostic marker, but also as a possible target for the development of future anticancer therapies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Superficial "non-muscle-invasive" bladder tumors represent a heterogeneous group of cancers, including those that are (1) papillary in nature and limited to the mucosa, (2) high grade and flat and confined to the epithelium, and (3) invasive into the submucosa, or lamina propria. The goal of treatment is 2-fold: (1) to reduce tumor recurrence and the subsequent need for additional therapies and the morbidity associated with these treatments and (2) to prevent tumor progression and the subsequent need for more aggressive therapy. This update reviews important contemporary concepts in the etiology, molecular mechanisms, classification, and natural history of superficial bladder cancer.