Search

Our aim was to describe the incidence and mortality of genitourinary (GU) cancers in rural and urban Pennsylvania counties. We calculated age-adjusted incidence and mortality rates of GU (prostate, bladder, and kidney) cancers from 1990 to 2019 in the Pennsylvania Cancer Registry. We defined rurality using the Center for Rural Pennsylvania's population density-based definition. We modeled average annual percent changes (AAPC) in age-adjusted incidence and mortality rates using joinpoint regression. Overall GU cancer incidence decreased in rural and urban counties (AAPC -7.5%, p = 0.04 and AAPC -6.6%, p = 0.02, respectively). Prostate cancer incidence decreased in rural and urban counties by -10.5% ( p = 0.02) and -9.1% ( p = 0.01), respectively. Kidney cancer incidence increased in both rural and urban counties, respectively (AAPC = +11.2, p = 0.002 and +9.3%, p = 0.01). GU cancer mortality decreased in rural and urban counties (AAPC = -11.6, p = 0.047 and AAPC -12.2, p = 0.01, respectively). Prostate cancer mortality decreased at similar rates in rural and urban counties (AAPC -15.5, p = 0.03 and -15.4, p = 0.02, respectively). Kidney cancer mortality decreased in urban (AAPC -6.9% p = 0.03) but remained stable in rural counties. Bladder cancer incidence and mortality were unchanged in both types of counties. Over three decades, GU cancer incidence and mortality decreased across Pennsylvania counties.

Purpose: Pediatric Rhabdomyosarcoma (RMS) is a morbid and often lethal condition characterized by a paucity of clinical data. Beyond a detailed risk categorization system, it is unclear if genitourinary (GU) sites (bladder/prostate, paratesticular, female organs) have outcomes distinct from non-GU sites. This study pools primary data from phase-3 clinical trials involving pediatric RMS to evaluate this question., Methods and Materials: We obtained primary data from three Children's Oncology Group pediatric RMS trials (NCT00075582, NCT00354835, NCT00354744) evaluating low- (LR), intermediate- (IMR), and high risk (HR) Pediatric RMS. Survival analysis was conducted using the Kaplan-Meier method, with Event-Free Survival (EFS) defined per protocol specifications., Results: 599 subject records were included in the analysis (111 GU RMS, 488 non-GU RMS). For subjects with GU RMS, overall survival (OS) was superior to non-GU RMS (HRR 0.55 [95% CI, 0.35-0.87], p = 0.009). In this same group, EFS superiority was not statistically significant compared to non-GU RMS (HRR 0.88 [95% CI, 0.63-1.22], p = 0.43). In the LR population, GU primary site was associated with improved OS that was not statistically significant (HRR 0.37 [95% CI 0.07-1.84], p = 0.21) and less favorable EFS (HRR 2.84 [95% CI, 1.13-7.12], p = 0.02)., Conclusions: In RMS, a GU primary site is linked to improved OS compared to non-GU sites, although LR GU RMS shows less favorable EFS. Our findings reinforce the association between GU primary sites and better OS outcomes in RMS, warranting further investigation into the surrogacy of EFS for OS in GU RMS., Clinical Trial Registration: Not applicable., Competing Interests: Declarations. Ethical approval: This study was conducted in accordance with the Declaration of Helsinki. Patients consent: No patients consent was needed for this study. Permission to reproduce material from other sources: Yes. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: This study aimed to evaluate if combining low muscle mass with additional body composition abnormalities, such as myosteatosis or adiposity, could improve survival prediction accuracy in a large cohort of gastrointestinal and genitourinary malignancies., Methods: In total, 2015 patients with surgically-treated gastrointestinal or genitourinary cancer were retrospectively analyzed. Skeletal muscle index, skeletal muscle radiodensity, and visceral/subcutaneous adipose tissue index were determined. The primary outcome was overall survival determined by hospital records. Multivariate Cox hazard models were used to identify independent predictors for poor survival. C-statistics were assessed to quantify the prognostic capability of the models with or without incorporating body composition parameters., Results: Survival curves were significantly demarcated by all 4 measures. Skeletal muscle radiodensity was associated with non-cancer-related deaths but not with cancer-specific survival. The survival outcome of patients with low skeletal muscle index was poor (5-year OS; 65.2%), especially when present in combination with low skeletal muscle radiodensity (5-year overall survival; 50.2%). All examined body composition parameters were independent predictors of lower overall survival. The model for predicting overall survival without incorporating body composition parameters had a c-index of 0.68 but increased to 0.71 with the inclusion of low skeletal muscle index and 0.72 when incorporating both low skeletal muscle index and low skeletal muscle radiodensity/visceral adipose tissue index/subcutaneous adipose tissue index., Conclusion: Patients exhibiting both low skeletal muscle index and other body composition abnormalities, particularly low skeletal muscle radiodensity, had poorer overall survival. Models incorporating multiple body composition prove valuable for mortality prediction in oncology settings., (© 2024 The Author(s). Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Background: Cancers of the genitourinary system, particularly prostate, bladder, and kidney cancer, exhibit a high prevalence. Consequently, predicting the morbidity and mortality of genitourinary cancers holds great significance for future planning and implementation. This study aimed to examine the crude and age-standardized rates of mortality and the trend of genitourinary cancers over nine years in northern Iran., Methods: This cross-sectional study used data on the number of deaths attributed to genitourinary cancers recorded in Babol City between 2013 and 2021 through the cause of death registration and classification system. Population estimates were derived from the latest census reports. Subsequently, crude and age-standardized rates, as well as trends for genitourinary cancers, were calculated., Results: A total of 307 deaths occurred, with an average age of 75.6 ± 14.3 years due to genitourinary cancers. The crude and age-standardized rates of genitourinary cancers increased from 2.7 and 1.9 per hundred thousand people in 2013 to 7.7 and 5.9 per hundred thousand people in 2021, respectively. Over the study period, death rates significantly rose for men (P < 0.001) and remained constant for women (P = 0.444). Examination of genitourinary cancers revealed an upward trend for bladder (P = 0.012) and prostate (P = 0.012) cancers, while a stable trend was observed for kidney (P = 0.070) and testicular (P = 0.139) cancers., Conclusions: The age-standardized rate and trend of genitourinary cancers are rising. Consequently, this study emphasizes the importance of prevention through screening programs, raising awareness, and utilizing appropriate diagnostic methods., (© 2024. The Author(s).)

