Bladder Cancer最新文献

The National Cancer Institute organized a virtual Clinical Trials Planning Meeting (CTPM) on 'Defining the next generation of clinical trials with combination therapies in non-muscle invasive bladder cancer (NMIBC)' led by the Bladder Cancer Task Force of the NCI Genitourinary Cancers Steering Committee. The purpose of this meeting was to accelerate advances in clinical trials for patients with high-risk NMIBC. The meeting delivered a multidisciplinary expert consensus on optimal strategies for next-generation clinical trial designs in NMIBC with prioritization of combination therapies. Two clinical trial concepts were developed for potential implementation within the National Clinical Trials Network.

Background: Bladder cancer in the setting of previous a kidney transplant (KT) is challenging to manage due to complex medical and surgical considerations.

Objective: To provide a comprehensive evaluation of the scope of management of bladder cancer in KT patients, and describe the controversies surrounding these management options.

Methods: A systematic review of studies reporting management of KT patients with bladder cancer and involving ≥3 patients was performed. A narrative review was also performed for various aspects of management such as pathophysiology, surgical considerations, intravesical therapy, immunosuppression and oncological surveillance.

Results: Bladder cancer incidence in KT recipients is 2.8-4.1 times higher than the general population, and there is a notable association with aristolochic acid nephropathy as well as BK virus oncogenesis. Regarding surgical treatment, transurethral resection is preferred for non-muscle invasive tumors, and intravesical BCG for intermediate- and high-risk patients appears to be underutilized despite its safety and associated reduction in recurrence. Radical cystectomy with limited pelvic lymph node dissection, urinary diversion, and consideration of bilateral nephroureterectomy appears to be the safest method of oncological control in muscle-invasive tumors. A switch in immunosuppressive regimens to mTOR inhibitors may be considered in lieu of its antitumor effects. Routine surveillance in KT patients with risk factors for bladder cancer is challenging and may be warranted especially in the Asian population which has a higher rate of urothelial malignancy.

Conclusions: This review provides a thorough summary of management strategies for bladder cancer in the setting of previous KT.

Background: Bladder cancer is one of the most prevalent malignancies, and the mechanisms underlying its progression and the role of the tumor microenvironment (TME) are unclear. Recent advancements in single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) enable detailed analysis of the cellular heterogeneity, gene expression, and cell-cell interactions in bladder diseases.

Methodology: We conducted a comprehensive search for recent articles that have investigated bladder diseases using scRNA-seq and ST.

Results: scRNA-seq and ST have led to significant discoveries in bladder disease research. These technologies have enabled the identification of multiple molecular subtypes within individual tumors and of the mechanisms of treatment resistance. Additionally, molecular differences based on gender have been explored, explaining the heterogeneity of the incidence and progression of bladder cancer. These findings deepen our understanding of the pathology of bladder diseases and highlight the transformative potential of scRNA-seq and ST in identifying novel biomarkers and therapeutic targets.

Conclusions: Integrating scRNA-seq and ST has considerably enhanced our understanding of tumor heterogeneity and the tumor microenvironment within tissues. These insights may lead to the development of personalized therapies and the improvement of patient outcomes. Several challenges, such as technical limitations and access difficulties, need to be addressed for the future clinical application of these technologies.

Background: Enfortumab vedotin (EV) and Sacituzumab govitecan (SG) are antibody-drug conjugates (ADCs) with demonstrated activity in advanced bladder cancer. A subset of bladder tumors harbors a DNA repair deficiency in either the homologous recombination (HR) or nucleotide excision repair (NER) pathway that has the potential to impact sensitivity to specific classes of therapeutics.

Objective: Define the impact of HR or NER deficiency on sensitivity to ADC payloads alone or in combination with DNA repair targeted agents in bladder cancer.

Methods: Isogenic cell pairs with versus without HR or NER deficiency were profiled using DNA repair and drug sensitivity assays. Sensitivity to the ADC payloads monomethyl auristatin E (MMAE) and SN-38 alone or in combination with small molecule inhibitors of poly(ADP-ribose) polymerase (PARP), ATR, or USP1 were measured using cell viability assays.

Results: BRCA2 loss was sufficient to confer an HR deficient phenotype and increase sensitivity to cisplatin and PARP inhibition in bladder cancer cell lines. HR deficiency, but not NER deficiency, increased sensitivity to MMAE and SN-38 in bladder cancer cells. The combination of SN-38 and PARP inhibition displayed synergistic cell killing independent of HR or NER status.

