Intraoperative Sentinel Node Detection Improves Nodal Staging in Invasive Bladder Cancer Fredrik Liedberg,* Gunilla Chebil, Thomas Davidsson, Sigurdur Gudjonsson and Wiking Månsson From the Department of Urology, Lund University Hospital, Lund and Department of Pathology, Helsingborg County Hospital (GC), Helsingborg, Sweden Purpose: We evaluated intraoperative SN detection in patients with invasive bladder cancer during radical cystectomy in conjunction with extended lymphadenectomy. Materials and Methods: A total of 75 patients with invasive bladder cancer underwent radical cystectomy with extende lymphadenectomy. SNs were identified by preoperative lymphoscintigraphy, intraoperative dynamic lymphoscintigraphy and blue dye detection. An isotope (70 MBq 99m Tc-nanocolloid) and Patent Blue® blue dye were injected peritumorally via a cystoscope. Excised lymph nodes were examined ex vivo using a handheld ␥probe. Identified SNs were evaluated by extended serial sectioning, hematoxylin and eosin staining, and immunohistochemistry. Results: At lymphadenectomy an average of 40 nodes (range 8 to 67) were removed. Of 75 patients 32 (43%) were lymp positive, of whom 13 (41%) had all lymph node metastases located only outside of the obturator spaces. An SN was ident in 65 of 75 patients (87%). In 7 patients an SN was recognized when the nodal basins were assessed with the ␥ probe after lymphadenectomy and cystectomy. Of the 32 lymph node positive cases 26 (81%) had a positive (metastatic) SN. Thus, t false-negative rate was 6 of 32 cases (19%). Five false-negative cases had macrometastases and/or perivesical metastase 9 patients (14%)the SN contained micrometastases (less than 2 mm), in 5 of whom the micrometastasis was the only metastatic deposit. Conclusions: SN detection is feasible in invasive bladder cancer, although the false- negative rate was 19% in this study Extended serialsectioning and immunohistochemistry revealed micrometastases in SNs in 9 patients and radio guided surgery after the completion of lymphadenectomy identified SNs in an additional 7. We believe that the technique that we used in this study improved nodal staging in these 16 of 65 patients (25%). Key Words: bladder, bladder neoplasms, neoplasm invasiveness, cystectomy, lymph nodes I n addition to pathological stage, nodal status represents the most important predictor of the outcome of radical cystectomy for muscle invasive bladder cancer. In the last 2 decades the technique of radical cystectomy has evolved to include fairly extended lymphadenectomy, 1 with published 5-year survival rates of 23% to 35% for node positive disease. 2,3 Nevertheless,there is still considerable controversy regarding the appropriate extent of lymphade- nectomy and the number of nodes that should be dissected. It has been suggested that nodal staging can be improved by removing more than 16 nodes because that strategy would increase the detection of lymph node metastases. 4 However, a study of Bochner et al did not reveal any staging advan- tage when lymphadenectomy extended to the aortic bifurca- tion was compared with standard lymphadenectomy to the iliac bifurcation. 5 Knowledge of the pathway of the spread of tumor cells is a prerequisite for complete clearance and it is also the basis of the SN concept. According to this view tumor cells metas- tasizing via the lymphatics enter the SN,that is the first node of the regional lymph node basin, before they dissem- inate sequentially to other lymph nodes. The SN is specific in each individual. SN detection allows the identification of a small volume of representative nodal tissue for thorough pathologicalevaluation.The detection ofmicrometastases can be improved by ultrastaging, which entails SN analysis by extended serial sectioning combined with IHC tech- niques. 6 Radio guided surgery,in which ␥ emitting sub- stances are injected close to the tumor and a ␥ detecting probe is used, is done to identify the SN. 7 A small pilot study was recently performed to evaluate SN detection in patients with invasive bladder cancer in conjunction with limited lymphadenectomy. 8 We deter- mined whether nodal staging in such cancer cases could be improved by SN detection along with careful examination of the nodes at extended pelvic lymphadenectomy. MATERIALS AND METHODS The study was performed from May 2001 to December 2004 in 75 patients, including 59 men and 16 women with a mean age of 65 years (range 46 to 81)who were scheduled for radical cystectomy at the Department of Urology, Lund Uni- versity Hospital due to locally advanced urothelialcarci- noma of the bladder.Two patients had clinical stage T4b disease and received neoadjuvantchemotherapy prior to cystectomy. During the same period 22 additional patients Submitted for publication March 31, 2005. Study received Ethics Committee, Lund University approval. * Correspondence: Department of Urology, Lund University Hos- pital, SE-221 85 Lund, Sweden (FAX: ⫹46462112598; e-mail: fredrik.liedberg@skane.se). 0022-5347/06/1751-0084/0 Vol. 175, 84-89, January 2006 THE J OURNAL OF UROLOGY ® Printed in U.S.A. Copyright © 2006 by A MERICAN U ROLOGICAL ASSOCIATION DOI:10.1016/S0022-5347(05)00066-2 84