invasive bladder cancer: long-term results. J Clin Oncol 2002;20:3061–9. [9] Herr HW. Outcome of patients who refuse cystectomy after receiving neoadjuvant chemotherapy for muscle- invasive bladder cancer. Eur Urol 2008;54:126–32. [10] Solsona E, Climent MA, Iborra I, et al. Bladder preservation in selected patients with muscle-invasive bladder cancer by complete transurethral resection of the bladder plus systemic chemotherapy: long-term follow-up of a phase 2 nonrandomized comparative trial with radical cystectomy. Eur Urol. In press. doi:10.1016/j.eururo. 2008.08.027. doi:10.1016/j.eururo.2008.10.033 Rebuttal from Authors re: Harry W. Herr. Neo- adjuvant Chemotherapy: A New Treatment Paradigm for Muscle-Invasive Bladder Cancer. Eur Urol 2009;55:303–5 Cora N. Sternberg *, Fabio Calabro ` Department of Medical Oncology, San Camillo Forlanini Hospital, Nuovi Padiglioni, 4th floor, Circonvallazione Gianicolense 87, Rome 00152, Italy The authors basically agree with Dr. Herr’s point of view. As other investigators have, we have used response to neoadjuvant methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin (M-VAC) chemotherapy combined with other pathologic tumor features to select patients for bladder preservation [1]. Undoubtedly, it would be better to guide future decision making on the basis of more sophisticated molecular features. Urothelial cancer has countless molecular targets that make it very attractive for the investigation of novel agents; however, in contrast with other more common epithelial cancer, evaluation of novel agents in this disease has been limited. We agree that the neoadjuvant paradigm is an excellent strategy for evaluating molecular char- acteristics and other tumor-tissue studies, aiming to predict drug responses with the hope of ulti- mately leading to tailored or risk-adjusted indivi- dualized therapy [2]. This is an experimental strategy that can pave the way for future advances, as tissue is readily available at transurethral resection of the bladder (TURB) and after therapy at cystectomy. Unfortunately, we have come up against a dead end in our ability to properly collaborate and to perform adjuvant chemotherapy trials on an international basis. Dr. Herr was the pioneer in demonstrating that the quality of cystectomy and pelvic lymph node dissection were just as important as whether or not patients actually received neoadjuvant M-VAC chemotherapy in the Southwest Oncology Group (SWOG) trial [3]. The investigators at Memorial Sloan-Kettering Cancer Center (MSKCC) now have retrospective evidence from 42 patients that neoad- juvant gemcitabine and cisplatin (GC) result in a similar pT0 rate when compared with M-VAC. While these results are intriguing, this is a phase 2 trial from an exceptional cancer center with a limited number of patients and a median follow-up of 30 months [4]. Hopefully, sustained disease-free survival for these patients status will be achieved. Notably, prior meta-analyses of neoadjuvant che- motherapy trials have not included any studies containing neoadjuvant GC. Lastly, the recently launched MSKCC neoadjuvant protocol using four cycles of GC combined with sunitinib, a multi- targeted tyrosine inhibitor, is entirely experimental; this combination has never been shown to be effective in the metastatic setting. Hopefully, this combination will not accentuate the myelosuppres- sion and thrombocytopenia often associated with both GC and with sunitinb and will not lead to increased surgical complications related to targeting the vascular endothelial growth factor receptor (VEGFR). Nonetheless, this approach is a commend- able attempt to move forward. We can surely do better than a 5% improvement in survival by giving upfront neoadjuvant chemotherapy, which may be what is required to overcome the resistance to neoadjuvant chemotherapy in the urologic community. Conflicts of interest: The authors have nothing to disclose. References [1] Sternberg CN, Pansadoro V, Calabro ` F, et al. Can patient selection for bladder preservation be based on response to chemotherapy? Cancer 2003;97:1644–52. [2] Sweeney C, Bajorin D, Sternberg CN. Muscle invasive blad- der cancer: what have we learned and what’s new on the DOIs of original articles: 10.1016/j.eururo.2008.10.016, 10.1016/ j.eururo.2008.10.033 * Corresponding author. E-mail address: cstern@mclink.it (C.N. Sternberg). european urology 55 (2009) 303–306 305