Patients with advanced or malignant renal cell carcinoma at the time of diagnosis have historically had a poor prognosis. Immunonologic agents have significantly altered the therapeutic landscape and clinical outcomes of these patients. In this review, we highlight recent and upcoming clinical trials investigating the role of immunotherapies in clear cell RCC. In particular, we emphasize immunotherapy-based combinations, including immune checkpoint inhibitor (ICI) combinations, neoadjuvant, and adjuvant ICI, and ICI agents combined with anti-VEGF therapy.
Introduction: Anticholinergics are associated with cognitive side effects and dementia. Agents such as trospium, fesoterodine and darifenacin have been shown to be less likely to cross the blood-brain barrier. Furthermore, in 2012, mirabegron was approved by the U.S. Food and Drug Administration as the first beta-3 adrenoreceptor agonist to treat overactive bladder (OAB). This study aims to examine prescribing patterns of OAB medications in the United States over time. Methods:The 2013e2017 Medicare Part D Public Use File was used to identify prescribers of OAB medications including oxybutynin, tolterodine, trospium, darifenacin, solifenacin, fesoterodine and mirabegron. The number of claims and total annual expenditure for each medication for all prescribers, nonurologists and urologists were analyzed from 2013 to 2017.Results: Oxybutynin was consistently the most prescribed OAB medication each year, comprising 53.9% of all OAB medication prescriptions in 2017. From 2013 to 2017, mirabegron claims increased from 140,401 to 1,617,439, making it the second most prescribed OAB medication. Solifenacin usage decreased each year. Trospium, darifenacin and fesoterodine were the least prescribed agents each year. These trends were similar for those !65 years old. Total annual expenditure for mirabegron increased yearly, and it had the highest total expenditure of OAB medications, with $658.6 million in 2017.Conclusions: Oxybutynin was consistently the most prescribed OAB medication every year. Mirabegron utilization steadily increased each year. Anticholinergic medications associated with fewer cognitive adverse effects, such as trospium, darifenacin and fesoterodine, were among the least prescribed.
Treatment of metastatic renal cell carcinoma (mRCC) has evolved with the development of a variety of systemic agents; however, these therapies alone rarely lead to a complete response. Complete consolidative surgery with surgical metastasectomy has been associated with improved survival outcomes in well-selected patients in previous reports. No randomized control trial exists to determine the effectiveness of metastasectomy. Therefore, reviewing observational studies is important to best determine which patients are most appropriate for metastasectomy for mRCC and if such treatment continues to be effective with the development of new systemic therapies such as immunotherapy. In this narrative review, we discuss the indications for metastasectomies, outcomes, factors associated with improved survival, and special considerations such as location of metastasis, number of metastases, synchronous metastases, and use of systemic therapy. Additionally, alternative treatment options and trials involving metastasectomy will be reviewed.
The role of CN in the treatment of metastatic renal cell carcinoma (mRCC) has been studied over the course of the past few decades. With the advent of immuno-oncologic (IO) agents, there has been a paradigm shift in the treatment of RCC. Within this new era of cancer care, the role of CN is unclear. There are several studies currently underway that aim to assess the role of CN in combination with these therapies. We reviewed articles examining CN, both historically and in the modern immunotherapy era. While immune-oncologic agents are relatively new and large clinical trials have yet to be completed, data thus far is promising that CN may provide clinical benefit. Multiple ongoing trials may clarify the role of CN in this new era of cancer care.
Upper tract urothelial carcinoma (UTUC) has traditionally been managed with radical nephroureterectomy, and while this approach remains the gold standard for high-risk disease, endoscopic, kidney-sparing management has increasingly been adopted for low-risk disease as it preserves kidney function without compromising oncologic outcomes. Ureteroscopy and percutaneous renal access not only provide diagnoses by tumor visualization and biopsy, but also enable treatment with electrocautery or laser ablation. Several modalities exist for laser ablative treatments including thulium:YAG, neodymium:YAG, holmium:YAG, and combinations of the preceding. Furthermore, due to high recurrence rates after endoscopic management, adjuvant intracavitary instillation of various agents such as mitomycin C and bacillus Calmette-Guerin have been used given benefits seen in non-muscle invasive urothelial bladder cancer. Other formulations also being studied include gemcitabine, anthracyclines, and immunotherapies. More recently, Jelmyto, a mitomycin reverse thermal gel, has been developed to allow for adequate drug delivery time and potency since urine flow could otherwise dilute and washout topical therapy. In this article, the authors review techniques, indications, best practices, and areas of current investigation in endoscopic management and adjuvant topical therapy for UTUC.
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