Lymphovascular Invasion Is Independently Associated With Overall Survival, Cause-Specific Survival, and Local and Distant Recurrence in Patients With Negative Lymph Nodes at Radical Cystectomy Yair Lotan, Amit Gupta, Shahrokh F. Shariat, Ganesh S. Palapattu, Amnon Vazina, Pierre I. Karakiewicz, Patrick J. Bastian, Craig G. Rogers, Gilad Amiel, Paul Perotte, Mark P. Schoenberg, Seth P. Lerner, and Arthur I. Sagalowsky A B S T R A C T Purpose We hypothesized that bladder cancer patients with associated lymphovascular invasion (LVI) are at increased risk of occult metastases. Methods A multi-institutional group (University of Texas Southwestern [Dallas, TX], Baylor College of Medicine [Houston, TX], Johns Hopkins University [Baltimore, MD]) carried out a retrospec- tive study of 958 patients who underwent cystectomy for bladder cancer between 1984 and 2003. Of patients with transitional-cell carcinoma (n = 776), LVI status was available for 750. LVI was defined as the presence of tumor cells within an endothelium-lined space. Results LVI was present in 36.4% (273 of 750) overall, involving 26% (151 of 581) and 72% (122 of 169) of node-negative and node-positive patients, respectively. Prevalence of LVI increased with higher pathologic stage (9.0%, 23%, 60%, and 78%, for T1, T2, T3, and T4, respectively; P  .001). Using multivariate Cox regression analyses including age, stage, grade, and number of pelvic lymph nodes removed, LVI was an independent predictor of local (HR = 2.03, P = .049), distant (HR = 2.60, P = .0011), and overall (HR = 2.02, P = .0003) recurrence in node-negative patients. LVI was an independent predictor of overall (HR = 1.84, P = .0002) and cause-specific (HR = 2.07, P = .0012) survival in node-negative patients. LVI maintained its independent predictor status in competing risks regression models (P = .013), where other-cause mortality was considered as a competing risk. LVI was not a predictor of recurrence or survival in node-positive patients. Conclusion LVI is an independent predictor of recurrence and decreased cause-specific and overall survival in patients who undergo cystectomy for invasive bladder cancer and are node- negative. These patients represent a high risk group that may benefit from integrated therapy with cystectomy and perioperative systemic chemotherapy. J Clin Oncol 23:6533-6539. © 2005 by American Society of Clinical Oncology INTRODUCTION Bladder cancer is the fourth most common cancer in men (6%) and the 10th most com- mon cancer in women (2%), accounting in men for 3% of cancer deaths in the year 2004 in the United States. 1 On average, 15% to 30% of all patients with bladder cancer are diag- nosed with muscle-invasive tumors, for which radical cystectomy is the current gold standard therapy. 2 Unfortunately, as many as 40% of patients with organ-confined disease at the From the Department of Urology, University of Texas Southwestern Medical Center, Dallas; Baylor College of Medicine, Houston, TX; The James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD; Centre Hospitalier de l’Université de Montréal, Campus St-Luc, Montreal, Quebec, Canada. Submitted February 8, 2005; accepted March 1, 2005. Drs Lotan and Gupta contributed equally to this study. Authors’ disclosures of potential con- flicts of interest are found at the end of this article. Address reprint requests to Yair Lotan, MD, Department of Urology, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, J8.112, Dallas, TX 75390- 9110; e-mail: yair.lotan@ UTSouthwestern.edu. © 2005 by American Society of Clinical Oncology 0732-183X/05/2327-6533/$20.00 DOI: 10.1200/JCO.2005.05.516 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 23  NUMBER 27  SEPTEMBER 20 2005 6533 Downloaded from jco.ascopubs.org on July 5, 2016. For personal use only. No other uses without permission. Copyright © 2005 American Society of Clinical Oncology. All rights reserved.