Genitourinary malignancies in kidney transplant recipients.

Advances in immunosuppressive therapy and postoperative management have greatly improved the graft and patient survival rates after kidney transplantation; however, the incidence of post-transplant malignant tumors is increasing. Post-renal transplantation malignant tumors are associated with renal failure, immunosuppression, and viral infections. Moreover, the risk of developing cancer is higher in kidney transplant recipients than in the general population, and the tendency to develop cancer is affected by the background and environment of each patient. Recently, cancer after kidney transplantation has become the leading cause of death in Japan. Owing to the aggressive nature and poor prognosis of genitourinary malignancies, it is crucial to understand their epidemiology, risk factors, and best practices in kidney transplant recipients. This review has a special emphasis on the epidemiology, risk factors, and treatment protocols of genitourinary malignancies in kidney transplant recipients to enhance our understanding of the appropriate management strategies. Optimal immunosuppressive therapy and cancer management for these patients remain controversial, but adherence to the general guidelines is recommended.

18F-Sodium fluoride PET/CT predicts overall survival in patients with advanced genitourinary malignancies treated with cabozantinib and nivolumab with or without ipilimumab.

PURPOSE: We evaluated the prognostic value of 18F-sodium fluoride (NaF) PET/CT in patients with urological malignancies treated with cabozantinib and nivolumab with or without ipilimumab. METHODS: We prospectively recruited patients with advanced urological malignancies into a phase I trial of cabozantinib plus nivolumab with or without ipilimumab. NaF PET/CT scans were performed pre- and 8 weeks post-treatment. We measured the total volume of fluoride avid bone (FTV) using a standardized uptake value (SUV) threshold of 10. We used Kaplan-Meier analysis to predict the overall survival (OS) of patients in terms of SUVmax, FTV, total lesion fluoride (TLF) uptake at baseline and 8 weeks post-treatment, and percent change in FTV and TLF. RESULT: Of 111 patients who underwent NaF PET/CT, 30 had bone metastases at baseline. Four of the 30 patients survived for the duration of the study period. OS ranged from 0.23 to 34 months (m) (median 6.0 m). The baseline FTV of all 30 patients ranged from 9.6 to 1570 ml (median 439 ml). The FTV 8 weeks post-treatment was 56-6296 ml (median 448 ml) from 19 available patients. Patients with higher TLF at baseline had shorter OS than patients with lower TLF (3.4 vs 14 m; p = 0.022). Patients with higher SUVmax at follow-up had shorter OS than patients with lower SUVmax (5.6 vs 24 m; p = 0.010). However, FTV and TLF 8 weeks post-treatment did not show a significant difference between groups (5.6 vs 17 m; p = 0.49), and the percent changes in FTV (12 vs 14 m; p = 0.49) and TLF (5.6 vs 17 m; p = 0.54) also were not significant. CONCLUSION: Higher TLF at baseline and higher SUVmax at follow-up NaF PET/CT corresponded with shorter survival in patients with bone metastases from urological malignancies who underwent treatment. NaF PET/CT may be a useful predictor of OS in this population.

Disparities in Bladder Cancer Outcomes Based on Key Sociodemographic Characteristics.

PURPOSE OF REVIEW: A review of the impact of several key patient characteristics on oncologic outcomes in bladder cancer (BC) summarized and analyzed in a narrative fashion. RECENT FINDINGS: The bulk of the published literature suggests that females and blacks have poorer cancer-specific outcomes. Both groups tend to present with worse disease, which may be driven by differences in access to timely and quality care. Attempts to assess the association between smoking status and history and BC outcomes have been hindered by the quality and heterogeneity of the data, although several studies have linked smoking with higher rates of recurrence and poorer survival. Being married, particularly in men, may improve survival after radical cystectomy (RC). Limited data suggests that socioeconomic and education levels may be associated with poorer survival; however, the data is limited. A growing body of investigation suggests that there are significant differences in oncologic outcomes in BC patients based on race, gender, smoking status, socioeconomic status, and others. Further focus and investigation is needed to validate these findings, investigate the root cause of these differences, and offer solutions to mitigate them.

