Bladder Cancer最新文献

Background: Neoadjuvant cisplatin-based chemotherapy is standard care prior to radical cystectomy in patients with muscle-invasive bladder cancer (MIBC).

Objective: To assess efficacy and safety of two commonly used neoadjuvant schedules with different total doses and dose-intensities of gemcitabine and cisplatin (GC).

Methods: Data were collected retrospectively from all patients treated between 2010 and 2018 with neoadjuvant chemotherapy according to clinical routine at seven centres in Sweden and Denmark. Patients in Sweden received three cycles of a 4-week schedule (GC-4w: cisplatin 70 mg/m² day 1, gemcitabine 1000 mg/m² days 1, 8, 15, q 28 days) and in Denmark four cycles of a 3-week schedule (GC-3w: cisplatin 70 mg/m² day 1, gemcitabine 1000 mg/m² days 1, 8, q 21 days). Primary endpoint was pathological response at cystectomy (pT0N0 and < pT2N0).

Results: A total of 251 patients were treated with GC-4w and 455 with GC-3w. pT0N0 was significantly higher for patients treated with GC-3w compared to GC-4w, 46% versus 32% (adjusted odds ratio [aOR] 1.80; 95% confidence interval [CI] 1.16-2.80; P = 0.009); and for < pT2N0 60% versus 47% (aOR 1.08; 95% CI 0.70-1.66; P = 0.743). There were no significant differences between GC-4w and GC-3w regarding survival parameters. GC-3w patients discontinued treatment more frequently and showed a higher degree of neutropenia.

Conclusions: A significantly higher complete response-rate was observed in the patient group treated with the more cisplatin-dose-intense 3-week schedule. The side-effect profile was in favor of the 4-week approach while relapse-free and overall survival were similar.

Background: Atezolizumab is an immune checkpoint inhibitor (ICI) and a frontline treatment of patients with cisplatin-ineligible advanced urothelial carcinoma (UC). There is limited evidence on the prognostic value of patient reported outcomes (PROs) in advanced UC treatment, particularly in the context of ICI therapy.

Objective: To investigate the prognostic association of PROs with survival in patients with advanced UC treated with atezolizumab.

Methods: This study used data from 467 patients with advanced UC initiating atezolizumab in the IMvigor211 trial. Pre-treatment PROs association with overall survival (OS) and progression free survival (PFS) was assessed using Cox proportional hazard analysis. PROs were recorded via the European Organisation for Research and Treatment of Cancer QLQ-C30. Discrimination performance was assessed via the C-statistic (c).

Results: Patient reported physical function, pain, appetite loss, global health, fatigue, role function, constipation, nausea and vomiting, dyspnoea, and insomnia were significantly associated with OS and PFS on univariable and adjusted analysis (P < 0.05). Physical function (c = 0.63), pain (c = 0.63), appetite loss (c = 0.62), global health status (c = 0.62), and fatigue (c = 0.62), were the most prognostic factors of OS. The OS discrimination performance of physical function (c = 0.61) was superior to ECOG PS (c = 0.58). Of patients assessed by investigators as having no performance restrictions (ECOG PS of 0), 38 (18%) and 91 (42%) self-reported low and intermediate physical function scores, respectively.

Conclusion: Pre-treatment PROs were identified as independent prognostic factors of OS and PFS. Patient-reported physical function was more prognostic of OS than ECOG PS. This highlights a potential for PROs to enable improved patient stratification in ICI trials.

Marker research, and in particular urine bladder cancer marker research throughout the past three decades, devours enormous scientific resources in terms of manpower (not to mention time spent on reviewing and editorial efforts) and financial resources, finally generating large numbers of manuscripts without affecting clinical decision making. This is mirrored by the fact that current guidelines do not recommend marker use due to missing level 1 evidence. Although we recognize the problems and obstacles, the authors of this commentary feel that the time has come to abandon the current procedures and move on to prospective trial designs implementing marker results into clinical decision making. Our thoughts and concerns are summarized in this comment.

Background: Inchworm sign is a finding on diffusion-weighted magnetic resonance imaging (DWI-MRI) and is used to better stratify T-staging in muscle invasive (MIBC) and non-muscle-invasive bladder cancer (NMIBC). An uninterrupted low submucosal signal on DWI, defined as inchworm sign (IS), indicates NMIBC.

Objective: We aimed to define the diagnostic accuracy of IS in primary bladder cancer, as well as find agreement between the urologists and the radiologist.

Methods: Between December 2018 and December 2020, we retrospectively analyzed 95 primary bladder cancer patients who had undergone multiparametric-MRI before transurethral resection. Patients with former bladder cancer history, tumors smaller than 10 mm, and MRI without proper protocol, as well as patients who did not attend follow-up, were excluded. In total, 71 patients' images were evaluated by a genitourinary specialist radiologist and two urologists. Sensitivity, specificity, positive and negative predictive values of IS and VI-RADS in differentiating MIBC and NMIBC, and interreader agreement between the radiologist and urologists were analyzed.