Conclusion: HR and NER deficiency have distinct impacts on sensitivity to cisplatin and ADC payloads in bladder cancer preclinical models.

Background: The practice patterns and efficacy of ddMVAC administered with split-dose cisplatin for patients with muscle-invasive bladder cancer (MIBC) remains largely undefined.

Objective: To characterize the application and overall survival (OS) in patients with MIBC receiving conventional ddMVAC versus split-dosed ddMVAC and to examine the predictive variables in those receiving split-dosed cisplatin.

Methods: Using data from the CancerLinQ Discovery database, we identified 626 patients with bladder cancer between 2000-2023 with receipt of ddMVAC. The primary outcome was OS by receipt of split-dose versus conventional ddMVAC. A secondary outcome of interest assessed predictors of receipt of split-dose ddMVAC. Use of split-dose versus conventional ddMVAC was compared using chi-square tests. Univariate and multivariable OS were estimated using Cox proportional hazards models. Predictors of receipt of split dose versus conventional ddMVAC were estimated using logistic regression models.

Results: Most patients with MIBC are treated with standard dose ddMVAC. In multivariate analysis, no statistically significant difference in OS was observed between split-dose and conventional ddMVAC (HR 1.3, CI 0.78-2.18, p = 0.316). We demonstrate a notable decline in the use of split-dose cisplatin over time. Baseline GFR and performance status were not predictors of split-dosing in this cohort.

Conclusions: Most patients with MIBC received conventional ddMVAC with decreasing frequency of split-dose cisplatin use over time. We did not observe a difference in OS between patients with MIBC who received standard versus split-dose cisplatin.

Background: Bladder EpiCheck (BE) is a novel methylation-based PCR urine test for the detection of non-muscle invasive bladder cancer (NMIBC) recurrences.

Objective: We present the results of a North American study evaluating BE and meta-analysis of literature.

Methods: A prospective, blinded, multicenter study was conducted in North America. Voided urine was collected from NMIBC patients prior to cystoscopic surveillance. BE testing was performed centrally. For the meta-analysis, a PUBMED search was performed to identify all published peer-reviewed clinical studies of BE for NMIBC surveillance.

Results: In this study, 674 patients were enrolled of which 449 were included. Overall sensitivity was 67% (95%CI 58%-74%), specificity was 84% (80%-88%), PPV was 65% (57%-73%) and NPV was 85% (81%-89%). For high-grade (HG) recurrence, sensitivity was 77% (65%-85%) and NPV was 95% (92%-97%).In patients with negative cystoscopy and cytology at the first study visit, risk of subsequent recurrence in 12 months was 5.3 (2.7-10.3) times higher in patients with positive BE vs. negative BE (p < 0.0001). In patients with negative cystoscopy and equivocal cytology, BE was positive in 75-89% of those with later HG recurrence, with PPV of 42% (15%-72%)-63% (38%-84%).The meta-analysis included 7 studies and 1564 patients. Overall sensitivity was 82% (66-92%), HG sensitivity was 91% (82-95%), specificity was 85% (80-88%), PPV was 60% (55-64%) and HG NPV was 98% (97-99%).

Conclusions: The consistently strong performance of BE indicate that a positive test could improve timely disease recurrence detection and a negative test could rule-out HG disease. Furthermore, the low rate of false positive results, potentially minimizes unnecessary downstream procedures and patient anxiety.

The United States has seen a decrease in the incidence of bladder cancer and a decline in mortality rates over the past 20 years. However, not all groups have benefited equally from this trend. The American Association of Community Cancer Centers (ACCC) has issued ten strategies to improve cancer care delivery for underserved patient populations. Unfortunately, the evidence supporting the best methods for reducing disparities in different patient groups and care delivery settings remains severely limited. In this short communication, using a personalized narrative woven into a clinical case, we highlight the need for more research on bladder cancer care delivery to ensure that significant investments in precision oncology translate into genuine improvements for all patients diagnosed with bladder cancer.

Background: There is a notable disparity between the guidelines for BCG therapy in non-muscle invasive bladder cancer (NMIBC). Reddit has emerged as a popular online platform for individuals seeking information and exchanging their experiences related to bladder cancer.

Objective: To investigate and classify public opinions about intravesical BCG therapy as shared on Reddit, a popular social media platform.

