Redefining Rare Genitourinary Cancers: An Initiative Led by the Global Society of Rare Genitourinary Tumors.

Rare cancers account for 20-25% of all cancers diagnosed annually but there is no consensus on the definition of a rare cancer and substantial geographic heterogeneity. The Global Society of Rare Genitourinary Tumors is dedicated to education and research for rare genitourinary tumors.

The Application and Pitfalls of Immunohistochemical Markers in Challenging Diagnosis of Genitourinary Pathology.

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.

MicroRNAs for detecting occult genitourinary cancer.

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.

Prognostic value of various nutritional risk markers in patients hospitalized for the treatment of genitourinary cancer: A retrospective study.

BACKGROUND & AIMS: Because malnutrition adversely affects the prognosis of patients with cancer, accurate nutritional status assessment is important. Therefore, this study aimed to verify the prognostic value of various nutritional assessment tools and compare their predictability. METHODS: We retrospectively enrolled 200 patients hospitalized for genitourinary cancer between April 2018 and December 2021. Four nutritional risk markers, namely, Subjective Global Assessment (SGA) score, Mini-Nutritional Assessment-Short Form (MNA-SF) score, Controlling Nutritional Status (CONUT) score, and Geriatric Nutritional Risk Index (GNRI), were measured at admission. The endpoint was all-cause mortality. RESULTS: SGA, MNA-SF, CONUT, and GNRI values were all independent predictors of all-cause mortality (hazard ratio [HR] = 7.72, 95% confidence interval [CI]: 1.75-34.1, P = 0.007; HR = 0.83, 95% CI: 0.75-0.93, P = 0.001; HR = 1.29, 95% CI: 1.16-1.43, P < 0.001; and HR = 0.95, 95% CI: 0.93-0.98, P < 0.001, respectively) even after adjustment for age, sex, cancer stage, and surgery or medication. However, in the model discrimination analysis, the net reclassification improvement of the CONUT model (vs. SGA: 0.420, P = 0.006 and vs. MNA-SF: 0.57, P < 0.001) and GNRI model (vs. SGA: 0.59, P < 0.001 and vs. MNA-SF: 0.671, P < 0.001) were significantly improved compared to the SGA and MNA-SF models, respectively. The combination of CONUT and GNRI models also had the highest predictability (C-index = 0.892). CONCLUSIONS: Objective nutritional assessment tools were superior to subjective nutritional tools in predicting all-cause mortality in inpatients with genitourinary cancer. Measurement of both the CONUT score and GNRI might contribute to a more accurate prediction.

Pulmonary metastases in urogenital cancers: Surgical treatment and outcomes / Metástasis pulmonares en cánceres urogenitales; tratamiento quirúrgico y resultados

Introduction: Metastasis is remaining one of the major problems in cancer treatment. Like many other malignancies, urogenital tumors originating from kidney, prostate, testes, and bladder tend to metastasize to the lungs. The aim of this retrospective study is to evaluate the operative results and prognosis of pulmonary metastasectomy in patients with primary urogenital tumors. Methods: This study was approved by the local ethical committee. We retrospectively analyzed the surgical and oncological results of patients who underwent lung resections for urogenital cancer metastases in our department between 2002 and 2018. Demographic data and clinicopathological features were extracted from the medical records. Survival outcomes according to cancer subtypes and early postoperative results of VATS and thoracotomy were analyzed. Results: 22 out of 126 patients referred for pulmonary metastasectomy to our department had metastases from urogenital tumors. These patients consisted of 17 males and five females. Their metastasis originated from renal cell carcinoma (RCC; n=9), bladder tumor (n=7), testis tumors (n=4), and prostate cancer (n=2). There was no intraoperative complication. Postoperative complications were seen in 2 patients. Conclusions: Although pulmonary metastasectomy in various types of tumors is well known and documented, the data is limited for metastases of urogenital cancers in the literature. Despite the limitations of this study, we aim to document our promising results of pulmonary metastasectomy in patients with primary urogenital tumors and wanted to emphasize the role of minimally invasive approaches. (AU)