Introduction: Sociodemographic disparities in genitourinary cancer-related mortality have been insufficiently studied, particularly across multiple cancer types. This study aimed to investigate gender, racial, and geographic disparities in mortality rates for the most common genitourinary cancers in the United States., Methods: Mortality data for prostate, bladder, kidney, and testicular cancers were obtained from the Centers for Disease Control and Prevention (CDC) WONDER database between 1999 and 2020. Age-adjusted mortality rates (AAMRs) were analyzed by year, gender, race, urban-rural status, and geographic region using a significance level of p < 0.05., Results: Overall, AAMRs for prostate, bladder, and kidney cancer declined significantly, while testicular cancer-related mortality remained stable. Bladder and kidney cancer AAMRs were 3-4 times higher in males than females. Prostate cancer mortality was highest in black individuals/African Americans and began increasing after 2015. Bladder cancer mortality decreased significantly in White individuals, Black individuals, African Americans, and Asians/Pacific Islanders but remained stable in American Indian/Alaska Natives. Kidney cancer-related mortality was highest in White individuals but declined significantly in other races. Testicular cancer mortality increased significantly in White individuals but remained stable in Black individuals and African Americans. Genitourinary cancer mortality decreased in metropolitan areas but either increased (bladder and testicular cancer) or remained stable (kidney cancer) in non-metropolitan areas. Prostate and kidney cancer mortality was highest in the Midwest, bladder cancer in the South, and testicular cancer in the West., Discussion: Significant sociodemographic disparities exist in the mortality trends of genitourinary cancers in the United States. These findings highlight the need for targeted interventions and further research to address these disparities and improve outcomes for all populations affected by genitourinary 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 © 2024 Ghazwani, Alghafees, Suheb, Shafqat, Sabbah, Arabi, Razak, Sabbah, Alaswad, AlKattan, Ouban, Abdul Rab, Shawwaf, AlKhamees, Alasker, Al-Khayal, Alsaikhan, Addar, Aldosari, Al Qurashi and Musalli.)

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.)

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.)

Purpose: To conduct an updated and comprehensive study on the risks of subsequent primary urogenital cancers for childhood and adolescent cancer survivors., Methods: This longitudinal study was conducted using 9 cancer registries from the Surveillance, Epidemiology and End Results (SEER) Program with follow-up from 1975 to 2017. There were 43,991 patients diagnosed with first primary cancer from 1975 to 2016 before the age of 20 years who subsequently survived for at least 1 year. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) for urogenital cancers were calculated., Results: Compared with the general population, the risk of urinary system cancer was significantly higher in both female (SIR = 5.18, 95% CI: 3.65-7.14) and male (SIR = 2.80, 95% CI: 1.94-3.92) survivors of any first cancer, with shorter median interval length between first cancer and subsequent urinary system cancer for male survivors (19.9 years) than female survivors (29.3 years). Females also had significantly higher SIR than males for subsequent urinary system cancer (SIR female:male =1.86, 95% CI: 1.13-3.03) and kidney cancer (SIR female:male  = 1.97, 95% CI: 1.11-3.53). Compared with the general population, females with any first cancer had significantly higher risks for cancers of the corpus uteri (SIR = 2.32, 95% CI: 1.49-3.45) and vulva (SIR = 4.27, 95% CI: 1.38-9.95)., Conclusions: Childhood and adolescent cancer survivors may have greater female susceptibility for developing subsequent urinary system and kidney cancers, and these survivors may have higher risks for specific types of reproductive system cancers. Our findings may lead to better awareness and surveillance for urogenital cancer by these cancer survivors and their physicians., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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.)

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: In this multicenter, single-arm, multicohort, phase 2 trial, the efficacy of nivolumab and ipilimumab was evaluated in patients with advanced rare genitourinary cancers, including bladder and upper tract carcinoma of variant histology (BUTCVH), adrenal tumors, platinum-refractory germ cell tumors, penile carcinoma, and prostate cancer of variant histology (NCT03333616)., Methods: Patients with rare genitourinary malignancies and no prior immune checkpoint inhibitor exposure were enrolled. Patients received nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg intravenously every 3 weeks for 4 doses, and this was followed by 480 mg of nivolumab intravenously every 4 weeks. The primary endpoint was the objective response rate (ORR) by the Response Evaluation Criteria in Solid Tumors (version 1.1)., Results: Fifty-five patients were enrolled at 6 institutions between April 2018 and July 2019 in 3 cohorts: BUTCVH (n = 19), adrenal tumors (n = 18), and other tumors (n = 18). The median follow-up was 9.9 months (range, 1 to 21 months). Twenty-eight patients (51%) received 4 doses of nivolumab and ipilimumab; 25 patients received nivolumab maintenance for a median of 4 cycles (range, 1-18 cycles). The ORR for the entire study was 16% (80% confidence interval, 10%-25%); the ORR in the BUTCVH cohort, including 2 complete responses, was 37%, and it was 6% in the other 2 cohorts. Twenty-two patients (40%) developed treatment-related grade 3 or higher toxicities; 24% (n = 13) required high-dose steroids (≥40 mg of prednisone or the equivalent). Grade 5 events occurred in 3 patients; 1 death was treatment related., Conclusions: Nivolumab and ipilimumab resulted in objective responses in a subset of patients with rare genitourinary malignancies, especially those with BUTCVH. An additional cohort exploring their activity in genitourinary tumors with neuroendocrine differentiation is ongoing., Lay Summary: Patients with rare cancers are often excluded from studies and have limited treatment options. Fifty-five patients with rare tumors of the genitourinary system were enrolled from multiple sites and were treated with nivolumab and ipilimumab, a regimen used for kidney cancer. The regimen showed activity in some patients, particularly those with bladder or upper tract cancers of unusual or variant histology; 37% of those patients responded to therapy. Additional studies are ongoing to better determine who benefits the most from this combination., (© 2020 American Cancer Society.)

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.)

Pembrolizumab was recently approved for treatment of cancers with high tumor mutational burden (TMB). We conduct a focused literature review of TMB as a predictive biomarker. TMB quantifies the sum of nonsynonymous coding mutations (typically single nucleotide substitutions and short insertion-deletions) per megabase of sequenced DNA. As a proxy for expression of immunogenic neoantigens, TMB may be an effective predictive biomarker for response to immune checkpoint inhibitors. However, like other biomarkers in this setting, TMB has many limitations; the effect of this FDA approval in the current management of genitourinary cancers is likely limited to select situations., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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: To assess the spectrum of computed tomography (CT) findings in patients with genitourinary cancers visiting the emergency room (ER) and evaluate the relationship between CT findings and overall survival (OS)., Methods: Retrospective analysis of consecutive patients with genitourinary cancers undergoing CT during an ER visit at a tertiary cancer center during a 20-month period. CTs were considered positive if there were findings relevant to the presenting complaint(s). Demographic/clinical variables were recorded. OS was evaluated using Kaplan-Meier curves. Univariate and multivariate Cox proportional hazards regression (HR) was used to evaluate OS predictors., Results: Two hundred twenty-seven patients (243 visits) were included. The most common primary tumors were prostate (121 [49.8%]), bladder/urothelial (78 [32.1%]), and renal (69 [28.4%]). Common presenting complaints were abdominal pain (67 [27.6%]), respiratory symptoms (49 [20.2%]), neurological signs (37 [15.2%]), and fever (34 [14.0%]). CT findings were positive in 172 patients (70.8%) and included new/increased metastases (21.4% [52/243]), fluid collections (7.4% [18/243]), urinary tract infection/inflammation (6.2% [15/243]), enteritis/colitis (5.3% [13/243]), and pneumonia (4.9% [12/243]). A positive ER CT was associated with patient admission (p = 0.01). At multivariate analysis, independently predictive factors of shorter survival were positive ER CT (HR = 2.09 [95% CI 1.16-3.76, p = 0.01), hospital admission (HR = 2.17 [95% CI 1.38-3.41], p < 0.01), and recent systemic treatment (HR = 2.10 [95% CI 1.32-3.35], p < 0.01)., Conclusion: When CT was performed, it was able to identify a structural cause for the presenting complaint in the majority of patients with genitourinary cancers attending the ER. A positive ER CT was associated with hospital admission and poorer overall survival.

