Deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma: A systematic review and patient-level meta-analysis
There has been much controversy regarding the order in which cytoreductive nephrectomy (CN) and systemic therapy (ST) are applied for patients with metastatic renal cell carcinoma (mRCC). We aimed to investigate the role of deferred CN (dCN) in mRCC, particularly in the current era of immunotherapy. A systematic literature search was conducted on PubMed, Embase, and Scopus for studies comparing dCN versus any non-dCN strategy, in any temporal sequence, with the provision of Kaplan-Meier curves for overall survival (OS). A graphical reconstructive algorithm was used to obtain OS of individual patients, which was then pooled under random-effects individual patient data (IPD) meta-analysis using Cox-models to determine hazard ratios (HRs) and 95% CI. Altogether, 12 studies (5,350 patients) were analyzed. dCN (ST followed by CN) was associated with significantly improved OS over nondeferred CN (CN followed by ST, ST alone, or CN alone) (HR = 0.60, 95% CI, 0.53-0.67, P < 0.001). Subgroup comparisons restricted to studies comparing dCN versus upfront CN (uCN, CN then ST) were also in favor of dCN (HR = 0.69, 95% CI, 0.61-0.78, P < 0.001), even among those in which immunotherapy as ST was used in all patients (HR = 0.57, 95% CI, 0.39-0.84, P = 0.005). In mRCC patients suitable for CN, dCN is associated with significantly improved OS over nondeferred CN strategies, including uCN. Although limited by inclusion of nonrandomized studies and immortal time bias, this meta-analysis strengthens existing guidelines to offer dCN to surgically fit patients who do not progress on ST in the current age of immunotherapy.
Immediate second resection versus restage transurethral resection of bladder tumor: A prospective randomized clinical trial (IMMERSE trial)
The role of repeat transurethral resection of bladder tumor (TURBT) for the management of nonmuscle invasive bladder carcinoma is debated, especially when initial resections include detrusor muscle. This study compares immediate second resection (additional deep biopsies in the same session) with standard restage TURBT performed 2-6 weeks post-initial TURBT to determine adequacy in detrusor muscle sampling and compare the disease rate at restage TURBT in both groups.
A nomogram for predicting survival in patients with primary testicular lymphoma: A population-based study
Primary testicular lymphoma (PTL) is a rare malignancy whose epidemiology and prognosis have not been studied.
Investigating the association of VHL gene variants with disease risk and clinicopathological outcomes in ccRCC patients from West Bengal, India
Clear cell renal cell carcinoma (ccRCC) is a prevalent and aggressive malignancy, with the von Hippel-Lindau (VHL) gene playing a critical role in its pathogenesis. However, the association between VHL gene variants and sporadic ccRCC risk remains unexplored in the Indian population. This study aimed to investigate the somatic and germline variants of the VHL gene in sporadic ccRCC patients from West Bengal, India, and their association with disease risk and clinicopathological parameters.
Diet and the microbiome as mediators of prostate cancer risk, progression, and therapy response
Complex relationships between the human microbiome and cancer are increasingly recognized for cancer sites that harbor commensal microbial communities such as the gut, genitourinary tract, and skin. For organ sites that likely do not contain commensal microbiota, there is still a substantial capacity for the human-associated microbiota to influence disease etiology across the cancer spectrum. We propose such a relationship for prostate cancer, the most commonly diagnosed cancer in males in the United States. This review explores the current evidence for a role for the urinary and gut microbiota in prostate cancer risk, via both direct interactions (prostate infections) and long-distance interactions such as via the metabolism of procarcinogenic or anticarcinogenic dietary metabolites. We further explore a newly recognized role of the gut microbiota in mediating cancer treatment response or resistance either via production of androgens and/or procarcinogenic metabolites or via direct metabolism of anticancer drugs that are used to treat advanced disease. Overall, we present the current state of knowledge relating to how the human microbiome mediates prostate cancer risk, progression, and therapy response, as well as suggest future research directions for the field.
Recurrence after surgery for clear cell and papillary renal cell carcinoma: Head-to head comparison of validated risk scores
The American Urology Association (AUA) recently introduced in their guidelines a subtype-agnostic, 4-tiered risk classification score to assess oncologic outcomes after surgery in patients with localized renal cell carcinoma (RCC). We provide a head-to-head comparison of the AUA score with 3, internationally validated and EAU recommended, histological-specific models.