Introducción: La metástasis continua siendo uno de los principales problemas en el tratamiento del cáncer. Como muchas otras neoplasias malignas, los tumores urogenitales que se originan en el riñón, la próstata, los testículos y la vejiga tienden a hacer metástasis a los pulmones. El objetivo de este estudio retrospectivo es evaluar los resultados quirúrgicos y el pronóstico de la metastasectomía pulmonar en pacientes con tumores urogenitales primarios. Métodos: Este estudio fue aprobado por el comité de ética local. Analizamos retrospectivamente los resultados quirúrgicos y oncológicos de los pacientes que fueron sometidos a resecciones pulmonares por metástasis de cáncer urogenital en nuestro servicio entre 2002 y 2018. Se extrajeron datos demográficos y características clínico-patológicas de las historias clínicas. Se analizaron los resultados de supervivencia según los subtipos de cáncer y los resultados postoperatorios tempranos de VATS y toracotomía. Resultados: Veintidós de 126 pacientes remitidos para metastasectomía pulmonar a nuestro servicio tenían metástasis de tumores urogenitales. Estos pacientes consistieron en 17 varones y 5 mujeres. Su metástasis se originó a partir de carcinoma de células renales (CCR; n=9), tumor de vejiga (n=7), tumores de testículo (n=4) y cáncer de próstata (n=2). No hubo ninguna complicación intraoperatoria. Se observaron complicaciones posoperatorias en 2 pacientes. Conclusiones: Aunque la metastasectomía pulmonar en varios tipos de tumores es bien conocida y documentada, los datos son limitados para las metástasis de cánceres urogenitales en la literatura. A pesar de las limitaciones de este estudio, nuestro objetivo es documentar nuestros prometedores resultados de la metastasectomía pulmonar en pacientes con tumores urogenitales primarios y queríamos enfatizar el papel de los enfoques mínimamente invasivos. (AU)

Genomic Sequencing Should Not be Part of the Standard of Care for Most Urologic Cancers.

There are currently few situations in which genomic testing is actionable for genitourinary tumors. Without clear indications or treatment paradigms, genomic sequencing cannot be recommended as a standard of care for genitourinary tumors.

piRNAs and PIWI Proteins as Diagnostic and Prognostic Markers of Genitourinary Cancers.

piRNAs (PIWI-interacting RNAs) are small non-coding RNAs capable of regulation of transposon and gene expression. piRNAs utilise multiple mechanisms to affect gene expression, which makes them potentially more powerful regulators than microRNAs. The mechanisms by which piRNAs regulate transposon and gene expression include DNA methylation, histone modifications, and mRNA degradation. Genitourinary cancers (GC) are a large group of neoplasms that differ by their incidence, clinical course, biology, and prognosis for patients. Regardless of the GC type, metastatic disease remains a key therapeutic challenge, largely affecting patients' survival rates. Recent studies indicate that piRNAs could serve as potentially useful biomarkers allowing for early cancer detection and therapeutic interventions at the stage of non-advanced tumour, improving patient's outcomes. Furthermore, studies in prostate cancer show that piRNAs contribute to cancer progression by affecting key oncogenic pathways such as PI3K/AKT. Here, we discuss recent findings on biogenesis, mechanisms of action and the role of piRNAs and the associated PIWI proteins in GC. We also present tools that may be useful for studies on the functioning of piRNAs in cancers.

Genitourinary Tract Tumors in Children: An Update.

BACKGROUND: Genitourinary tract tumors in children are less common than in adults. Most of these tumors have different genetic backgrounds, clinical presentation, and oncologic behavior than their adult counterpart. As a result of low prevalence in children, some of the treatment approaches and recommendations are based on treatment experience in adult patients. However, thanks to scientific and technological development, survival rates have risen considerably. OBJECTIVE: This paper presents a review of the principal features of the tumors involving the genitourinary tract in children and an update in genetic background, diagnosis, and treatment. METHODS: A narrative review was performed on published literature about genitourinary tract tumors in pediatric patients. Papers presented in English and Spanish literature were reviewed. PubMed, Science Direct, and SciELO databases were used to collect information and present this article. RESULTS: Kidney tumors are the most common type of genitourinary tumors in children. Among those, Wilms tumor represents the majority of cases and shows the successful work of clinical trial groups studying this tumor type. Other tumors involving the genitourinary tract in children include Rhabdomyosarcoma, Transitional cell carcinoma, Testicular, and Adrenal tumors. CONCLUSION: Genitourinary tract tumors in children represent significant morbidity and economic burden, so awareness in early diagnosis represents improvement in treatment, clinical, and oncological outcomes.

Characteristics of 1270 Chinese sibling pairs with cancer.

BACKGROUND: Previous research found that the cancer history of an individual's sibling may be a better indicator than that of the parents. We aim to provide recommendations for opportunistic screening for individuals whose sibling had been diagnosed with cancer. METHODS: During the physical examination in Cancer Hospital, Chinese Academy of Medical Sciences, 43,300 people were asked if they have at least two siblings who developed cancer. RESULTS: A total of 1270 sibling-pairs from 766 families developed cancer, including 367 pairs of brothers (Bro-pairs), 368 pairs of sisters (Sis-pairs), and 535 pairs of brother-and-sister (BroSis-pairs). The mean ages at diagnosis of cancer for the three groups were from 58 to 62 years. More than half of Bro-pairs (55.3%) or Sis-pairs (51.1%) had cancer from the same systemic origin, and more than a quarter of Bro-pairs (28.1%) and Sis-pairs (37.2%) developed the same type of cancer. However, only 36.0% of BroSis-pairs developed cancers from the same systemic origin, and 18.9% developed the same type of cancer. In Bro-pairs and BroSis-pairs, lung cancer and digestive system cancer were the most common cancers, while in Sis-pairs, breast cancer, lung cancer, cervical cancer, liver cancer and thyroid cancer were the most common ones. CONCLUSIONS: If an individual's sibling is diagnosed with cancer, the individual should consider participating in opportunistic screening annually, especially for lung cancer and digestive system cancers for both sexes. For sisters, breast cancer, cervical cancer and thyroid cancer should be screened early. Additionally, genetic services are essential for individuals who have siblings with cancer.

