Urologic Oncology-seminars and Original Investigations最新文献

Background: 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.

Methods: A total of 210 ccRCC patients and 255 ethnicity-matched healthy controls were enrolled. Genomic DNA from blood and tissue samples was analyzed using PCR-based Sanger sequencing. The association of VHL variants with ccRCC risk was assessed using Chi-square tests. The impact of genetic variants on patient clinicopathological features and overall survival was evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models.

Results: We identified twenty-three single nucleotide variants (SNVs) in the VHL gene, including 3 novel variants, OR250433 T > G, OR125589 C > T and OQ627404 G > C. The intronic variant rs61758376 G > C and 3'UTR variant rs1642742 A > G were significantly associated with an increased risk of ccRCC (OR = 1.676, P = 0.0074; OR = 1.735, P = 0.0171, respectively). The rs1642742 GG genotype was also significantly associated with larger tumor size (P < 0.05) and advanced tumor stage (pT4). Kaplan-Meier analysis indicated poorer overall survival for patients with the rs1642742 GG genotype (log-rank P = 0.029).

Conclusion: Our study is the first to document the association of VHL gene variants with sporadic ccRCC risk and clinical outcomes in the Indian population. The identified variants, particularly rs61758376 and rs1642742, could serve as potential biomarkers for ccRCC susceptibility and prognosis.

Background: 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.

Material and methods: A randomized trial was conducted at a tertiary care hospital, including patients aged ≥18 years undergoing TURBT with complete primary tumor resection. Cases were randomized into two groups i.e., 'standard TURBT' (complete tumor resection with a deep biopsy) and "immediate second resection" (complete tumor resection, deep biopsy and additional deep biopsies). The primary endpoint was the presence of detrusor muscle in biopsy specimens, analyzed by a single pathologist. Secondary endpoints included perioperative complications, residual/ recurrent tumors, and factors affecting these recurrences.

Result: The study included 83 patients: 44 in the 'standard TURBT' group and 39 in the 'immediate second resection' group. The detrusor muscle was present in 66% of standard TURBT cases and 97% of immediate second resection cases, showing a statistically significant improvement (P = 0.000). Residual disease was found in 41% of restage TURBT patients in the standard group and 15% in the immediate second resection group, the majority being high-grade and T1 tumors (P = 0.028). There were no significant differences in tumor grade or perioperative complications between the groups. However, immediate second resection showed 18% higher detrusor muscle sampling rates than standard re-stage TURBT done at 2-6 weeks (P = 0.021).

Conclusion: Immediate second resection at the time of initial TURBT significantly improves detrusor muscle sampling rates and decreases residual tumors at restage. Despite higher muscle sampling, a considerable proportion of patients still exhibited residual or recurrent tumors in both groups, emphasizing the need for improved detection and biopsy techniques during primary TURBT.

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.

Background and objective: 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.

Methods: This study carefully selected 129 participants, including 67 NMIBC patients, 31 hematuria patients due to nonmalignant urological disorders, and 31 healthy individuals. Subsequently, ten significantly dysregulated mRNAs were identified in the urine specimens of these participants using RT-qPCR.

Key findings: Expression levels of CA9, CDK1, CD24, TERT, CEP55, TOP2A, IQGAP3, UBE2C, and CRH in urine samples from NMIBC patients were higher than those in healthy individuals. Notably, CD24, TOP2A, IQGAP3, UBE2C, and CRH mRNA levels in NMIBC patients were significantly higher than in the hematuria group. In diagnosing low-grade from healthy and hematuria groups, analysis of the 5-gene profile yielded a sensitivity of 98 % and a specificity of 100 % and 90 %, respectively. For diagnosing high-grade tumors from healthy and hematuria groups, sensitivity was 96 % and 100 %, and specificity was 100 % and 83 %, respectively.

Conclusions and clinical implications: These results emphasize the potential application of urine mRNA profiling in the early diagnosis of NMIBC and provide new insights into the molecular mechanisms involved.

Background: 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.

Aim: The current study probed into the potential of PVA as a substitute for NRS in assessing SRF before and after PN with warm ischemia.

Methods: This study included 318 patients who underwent unilateral PN with warm ischemia at Sun Yat-Sen University Cancer Center (SYSUCC) and had a functional contralateral kidney. All patients underwent PVA and NRS assessments both pre-PN and at 1-12 months post-PN. PVA was analyzed using Mimics software in the venous phase. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation. The correlation between ipsilateral eGFR values derived from SRF assessed via PVA and NRS was examined using Pearson correlation. Concordance between different methods of SRF estimation was analyzed using the Friedman test, Bland-Altman plots, and Kendall's consistency coefficient. Similar study was conducted on a comparable cohort from Sun Yat-Sen Memorial Hospital.