Comparison of Industry-Sponsored Trials (IST) and Investigator-Initiated Trials (IIT) in Advanced Genitourinary Cancers in the United States, Canada, United Kingdom and France.

BACKGROUND: Clinical trials are categorized as industry sponsored trials (ISTs) or investigator-initiated trials (IITs) based on the source of funding and sponsor of the trial. ISTs are usually run by pharmaceutical companies, and are primarily aimed at developing new drugs that ultimately gain regulatory approval. IITs are developed by academic investigators or cooperative groups, often sparked by a clinical need. Both are vital in advancing the field of oncology. To date, little has been published about current trends in ISTs or IITs in genitourinary (GU) oncology. The aim of this study was to assess growth trends of GU oncology ISTs and IITs in 4 countries with similar healthcare infrastructures. METHODS: We searched ClinicalTrials.gov for bladder, kidney, and prostate cancer trials conducted in the United States (US), Canada, France, and United Kingdom (UK) from January 2007 to December 2021. Trials were determined to be ISTs or IITs based on their funding source and sponsor. Trials were characterized based on type, purpose, phase, participants, masking, assignment, and allocation. RESULTS: Overall, 5,834 GU trials were identified, with a balanced distribution of ISTs (n = 3064, n = 52.5%) and IITs (n = 2770, 47.4%). By country, the US conducted the most GU trials (n = 3814) followed by Canada (n = 709), France (n = 677), and the UK (n = 634). Most ISTs were phase 3 trials with over 500 participants while most IITs were open-label phase 2 studies with only 20-49 participants. From 2017 onwards, there was a shift towards more ISTs, most noticeably in Canada and the UK. The COVID-19 pandemic did not have a major impact on the growth of ISTs and IITs. CONCLUSION: The gap between ISTs and IITs continues to widen, likely driven by resource and funding challenges faced by investigators. Barriers to completing IITs need to be better understood to promote IIT development and maintain their academically driven intentions.

Access to Care and Healthcare Quality Metrics for Patients with Advanced Genitourinary Cancers in Urban versus Rural Areas.

Compared to the urban population, patients in rural areas face healthcare disparities and experience inferior healthcare-related outcomes. To compare the healthcare quality metrics and outcomes between patients with advanced genitourinary cancers from rural versus urban areas treated at a tertiary cancer hospital, in this retrospective study, eligible patients with advanced genitourinary cancers were treated at Huntsman Cancer Institute, an NCI-Designated Comprehensive Cancer Center in Utah. Rural-urban commuting area codes were used to classify the patients' residences as being in urban (1-3) or rural (4-10) areas. The straight line distances of the patients' residences from the cancer center were also calculated and included in the analysis. The median household income data were obtained and calculated from "The Michigan Population Studies Center", based on individual zip codes. In this study, 2312 patients were screened, and 1025 eligible patients were included for further analysis (metastatic prostate cancer (n = 679), metastatic bladder cancer (n = 184), and metastatic renal cell carcinoma (n = 162). Most patients (83.9%) came from urban areas, while the remainder were from rural areas. Both groups had comparable demographic profiles and tumor characteristics at baseline. The annual median household income of urban patients was $8604 higher than that of rural patients (p < 0.001). There were fewer urban patients with Medicare (44.9% vs. 50.9%) and more urban patients with private insurance (40.4% vs. 35.1%). There was no difference between the urban and rural patients regarding receiving systemic therapies, enrollment in clinical trials, or tumor genomic profiling. The overall survival rate was not significantly different between the two populations in metastatic prostate, bladder, and kidney cancer, respectively. As available in a tertiary cancer hospital, access to care can mitigate the difference in the quality of healthcare and clinical outcomes in urban versus rural patients.

Characterization of outcomes in patients with advanced genitourinary malignancies treated with immune checkpoint inhibitors.

