European Association of Urology (EAU) Prognostic Factor Risk Groups for Non–muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel

Sylvester, Richard; Rodríguez, Ó.; Hernández, Virginia; Turturica, Diana; Bauerová, Lenka; Bruins, Harman Max; Bründl, Johannes; Kwast, Theo H. van der; Brisuda, A.; Rubio‐Briones, J.; Seles, Maximilian; Hentschel, Anouk E.; Kusuma, V.R.M.; Huebner, Nicolai; Cotte, Juliette; Mertens, Laura S.; Volanis, Dimitrios; Cussenot, Olivier; Henríquez, J.D. Subiela; Peña, Enrique de la; Pisano, Francesca; Pešl, Michael; Heijden, Antoine G. van der; Herdegen, Sonja; Zlotta, Alexandre R.; Háček, Jaromír; Calatrava, Ana; Mannweiler, Sebastian; Bosschieter, Judith; Ashabere, David; Haitel, Andrea; Côté, Jean; Sheikh, Soha El; Lunelli, Luca; Algaba, Ferrán; Alemany, Isabel; Soria, Francesco; Runneboom, Willemien; Breyer, Johannes; Nieuwenhuijzen, Jakko A.; Llorente, C.; Molinaro, Luca; Kaa, Christina A. Hulsbergen‐van de; Evert, Matthias; Kiemeney, Lambertus A.; N’Dow, James; Plass, Karin; Čapoun, Otakar; Soukup, Viktor; Domínguez-Escrig, José; Cohen, Daniel L.; Palou, Joan; Gontero, Paolo; Burger, Maximilian; Zigeuner, Richard; Mostafid, Amir Hugh; Shariat, Shahrokh F.; Rouprêt, Morgan; Compérat, Éva; Babjuk, Marko; Rhijn, Bas W.G. van

doi:10.1016/j.eururo.2020.12.033

Cited by 233 publications

(245 citation statements)

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“…The pathologic stage was reassigned using the 2010 American Joint Committee on Cancer TNM staging system and tumor grade according to the 1973 World Health Organization (WHO) grading system. Patients were categorized into low, intermediate, and high (added highest only for progression risk classification) risk groups for the prediction of disease progression and recurrence according to the European Association of Urology (EAU) guidelines and European Organization for Research and Treatment of Cancer risk tables (EORTC) [1,15,16].…”

Section: Data Collection and Pathologic Evaluationmentioning

confidence: 99%

Prognostic value of the systemic immune-inflammation index in non-muscle invasive bladder cancer

Katayama

Mori²,

Pradère³

et al. 2021

World J Urol

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Purpose We assessed the prognostic value of systemic immune-inflammation index (SII) to refine risk stratification of the heterogeneous spectrum of patients with non-muscle-invasive bladder cancer (NMIBC) Methods In this multi-institutional cohort, preoperative blood-based SII was retrospectively assessed in 1117 patients with NMIBC who underwent transurethral resection of bladder (TURB) between 1996 and 2007. The optimal cut-off value of SII was determined as 580 using the best Youden index. Cox regression analyses were performed. The concordance index (C-index) and decision curve analysis (DCA) were used to assess the discrimination of the predictive models. Results Overall, 309 (28%) patients had high SII. On multivariable analyses, high SII was significantly associated with worse PFS (hazard ratio [HR] 1.84; 95% confidence interval [CI] 1.23–2.77; P = 0.003) and CSS (HR 2.53; 95% CI 1.42–4.48; P = 0.001). Subgroup analyses, according to the European Association of Urology guidelines, demonstrated the main prognostic impact of high SII, with regards to PFS (HR 3.39; 95%CI 1.57–7.31; P = 0.002) and CSS (HR 4.93; 95% CI 1.70–14.3; P = 0.005), in patients with intermediate-risk group; addition of SII to the standard predictive model improved its discrimination ability both on C-index (6% and 12%, respectively) and DCA. In exploratory intergroup analyses of patients with intermediate-risk, the improved discrimination ability was retained the prediction of PFS and CSS. Conclusion Preoperative SII seems to identify NMIBC patients who have a worse disease and prognosis. Such easily available and cheap standard biomarkers may help refine the decision-making process regarding adjuvant treatment in patients with intermediate-risk NMIBC.

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Section: Data Collection and Pathologic Evaluationmentioning

confidence: 99%

Prognostic value of the systemic immune-inflammation index in non-muscle invasive bladder cancer

