Development and validation of nomograms to predict survival of neuroendocrine carcinoma in genitourinary system: A population-based retrospective study.

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.

Impact of implementing the first edition of the Paris system for reporting: A systematic review and meta-analysis.

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.

Role of Metastasis-Directed Therapy in Genitourinary Cancers.

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.

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.

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.

Enhanced Detection of Genitourinary Cancers Using Fragmentation and Copy Number Profiles Obtained from Urinary Cell-Free DNA.

BACKGROUND: Recent studies have reported that examining the fragmentation profiles (FP) of plasma cell-free DNA (cfDNA) further improves the clinical sensitivity of tumor detection. We hypothesized that considering the differences of the FP of urinary cfDNA would increase the clinical sensitivity of genitourinary (GU) cancer detection. METHODS: 177 patients with GU cancer and 94 individuals without tumors were enrolled in the discovery cohort. An independent validation dataset comprising 30 patients without tumors and 66 patients with GU cancer was also collected. We constructed an ensemble classifier, GUIDER, to detect and localize GU cancers using fragmentation and copy number profiles obtained from shallow whole-genome sequencing of urinary cfDNA. RESULTS: Urinary cfDNA of patients with GU cancer had a higher proportion of long fragments (209-280 bp) and a lower proportion of short fragments (140-208 bp) compared to controls. The overall mean classification accuracy of the FP was 74.62%-85.39% for different algorithms, and integration of the FP and copy number alteration (CNA) features further enhanced the classification of samples from patients with GU cancer. The mean diagnostic accuracy was further improved by the ensemble classifier GUIDER, which integrated the FP and CNA profiles and resulted in a higher mean accuracy (87.52%) compared to the analysis performed without FP features (74.62%). GUIDER performed well in an independent validation dataset. CONCLUSIONS: The lengthening and shortening of urinary cfDNA within specific size ranges were identified in patients with GU cancer. Integration of the FP should further enhance the ability to use urinary cfDNA as a molecular diagnostic tool.