The pan-immune-inflammation value: A novel independent predictive factor for overall survival in ≥pT2a nonmetastatic renal cell carcinoma
Aimed to evaluate the prognostic value of Pan-Immune-Inflammation Value (PIV) for overall survival (OS) in the localized RCC. We also tested the feasibility of incorporating the PIV into UCLA Integrated Staging System (UISS).
Harnessing nature's therapeutic potential: A review of natural products in prostate cancer management
Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer-related death among men in the United States. The global burden of this disease is rising, placing significant strain on healthcare systems worldwide. Although definitive therapies like surgery and radiation are often effective, prostate cancer can recur and progress to castration-resistant prostate cancer in some cases. Conventional treatments for prostate cancer often have substantial side effects that can greatly impact patients' quality of life. Therefore, many patients turn to complementary therapies to improve outcomes, manage side effects, and enhance overall well-being. Natural products show promise as complementary treatments for prostate cancer, offering anticancer properties with a low risk of adverse effects. While preclinical research has produced encouraging results, their role in prostate cancer treatment remains controversial, largely due to inconsistent and limited success in clinical trials. This review explores the mechanisms of action of key natural products in prostate cancer management and summarizes clinical trials evaluating their efficacy and safety. It underscores the need for high-quality, rigorously designed, and adequately powered studies to validate the therapeutic potential and safety of these supplements in cancer care. Additionally, we propose future directions to enhance their role in addressing the complex challenges associated with prostate cancer.
Durability of response of UGN-101: Longitudinal follow up of multicenter study
UGN-101, a reverse thermal mitomycin gel for upper tract instillation, recently became the first FDA approved treatment for upper tract urothelial carcinoma (UTUC). However, the durability of UGN-101 treatment has not been well described. Here we present long term outcomes from our multi-institutional cohort for patients who initially responded to treatment.
Cancer-specific mortality after radical prostatectomy versus radiotherapy in incidental prostate cancer
To test for cancer specific mortality (CSM) differences after either radical prostatectomy (RP) or radiotherapy (RT) in incidental prostate cancer (IPCa) patients.
Concordance between intraoperative macroscopic evaluation and permanent section analysis of tumor bed margin in partial nephrectomy: A prospective study
To evaluate the concordance between the intraoperative visual assessment of the tumor bed for completeness of resection following partial nephrectomy and the permanent section analysis of biopsies taken from the tumor bed.
Metformin intake and risk of metabolic acidosis after radical cystectomy with urinary diversion: A comparative study using data from the TriNetX research network
To investigate the association of diabetes mellitus and metformin use with metabolic acidosis risk after radical cystectomy (RC) and urinary diversion for bladder cancer.
Association between frailty and specific comorbidities on oncological outcomes in metastatic hormone-sensitive and castration resistant prostate cancer
Demographic changes will lead to higher proportions of metastatic hormone-sensitive (mHSPC) and castration resistant metastatic prostate cancer (mCRPC) patients with higher frailty index and multiple comorbidities.
Study of urine-based mRNA biomarkers for early detection of nonmuscle invasive bladder cancer (NMIBC)
Research into new noninvasive diagnostic tools for bladder cancer (BCa) with superior sensitivity and specificity to cystoscopy and cytology is promising. The current study evaluated a diagnostic panel of tumor progression-related mRNAs in urine samples of NMIBC patients and controls.
Clinical translation of the interconnected role of the microbiome and diet in genitourinary malignancies
A complex and often under-appreciated relationship exists between the human microbiome, diet, and the development or progression of cancer. There is likewise an emerging appreciation for the role that the human-associated microbiota play in mediating cancer treatment response. This seminar series covers our current understanding of the interplay between the microbiome and cancer in genitourinary malignancies inclusive of bladder, kidney, and prostate cancers.
Can parenchymal volume analysis replace nuclear renal scans for split renal function before and after partial nephrectomy with warm ischemia?
The assessment of split renal function (SRF) before and after partial nephrectomy (PN) is crucial. While nuclear renal scan (NRS) is a traditional method for evaluating SRF, its extensive use is hindered by concerns regarding radioactivity. Parenchymal volume analysis (PVA) has been employed to assess SRF for kidney donors. Nonetheless, the efficacy of PVA in evaluating SRF in kidneys with renal masses before and after PN with warm ischemia remains uncertain.