Katayama

Mori²,

Pradère³

et al. 2021

World J Urol

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“…Bladder cancer is the seventh most common cancer worldwide and the second most common urological malignancy. Although patients with superficial tumors initially respond well to transurethral resection and intravesical chemotherapy or immune therapy, approximately 60% of patients ultimately experience local recurrence, and up to 40% of patients progress to invasive metastatic disease with potential lethality [ 1 , 2 ]. The combined treatment of gemcitabine (GCB) and platinum analogs, such as cisplatin and carboplatin, is the standard first-line chemotherapy for patients with locally advanced and metastatic bladder cancer [ 3 , 4 ], but the nephrotoxicity of platinum analogs has become the major dose-limiting side effect [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Ellagic Acid Resensitizes Gemcitabine-Resistant Bladder Cancer Cells by Inhibiting Epithelial-Mesenchymal Transition and Gemcitabine Transporters

et al. 2021

Cancers

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Gemcitabine (GCB) resistance is a major issue in bladder cancer chemoresistance, but its underlying mechanism has not been determined. Epithelial-mesenchymal transition (EMT) has been shown to be comprehensively involved in GCB resistance in several other cancer types, but the direct connection between EMT and GCB remains unclear. This study was designed to elucidate the mechanism of EMT-related GCB resistance in bladder cancer and identify a potential phytochemical to modulate drug sensitivity. The biological effects of ellagic acid (EA) or its combined effects with GCB were compared in GCB-resistant cells and the GCB-sensitive line in terms of cell viability, apoptosis, motility, and in vivo tumorigenicity. The molecular regulation of EMT-related GCB resistance was evaluated at both the mRNA and protein expression levels. Our results indicated that TGF-β/Smad induced the overactivation of EMT in GCB-resistant cells and reduced the expression of GCB influx transporters (hCNT1 and hENT1). Moreover, ellagic acid (EA) inhibited the TGF-β signaling pathway both in vitro and in vivo by reducing Smad2, Smad3, and Smad4 expression and thereby resensitized GCB sensitivity. In conclusion, our results demonstrate that TGF-β/Smad-induced EMT contributes to GCB resistance in bladder cancer by reducing GCB influx and also elucidate the novel mechanisms of EA-mediated inhibition of TGF-β/Smad-induced EMT to overcome GCB resistance. Our study warrants further investigation of EA as an effective therapeutic adjuvant agent for overcoming GCB resistance in bladder cancer.

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“…Approximately 75% of newly diagnosed urothelial carcinomas of the bladder (UCB) are non-muscle-invasive bladder cancers (NMIBC) [ 1 ]. High-risk NMIBC is especially difficult to treat, given that recurrence and progression to muscle-invasive bladder cancer (MIBC) occurs in almost two-thirds of cases [ 2 ]. This can be overcome by early cystectomy with cancer-specific survival (CSS) in over 90% of cases; however, 40% of patients experience intra- and postoperative complications as well as the psychological burden of losing a functioning urinary bladder [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

High Androgen Receptor mRNA Expression Is Associated with Improved Outcome in Patients with High-Risk Non-Muscle-Invasive Bladder Cancer

Sikic

Täubert

Wirtz³

et al. 2021

Life

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The role of the androgen receptor (AR) in non-muscle-invasive bladder cancer (NMIBC) remains controversial. We retrospectively analyzed the mRNA expression of AR using RT-qPCR in 95 patients with high-risk NMIBC treated with a bladder-sparing approach and correlated AR with clinical data and recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). The mRNA expression of AR and KRT5, i.e., the basal-like subtype, was strongly correlated (rs = 0.456; p < 0.001). AR (p = 0.053) and KRT5 (p = 0.029) mRNA expression was negatively correlated with tumor grade. Kaplan–Meier analyses indicated significantly prolonged CSS (p = 0.020) and OS (p = 0.015) and a trend towards longer RFS (p = 0.051) in patients with high AR expression. High KRT5 expression was associated with significantly longer RFS (p = 0.033), CSS (p = 0.029) and OS (p = 0.030), while high KRT20 expression was associated with reduced RFS (p = 0.042). In multivariable analysis, none of the molecular markers was an independent prognostic factor. When performing a substratification with regard to molecular markers and clinicopathological parameters, high AR expression showed improved OS in patients with high KRT20 mRNA expression (p = 0.041). Women showed significantly longer OS in cases with high AR expression (p = 0.011). High AR was associated with significantly improved CSS in males (p = 0.044) and patients with instillation therapy (p = 0.040), while OS was improved regardless of instillation therapy. Younger patients with high AR expression had significantly improved RFS (p = 0.021), CSS (p = 0.014) and OS (p = 0.007). RFS was also improved in patients with high AR and low expression of either KRT5 (p = 0.003) or KRT20 (p = 0.014), but not in patients with high expression of KRT5 or KRT20. In conclusion, high AR mRNA expression is correlated with KRT5 mRNA expression and is associated with an improved outcome in high-risk NMIBC.

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European Association of Urology (EAU) Prognostic Factor Risk Groups for Non–muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel

Cited by 233 publications

References 31 publications

Prognostic value of the systemic immune-inflammation index in non-muscle invasive bladder cancer

Prognostic value of the systemic immune-inflammation index in non-muscle invasive bladder cancer

Ellagic Acid Resensitizes Gemcitabine-Resistant Bladder Cancer Cells by Inhibiting Epithelial-Mesenchymal Transition and Gemcitabine Transporters

High Androgen Receptor mRNA Expression Is Associated with Improved Outcome in Patients with High-Risk Non-Muscle-Invasive Bladder Cancer

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