Results: During follow-up, 38 patients (53.5%) were IS-positive, while 33 patients (46.5%) were negative. Among the 33 patients with negative IS, 14 patients (42.4%) had MIBC. Meanwhile, two out of the 38 IS-positive patients (5.3%) had MIBC (p = 0.00). Sensitivity, specificity, and positive and negative predictive values of IS in predicting MIBC were 87.5%, 63.6%, 41.2%and 94.6%, respectively. The interobserver agreement between the urologists and radiologist was almost perfect ( _K  = 0.802 and _K  = 0.745).

Conclusion: The absence of IS on DWI is useful in differentiating MIBC from NMIBC. It is a simple finding that can be interpreted by urologists.

Background: Bladder cancer treatments may variably impact health-related quality of life (QOL).

Objective: To characterize the quality of life of patients with bladder cancer at various time points across the continuum of bladder cancer care from non-muscle-invasive disease to metastatic bladder cancer and develop utility scores to inform cost-effective analyses.

Methods: We performed a cross-sectional survey of bladder cancer patients in the Bladder Cancer Advocacy Network Patient Survey Network. Participants were classified into mutually exclusive health states based upon non-muscle invasive (NMIBC), muscle-invasive (MIBC), or metastatic bladder cancer and completed surveys of generic cancer and bladder cancer-specific quality of life, financial toxicity, and work impairment. We constructed generalized linear mixed models to identify patient, clinical, and treatment factors associated with quality of life over time and derived health state utilities.

Results: Among 911 self-identified patients with bladder cancer, overall QOL scores and function domains were worse among those with advanced cancer. Financial toxicity was similar among non-metastatic disease states. Work and activity impairment increased with advancing disease (13%and 12%among non-recurrent NMIBC to 63%and 31%for metastatic disease respectively; p < 0.01). On multivariable analysis, bowel-related QOL was diminished among patients with MIBC, with urinary symptoms and physical function most diminished among patients with metastatic disease. Patients with metastatic and MIBC experienced worse emotional functioning (p = 0.04; p = 0.048). Health state utilities were calculated, highest among those with non-recurrent NMIBC and lowest among those with metastatic disease.

Conclusion: Generic and bladder cancer-specific QOL diminishes with advancing disease. Health state utility estimates derived from this study can inform shared decision making with patients and may be used to inform future cost-effective analyses.

Background: sBladder urothelial carcinoma is the most prevalent type of bladder cancer, characterized by drug resistance, high recurrence rate, and unfavorable prognosis. Ferroptosis is a newly discovered type of non-apoptotic cell death, which has been reported to be strongly correlated with tumor occurrence and development.

Objective: In this study, we characterized ferroptosis-specific biomarkers to elucidate the association between ferroptosis-related genes (FRGs) and bladder urothelial carcinoma.

Methods: The TCGA and GEO database were adopted to obtain data and corresponding clinicopathological information. Univariate and multivariate cox regression were performed to establish a ferroptosis-related model. Besides, the KM plot visualized prognosis between high risk and low risk groups. Moreover, cBioportal platform was used to gather information on genetic alteration and DNA methylation of hub FRGs in BLCA patients. Additionally, the GSEA software was used to detect the difference in gene expression between high-risk and low-risk subgroups.

Results: Six ferroptosis-related genes were identified to be highly correlated with overall survival. Besides, we explored the genetic variations of these FRGs, as well as the correlation between FRG expression and copy number values. Additionally, the DNA methylation status of these FRGs was determined. Moreover, we constructed a ferroptosis risk model with the six FRGs to predict the prognosis of BLCA. The results demonstrated that a higher risk score indicated an unfavorable prognosis. The ferroptosis signature was associated with clinical and molecular characteristics and could be regarded as an independent prognostic factor for BLCA patients.

Conclusions: In summary, we established and verified a ferroptosis risk model which had the potential to independently predict the prognosis of bladder urothelial carcinoma.

Abstract

BACKGROUND:

The benefit of surgery of the primary tumor in metastatic bladder cancer is unknown.

OBJECTIVE:

Perform a comprehensive contemporary literature review on the benefit of surgery of the primary tumor in metastatic bladder cancer.

METHODS:

Ovid MEDLINE, Ovid EMBASE, and Cochrane Library from January 1, 1990 to April 20, 2020 were queried for relevant articles published in English. Each article was evaluated by at least two content experts prior to inclusion which were blinded to the other’s evaluation. A third content expert was used when there was not a unanimous decision. Additional articles were added at the discretion of the authors.

RESULTS:

Long-term survival is possible in patients with initially unresectable and/or limited metastatic disease. Multi-modal therapy with chemotherapy and surgery have the most favorable outcomes when compared to single treatment modalities in selected populations. Patients who demonstrate a robust response to pre-surgical therapy are likely to benefit the most from consolidative surgery. Patients with distant metastatic disease may benefit from consolidative surgery; however, this benefit may only be seen in those with metastatic disease limited to one site.

CONCLUSIONS:

Surgery of the primary tumor in metastatic bladder cancer either in the setting of surgery alone, consolidative therapy or coupled with adjuvant therapy may be beneficial in well selected patients and should generally be limited to those who have a response to primary chemotherapy. Randomized clinical control trials are needed to further our understanding of the role of surgery in metastatic bladder cancer.

Systematic Review Registration number: CRD42020182861