Urologic Oncology-seminars and Original Investigations最新文献

Prognostic models can be valuable for clinicians in counseling and monitoring patients after the surgical resection of nonmetastatic renal cell carcinoma (nmRCC). Over the years, several risk prediction models have been developed, evolving significantly in their ability to predict recurrence and overall survival following surgery. This review comprehensively evaluates and critically appraises current prognostic models for nm-RCC after nephrectomy. The last 2 decades have witnessed a notable increase in the development of various prognostic risk models for RCC, incorporating clinical, pathological, genomic, and molecular factors, primarily using retrospective data. Only a limited number of these models have been developed using prospective data, and their performance has been less effective than expected when applied to broader, real-life patient populations. Recently, artificial intelligence (AI), especially machine learning and deep learning algorithms, has emerged as a significant tool in creating survival prediction models. However, their widespread application remains constrained due to limited external validation, a lack of cost-effectiveness analysis, and unconfirmed clinical utility. Although numerous models that integrate clinical, pathological, and molecular data have been proposed for nm-RCC risk stratification, none have conclusively demonstrated practical effectiveness. As a result, current guidelines do not endorse a specific model. The ongoing development and validation of AI algorithms in RCC risk prediction are crucial areas for future research.

Introduction: Heavy metals exposure is a known carcinogen in humans. The impact of heavy metals in the pathogenesis of renal cell carcinoma (RCC) is unclear with scant available literature. Though previous studies have evaluated the role of heavy metals in RCC, majority of those studies have evaluated either single or few heavy metals in urine. None of the prior studies have evaluated an extensive panel of heavy metals in blood, urine, and tissue in the same patient along with the serum oxidation status and gene expression to establish a cause-and-effect relationship. This study aims to evaluate the role of extensive panel of heavy metals, oxidative status, and gene expression in RCC.

Methodology: This observational study recruited RCC patients who visited our tertiary care centre from 2019 to 2023. Age matched healthy volunteers were included as controls. Blood, urine, and tissue samples (tumor and adjacent normal tissue) were collected from RCC patients. Levels of arsenic, copper, manganese, selenium, cadmium, lead, and mercury were measured in each of the samples. Serum oxidative stress markers like glutathione peroxidase (GPX), lipid peroxidase (LPO), and superoxide dismutase (SOD) were measured. Genetic expression of Von Hippel-Lindau (VHL), catalase (CAT), superoxide dismutase (SOD1), and glutathione peroxidase (GPX1) genes were measured in the tumor tissue and adjacent normal parenchyma.

Results: 150 cases and 150 age matched controls were enrolled. RCC cases had elevated blood levels of arsenic (P = 0.02), copper (P = 0.01), manganese (P < 0.001), cadmium (P < 0.001), lead (P < 0.001), and mercury (P = 0.02) compared to controls. Urine levels of selenium (P = 0.02), mercury (P = 0.03), and lead (P = 0.04) were higher in cases. Reduced levels of serum GPx (P = 0.02) and higher levels of LPO (P = 0.04) were detected in cases. Elevated levels of copper (P = 0.03), manganese (P = 0.002), selenium (P < 0.001), and cadmium (P < 0.001) were found in the adjacent normal parenchyma compared to the tumor tissue. VHL (P = 0.03) and oxidative stress gene expressions were lower in the tumour tissue compared to the normal parenchyma.

Conclusion: Elevated levels of heavy metals in the blood, urine, tissue, and imbalance in the serum oxidative status along with downregulated tumor suppressor VHL and oxidative stress genes in the tumor tissues likely explain the carcinogenic role of heavy metals in RCC. Environmental exposure is the main cause of heavy metal toxicity. Mitigating the environmental exposure of heavy metals and thereby their toxicity might play a role in cancer prevention.

Objective: Medical and surgical advancements have been made in testicular cancer management over the past 50 years. The evolution of practice standards is expected to provide patients benefits in quality of life and oncologic outcomes, but changes in care standards can introduce potential opportunities for increased malpractice claims against providers. We seek to evaluate if modifications in testicular cancer management have translated to a rise in malpractice lawsuits.

Methods: A retrospective review of testicular cancer malpractice cases within the Google Scholar Case Law database was performed from January 1, 1975, to January 1, 2024.

Results: Of 102 cases initially screened, 24 were identified after duplicates were excluded and cases irrelevant to malpractice litigation in testicular cancer patients. Most cases were related to delays in diagnosis or treatment (n = 21, 87.5%). Two cases (8.3%) were in response to complications from radiation treatment, and 1 case (4.2%) was a suit in response to the loss of semen specimen for fertility preservation after testicular cancer diagnosis. No malpractice claims were filed in response to surveillance practices or surgical techniques utilized for retroperitoneal lymph node dissection.

