Oncology Outcomes of Patients with Clinical T1 Grade 3 Urothelial Cell Bladder Carcinoma Treated with Radical Cystectomy Amit Gupta, Yair Lotan, Patrick J. Bastian, Ganesh S. Palapattu, Pierre I. Karakiewicz, Ganesh V. Raj, Mark P. Schoenberg, Seth P. Lerner, Arthur I. Sagalowsky, and Shahrokh F. Shariat OBJECTIVES Urothelial tumors that invade the lamina propria but not the muscularis propria are a particularly problematic clinical entity. The aim of the present study was to assess the pathologic features and clinical outcomes of patients with clinical T1 grade 3 urothelial cell bladder carcinoma (UCBC) treated with radical cystectomy. METHODS We reviewed the records of 958 consecutive patients who underwent radical cystectomy and pelvic lymphadenectomy for bladder cancer at three U.S. academic centers. Of these patients, 167 (median age, 66.7 years) underwent radical cystectomy for clinical stage T1 grade 3 UCBC. RESULTS The median follow-up was 33.8 months (mean  standard deviation: 45.9  39.2 months, range, 0.4 to 177.1) for patients alive at last follow-up. Disease recurred in 48 of 167 of patients (29.4%) and 30 of 162 patients (18.5%) died from bladder cancer. A total of 29 of 166 patients (17.5%) had lymph nodal metastases. Of 167 patients, 84 (50%) were pathologically upstaged and 167 (27.5%) had extravesical disease. Patients with disease upstaging had poorer survival (P 0.001). A greater than 3-month delay between cystectomy and last transurethral resection showed a trend toward upstaging (P = 0.06). Presence of carcinoma in situ (CIS) was the only precys- tecomy factor that predicted disease recurrence (hazard ratio [HR]: 2.13, 95% confidence interval [CI]: 1.14 to 3.98) and mortality (HR: 2.75, 95% CI: 1.17 to 6.46). CONCLUSIONS A large proportion of patients undergoing cystectomy for clinical T1 grade 3 disease have adverse pathological features. The recurrence and survival outcomes in this group are suboptimal. Presence of CIS precystectomy predicts outcomes. Better markers are needed to identify patients at high risk for adverse outcomes. UROLOGY 71: 302–307, 2008. © 2008 Elsevier Inc. O ptimal management of clinical T1 grade 3 urothelial cell bladder cancer (UCBC) lesions is controversial. Understaging of disease is com- mon 1–8 and residual disease is present up to 78% of the times on reresection. 9 Although some patients have good long-term outcomes with transurethral resection (TUR) and intravesical therapy, others develop disease progres- sion and metastases, and die despite radical cystectomy. 10 Early cystectomy offers definitive therapy but must be balanced with the morbidity related to treatment. 11 Fur- thermore, the optimal timing of cystectomy and the factors that predict outcomes in patients undergoing rad- ical cystectomy are unclear. In this large, multi-institu- tional, retrospective study we describe the outcomes of patients who underwent cystectomy for clinical T1 grade 3 disease, and investigate the precystectomy factors that predicted outcomes for these patients. MATERIAL AND METHODS Patient Population All studies were undertaken with the approval of the institu- tional review board at each institution. A total of 958 consec- utive patients who underwent radical cystectomy and pelvic lymphadenectomy with curative intent by select surgeons at three academic medical centers during the period March 11, 1984 through January 24, 2003, and who had data available, were candidates for this analysis. Indications for radical cystec- tomy were tumor invasion into the muscularis propria or pros- tatic stroma or Ta, T1, or carcinoma in situ (CIS) refractory to TUR with intravesical chemotherapy and/or immunotherapy. Clinical stage was assigned according to the 1997 Tumor, Nodes, and Metastases (TNM) system. A total of 202 two patients had clinical tumor stage T1. We excluded 17 patients From the Bladder Cancer Research Consortium (BCRC). From the Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas; the James Buchanan Brady Urological Institute, The Johns Hopkins Hospital, Baltimore, Maryland; the Cancer Prognostics and Health Outcomes Unit, University of Montreal, Montreal, Quebec, Canada; and the Scott Department of Urology, Baylor College of Medicine, Houston, Texas Reprint requests: Shahrokh F. Shariat, M.D., Department of Urology, The Univer- sity of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9110. E-mail: shahrokh.shariat@utsouthwestern.edu Submitted: May 17, 2007, accepted (with revisions): October 22, 2007 302 © 2008 Elsevier Inc. 0090-4295/08/$34.00 All Rights Reserved doi:10.1016/j.urology.2007.10.041