Risk Stratification Tools and Prognostic Models in Non-muscle-invasive Bladder Cancer: A Critical Assessment from the European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel.

CONTEXT: This review focuses on the most widely used risk stratification and prediction tools for non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To assess the clinical use and relevance of risk stratification and prediction tools to enhance clinical decision making and counselling of patients with NMIBC. EVIDENCE ACQUISITION: The most frequent, currently used risk stratification tools and prognostic models for NMIBC patients were identified by the members of the European Association of Urology (EAU) Guidelines Panel on NMIBC. EVIDENCE SYNTHESIS: The 2006 European Organization for Research and Treatment of Cancer (EORTC) risk tables are the most widely used and validated tools for risk stratification and prognosis prediction in NMIBC patients. The EAU risk categories constitute a simple alternative to the EORTC risk tables and can be used for comparable risk stratification. In the subgroup of NMIBC patients treated with a short maintenance schedule of bacillus Calmette-Guerin (BCG), the Club Urológico Español de Tratamiento Oncológico (CUETO) scoring model is more accurate than the EORTC risk tables. Both the EORTC risk tables and the CUETO scoring model overestimate the recurrence and progression risks in patients treated according to current guidelines. The new concept of conditional recurrence and progression estimates is very promising during follow-up but should be validated. CONCLUSIONS: Risk stratification and prognostic models enable outcome comparisons and standardisation of treatment and follow-up. At present, none of the available risk stratification and prognostic models reflects current standards of treatment. The EORTC risk tables and CUETO scoring model should be updated with previously unavailable data and recalculated. PATIENT SUMMARY: Non-muscle-invasive bladder cancer is a heterogeneous disease. A risk-based therapeutic approach is recommended. We present available risk stratification and prediction tools and the degree of their validation with the aim to increase their use in everyday clinical practice.

The European Medicines Agency approval of axitinib (Inlyta) for the treatment of advanced renal cell carcinoma after failure of prior treatment with sunitinib or a cytokine: summary of the scientific assessment of the committee for medicinal products for human use.

Axitinib is a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR-1), VEGFR-2, and VEGFR-3. Based on the positive opinion from the European Medicines Agency (EMA), a marketing authorization valid throughout the European Union (EU) was issued for the treatment of advanced renal cell carcinoma (RCC) after failure of prior treatment with sunitinib or a cytokine. The demonstration of clinical benefit for axitinib was based on a phase III, randomized, open-label, multicenter study of axitinib compared with sorafenib in patients with advanced RCC after failure of a prior systemic first-line regimen containing one or more of the following agents: sunitinib, bevacizumab plus interferon-α, temsirolimus, or cytokines. In the primary analysis, a 2-month increase in median progression-free survival (PFS) was observed for axitinib compared with sorafenib (hazard ratio [HR]: 0.665; 95% confidence interval [CI]: 0.544-0.812; p < .0001). In the subgroup of patients with a prior cytokine-containing regimen, the increase in median PFS associated with axitinib was 5.4 months (updated analysis, HR: 0.519; 95% CI: 0.375-0.720; p < .0001). In the subgroup of patients with prior sunitinib treatment, the increase in median PFS was 1.4 months (updated analysis, HR: 0.736; 95% CI: 0.578-0.937; p = .0063). The analysis of overall survival showed no statistically significant survival benefit of axitinib over sorafenib in patients previously treated with cytokine-containing regimens (HR: 0.813; 95% CI: 0.556-1.191) or sunitinib (HR: 0.997; 95% CI: 0.782-1.270). The most common treatment-related adverse events associated with axitinib included diarrhea, hypertension, fatigue, nausea, decreased appetite, dysphonia, and palmar-plantar erythrodysesthesia. Most of these events were mild or moderate in severity. This paper summarizes the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the EMA website (http://www.ema.europa.eu).

Recurrence and progression of disease in non-muscle-invasive bladder cancer: from epidemiology to treatment strategy.

CONTEXT: This review focuses on the prediction of recurrence and progression in non-muscle invasive bladder cancer (NMIBC) and the treatments advocated for this disease. OBJECTIVE: To review the current status of epidemiology, recurrence, and progression of NMIBC and the state-of-the art treatment for this disease. EVIDENCE ACQUISITION: A literature search in English was performed using PubMed and the guidelines of the European Association of Urology and the American Urological Association. Relevant papers on epidemiology, recurrence, progression, and management of NMIBC were selected. Special attention was given to fluorescent cystoscopy, the new World Health Organisation 2004 classification system for grade, and the role of substaging of T1 NMIBC. EVIDENCE SYNTHESIS: In NMIBC, approximately 70% of patients present as pTa, 20% as pT1, and 10% with carcinoma in situ (CIS) lesions. Bladder cancer (BCa) is the fifth most frequent type of cancer in western society and the most expensive cancer per patient. Recurrence (in < or = 80% of patients) is the main problem for pTa NMIBC patients, whereas progression (in < or = 45% of patients) is the main threat in pT1 and CIS NMIBC. In a recent European Organisation for Research and Treatment of Cancer analysis, multiplicity, tumour size, and prior recurrence rate are the most important variables for recurrence. Tumour grade, stage, and CIS are the most important variables for progression. Treatment ranges from transurethral resection (TUR) followed by a single chemotherapy instillation in low-risk NMIBC to, sometimes, re-TUR and adjuvant intravesical therapy in intermediate- and high-risk patients to early cystectomy for treatment-refractory high-risk NMIBC. CONCLUSIONS: NMIBC is a heterogeneous disease with varying therapies, follow-up strategies, and oncologic outcomes for an individual patient.