Conclusions: Despite the adoption of changes in testicular cancer management and ongoing controversies in care, an increase in malpractice lawsuits in response to changing paradigms in testicular cancer was not seen.

Despite surgical resection, many patients with muscle invasive urothelial carcinoma (MIUC) experience recurrence. Adjuvant immune checkpoint inhibition (ICI) following radical resection in patients with MIUC demonstrates disparate outcomes among phase III randomized controlled trials (RCTs). Our objective was to synthesize available data regarding the disease-free survival (DFS) benefit of adjuvant ICIs for patients with MIUC and evaluate the overall safety profile of ICIs in this setting. The protocol was registered with PROSPERO, CRD42022352587. We searched MEDLINE, Embase, CENTRAL, and relevant conference proceedings from inception up to January 29, 2024. Only phase III RCTs comparing adjuvant ICI versus placebo/observation were selected. Study screening and selection, along with data extraction was performed in duplicate according to a predefined registered protocol. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was used. Quality assessment was performed using the Cochrane risk-of-bias (RoB 2) tool for randomized trials. The primary and secondary endpoints were DFS and serious adverse events, respectively. All outcomes were analyzed using random-effects meta-analysis owing to inter-study heterogeneity. Sensitivity and subgroup analyses were performed to identify potential sources of heterogeneity. A priori defined subgroups of interest included positive program death-ligand 1 (PD-L1) expression, previous use of neoadjuvant chemotherapy (NAC), primary tumor origin, pathologic lymph node status, and baseline Eastern Cooperative Oncology Group performance status. Pooled results across the 3 RCTs (2,220 patients) demonstrated significantly improved DFS for patients treated with ICI in the intention-to-treat cohorts (HR 0.76, 95% CI 0.65-0.90). There was considerable clinical and statistical heterogeneity (I² = 44%) due to differences in inclusion criteria and interventions. Overall, there was a low risk of bias among the RCTs. Regarding subgroup analyses, there was significant benefit among patients with negative PD-L1 expression (HR 0.76, 95% CI 0.64-0.90), those who received prior NAC (HR 0.69, 95% CI 0.52-0.91), and patients with lower tract (HR 0.71, 95% CI 0.55-0.92) but not upper tract disease (HR 1.21, 95% CI 0.87-1.68). This pooled analysis of DFS and safety provides support for ICI utilization in the setting of high-risk resected MIUC.

Background and objective: Neoadjuvant therapy followed by radical cystectomy with lymphadenectomy remains the gold standard of treatment in patients with muscle-invasive bladder cancer. Pathologically positive lymph node (pN+) disease is known to convey a poor prognosis. Tumor-informed circulating tumor DNA (ctDNA) has emerged as a possible novel prognostic biomarker in the field. We seek to assess recurrence-free survival (RFS) for patients undergoing robotic-assisted radical cystectomy (RARC) with extended pelvic lymphadenectomy (ePLND) and to assess whether ctDNA status can be a prognostic marker for RFS outcomes in patients with pN+ disease.

Methods: Patients who underwent RARC + ePLND during 2015 to 2023 were included. A sub-group analysis (n = 109) of patients who had prospectively collected serial-longitudinal tumor-informed ctDNA analyses during 2021-2023 was performed. Survival analysis and Cox-regression models were conducted.

Results: Included were 458 patients with a median age of 69 (IQR 63-76), and a median follow-up time of 20 months (IQR 10-37). RFS for pN0 (n = 353) and pN+ (n = 105) at 12, 24 and 36 months were 87% vs. 54%, 80% vs. 39%, and 74% vs. 35%, respectively (log-rank, P < 0.0001). On Cox multivariate analysis ≥pT3 disease (Hazzard ratio [HR] = 3.36 [2.18-5.18], P < 0.001), pN+ disease (HR = 2.39 [1.55-3.7], P < 0.001), and recipients of neoadjuvant treatment (HR = 1.61 [1.11-2.34], P = 0.013) were predictive of disease relapse. Patients with pN+ disease and undetectable precystectomy or postcystectomy ctDNA status had similar RFS to patients with pN0 with undetectable ctDNA. On Cox-regression multivariate sub-group analysis, detectable precystectomy ctDNA status (HR = 3.89 [1.32-11.4], P = 0.014), detectable ctDNA status in the minimal residual disease window ([MRD], HR = 2.89 [1.12-7.47], P = 0.028), and having ≥pT3 with pN+ disease (HR = 4.2 [1.43-12.3], P = 0.009) were predictive of disease relapse.

Conclusions: Patients with pN+ .after RARC had worse oncological outcomes than patients with pN0 disease. Undetectable ctDNA status was informative of RFS regardless of nodal status at both the precystectomy and the MRD window. Patients with undetectable ctDNA status and pN+ disease may benefit from treatment de-escalation.