PURPOSE: Several immune checkpoint inhibitors (ICIs) are FDA approved for treatment of genitourinary (GU) malignancies. We aim to determine demographic and clinicopathologic characteristics that significantly affect clinical outcomes in patients with advanced stage GU malignancies treated with ICIs. MATERIALS AND METHODS: We performed a single-center, consecutive, retrospective cohort analysis on patients with metastatic or unresectable GU malignancies who were treated with ICIs at the University of Michigan. Immune-related adverse events (irAEs), putative immune-mediated allergies, and overall response rates (ORR) were assessed. Comorbidity index scores were calculated. Survival analysis was performed to evaluate progression-free survival (PFS) and overall survival (OS), stratifying and controlling for a variety of clinicopathologic baseline factors including site of metastases. RESULTS: A total of 160 patients were identified with advanced renal cell carcinoma (RCC) or urothelial carcinoma. Median PFS and OS were 5.0 and 23.6 months for RCC, and 2.8 and 9.6 months for urothelial carcinoma, respectively. Patients who experienced increased frequency and higher grade irAEs had better ICI treatment response (P < 0.0001). Presence of liver metastases was associated with poor response to ICI therapy (P = 0.001). Multivariable modeling demonstrates that patients with urothelial carcinoma and liver metastases had statistically worse PFS and OS compared to patients with RCC or other sites of metastases, respectively. CONCLUSION: Greater frequency and higher grades of irAEs are associated with better treatment response in patients with RCC and urothelial malignancy receiving ICI therapy. The presence of liver metastases denotes a negative predictive marker for immunotherapy efficacy. SUMMARY: Immune checkpoint inhibitors (ICI) are increasingly used to treat genitourinary (GU) malignancies. However, clinical data regarding patients with advanced-stage GU malignancies treated with ICI is lacking. Thus, we performed a single-center, retrospective cohort study on patients with metastatic and unresectable renal cell carcinoma (RCC) and urothelial carcinoma who were treated with ICIs at the University of Michigan to provide demographic and clinicopathologic data regarding this population. We specifically focused on immune-related adverse events (irAEs), immune-mediated allergies, and the associated overall response rates (ORR). To better assess performance status, we calculated comorbidity scores for all patients. Finally, survival analyses for progression-free survival (PFS) and overall survival (OS) were performed using Kaplan-Meier analysis and Cox proportional hazards modeling, stratifying and controlling for clinicopathologic baseline factors, including sites of metastases, in our multivariable analysis. A total of 160 patients were identified with advanced RCC or urothelial carcinoma. We found decreased PFS (2.8 vs. 5.0 months) and decreased OS (9.8 vs. 23.6 months) for urothelial carcinoma compared to RCC patients. We noted that patients who experienced increased frequency and higher grades of irAEs had better treatment ORR with ICI therapy (P ≤ 0.0001). The presence of liver metastases was associated with worse ORR (P = 0.001), PFS (P = 0.0014), and OS (P = 0.0028) compared to other sites of metastases including lymph node, lung, and CNS/bone. The poor PFS and OS associated with urothelial carcinoma and liver metastases were preserved in our multivariable modeling after controlling for pertinent clinical factors. We conclude that greater frequency and higher grades of irAEs are associated with better treatment response in GU malignancy patients receiving ICI, a finding that is consistent with published studies in other cancers. The presence of liver metastases represents a significantly poor predictive marker in GU malignancy treated with ICI. Our findings contribute to the growing body of literature that seeks to understand the clinicopathologic variables and outcomes associated with ICI therapy.

The human microbiome and genitourinary malignancies.