Methods: This study employed an artificial intelligence-based approach to examine discussions related to intravesical BCG therapy on a social media platform over the past ten years. An artificial intelligence framework was developed to categorize these conversations into distinct topics and thematic categories. This framework included a partially supervised model for processing natural language (using BERT [Bidirectional Encoder Representations from Transformers]), a method for reducing data complexity, and an algorithm for clustering. Additionally, each conversation was assessed for sentiment.

Results: A total of 1223 unique discussions related to BCG therapy were analyzed, comprising 110 unique posts and 1113 comments from 268 distinct authors. We identified four overarching thematic groups: 1) BCG administration procedures, (2) hesitancy in initiating or maintaining BCG treatment, (3) issues related to BCG shortage and alternative treatments, and (4) side effects of BCG treatment. Sentiment analysis of the 1223 discussions revealed that 25.2% (308) exhibited a negative sentiment, 58.3% (713) were neutral, and 16.5% (202) showed a positive sentiment.

Conclusion: Online social media often contains detailed personal experiences with BCG therapy, not commonly found in medical literature. Understanding these experiences can help medical professionals improve care and treatment adherence in NMIBC.

Background: The American Urological Association (AUA)/Society of Urology Oncology (SUO) guidelines recommend a repeat transurethral resection of bladder tumor (TURBT) for high-risk, non-invasive (HR Ta) nonmuscle invasive bladder cancer (NMIBC) patients. The evidence base for this recommendation is weak (grade C) and fraught with methodological shortcomings, such as the lack of adjuvant intravesical Bacillus Calmette Guerin (BCG) and single-center study designs.

Objective: We sought to evaluate the effect of repeat TURBT on recurrence-free survival at a population level in HR Ta NMIBC patients who completed BCG induction therapy.

Methods: High-grade Ta NMIBC patients who underwent TURBT for a ≥5 cm tumor were identified within the SEER-Medicare database. All patients completed induction BCG and were stratified into two groups: repeat TURBT within eight weeks of initial TURBT and a group without repeat TURBT (control group). The primary endpoint was the 3-year high-risk recurrence rate.

Results: A cohort of 604 patients was identified, with 93 (15.4%) undergoing a repeat TURBT within eight weeks of initial TURBT and 511 (84.6%) without a repeat TURBT. Patient demographic and clinical characteristics were similar overall. No significant difference in the 3-year recurrence rate was noted (repeat TURBT: 20.4% vs. control group: 15.7%, p = 0.25). After adjusting for demographic and clinical characteristics, no association between repeat TURBT and 3-year high-risk recurrence was observed (HR (95% CI): 1.27 (0.76, 2.11); p = 0.36).

Conclusion: Although our study contains several major limitations, our results suggest that repeat TURBT in large volume HG Ta NMIBC treated with induction BCG therapy was not associated with improved high-risk recurrence-free survival.

Background: Antiangiogenic therapy had been tested in urothelial cancer (UC) without reaching the clinic.

Objective: We provide a systematic review and meta-analysis of trials to assess efficacy of immune checkpoint inhibitors (ICI) combined with antiangiogenic agents in UC.

Methods: Following PRISMA guidelines, we searched for trials with at least one arm of patients with UC treated with ICI plus antiangiogenics. Data were analyzed with the "meta" package from R using a one-staged frequentist meta-analysis.

Results: After screening 13,708 titles and abstracts, 9 studies were selected for analysis with 14 identified cohorts comprising 621 patients: 448 were ICI-naïve (ICI-N) and 173 were ICI-exposed (ICI-E). The estimated objective response rate (ORR) in all patients was 27% (21-35). In the ICI-N group, ORR was 34% (28-41). Conversely, the ICI-E group had a lower ORR of 16% (9-28). This difference was mainly driven by a higher partial response rate of 27% (23-31) in ICI-N group compared to 13% (8-20) in the ICI-E group. Disease control rate was 72% (66-77) ICI-N group vs. 71% (64-78) in ICI-E group. Median overall survival ranged from 6.4 to 24.9 months in the ICI-N group, and 8.2 to 10.4 months in ICI-E group. Median progression free survival ranged from 1.9 to 10.1 months and from 3 to 3.9 months in both groups, respectively.

Conclusion: ORR with ICI plus antiangiogenics was lower after prior ICI exposure, with substantial variability estimates among included trials, either due to differences among antiangiogenic agents used or trial-related factors. Future exploration of ICI combined with antiangiogenics in UC, especially in ICI-refractory setting, will benefit from better patient selection.