M. Babjuk, M. Burger, R. Zigeuner, S. F. Shariat, B. Van-rhijn et al., EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update, Eur Urol, vol.64, pp.639-53, 2013.

S. Antoni, J. Ferlay, I. Soerjomataram, A. Znaor, A. Jemal et al., Bladder cancer incidence and mortality: a global overview and recent trends, Eur Urol, vol.71, pp.96-108, 2017.

M. Ploeg, K. Aben, and L. A. Kiemeney, The present and future burden of urinary bladder cancer in the world, World J Urol, vol.27, pp.289-93, 2009.

D. C. Johnson, P. S. Greene, and M. E. Nielsen, Surgical advances in bladder cancer: at what cost?, Urol Clin North Am, vol.42, pp.235-52, 2015.

J. Bellmunt, A. Orsola, J. J. Leow, T. Wiegel, D. Santis et al., ESMO practice guidelines for diagnosis, treatment and follow-up, Ann Oncol, vol.25, issue.3, pp.40-48, 2014.

B. Van-rhijn, M. Burger, Y. Lotan, E. Solsona, C. G. Stief et al., Recurrence and progression of disease in non-muscle-invasive bladder cancer: from epidemiology to treatment strategy, Eur Urol, vol.56, pp.430-472, 2009.

M. Rouprêt, Y. Neuzillet, A. Masson-lecomte, C. P. Compérat, E. Dubosq et al., CCAFU french national guidelines 2016-2018 on bladder cancer, Progres En Urol, vol.27, issue.1, pp.67-91, 2016.

J. Bellmunt and S. Albiol, Chemotherapy for metastatic or unresectable bladder cancer, Semin Oncol, vol.34, pp.135-179, 2007.

J. Bellmunt, C. Théodore, T. Demkov, B. Komyakov, L. Sengelov et al., Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract, J Clin Oncol, vol.27, pp.4454-61, 2009.

T. Powles, J. P. Eder, G. D. Fine, F. S. Braiteh, Y. Loriot et al., MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer, Nature, vol.515, pp.558-62, 2014.

J. E. Rosenberg, J. Hoffman-censits, T. Powles, M. S. Van-der-heijden, A. V. Balar et al., Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial, Lancet, vol.387, pp.1909-1929, 2016.

J. Bellmunt, R. De-wit, D. J. Vaughn, Y. Fradet, J. Lee et al., Pembrolizumab as second-line therapy for advanced Urothelial carcinoma, N Engl J Med, vol.376, pp.1015-1041, 2017.

P. Sharma, M. Retz, A. Siefker-radtke, A. Baron, A. Necchi et al., Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial, Lancet Oncol, vol.18, pp.312-334, 2017.

N. M. Hahn, T. Powles, C. Massard, H. Arkenau, T. W. Friedlander et al., Updated efficacy and tolerability of durvalumab in locally advanced or metastatic urothelial carcinoma (UC), J Clin Oncol, vol.35, p.4525, 2017.

M. R. Patel, J. A. Ellerton, J. R. Infante, M. Agrawal, M. S. Gordon et al., Avelumab in patients with metastatic urothelial carcinoma: pooled results from two cohorts of the phase 1b JAVELIN solid tumor trial, J Clin Oncol, vol.35, p.330, 2017.

N. Houédé and P. Pourquier, Targeting the genetic alterations of the PI3K-AKT-mTOR pathway: its potential use in the treatment of bladder cancers, Pharmacol Ther, vol.145, pp.1-18, 2015.

G. Fechner, K. Classen, D. Schmidt, S. Hauser, and S. C. Müller, Rapamycin inhibits in vitro growth and release of angiogenetic factors in human bladder cancer, Urology, vol.73, pp.665-674, 2009.

F. Schedel, R. Pries, B. Thode, B. Wollmann, S. Wulff et al., mTOR inhibitors show promising in vitro activity in bladder cancer and head and neck squamous cell carcinoma, Oncol Rep, vol.25, pp.763-771, 2011.

J. J. Mansure, R. Nassim, S. Chevalier, J. Rocha, E. Scarlata et al., Inhibition of mammalian target of rapamycin as a therapeutic strategy in the management of bladder cancer, Cancer Biol Ther, vol.8, pp.2339-2386, 2009.

C. Vasconcelos-nóbrega, R. Pinto-leite, R. Arantes-rodrigues, R. Ferreira, P. Brochado et al., In vivo and in vitro effects of RAD001 on bladder cancer, Urol Oncol, vol.31, pp.1212-1233, 2013.

D. N. Franz, E. Belousova, S. Sparagana, E. M. Bebin, M. Frost et al., Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial, Lancet, vol.381, pp.125-157, 2013.