The human microbiome contains a vast network of understudied organisms that have an intimate role in our health and wellness. These microbiomes differ greatly between individuals, creating what may be thought of as a unique and dynamic microbial signature. Microbes have been shown to have various roles in metabolism, local and systemic inflammation, as well as immunity. Recent findings have confirmed the importance of both the gut and urinary microbiomes in genitourinary malignancies. Numerous studies have identified differences in microbial signatures between healthy patients and those with urologic malignancies. The microbiomes have been shown to contain microbes that may contribute to the etiology of disease state as well as yield information in regard to a person's health and their responsiveness to certain drugs such as immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs). Less well understood are the effects of antibiotics on oncologic outcomes in such treatment courses. This review will explore our current understanding and advancements in the field of microbiome research and discuss its intimate association with genitourinary diseases including bladder cancer, prostate cancer, and kidney cancer. With a better understanding of the association between the microbiome and genitourinary malignancy, further investigation may produce reliable predictors of disease, prognostic indicators as well as therapeutic targets.

Management of bone complications in patients with genitourinary malignancies.

Skeletal metastases are common in genitourinary malignancies-including prostate cancer, renal cell carcinoma, and urothelial cancer-and portend significant morbidity and poor prognosis. The presence of skeletal metastases can result in decreased quality of life and increased morbidity. Strategies can be employed to prevent bone-related complications including lifestyle modifications and dietary supplementation. Additionally, pharmacologic agents exist to prevent bone loss and may be appropriate for patients at high risk of fragility-related or skeletal complications, such as pathologic fracture related to bone metastases. Finally, advancement in effective systemic treatments, particularly novel hormone-targeted agents and immunotherapies, may limit the morbidity of advanced disease and delay the onset of skeletal-related complications.

Myofibroblastoma of the male breast: a rare entity with radiologic-pathologic correlation.

A 73-year old man with a history of multiple genitourinary malignancies was found to have a left retroareolar soft tissue mass on CT assessment of disease, and dedicated breast imaging was recommended. Diagnostic mammography and ultrasonography confirmed a solid mass, for which biopsy was recommended. Pathologic analysis demonstrated a spindle cell neoplasm with an immunoreactivity pattern consistent with myofibroblastoma. While this entity is benign, nonspecific imaging features necessitate tissue sampling for pathologic diagnosis, and, given pathologic rarity, open communication between the radiologist and pathologist is important to establish the correct diagnosis and to recommend appropriate management.

Survival Outcomes of Radical Prostatectomy Versus Radiotherapy in Intermediate-Risk Prostate Cancer: A NCDB Study.

BACKGROUND: Studies of various prostate cancer patient cohorts found men receiving external-beam radiotherapy (EBRT) had higher mortality than men undergoing radical prostatectomy (RP). Conversely, a recent clinical trial showed no survival differences between treatment groups. We used the National Cancer Data Base (NCDB) to evaluate overall survival in intermediate-risk (T2b-T2c or Gleason 7 [grade group II or III] or prostate-specific antigen 10-20 ng/mL) prostate cancer patients undergoing EBRT with or without androgen deprivation therapy (ADT), RP, or no initial treatment. PATIENTS AND METHODS: We analyzed 268,378 men with intermediate-risk prostate cancer from 2004 to 2012. Kaplan-Meier estimates and multivariable Cox proportional hazards models were used to compare survival between treatments. RESULTS: After adjusting for patient and facility covariables, men receiving no initial treatment averaged greater adjusted mortality risk than men receiving EBRT (hazard ratio [HR], 1.71; 95% confidence interval [CI] 1.62-1.80; P < .001), EBRT + ADT (HR, 1.73; 95% CI 1.64-1.81; P < .001), or RP (HR, 4.18; 95% CI 3.94-4.43; P < .001). Men undergoing RP had significantly lower adjusted mortality risk than men receiving either EBRT (HR, 0.41; 95% CI 0.39-0.43; P < .001) or EBRT + ADT (HR, 0.41; 95% CI 0.39-0.43; P < .001). No difference was observed between men receiving EBRT or EBRT + ADT (HR, 1.01; 95% CI 0.97-1.05; P = .624). CONCLUSION: Men treated with RP experienced significantly lower overall mortality risk than EBRT with or without ADT and no treatment patients, regardless of patient, demographic, or facility characteristics. The results are limited by the lack of cancer-specific mortality in this database.