Extracellular Vesicles: New Tools for Early Diagnosis of Breast and Genitourinary Cancers.

Breast cancers and cancers of the genitourinary tract are the most common malignancies among men and women and are still characterized by high mortality rates. In order to improve the outcomes, early diagnosis is crucial, ideally by applying non-invasive and specific biomarkers. A key role in this field is played by extracellular vesicles (EVs), lipid bilayer-delimited structures shed from the surface of almost all cell types, including cancer cells. Subcellular structures contained in EVs such as nucleic acids, proteins, and lipids can be isolated and exploited as biomarkers, since they directly stem from parental cells. Furthermore, it is becoming even more evident that different body fluids can also serve as sources of EVs for diagnostic purposes. In this review, EV isolation and characterization methods are described. Moreover, the potential contribution of EV cargo for diagnostic discovery purposes is described for each tumor.

Biorepositories and Databanks for the Development of Novel Biomarkers for Genitourinary Cancer Prevention and Management.

CONTEXT: Translational research in uro-oncology depends on the availability of high-quality biospecimens and associated data to advance precision medicine and improve clinical outcomes. Procurement, storage, and annotation of these specimens represent critical steps towards this end. OBJECTIVE: To review best-practice experiences gained via the McCain GU BioBank, a repository of more than 750 000 biospecimens obtained from more than 16 000 patients attending clinics at the University Health Network in Toronto, Canada. EVIDENCE ACQUISITION: The review summarizes our experiences at a large single-institution genitourinary oncology biorepository. EVIDENCE SYNTHESIS: Key findings are placed in the context of emerging trends in genitourinary oncology, with a focus on integration of molecular profiling and clinical data with traditional biorepository management. Proposed approaches provide high-quality biospecimens with comprehensive and reliable clinical data that can fuel innovation and discovery in research. CONCLUSIONS: Biorepositories are vital for improving clinical outcomes and advancing personalized medicine. High-quality biospecimens and their associated clinical data are crucial for validation of biomarkers in oncology. Efforts to procure, store, and annotate clinical specimens represent critical steps in translational research. Elements such as biobank size, biospecimen types, disease cohorts, predetermined collection protocols, broad informed consent, sample handling and storage protocols, and available infrastructure directly influence the effectiveness and capacity of a biobank. PATIENT SUMMARY: Biorepositories, or biobanks, are facilities that store biospecimens such as blood, urine, or tissue (usually collected from humans) for use in research. Biobanks have become an important resource in medical research, as they provide high-quality specimens to support different types of contemporary research such as genomics, biomarker discovery, and personalized medicine. Clinical management and treatment of genitourinary cancers, such as prostate, kidney, and bladder cancers, are particularly suited for biomarker research. The provision of biospecimens and their associated clinical data have become crucial for validation of biomarkers in these cancers.

Associations of Medicaid Expansion With Insurance Coverage, Stage at Diagnosis, and Treatment Among Patients With Genitourinary Malignant Neoplasms.

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.

Genitourinary Medical Oncology Expert Opinion Survey Regarding Treatment Management in the COVID-19 Pandemic.

BACKGROUND: The worldwide Coronavirus disease 2019 (COVID-19) public health pandemic has restructured clinical care of patients with cancer throughout the world. The specific changes in the management of genitourinary (GU) cancers in different cancer centers owing to COVID-19 are not known, and some clinical scenarios remain controversial. We conducted an opinion survey to determine what changes in cancer treatment strategies are occurring owing to the COVID-19 pandemic. MATERIALS AND METHODS: A 20-item online survey was sent on May 25, 2020 to 170 expert GU medical oncologists from Europe and North America. The survey solicited responses to changes in GU cancer management in the setting of the COVID-19 pandemic. Data was collected and managed via a secure REDCap Database. RESULTS: Surveys were completed by 78 (45.8%) of 170 GU oncologists between May 25, 2020 and June 25, 2020. Clinical practice changes owing to COVID-19 in at least one scenario were reported by 79.1% of responders, most pronounced in prostate cancer (71.8%) and least pronounced in urothelial cancer (23%). Preferences for change in management varied by country, with 78% (37/47) of United States oncologists indicating a change in their practice, 57% (4/7) of Canadian oncologists, and 79% (19/24) of European oncologists. CONCLUSIONS: This study suggests international practice changes are occurring in GU cancer care during the COVID-19 pandemic. The variability in practice changes between countries may reflect differences in COVID-19 case load during the time point of data collection. These results, based on expert opinion during this rapidly changing crisis, may inform the oncologic community regarding the effects of COVID-19 on GU cancer care.