Location of Metastatic Bladder Cancer as a Determinant of In-hospital Mortality After Radical Cystectomy

Zaffuto, Emanuele; Bandini, Marco; Moschini, Marco; Leyh-Bannurah, Sami-Ramzi; Gazdovich, Stéphanie; Dell’Oglio, Paolo; Gallina, Andrea; Shariat, Shahrokh F.; Briganti, Alberto; Montorsi, Francesco; Saad, Fred; Karakiewicz, Pierre I.

doi:10.1016/j.euo.2018.02.001

Cited by 17 publications

(10 citation statements)

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“…Moreover, we observed a lack of metastases or tumor development in other sites than the bladder which were previously recorded in studies while using Hgf-Cdk4 R24C mice [ 49 – 51 ]. It is possible that this is a cancer specific property, as multiple metastases arise in very advanced stages in human patients usually after surgical removal of the bladder [ 72 ] or that circulating tumor cells did not evolve into tumor metastases due to the necessary humane endpoint reached when the animals reached the muscle invasive bladder tumor stage. We could not examine the metastatic potential, in relation to patients who present metastatic tumor growth after surgical removal of the bladder, due to lack of surgical measures as well as due to ethical constraints.…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNAseq and longitudinal proteomic analysis of a novel semi-spontaneous urothelial cancer model reveals tumor cell heterogeneity and pretumoral urine protein alterations

et al. 2021

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Bladder cancer, one of the most prevalent malignancies worldwide, remains hard to classify due to a staggering molecular complexity. Despite a plethora of diagnostic tools and therapies, it is hard to outline the key steps leading up to the transition from high-risk non–muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC). Carcinogen-induced murine models can recapitulate urothelial carcinogenesis and natural anti-tumor immunity. Herein, we have developed and profiled a novel model of progressive NMIBC based on 10 weeks of OH-BBN exposure in hepatocyte growth factor/cyclin dependent kinase 4 (R24C) (Hgf-Cdk4R24C) mice. The profiling of the model was performed by histology grading, single cell transcriptomic and proteomic analysis, while the derivation of a tumorigenic cell line was validated and used to assess in vivo anti-tumor effects in response to immunotherapy. Established NMIBC was present in females at 10 weeks post OH-BBN exposure while neoplasia was not as advanced in male mice, however all mice progressed to MIBC. Single cell RNA sequencing analysis revealed an intratumoral heterogeneity also described in the human disease trajectory. Moreover, although immune activation biomarkers were elevated in urine during carcinogen exposure, anti-programmed cell death protein 1 (anti-PD1) monotherapy did not prevent tumor progression. Furthermore, anti-PD1 immunotherapy did not control the growth of subcutaneous tumors formed by the newly derived urothelial cancer cell line. However, treatment with CpG-oligodeoxynucleotides (ODN) significantly decreased tumor volume, but only in females. In conclusion, the molecular map of this novel preclinical model of bladder cancer provides an opportunity to further investigate pharmacological therapies ahead with regards to both targeted drugs and immunotherapies to improve the strategies of how we should tackle the heterogeneous tumor microenvironment in urothelial bladder cancer to improve responses rates in the clinic.

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Section: Discussionmentioning

confidence: 99%

Single-cell RNAseq and longitudinal proteomic analysis of a novel semi-spontaneous urothelial cancer model reveals tumor cell heterogeneity and pretumoral urine protein alterations

et al. 2021

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“… 15 Metastatic and locally advanced diseases are also associated with increased mortality after RC. 30 …”

Section: Discussionmentioning

confidence: 99%

Dramatic Impact of Centralization and a Multidisciplinary Bladder Cancer Program in Reducing Mortality: The CABEM Project

