399 ISSN 1479-6694 Future Oncol. (2015) 11(3), 399–408 part of 10.2217/FON.14.267 © 2015 Future Medicine Ltd RESEARCH ARTICLE Three-tiered nodal classifcation system for bladder cancer: a new proposal Jose A Pedrosa 1 , Michael O Koch 1 , Hristos Z Kaimakliotis 1 , M Francesca Monn 1 , Timothy A Masterson 1 , Kevin R Rice 1 , K Clint Cary 1 , Richard S Foster 1 , Richard Bihrle 1 & Liang Cheng* ,1 1 Department of Pathology & Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA 2 Department of Urology, Indiana University School of Medicine, Indianapolis, IN 46202, USA *Author for correspondence: Tel.: +1 317 491 6442; Fax: +1 317 491 6419; liang_cheng@yahoo.com ABSTRACT Aim: To evaluate a three-tiered prognostic stratifcation using one, two to fve and >fve positive lymph nodes (LNs) and this nodal staging system performs across diferent pelvic LN dissection (PLND) templates and adjuvant chemotherapy status. Methods: We evaluated 244 patients with positive LN urothelial cancer who underwent radical cystectomy and PLND between 2000 and 2011. Survival analyses utilizing the Kaplan-Meier method and log rank test were performed. Median follow-up was 55.3 months (range: 0.4–141). Multivariable Cox proportional hazards models were built to evaluate the prognostic stratifcation. Results: Extended PLND template was performed on 152 (62.3%) patients and standard on 92 (37.7%). The median number of LNs resected was 14 in the standard group vs 22 in the extended group (p < 0.01) and positive LNs was 2 vs 3 (p = 0.09), respectively. Stratifcation in patients with: one positive LN, two to fve positive LNs or >fve positive LNs lead to 5-year recurrence-free survival of: 48.6, 34.5 and 15.9% for each group, while the 5-year overall survival was: 43.0, 22.1 and 11.3%, respectively. Stratifcation in the three groups was also verifed irrespective of PLND template and adjuvant chemotherapy. Two multivariable models confrmed the fndings when controlling for demographic features and known pathologic risk factors. Conclusion: Three-tiered nodal classifcation system using the number of metastatic LNs (one, two to fve and >fve) stratifes patients with lymphatic disease into distinct prognostic groups. KEYWORDS • adjuvant chemotherapy • cystectomy • lymph node dissection • neoadjuvant chemotherapy • nodal metastasis • prognosis • survival outcome • TNM classifcations • urinary bladder • urothelial carcinoma Several prognostic variables in the setting of lymph node (LN)-positive bladder cancer have been proposed, mainly represented by indicators of lymphatic disease burden, specific nodal pathologic features and markers of anatomic disease spread [1] . The American Joint Committee on Cancer (AJCC) 6th edition of the Tumor Nodal Metastasis (TNM) staging system used the size and number of LNs to stratify LN-positive patients [2] . Criticism of this staging system included the fact that node size can be influenced by reactive or inflammatory responses to the presence of a tumor or therapeutic interventions such as BCG. Thus, LN size may not, in fact, be directly associated with the burden of disease. In 2010, the 7th edition of the TNM staging system was introduced [3] . In the new system, metastasis to the common iliac nodes was incorporated as regional metastatic disease instead of distant metastasis. Differentiation between pelvic and common iliac LN involvement was maintained; the latter group is now defined as a new N3 category, replacing the earlier size criteria (Table 1) . These anatomic criteria are mainly based on cadaveric studies of pelvic lymphatic drainage and, to date, there are no clinical data to support its prognostic significance [4–8] . In addition, the current classification suffers from lack of applicability when considering patients submitted to standard versus extended pelvic LN dissection (PLND) or en bloc submission of LNs. At the same time, a number of For reprint orders, please contact: reprints@futuremedicine.com