Background: Early diagnosis and improved therapeutic options have contributed to prolonged survival in male genitourinary cancer. However, these cancer survivors may die due to other causes., Aims: This work is aimed to explore the death patterns among male genitourinary cancer patients due to other causes. The occurrence of death not related to cancer is defined as competing risk (CR)., Methods and Results: Data extracted between 1973 and 2014 for male patients (n = 638 393) diagnosed with genitourinary cancer and registered in the Surveillance, Epidemiology, and End Results (SEER) Program were included for analysis. A CR analysis was performed to explore the death patterns due to cancer or otherwise. Our study evidenced a huge proportion of patients' death due to associated factors including but not limited to cancer. Interestingly, the computed hazard ratios obtained in cancers of male organ sites such as prepuce, glans penis, penis, and spermatic cord were 1.28 (0.98-1.67), 1.53 (1.33-1.77), 1.35 (0.19-1.53), and 1.57 (1.24-2.0), respectively. However, the hazard ratios evaluated on factors other than cancer in the same organ sites were 0.95 (0.76-1.18), 1.14 (0.99-1.3), 1.09 (0.97-1.22), and 1.12 (0.86-1.46), respectively., Conclusion: This study shows that among the male genitourinary cancer patients, the significant proportion of deaths occurs due to reasons unrelated to cancer. It can be concluded that the magnitude of death due to only genitourinary cancer is minimal and is not as high as documented in the earlier literature., (© 2019 Wiley Periodicals, Inc.)

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.)

Background: Sarcomas of the genitourinary (GU) tract are exceedingly rare, accounting for just 1% to 2% of malignancies treated by urologic surgeons. We perform a thorough investigation of incidence and mortality in the United States using the Surveillance, Epidemiology, and End Results (SEER) database., Patients and Methods: The SEER 18 database was used to identify patients diagnosed with genitourinary sarcoma over the age of 16. Data on demographics and tumor characteristics were collected. Survival analysis was performed on the most common primary tumor sites., Results: The search identified 3,007 patients with GU sarcomas from 1973 to 2015. In order of descending incidence, tumors presented in the bladder, kidney, paratestis, and scrotum. Amongst sarcomas arising in the bladder, leiomyosarcomas exhibited the longest median survival time (overall survival (OS) 62 months), while carcinosarcomas had the shortest (OS 9 months). Metastatic disease decreased leiomyosarcoma OS to 3 months. When comparing renal tumors, liposarcomas had the longest median survival time (OS 45 months) and carcinosarcomas had the shortest (OS 6 months). Older age (P < 0.001 and P = 0.015) and T4 disease (P = 0.005 and P < 0.001) predicted for worse survival amongst bladder and renal sarcomas, respectively. High tumor grade (P < 0.001) and node positive disease (P = 0.024) also affected survival amongst renal tumors., Conclusions: Tumors most commonly present in the bladder, kidney, paratestis, and scrotum, with kidney sarcomas having markedly dismal survival outcomes. Survival of identical histologic types varied by primary tumor location, suggesting that treatment strategies should be refined by type of sarcoma and primary tumor location within the GU tract., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To investigate the incidence rates for different malignancies and assess the risk factors for all-cancer incidence in Tehran., Study Design: Cohort study., Methods: This study consists of 8599 participants aged ≥ 30 years who were free of cancer (3935 men). Cancer diagnosis was based on pathology reports. Sex-stratified crude incidence rates and age-standardized incidence rates (ASRs) using Segi's method were calculated for all-cancers. Multivariate Poisson regression models were used to evaluate associations of potential risk factors, including sex, age, obesity status (body mass index [BMI]: 25-30 kg/m 2 as reference), education, smoking status, and diabetes mellitus with the incidence of cancers among the population. Incidence rate ratios (IRRs) with 95% confidence interval (CI) were also reported., Results: During a median follow-up of 13.9 years, there were 130 and 129 incident cancers for men and women, respectively; the corresponding ASRs were 356.1 and 243.6 per 100,000 person-years, respectively. The three most incident cancers among men were gastrointestinal (GI) (ASR = 127.5), hematopoietic (ASR = 99.5), and reproductive system malignancies (ASR = 46.3). The most common incident cancers in women were breast cancer (ASR = 92.1), GI (ASR = 65.4), and reproductive system malignancies (ASR = 16.8). Among risk factors for cancer incidence, age (IRR [95% CI]: 1.05 [1.03-1.06]) and having a BMI < 25 kg/m 2 (IRR [95% CI]: 1.38 [1.01-1.90]) had a statistically significant association with incident cancer., Conclusions: The high rates of cancers in Tehran during more than a decade of follow-up calls for a need to define risk factors as well as to implement programs for early screening., (Copyright © 2020 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: Mucosal melanomas (MM) arise within the lining of the gastrointestinal (GI), genitourinary (GU) and head and neck (HN) systems.  Method: A retrospective analysis of the National Comprehensive Database identified 4,961 MM patients. Primary objective was to compare survival outcomes across the different locations.  Results: Overall survival for GI melanomas was significantly shorter than HN and GU melanomas. Median survival (95% confidence interval) was 19.5 (18.0-21.5), 26.4 (24.9-28.3), and 43.9 (38.8-47.8), months for GI, HN and GU cases, respectively (p<0.0001).  Conclusion: This is the largest study of MM in a US based population, demonstrating worse overall survival for GI MM in comparison to HN and GU melanomas.