Results: The median tumor size was 3.5cm, and the median warm ischemia time was 25min. Preoperatively, ipsilateral SRF values based on PVA were notably consistent with those derived from NRS (49.4% vs 50.0%, P = .501). A strong correlation was observed between preoperative ipsilateral eGFR based on SRF from PVA and NRS (r = 0.89, P < .0001). Bland-Altman plots indicated minimal bias (-0.36%) between PVA and NRS in assessing SRF. However, post-PN, the median ipsilateral SRF based on PVA was slightly higher than that based on NRS (45.6% vs. 43.6%, P < .0001). Although there was still a strong correlation between post-PN ipsilateral eGFR based on SRF from PVA and NRS (r = 0.87, P < .0001), Bland-Altman plots revealed a non-negligible bias between the 2 methods (2.19 %). External study supported our findings.

Conclusions: PVA shows promise as a substitute for NRS in assessing SRF before PN with warm ischemia. However, this substitution may result in an overestimation of ipsilateral renal function in the post-PN phase.

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.

Objectives: 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.

Materials and methods: We relied on individual patient data from IMvigor210 (phase II single-arm trial on second line atezolizumab for mUC) and IMvigor211 trials (phase III randomized trial on second line atezolizumab vs chemotherapy for mUC). Among individuals treated with IO we identified patients who did and did not receive antihistamines. Multivariable Cox or competing-risks regression models were used to predict progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS). The impact of antihistamines on the outcomes was assessed after adjusting for potential confounders.

Results: Among 896 patients with locally advanced or metastatic urothelial cancer who had progressed after first-line chemotherapy, 155 (17 %) received antihistamines during the delivery of IO. Patients receiving antihistamines had longer OS (Hazard Ratio [HR]:0.59; 95 % Confidence interval [CI]: 0.47-0.74; P < 0.001), PFS (HR:0.70; 95 %CI: 0.57-0.87; P = 0.001) and CSS [sHR:0.58; 95 %CI:0.45-0.75; P < 0.001)] relative to those who had not used antihistamine drugs. A sensitivity analysis, after the exclusion of patients who experienced adverse events and received antihistamines, yielded similar findings of prolonged CSS (sHR 0.78; 95 %CI: 0.59-0.98, P = 0.031) and OS (HR 0.71; 95 %CI: 0.52-0.94, P = 0.021).

Conclusions: Concomitant antihistamines administration was associated with improved OS, CSS, and PFS in patients receiving atezolizumab as second line treatment for mUC. Further mechanistic and clinical investigation is warranted to elucidate the role of antihistamines in IO.

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.

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^TM 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^TM) 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.

Objectives: Higher body mass index (BMI) is reportedly associated with improved prognosis of patients with various cancers. However, it is unclear whether this phenomenon, also known as the obesity paradox, applies to metastatic renal cell carcinoma (mRCC). We aimed to determine the prognostic significance of BMI in patients with mRCC receiving first-line therapies.

Materials and methods: We retrospectively reviewed patients with mRCC receiving first-line immune checkpoint inhibitor (ICI)-based combination therapy or tyrosine kinase inhibitor monotherapy. Overall survival (OS) was defined as the time from systemic therapy initiation to death from any cause or last follow-up. Baseline patient characteristics were compared by Mann-Whitney U test or Fisher's exact test. OS curves were constructed by Kaplan-Meier estimates and were compared by log-rank test. Multivariable analysis was performed via Cox proportional-hazards regression.

Results: Of the 183 patients included, 130 (71 %) were overweight (≥22 and 18 kg/m² in men and women, respectively), and 63 (34 %) received ICI-based combination therapy. There was a significantly higher proportion of men in the overweight subgroup (87 % versus 64 %; P = 0.002). During the study period, 97 patients died, and median (95 % confidence interval) OS was 39.0 months (31.5-66.3 months) and 28.1 months (17.6-39.7 months) in overweight and normoweight patients, respectively (P = 0.015). On multivariable analysis, overweight was independently associated with longer OS (HR 0.57; P = 0.014). Subgroup analyses of patients receiving ICI-based combination therapy yielded similar results.

Conclusion: Overweight is associated with favorable outcomes in patients with mRCC receiving first-line therapies.