T. E. Hutson, B. Escudier, E. E. Bjarnason, G. A. Lim, H. Y. Pittman et al., Randomized phase III trial of temsirolimus versus sorafenib as second-line therapy after sunitinib in patients with metastatic renal cell carcinoma, J Clin Oncol, vol.32, pp.760-767, 2014.

B. I. Rini, J. Bellmunt, J. Clancy, K. Wang, A. G. Niethammer et al., Randomized phase III trial of temsirolimus and bevacizumab versus interferon alfa and bevacizumab in metastatic renal cell carcinoma: INTORACT trial, J Clin Oncol, vol.32, pp.752-761, 2014.

J. Baselga, M. Campone, M. Piccart, H. A. Burris, H. S. Rugo et al., Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer, N Engl J Med, vol.366, pp.520-529, 2012.

J. C. Yao, M. H. Shah, T. Ito, C. L. Bohas, E. M. Wolin et al., Everolimus for advanced pancreatic neuroendocrine tumors, N Engl J Med, vol.364, pp.514-537, 2011.

E. Seront, S. Rottey, B. Sautois, J. Kerger, D. 'hondt et al., Phase II study of everolimus in patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract: clinical activity, molecular response, and biomarkers, Ann Oncol, vol.23, pp.2663-70, 2012.

M. I. Milowsky, G. Iyer, A. M. Regazzi, H. Al-ahmadie, S. R. Gerst et al., Phase II study of everolimus in metastatic urothelial cancer, BJU Int, vol.112, pp.462-70, 2013.

G. Iyer, H. Al-ahmadie, N. Schultz, A. J. Hanrahan, I. Ostrovnaya et al., Prevalence and co-occurrence of actionable genomic alterations in highgrade bladder cancer, J Clin Oncol, vol.31, pp.3133-3173, 2013.

H. Gerullis, C. Eimer, T. H. Ecke, E. Georgas, C. Freitas et al., A phase II trial of temsirolimus in second-line metastatic urothelial cancer, Med Oncol, vol.29, pp.2870-2876, 2012.

N. Houédé, G. Roubaud, H. Mahammedi, L. Vedrine, F. Joly et al., Safety and efficacy of temsirolimus as second-line treatment for patients with recurrent bladder cancer, J Clin Oncol, vol.33, issue.7, p.304, 2015.

E. A. Eisenhauer, P. Therasse, J. Bogaerts, L. H. Schwartz, D. Sargent et al., New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1), Eur J Cancer, vol.45, pp.228-275, 2009.

R. Simon, Optimal two-stage designs for phase II clinical trials, Control Clin Trials, vol.10, pp.1-10, 1989.

D. Machin, M. J. Campbell, S. Tan, and S. Tan, Sample size tables for clinical studies, 2009.

C. Costa, S. Pereira, L. Lima, A. Peixoto, E. Fernandes et al., Role in bladder cancer prognosis and targeted therapeutics, PLoS One, vol.10, p.141253, 2015.

J. Bellmunt, J. M. Kerst, F. Vázquez, R. Morales-barrera, E. Grande et al., A randomized phase II/III study of cabazitaxel versus vinflunine in metastatic or locally advanced transitional cell carcinoma of the urothelium (SECAVIN), Ann Oncol, vol.28, pp.1517-1539, 2017.

E. Seront, S. Rottey, B. Filleul, P. Glorieux, J. Goeminne et al., Phase II study of dual phosphoinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor BEZ235 in patients with locally advanced or metastatic transitional cell carcinoma, BJU Int, vol.118, pp.408-423, 2016.

G. Iyer, A. J. Hanrahan, M. I. Milowsky, H. Al-ahmadie, S. N. Scott et al., Genome sequencing identifies a basis for everolimus sensitivity, Science, vol.338, p.221, 2012.

H. Öztürk, Comparing RECIST with EORTC criteria in metastatic bladder cancer, J Cancer Res Clin Oncol, vol.142, pp.187-94, 2016.

S. Gupta, D. Gill, A. Poole, and N. Agarwal, Systemic immunotherapy for Urothelial cancer: current trends and future directions, Cancers, vol.9, p.15, 2017.

M. Vanneman and G. Dranoff, Combining immunotherapy and targeted therapies in cancer treatment, Nat Rev Cancer, vol.12, pp.237-51, 2012.

A. M. Hau, M. Nakasaki, K. Nakashima, G. Krish, and D. E. Hansel, Differential mTOR pathway profiles in bladder cancer cell line subtypes to predict sensitivity to mTOR inhibition, Urol Oncol, vol.35, pp.593-602, 2017.