Objective: To examine the changes in exenterative surgery over three decades analysing oncological outcomes and whether changes in surgical approach have led to improved patient outcomes., Background: Advances in surgical technology, perioperative care and pattern of disease recurrence have coincided with an evolutionary change in exenterative surgery., Methods: A review of a prospectively maintained databases of pelvic exenteration surgery from 1988 to 2018  at two high volume specialised institutions. The total cohort was divided into three major time points (1988-2004, 2005-2010 and 2011 to 2018) to allow comparative analysis. Primary endpoints were overall survival in primary and recurrent disease at each time point. Secondary endpoints included anastomotic leak, blood transfusion, ileus, wound infection rates and evolution of case complexity. Data were analysed using R with a p < 0.05 considered significant., Results: Six hundred and seventy patients underwent exenterative surgery. In 2011-2018 there was an increase in resection of recurrent malignancy with a continuous increase in GI malignancies resected over each time period(p < 0.001,<0.01) and a reduction in gynaecological malignancy(p < 0.001). A significant increase in sacrectomy, pelvic sidewall resection and ileal conduit reconstruction was observed (p < 0.01,<0.001).In 2005-2010 patients had increased rates of ileus and anastomotic leak(p < 0.05). Patients undergoing resection for primary disease had improved overall survival at time points 1988-2004 and 2011-2018 compared to those with recurrent disease(p = 0.007,<0.001). Overall survival was significantly improved in patients with primary versus recurrent disease(p = 0.022)., Conclusion: There has been a significant improvement in survival in patients undergoing pelvic exenteration surgery from primary disease. Case complexity has increased without significant morbidity., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: To summarize the clinical characteristics, treatment response and prognostic factors of rhabdomyosarcoma (RMS) in children. Methods: The clinical characteristics such as age at diagnosis, primary tumor site, tumor size, pathological type, clinical stage, and risk grouping of 213 RMS patients (140 males and 73 females) treated in Hematology Oncology Center of Beijing Children's Hospital, Capital Medical University, from May 2006 to June 2018 were analyzed retrospectively. The clinical characteristics, overall survival (OS), event free survival (EFS) and prognostic factors of children treated with the Beijing Children's Hospital-Rhabdomyosarcoma (BCH-RMS) regimen were analyzed. Survival data were analyzed by Kaplan-Meier survival analysis, and single factor analysis was performed by Log-Rank test. Results: The diagnostic age of 213 cases was 48.0 months (ranged 3.0-187.5 months), of which 136 cases (63.8%) were younger than 10 years old. The head and neck region was the most common primary site of tumor (30%, 64 cases), followed by the genitourinary tract (26.8%, 57 cases). Among pathological subtypes, embryonal RMS accounted for 71.4% (152 cases), while alveolar RMS and anaplastic RMS accounted for only 26.8% (57 cases) and 1.9% (4 cases), respectively. According to the Intergroup Rhabdomyosarcoma Study Group (IRS), IRS-Ⅲ and Ⅳ accounted for 85.0% (181 cases) of all RMS patients. In all patients, 9.4% (20 cases) patients were divided in to low-risk group, 52.1% (111 cases) patients in to intermediate -risk group, 25.8% (55 cases) patients in to high-risk group, and 12.7% (27 cases) patients in to the central nervous system invasion group, respectively. All patients with RMS received chemotherapy. The cycles of chemotherapy were 13.5 (ranged 5.0-18.0) for patients without event occurrence, while 14.2 (ranged 3.0-30.0) for patients with event occurrence. Among the 213 patients, 200 patients had surgical operation, of whom 103 patients underwent surgery before chemotherapy and 97 patients at the end of chemotherapy, 21 patients had secondary surgical resection. Radiotherapy was performed in 114 patients. The follow-up time was 23.0 months (ranged 0.5-151.0 months) . There were 98 patients with relapsed or progressed disease and 67 patients with death. The median time to progression was 10 months, of which 67 (68.4%) relapse occurred within 1 year and no recurrence occurred after follow-up for more than 5 years. The 3-year EFS and 5-year EFS were (52±4) % and (48±4) %, while the 3-year OS and 5-year OS were (65±4) % and (64±4) % by survival analysis. The 5-year OS of the low-risk, intermediate-risk, the high-risk were 100%, (74±5) %, (48±8) %, and the 2-year OS of the central nervous system invasion group was (36±11) % (χ(2)=33.52, P< 0.01). The 5-year EFS of the low-risk, intermediate-risk, the high-risk were (93±6) %, (51±5) %, (36±7) % and the 2-year EFS of the central nervous system invasion group was (31±10) % (χ(2)=24.73, P< 0.01) . Survival factor analysis suggested that the OS of children was correlated with age(χ(2)=4.16, P =0.038), tumor TNM stage (χ(2)=22.02, P= 0.001), IRS group (χ(2)=4.49, P< 0.01) and the risk group (χ(2)=33.52, P< 0.01). Conclusions: This study showed that the median age of newly diagnosed RMS patients was 4 years. The head and neck and the genitourinary tract were the most common primary origin of RMS. The OS was low in single-center RMS children. The median time to recurrence was 10 months, and recurrence was rare 3 years later.

The risk of second malignant neoplasms (SMN) in chronic myeloid leukemia (CML) survivors remains unclear. We utilized the Surveillance, Epidemiology and End Results 18 (SEER 18) registries to evaluate the risk and subsequent outcomes of SMN in CML survivors. There were 3407 patients included. Of these, 170 (4.99%) developed a SMN with SIR of 1.40 (95% C.I. 1.19-1.62). An increased risk was noted for cancers of the respiratory tract, genitourinary (GU) tract and skin excluding basal cell and squamous cell carcinoma. Using 3:1 matching (3 de novo malignancies to 1 post-CML SMN case), we compared survival data for cancers of the respiratory, GU and gastrointestinal (GI) tract. Patients with GU malignancies developing after CML had worse overall survival than patients without prior CML diagnosis (P = 0.018). There was no difference in survival between post-CML and non-post-CML patients with respiratory or GI malignancies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Context: The centralization of cancer care is associated with better clinical outcomes and may be a method for optimizing value-based health care systems., Objective: To systematically review the literature regarding the impact of centralization of care on clinical outcomes for genitourinary malignancies., Evidence Acquisition: A systematic review was conducted using Ovid and MEDLINE to identify studies between 1970 and 2018 reporting on the centralization of care for genitourinary malignancies. Prospective and retrospective studies were screened., Evidence Synthesis: There were no published randomized control trials (RCTs) on the centralization of care for genitourinary malignancies. Twenty-two retrospective studies met inclusion criteria. Centralization of radical cystectomy was the most studied. Care for bladder cancer, prostate cancer, penile cancer, testicular cancer, and renal cancer was reportedly associated with better morbidity and survival outcomes for patients treated at high-volume centers. However, evidence of better outcomes for centralization of care remains limited for penile, renal, and testicular cancers owing to the paucity of data and/or the lower incidence of these genitourinary malignancies., Conclusions: Care for genitourinary malignancies by high-volume providers was associated with greater utilization of cancer surgery, lower morbidity, and better survival outcomes. Centralization of care was most appropriate for complex procedures such as radical cystectomy when interpreted in the context of survival outcomes. Further research is needed to address the impact of centralizing care for all urologic malignancies with consideration of the associated costs and patient-reported measures, including quality of life and patient experience., Patient Summary: We explored the evidence for moving major operations into larger centers. We focused on surgery for cancers of the bladder, prostate, testicle, penis, and kidney, and found that larger-volume hospitals had better survival outcomes and fewer complications when compared to smaller hospitals. The difference may be greatest for complex major surgeries such as radical cystectomy., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Assessments supporting smokeless tobacco (SLT) disease risk are generally decades old. Newer epidemiological data may more accurately represent the health risks associated with contemporary US-based SLT products, many of which contain lower levels of hazardous and potentially hazardous chemicals compared to previously available SLT products., Methods: Data from two longitudinal datasets (National Longitudinal Mortality Study-NLMS, and the National Health Interview Survey-NHIS) were analyzed to determine potential associations between SLT use and/or cigarette smoking and all-cause and disease-specific mortality. Mortality hazard ratios (HR) were estimated using a Cox proportional hazards regression model applied to various groups, including never users of any tobacco or SLT product, and current and former SLT users and/or cigarette smokers., Results: The two datasets yielded consistent findings with similar patterns evident for the specific causes of death measured. All-cause mortality risk for exclusive SLT users was significantly lower than that observed for exclusive cigarette smokers and dual SLT/cigarette users. Similar trends were found for mortality from diseases of the heart, chronic lower respiratory diseases, and malignant neoplasms. Mortality risk for lung cancer in exclusive cigarette smokers was increased by about 12-fold over never-tobacco users but was rarely present in exclusive SLT users in either survey (NHIS, < 5 cases/1,563 observations; NLMS, 3 cases/1,863 observations). While the data in the surveys are limited, SLT use by former cigarette smokers was not associated with an increase in the lung cancer risk HR compared to that by former cigarette smokers who never used SLT., Conclusions: Emerging epidemiological data provides a new perspective on the health risks of SLT use compared to risks associated with cigarette smoking. HR estimates derived from two current US datasets, which include data on contemporary tobacco products, demonstrate a clear mortality risk differential between modern SLT products and cigarettes. Cigarette smokers had an increased overall mortality risk and risk for several disease-specific causes of death, while SLT users consistently had lower mortality risks.