Risk of cardiovascular disease following degarelix versus gonadotropin-releasing hormone agonists in patients with prostate cancer: a systematic review and meta-analysis
Prostate cancer treatment involves hormonal therapies that may carry cardiovascular risks, particularly for long-term use. Gonadotropin-releasing hormone (GnRH) antagonists, such as degarelix, may offer advantages over agonists, but comprehensive comparative cardiovascular outcomes are not well established. This study aimed to systematically review and analyze the cardiovascular safety profiles of degarelix compared to those of traditional GnRH agonists, providing critical insights for optimizing treatment strategies.
Concomitant antihistamine administration is associated with improved survival outcomes in patients with locally advanced or metastatic urothelial carcinoma treated with atezolizumab. Analysis of individual participant data from IMvigor210 and IMvigor211
Survival outcomes of patients with metastatic urothelial carcinoma (mUC) are still suboptimal and strategies to enhance response to immune-oncology (IO) compounds are under scrutiny. In preclinical studies, it has been demonstrated that antihistamines may reverse macrophage immunosuppression, reactivate T cell cytotoxicity, and enhance the immunotherapy response. We aimed to evaluate the role of concomitant antihistamines administration on oncological outcomes among patients with mUC.
Development of TAR-200: A novel targeted releasing system designed to provide sustained delivery of gemcitabine for patients with bladder cancer
Treatment options for recurrent high-risk non-muscle-invasive bladder cancer (HR NMIBC) and muscle-invasive bladder cancer (MIBC) are limited, highlighting a need for clinically effective, accessible, and better-tolerated alternatives. In this review we examine the clinical development program of TAR-200, a novel targeted releasing system designed to provide sustained intravesical delivery of gemcitabine to address the needs of patients with NMIBC and of those with MIBC. We describe the concept and design of TAR-200 and the clinical development of this gemcitabine intravesical system in the SunRISe portfolio of studies. This includes 3 phase I studies evaluating the safety and initial tumor activity of TAR-200 and 5 phase II/III studies assessing the efficacy and safety of TAR-200, with or without systemic cetrelimab, as a treatment option for patients with HR NMIBC (bacillus Calmette-Guérin naive [papillary and carcinoma in situ] and MIBC (neoadjuvant and patients ineligible for or refusing radical cystectomy). Pharmacokinetics demonstrate intravesical gemcitabine delivery via TAR-200 over a prolonged period without detectable plasma levels. Phase I studies showed that TAR-200 is well tolerated, with preliminary antitumor activity in intermediate-risk NMIBC and MIBC. Preliminary data from the phase IIb SunRISe-1 study demonstrate that TAR-200 monotherapy is safe and effective in patients with bacillus Calmette-Guérin-unresponsive high-risk NMIBC. TAR-200 represents an innovative approach to the local treatment of bladder cancer.
Development of point-of-care tests for urinary bladder cancer - an historic review and view to future prospectives
Urine is an attractive biospecimen for noninvasive tests to facilitate bladder tumor diagnostics. Three different point-of-care (POC) tests based on lateral flow immunoassays (LFAs) are currently commercially available: UBC® Rapid Test, BTA stat®, and NMP22 BladderChek. The present review discusses these different tests based on their performance, clinical utility and the nature of the respective analytes. The level of sensitivities of UBC Rapid Test® and BTA stat® for detection of high-grade nonmuscle invasive bladder cancer using urine is in the order of 80%. Estimations of performance are highly dependent on patient selection criteria. UBC® Rapid Test shows a sensitivity of approximately 85% in patients presenting with macrohematuria which is the most common initial clinical symptom. Estimations of specificity are complicated by differences in how control groups are selected in different studies and are therefore more difficult to compare between published reports. Different POC tests differ with regard to the source of the analytes that are measured. The BTA Stat® test is based on detection of plasma proteins (Factor H/Factor H-related proteins), potentially leading to a lack of specificity during conditions of renal dysfunction. A large number of analytes to be used for urine-based bladder cancer tests have been described in the literature, including cytokines and proteases implicated in tumor invasion. These proteins, although biologically relevant, are often present at very low levels in urine that may be unsuitable for development of LFAs. Release of abundant intracellular structural proteins from cells such as cytokeratins (UBC® Rapid Test) and nuclear matrix proteins (NMP22) may therefore be advantageous. We conclude that available data support the use of urine-based POC tests as adjuncts during the clinical work up of suspected bladder cancer.
Concordance of surgical treatment selection with the AUA guidelines for localized renal masses
To examine and evaluate guideline concordance of surgical treatment selection at a community-based health system. The AUA guidelines provide specific guidance regarding appropriate utilization of radical nephrectomy (RN) and partial nephrectomy (PN). However, nearly 40% of patients did not fit a guideline-specified scenario in a prior report.