Korkes

Timóteo

Martins

et al. 2021

JCO Global Oncology

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PURPOSE Muscle-invasive bladder cancer (MIBC) is an aggressive disease with a complex treatment. In Brazil, as in most developing countries, data are scarce, but mortality seems exceedingly high. We have created a centralization program involving a multidisciplinary clinic in a region comprising seven municipalities. The aim of this study is to evaluate the impact of a multidisciplinary clinic and a centralization-of-care program (CABEM program) on MIBC treatment in Brazil. PATIENTS AND METHODS A total of 116 consecutive patients were evaluated. In group 1, 58 patients treated for MIBC before establishing a bladder cancer program from 2011 to 2017 were retrospectively evaluated. Group 2 represented 58 patients treated for MIBC after the implementation of the CABEM centralization program. Age, sex, staging, comorbidity indexes, mortality rates, type of treatment, and perioperative outcomes were compared. RESULTS Patients from group 2 versus 1 were older (68 v 64.2 years, P = .02) with a higher body mass index (25.5 v 22.6 kg/m2, P = .017) and had more comorbidities according to both age-adjusted Charlson Comorbidity Index (4.2 v 2.8, P = .0007) and Isbarn index (60.6 v 43.9, P = .0027). Radical cystectomy (RC) was the only treatment modality for patients in group 1, whereas in group 2, there were 31 (53%) RC; three (5%) partial cystectomies; seven (12%) trimodal therapies; 13 (22%) palliative chemotherapies; and three (5%) exclusive transurethral resections of the bladder tumor. No patient in group 1 received neoadjuvant chemotherapy, whereas it was offered to 69% of patients treated with RC. Ninety-day mortality rates were 34.5% versus 5% for groups 1 versus 2 ( P < .002). One-year mortality was also lower in group 2. CONCLUSION Our data support that a centralization program, a structured bladder clinic associated with protocols, a multidisciplinary team, and inclusion of chemotherapy and radiotherapy treatments can pleasingly improve outcomes for patients with MIBC.

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“…The current study relied on the National Inpatient Sample (NIS) database 19 (2000‐2015) that is composed of longitudinal hospital inpatient databases from the Healthcare Cost and Utilization Project family and includes 20% of United States inpatient hospitalizations 20 . Institutional ethical board had reviewed the research project and it meets requirements for protection of human subjects.…”

Section: Methodsmentioning

confidence: 99%

“…The current study relied on the National Inpatient Sample (NIS) database 19 (2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015) that Secondary procedure codes were used to identify lymph node dissection (ICD-9-CM codes 40.3 or 40.5). Overall, 11 258 assessable patients were identified.…”

Section: Study Populationmentioning

confidence: 99%

Preoperative frailty predicts adverse short‐term postoperative outcomes in patients treated with radical nephroureterectomy

Rosiello

Palumbo

Deuker

et al. 2020

Journal of Surgical Oncology

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Background To investigate the effect of frailty on short‐term postoperative outcomes and total hospital charges (THCs) in patients with non‐metastatic upper urinary tract carcinoma, treated with radical nephroureterectomy (RNU). Methods Within the National Inpatient Sample (NIS) database we identified 11 258 RNU patients (2000‐2015). We used the Johns Hopkins frailty‐indicator to stratify patients according to frailty status. Time trends and multivariable logistic, Poisson and linear regression models were applied. Results Overall, 1801 (16.0%) patients were frail, 4664 (41.4%) were older than 75 years and 1530 (13.6%) had Charlson comorbidity index ≥2. Rates of frail patients increased over time, from 7.3% to 24.9% (P < .001). Frail patients exhibited higher rates (all P < .05) of overall complications (62.6% vs 50.9%), in‐hospital mortality (1.6% vs 1.0%), non‐home–based discharge (22.7% vs 12.1%), longer length of stay (LOS) (6 vs 1 day) and higher THCs ($49 539 vs $39 644). Moreover, frailty independently predicted (all P < .05) overall complications (OR, 1.46), in‐hospital mortality (OR, 1.52), non‐home–based discharge (OR, 1.36), longer LOS (RR, 1.30) and higher THCs (RR, +$11 806). Conclusion Preoperative frailty is important in RNU patients. One of four RNU patients is frail. Moreover, frailty predicts short‐term postoperative complications, as well as longer LOS and higher THCs after RNU.

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Location of Metastatic Bladder Cancer as a Determinant of In-hospital Mortality After Radical Cystectomy

Cited by 17 publications

References 17 publications

Single-cell RNAseq and longitudinal proteomic analysis of a novel semi-spontaneous urothelial cancer model reveals tumor cell heterogeneity and pretumoral urine protein alterations

Single-cell RNAseq and longitudinal proteomic analysis of a novel semi-spontaneous urothelial cancer model reveals tumor cell heterogeneity and pretumoral urine protein alterations

Dramatic Impact of Centralization and a Multidisciplinary Bladder Cancer Program in Reducing Mortality: The CABEM Project

Preoperative frailty predicts adverse short‐term postoperative outcomes in patients treated with radical nephroureterectomy

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