Aim: The aim of this study was to develop a risk scoring system specific to patients with bone metastasis of genitourinary cancer., Materials and Methods: This study included 180 patients with bone metastasis of three major types of genitourinary cancer: prostate cancer (n=111), renal cell carcinoma (n=43,), and urothelial carcinoma (n=26). Clinical factors at diagnosis of bone metastasis were evaluated to identify independent prognostic factors., Results: Multivariate analysis showed that type of primary cancer, poor performance status, the presence of visceral metastases, high Glasgow prognostic score and elevated neutrophil-to-lymphocyte ratio were independently predictive of poor prognosis. Patients were able to be classified by the prognostic risk score into four prognostic groups with low, intermediate, high, and very high risk., Conclusion: This risk scoring system could be useful for predicting survival of patients with bone metastasis of genitourinary cancer and in making decisions on appropriate treatments for them., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Pediatric paired box 3:forkhead box protein O1 fusion-negative (PF-) rhabdomyosarcoma (RMS) represents a diverse spectrum of tumors with marked differences in histology, myogenic differentiation, and clinical behavior., Methods: This study sought to evaluate the clinical and mutational spectrum of 24 pediatric PF- human RMS tumors with high levels of myogenic differentiation. Tumors were sequenced with OncoPanel v.2, a panel consisting of the coding regions of 504 genes previously linked to human cancer., Results: Most of the tumors (19 of 24) arose at head/neck or genitourinary sites, and the overall survival rate was 100% with a median follow-up time of 4.6 years (range, 1.4-8.6 years). RAS pathway gene mutations were the most common mutations in PF-, highly differentiated RMS tumors. In addition, Hedgehog (Hh) and mechanistic target of rapamycin (mTOR) gene mutations with evidence for functional relevance (high-impact) were identified in subsets of tumors. The presence of Hh and mTOR pathway gene mutations was mutually exclusive and was associated with high-impact RAS pathway gene mutations in 3 of 4 Hh-mutated tumors and in 1 of 6 mTOR-mutated tumors., Conclusions: Interestingly, Hh and mTOR gene mutations were previously associated with rhabdomyomas, which are also known to preferentially arise at head/neck and genitourinary sites. Findings from this study further support the idea that PF-, highly differentiated RMS tumors and rhabdomyomas may represent a continuous spectrum of tumors. Cancer 2018;124:1973-81. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Comparative effectiveness research (CER) is imperative for objective and balanced assessment of treatment outcomes. CER that uses administrative databases (AD-CER) affords unique opportunities for large scale data analyses that potentially transcend limitations of small institutional datasets. Prostate cancer has received much attention from the AD-CER research community, whereas non-prostate genitourinary malignancies are less well-studied. The objective of this article is to review the currently available AD-CER that has been published in the non-prostate genitourinary malignancies space., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To investigate the prognostic value of elements of the Geriatric Assessment, in particular the Timed Up and Go (TUG) Test and the Barthel Index of Activities of Daily Living (ADL) for one-year post-operative mortality in elderly patients with cancer., Materials and Methods: This prospective cohort study included patients 65years of age or older undergoing elective major surgery for cancer between June 2008 and June 2010. Preoperative functional status was measured by the TUG Test and the Barthel Index of ADL Cognitive state was assessed by the Mini Mental State Examination (MMSE). Complications were recorded prospectively. The degree of resection was noted., Results: Data from 131 patients (56% women; median age, 71years) were analysed at 1year of follow-up. Mortality after 1year was 28.2%. Twenty-nine patients (22.3%) were dependent in ADLs, and 43 (35.2%) impaired in TUG. Thirteen patients (10.7%) were both, dependent in ADLs and impaired in TUG. Short-term complications after surgery occurred in 66% of patients, and major complications occurred in 29%. Patients who were dependent in ADLs and impaired in TUG had significantly higher 1-year mortality (OR, 4.5; 95% CI, 1.21-18.25; p=0.034). Lower scores on the MMSE (OR, 0.64; 95% CI, 0.43-0.95; p=0.048) and incomplete surgical resection (OR, 3.25; 95% CI, 1.15-9.20; p=0.026) were independently associated with higher 1-year mortality., Conclusion: Functional assessments, such as ADL and TUG scores, as well as mild cognitive impairment, are predictors of long-term outcome in elderly cancer patients., Trial Registration: German Clinical Trials Register (DRKS 00005150)., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To report our institutional experience in the management of adult genitourinary sarcoma., Methods: This was a retrospective analysis of data on adult genitourinary sarcoma treated at the West China Hospital, Sichuan University, Chengdu, Sichuan, China from 1985 to 2010. Clinicopathological parameters were analyzed to determine their impact on overall, recurrence-free and metastasis-free survivals., Results: A total of 46 women and 142 men were included, with a median age of 42 years. Of these, 152 cases were high-grade. The most common site was the paratesticular region. Surgical resection was carried out in 155 patients (82.4%), with negative margin in 106. After a minimum follow up of 5 years, 20 patients (11.6%) survived disease-free, 14 (8.1%) were alive with disease and 138 (80.2%) died of disease. Survival rates at 1, 3 and 5 years were 91.3%, 64.0% and 47.7%. In univariate analyses, liposarcoma, high grade, metastasis at diagnosis, a lack of surgical resection and positive margin were predictive of unfavorable survival. In multivariate analyses, high grade, a lack of surgical resection and chemotherapy were independent predictors of poor survival., Conclusions: Adult genitourinary sarcoma is an aggressive malignancy, usually presenting at advanced stage, with a high incidence of recurrence and metastasis. Complete resection and selective combination of chemotherapy and radiotherapy might constitute the optimal treatment for this disease., (© 2017 The Japanese Urological Association.)

Objective: Having a clear prognosis for patients with brain metastases allows health care practitioners (HCPs) to determine appropriate palliative management and assist patients when making informed treatment decisions. The objective of this study was to determine the prognostic significance of commonly experienced symptoms as well as their changes., Methods: Overall survival (OS) was calculated from the date of consultation for palliative radiotherapy to date of death or censored at last follow-up date. Symptom changes at follow up were defined as worsened, improved, or no change. Univariate and multivariate cox proportional hazard (PH) model of OS was conducted on 14 symptoms at baseline and on changes in those symptoms at 1-, 2-, and 3-month follow-ups., Results: From 1999 to 2013, 1,660 patients were included for baseline symptom analysis. Through univariate analysis, fatigue, nausea, appetite loss, coordination, concentration, balance and depression were significantly related to OS. Upon multivariate analysis, fatigue and appetite loss were most predictive of short survival. For symptom change, 201 patients were included. The actuarial median OS was 5.0 months [95% confidence interval (CI): 4.3-7.0], 7.1 months (95% CI: 5.2-9.5) and 8.8 months (95% CI: 5.8-11.5) for patients with month 1, 2, and 3 follow-ups, respectively. The most common symptom changes following whole brain radiotherapy (WBRT) were: worsened fatigue, appetite loss, and weakness. Worsened difficulty concentrating, fatigue, nausea and headaches were most predictive of a poorer survival outcome., Conclusions: HCPs should be aware of the shorter prognosis associated with patients exhibiting one or more of these symptoms and tailor care accordingly to maximize patients' remaining quality of life (QOL).