Sacituzumab govitecan: an antibody-drug conjugate.

INTRODUCTION: Despite advances in the diagnosis and treatment of patients with cancer, patients with metastatic cancer have limited therapeutic options after initial lines of therapy. Understanding tumor biology has translated into the identification of actionable targets that resulted in therapeutics. Antibody-drug conjugates (ADC) are capitalizing on this explosion of scientific information. ADCs allow an antibody to a unique target to be conjugated via an innovative linker, to a highly toxic drug which is delivered to its target. Sacituzumab govitecan is an ADC that combines the active molecule in irinotecan, SN-38, to an antibody targeting trop2. Areas covered: In this review, the authors introduce the reader to the ADC sacituzumab govitecan providing the reader with details about its pharmacokinetics, pharmacodynamics, efficacy and safety. The authors also give their expert analysis about its potential future use. Expert opinion: Sacituzumab govitecan is a novel and well-tolerated therapeutic showing promising results in difficult to treat cancers. Further studies are underway to optimize the group of patients that would benefit from it. Given its excellent performance, we are cautiously optimistic it will be approved by the FDA.

Immunotherapy in genitourinary malignancies.

Treatment of cancer patients involves a multidisciplinary approach including surgery, radiotherapy, and chemotherapy. Traditionally, patients with metastatic disease are treated with combination chemotherapies or targeted agents. These cytotoxic agents have good response rates and achieve palliation; however, complete responses are rarely seen. The field of cancer immunology has made rapid advances in the past 20 years. Recently, a number of agents and vaccines, which modulate the immune system to allow it to detect and target cancer cells, are being developed. The benefit of these agents is twofold, it enhances the ability the body's own immune system to fight cancer, thus has a lower incidence of side effects compared to conventional cytotoxic chemotherapy. Secondly, a small but substantial number of patients with metastatic disease are cured by immunotherapy or achieve durable responses lasting for a number of years. In this article, we review the FDA-approved immunotherapy agents in the field of genitourinary malignancies. We also summarize new immunotherapy agents being evaluated in clinical studies either as single agents or as a combination.

Smoking-related genitourinary cancers: A global call to action in smoking cessation.

Smoking is a known modifiable risk factor in the development of genitourinary malignancies. Although the association has long been supported by numerous research studies, the impact of smoking cessation on the decreased risk of genitourinary malignancies is less well studied. PubMed databases were searched using the terms smoking, smoking cessation, bladder cancer, kidney cancer, prostate cancer, penile cancer, testicular cancer, their synonyms, and also targeted manual searches to perform a literature review in order to summarize the benefits of cessation on disease progression and patient outcomes including survival and morbidities. Our review yielded substantial evidence highlighting the improved outcomes observed in those diagnosed with bladder, renal, and prostate cancers. The risk of bladder cancer is reduced by up to 60% in those who were able to quit for 25 years and the risk of kidney malignancy was reduced by 50% in those who abstained from smoking for 30 years. A similar trend of reduced risk was observed for prostate cancer with those who quit for more than 10 years, having prostate cancer mortality risks similar to those that never smoked. Although the data were encouraging for bladder, renal, and prostate malignancies, there are comparatively limited data quantifying the benefits of smoking cessation for penile and testicular cancers, highlighting an opportunity for further study. The role of urologists and their impact on their patients' likelihood to quit smoking shows more than half of urologists never discuss smoking cessation upon diagnosis of a malignancy. Most urologists said they did not provide cessation counseling because they do not believe it would alter their patients' disease progression. Studies show urologists have more influence at changing their patients' smoking behaviors than their primary care physicians. The diagnosis of cancer may lead to a teachable moment resulting in increased smoking quit rates. Furthermore, implementing a brief 5-minute clinic counseling session increases quit attempts and quit rates. Diagnosis of genitourinary cancers and the following appointments for treatment provide a unique opportunity for urologists to intervene and affect the progression and outcome of disease.