Gene therapy development has been limited by our inability to target multifocal cancer with systemic delivery. We developed a systemically administered, tumor-targeted liposomal nanodelivery complex (SGT-94) carrying a plasmid encoding RB94, a truncated form of the RB gene. In preclinical studies, RB94 showed marked cytotoxicity against tumor but not normal cells. SGT-94 was administered intravenously in a first-in-man study in metastatic genitourinary cancer. Minimal side effects were observed; dose-limiting toxicity (DLT) has not been reached in 11 evaluable patients. There was evidence of clinical activity at the 2.4 mg dose with one complete remission (CR) and one partial remission (PR). The patient in CR was retreated upon progression and had a second PR. Furthermore, there was tumor-specific targeting of the SGT-94 complex. One patient had wedge resections of two lung metastases which demonstrated RB94 expression at the DNA level by polymerase chain reaction (PCR) and at the protein level by Western blotting, with no RB94 present in normal contiguous lung. In conclusion, systemically delivered SGT-94 showed evidence of selective tumor targeting and was well tolerated with evidence of clinical activity. Additional studies are warranted to explore the activity of this drug as a single agent and in combination therapy.

Background: Primary melanoma arising in the genitourinary tract is rare and poorly characterized., Objectives: We sought to describe the epidemiology of genitourinary melanoma in the United States., Methods: Incident case and population data were obtained for genitourinary melanoma from the Surveillance, Epidemiology, and End Results 13 Registries Database between 1992 and 2012., Results: A total of 817 patients with genitourinary melanoma were identified; most cases occurred in the vulva. The incidence of genitourinary melanoma was much higher in women (1.74/1 million person-years) than men (0.17/1 million person-years). The highest rates occurred among non-Hispanic white women aged 85 years and older. Five-year melanoma-specific and overall survival were poor at 52.4% and 36.3%, respectively. Predictors of poor survival were increasing age, black race, and female sex., Limitations: The study population is small, therefore some rates reported may be unstable. In addition, cutaneous, mucosal, and other extracutaneous surfaces of the genitourinary tract cannot be reliably distinguished in Surveillance, Epidemiology, and End Results. Furthermore, melanomas may be underreported to cancer registries., Conclusion: From 1992 to 2012, genitourinary melanoma was 10 times more common in women than men. Survival was poor in women compared with men, which is different from cutaneous melanoma where women have a survival advantage., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Pediatric genitourinary rhabdomyosarcoma (RMS) accounts for 25 % of all pediatric soft tissue sarcomas. The treatment of these tumors has shifted over time from debilitating radical exenteration to organ-sparing techniques using multimodal therapy. Our review aims to summarize recent relevant literature regarding the current treatment practices of pediatric genitourinary RMS and how these practices have shifted over time., Methods: PubMed database search was utilized to identify relevant literature from 1997 to 2015 relating to the treatment of pediatric genitourinary RMS with emphasis on organ preservation and maintaining organ function., Results: A total of 31 articles from 1997 through 2015 were identified relating to current management concepts in pediatric genitourinary sarcomas. Relevant articles were reviewed in detail and discussed., Conclusion: The treatment of pediatric genitourinary RMS has shifted from debilitating pelvic exenteration to a multimodal treatment approach involving surgery, chemotherapy, and radiation therapy in an effort to preserve genitourinary organs and reduce treatment morbidity. Continued research is required to improve post-treatment organ function. Further studies utilizing objective urodynamic evaluation are necessary to better characterize bladder function after treatment for RMS. Exciting recent developments in RMS research of fusion proteins that induce cell transformation and inhibit apoptosis and myogenic differentiation may result in future management changes to treatment protocols.

The use of targeted therapies in patients with genitourinary malignancies has significantly improved outcomes. For example, androgen receptor (AR) pathway inhibitors have improved outcomes for patients with prostate cancer, and antiangiogenic agents have improved outcomes for those with kidney cancer. However, these advances have been accompanied by musculoskeletal side effects that manifest as physical dysfunction. Although the effects of androgen deprivation therapy on skeletal muscle are well-known, an additional concern is that the muscle loss associated with these newer drugs-especially AR pathway inhibitors-may result in insulin resistance and metabolic syndrome, thus increasing the risk for cardiovascular events and diabetes. Antiangiogenic agents also may cause muscle loss, although this has been poorly described in the literature. As these targeted therapies begin to be used in the earlier stages of treatment, there will be a critical need to prevent treatment-related toxicities with nonpharmacologic interventions. Over the past decade, exercise training has emerged as a novel nonpharmacologic adjunctive method to address toxicities resulting from these targeted therapies. Despite numerous studies in patients with prostate cancer, there remains a large gap in our knowledge of the true efficacy of exercise therapy, as well as the best way to prescribe exercise programs. Here, we suggest that the central role of skeletal muscle in the development of side effects of AR pathway inhibitors and antiangiogenic agents may unlock a number of unique opportunities to study how exercise prescriptions can be used more effectively. Resistance training may be a particularly important modality.

Background: Primary genitourinary (GU) melanoma is a rare disease, which is poorly characterized., Objective: To examine clinical characteristics and survival outcomes of primary GU melanoma among men and women., Design, Setting, and Participants: Retrospective study using the Surveillance, Epidemiology, and End Results database (1973-2010) was used to identify primary GU melanoma cases by tumor site and histology codes. We examined associations of GU melanoma with demographic, clinical, and pathologic characteristics, as well as disease-specific survival (DSS)., Outcome Measurements and Statistical Analysis: DSS was calculated using the Kaplan-Meier method. Cox-proportional hazard models were used to calculate hazard ratios and 95% CI for factors associated with worse DSS., Results and Limitations: A total of 1,586 histologically confirmed cases of primary GU melanoma were identified with a median age of 66.1 years (IQR: 55-80). Incidence of primary GU melanoma was 0.2cases/million among men and 1.80cases/million among women. Overall, 60.1% of patients had localized disease at presentation and 90.5% of patients had cancer-directed surgery. Patients with urothelial melanoma had the worst 5- and 10-year DSS (39% and 29%, respectively). Women with vulvar/vaginal melanoma had worse 5- and 10-year DSS compared to men with penile/scrotal melanoma. In multivariate analysis, decreased survival was associated with increasing age, distant stage, and lymph node involvement. Results are limited by the lack of standardized staging for primary GU melanoma and the retrospective design of our study., Conclusions: Patients with primary GU melanoma present with advanced stage and have a poor prognosis. Women have worse DSS compared to men. DSS is negatively associated with advanced age at diagnosis, higher stage, and lymph node involvement., Patient Summary: Clinicians and patients must be aware of the poor disease-specific outcomes associated with primary GU melanoma. Most importantly, women fare worse than men and mucosal melanomas have worse outcomes compared to cutaneous melanomas., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Malignant melanoma is a relatively common malignancy in the West, but has a significantly lower incidence in Asians. Stark contrast in clinicopathological characteristics and prognosis has been observed between the 2 populations, yet data are limited. Here, we evaluate 106 Asian patients from a tertiary referral center in Hong Kong during an 11-year period. The purpose of this study was to collectively review all types of melanomas to analyze the clinicopathological characteristics of this poorly understood condition in an Asian population., Methods: A total of 106 patients diagnosed with malignant melanoma from 2002 to 2012 were retrospectively reviewed. Demographics, clinical presentations, pathological subtypes, treatments, and survival outcomes were evaluated., Results: Cutaneous melanomas dominated with 46 (43.4%) cases, followed by mucosal (39.6%), ocular (9.4%), and melanomas of unknown primary (7.5%); 43.3% patients presented in stage I, 36.7% in stage II, 18.9% in stage III, and 1.1% in stage IV. Acral lentiginous melanoma was the commonest subtype of cutaneous melanomas (60.9%). When types of melanomas were reviewed collectively, the median overall survival, disease-specific survival, and recurrence-free survival were 37, 45, and 48 months, respectively. Cutaneous melanoma had the best median overall survival of 59 months, followed by ocular melanoma (58 months), mucosal melanoma (18 months), and melanoma of unknown primary (2 months). Similar patterns were observed for disease-specific survival and recurrence-free survival., Conclusions: Melanoma among Asians remains poorly understood. There is a clear distinction in the clinical patterns between Asians and whites and the difference is not solely accounted for by the lower incidence of cutaneous melanoma. Certain subtypes, such as mucosal melanoma and is acral lentiginous melanoma, seemed to have disproportionately high incidences. Further studies are warranted to elucidate these observations. The poor survival outcomes reflected the need for better awareness and understanding of the condition by both the general public and the physicians.

Mucosal melanoma represents a distinct minority of disease sites and portends a worse outcome. The ideal treatment and role of adjuvant therapy remains unknown at this time. We hypothesized that a combination of neoadjuvant and adjuvant therapies would improve survival in these aggressive melanomas. Our large, prospectively maintained melanoma database was queried for all patients diagnosed with mucosal melanoma. Over the past five decades, 227 patients were treated for mucosal melanoma. There were 82 patients with anorectal, 75 with sinonasal, and 70 with urogenital melanoma. Five-year overall survival and melanoma-specific survival for the entire cohort were 32.8 and 37.5 per cent, respectively, with median overall survival of 38.7 months. One hundred forty-two patients (63.8%) underwent adjuvant therapy and 15 were treated neoadjuvantly (6.6%). There was no survival difference by therapy type or timing, disease site, or decade of diagnosis. There was improved survival in patients undergoing multiple surgeries (Hazard Ratio [HR] 0.55, P = 0.0005). Patients receiving neoadjuvant therapy had significantly worse survival outcomes (HR 2.49, P = 0.013). Over the past five decades, improvements have not been seen in outcomes for mucosal melanoma. Although multiple surgical interventions portend a better outcome in patients with mucosal melanoma, adjuvant treatment decisions must be individualized.

Objectives: This retrospective study was carried out to define the clinical features and prognostic differences in non-cutaneous malignant melanoma (non-CMM) originating from different anatomic sites., Methods: Clinical and follow-up data for 71 patients with non-CMM were collected and reviewed., Results: Of the 71 non-CMM patients, 59 were diagnosed with mucosal malignant melanoma (MMM) and 12 with ocular malignant melanoma (OMM). In the 59 MMM patients, the nasal cavity was the most common anatomic site (n = 31, 43.7% of all non-CMM), followed by the oral cavity (n = 9, 12.7%), the genitourinary tract (n = 9, 12.7%), the anorectum (n = 8, 11.3%), and the gastrointestinal tract (n = 2, 2.8%). In the 12 patients with OMM, anatomic sites included the choroid (n = 8, 11.3% of all non-CMM) and the conjunctiva (n = 4, 5.6%). The survival outcome of patients with OMM was much better than that of patients with MMM (P < 0.001). In MMM patients, anorectal melanoma was associated with a worse survival outcome. Age of ≥ 70 years (P < 0.001) and tumor size of > 2 cm (P = 0.02) were significantly poor prognostic factors in MMM. Age (relative risk [RR] 1.068, 95% confidence interval [CI] 1.006-1.133; P = 0.03) and tumor size (RR 1.410, 95% CI 1.038-1.915; P = 0.028) were independent predictors for the postoperative survival of MMM patients. Patients with these two risk factors had a higher risk for recurrence or death (RR 3.107, 95% CI 1.627-5.595)., Conclusions: Our findings demonstrate that prognoses differ in patients with different anatomic sites of primary non-CMM. Advanced age and larger tumor size are the main factors affecting prognosis. Patients with poor risk factors should be treated differently to improve their survival outcome., (© 2015 The International Society of Dermatology.)

In Hong Kong, urological malignancy accounted for 9.55% of all the new cases of cancer in 2012. In the male population, prostate cancer was the third most commonly diagnosed cancer, and the fifth leading cause of cancer death. Age-standardized rate of prostate cancer incidence rose from 11.5 per 100 000 men in 1992 to 28.5 per 100 000 men in 2012. On the other hand, age-standardized rate of bladder cancer incidence dropped from 6.4 per 100 000 in 2003 to 3.0 per 100 000 in 2012. The incidence of kidney cancer remained stable in recent years, with an age-standardized rate of 4.8 per 100 000 in 2012. The introduction of the robotic surgical system has made robotic-assisted laparoscopic radical prostatectomy the most common mode of surgical treatment for prostate cancer in Hong Kong. Robotic-assisted laparoscopic radical cystectomy and robotic-assisted laparoscopic partial nephrectomy have been gaining popularity in the locality. Minimal-invasive surgical techniques as well as different systemic therapies have led to revolutionary changes in the urology community in Hong Kong. The existing territory-wide surveillance of cancer incidence and mortality trends continue to provide us with clues to aetiology and the effects of improved diagnostic and treatment techniques., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Genitourinary embryonal rhabdomyosarcoma is rarely reported in China. This retrospective analysis aimed to characterize the clinicopathologic features and treatment outcomes of genitourinary embryonal rhabdomyosarcoma in a sample of Chinese patients., Methods: Basic demographic and clinical data of 29 patients, who were diagnosed with genitourinary embryonal rhabdomyosarcoma between January 2000 and December 2011, were retrieved and analyzed., Results: In these patients, 25 were males and 4 were females with a median age of 12 years. Paratesticule was the most common lesion site, followed by the prostate, bladder, and vagina. The median tumor size was 5.80 cm. Six patients had clinically positive regional nodes. At the initial diagnosis, patients had a metastatic disease. According to the TNM staging classification for the IRS-IV, phase I lesions were detected in ten cases, phase II lesions in six cases, phase III lesions in four cases, and phase IV lesions in nine cases. The median survival of all patients was 63 (range from 6 to 118) months. The 1-, 3-, and 5-year survival rates for these patients were 93%, 83%, and 52%, respectively. Multivariate analyses demonstrated that staging and anemia were significant predictors of prognosis., Conclusions: Our findings suggest that metastasis predicts a poor prognosis. Chemotherapy played an important role in comprehensive treatment. Palliative and neo-adjuvant chemotherapy could increase median survival time.

Background: Cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC) has gained acceptance in the treatment of peritoneal carcinomatosis with reported morbidity and mortality rates of 27-56 and 0-11 %, respectively. The safety and oncologic outcome of genitourinary repair at the time of CRS and HIPEC remains unclear., Methods: We identified 170 patients who underwent CRS-HIPEC at our institution between July 2007 and August 2011 with a minimum follow-up of 6 months. Thirty-four (20 %) underwent concomitant urologic reconstruction at the time of CRS-HIPEC and were matched by disease burden (intraoperative peritoneal cancer index [PCI]) and extent of surgery (ΔPCI) with a cohort of 38 (22.3 %) subjects without genitourinary involvement. The primary end points considered for this analysis included the development of major surgical (Clavien-Dindo Class III-V) complications and overall survival., Results: Median follow-up was 9.4 months. The most commonly performed urologic interventions included partial cystectomy with primary repair in 23 (65.7 %) and segmental ureteral resection and repair in 11 (31.4 %). Patients with genitourinary reconstruction had more total organ involvement (6.5 vs. 4.3, p < 0.001) and more commonly underwent enteric anastomoses (82.4 vs. 57.9 %, p = 0.025). No significant differences were observed with regard to major morbidity, need for transfusion, operative time, intensive care unit admission, or length of stay. Among patients with appendiceal or colonic tumors (n = 46), overall survival was similar between genitourinary reconstruction and matched cohorts: 22.5 versus 15.1 months, respectively (p = 0.66)., Conclusions: Genitourinary reconstruction at the time of CRS-HIPEC occurs more commonly in patients with extensive disease burden undergoing radical debulking, yet does not adversely influence surgical morbidity or survival.

Background: Extramammary Paget's disease (EMPD) is a relatively rare malignancy, and there are few reports related to radiation therapy. In the present study, we investigated the outcome of radiation therapy for EMPD., Patients and Methods: Forty-one patients with EMPD in the genitalia underwent radiation therapy with curative intent. Fifteen patients had regional lymph node metastases before radiation therapy, but none had distant metastasis. Total doses of 45-80.2 Gy (median, 60 Gy) were delivered to tumor sites in 23-43 fractions (median, 33 fractions)., Results: At a median follow-up period of 41 months, 16 patients had developed recurrences, including 5 with local progression within the radiation field and 12 with lymph node or/and distant metastases outside the radiation field. The local progression-free and disease-free rates were 88% and 55% at 3 years, and 82% and 46% at 5 years, respectively. Nine patients died at 6-73 months after irradiation; the causes of death were tumor progression in five patients, infectious pneumonia in two, renal failure in one and old age in one. The overall and cause-specific survival rates were 93% and 96% at 3 years, and 68% and 84% at 5 years, respectively. Tumor invasion into the dermis and regional lymph node metastasis were significant prognostic factors for both distant metastasis and survival. No therapy-related toxicities of grade ≥3 were observed., Conclusions: Radiation therapy is safe and effective for patients with EMPD. It appeared to contribute to prolonged survival owing to good tumor control, and to be a promising curative treatment option.

Prevalence of advanced genitourinary cancer is high considering approximately 70,000 patients die annually of prostate, bladder and kidney cancer in the United States. Treatment is non-curative but along with the aim of relieving symptoms and improving quality of life, patients and doctors are driven by the goal of prolonging life. In modern urological practice, with the ever increasing number of novel therapies, clinical benefit to patients has to be measured by evaluating the trial endpoints of response and survival against adverse events. This is especially true as the population with advanced cancer is increasingly older and co-morbid. Currently, we are in a time of exponential drug development, innumerable registered trials and a vast amount of expenditure on pharmacological cancer treatment. In this era of financial uncertainty, it is even more important for clinicians to objectively assess the benefit of these expensive, moderately effective treatments that still have associated adverse sequelae. We aim to highlight the pivotal data available and put into context the survival benefit we can currently achieve with the pharmacological treatment of advanced genitourinary cancer, allowing us to critically judge whether a potentially toxic systemic treatment is worthwhile or whether it is better to defer to best supportive care. The figures presented are from the key publications that form the basis of international guideline recommendations and are the standard that newly developed treatments must emulate.

The most common childhood genitourinary cancers are Wilms tumour, rhabdomyosarcoma and germ cell tumour (GCT). Long-term survival rates for patients with these tumours are generally excellent, ranging from 80% to 100%. However, the high cure rates have highlighted the need to minimize the long-term complications of treatments (referred to as 'late effects'), which can be caused by the three treatment modalities used to treat genitourinary tumours: surgery, chemotherapy and radiation therapy. Serious late effects, such as death, second cancers and tumour recurrence, are uncommon but do occur occasionally. Chronic health conditions--such as cardiac, pulmonary and fertility disorders--are more prevalent. Given the high prevalence of late effects, survivors of childhood genitourinary malignancies require regular surveillance and health promotion delivered by health-care providers with specialist knowledge of the long-term complications of treatment.

Objective: The objective was to retrospectively review a large series of pediatric patients with genitourinary rhabdomyosarcoma from a developing country., Methods: A total of 49 children were treated over a 47-year period (1961-2008). Analysis of the clinical presentation, demographics, surgical records, histological results, and oncological management was performed. The patients were analyzed as a whole and also in 2 separate groups (pre- and post-1992)., Results: The median age at clinical presentation was 3½ years. The majority (59%) of patients were Intergroup Rhabdomyosarcoma Study group 3, with locally advanced disease at presentation. Twenty (41%) of the 49 patients presented with primary tumors greater than 10 cm in diameter. Sixteen (33%) of the 49 patients had positive regional lymph nodes at presentation. The overall survival of the series was 30 (65%) of 46. The survival for those treated after 1992 in Intergroup Rhabdomyosarcoma Study group 3 was superior (P = .04) to those treated before 1992 (80% vs 56%)., Conclusion: Children in this large African series of genitourinary rhabdomyosarcoma present with greater locally advanced disease (node positive and bulky disease) when compared with the developed world. Improvements in the last 2 decades in local surgical and oncological care have led to an improvement in survival in children with locally advanced disease., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Although hepatic metastasectomy is well established for colorectal and neuroendocrine cancer, the approach to hepatic metastases from other sites is not well defined. We sought to examine the management of noncolorectal non-neuroendocrine liver metastases., Study Design: A retrospective review from 4 major liver centers identified patients who underwent liver resection for noncolorectal non-neuroendocrine metastases between 1990 and 2009. The Kaplan-Meier method was used to analyze survival, and Cox regression models were used to examine prognostic variables., Results: There were 420 patients available for analysis. Breast cancer (n = 115; 27%) was the most common primary malignancy, followed by sarcoma (n = 98; 23%), and genitourinary cancers (n = 92; 22%). Crude postoperative morbidity and mortality rates were 20% and 2%, respectively. Overall median survival was 49 months, and 1, 3, and 5-year Kaplan-Meier survival rates were 73%, 50%, and 31%. Survival was not significantly different between the various primary tumor types. Recurrent disease was found after hepatectomy in 66% of patients. In multivariable models, lymphovascular invasion (p = 0.05) and metastases ≥5 cm (p = 0.04) were independent predictors of poorer survival. Median survival was shorter for resections performed between 1990 and 1999 (n = 101, 32 months) when compared with resections between 2000 and 2009 (n = 319, 66 months; p = 0.003)., Conclusions: Hepatic metastasectomy for noncolorectal non-neuroendocrine cancers is safe and feasible in selected patients. Lymphovascular invasion and metastases ≥5 cm were found to be associated with poorer survival. Patients undergoing metastasectomy in more recent years appear to be surviving longer, however, the reasons for this are not conclusively determined., (Copyright © 2012 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)