Originally published as JCO Early Release 10.1200/JCO.2008.17.2361 on December 15 2008

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Lymphovascular Invasion Predicts Clinical Outcomes in Patients With Node-Negative Upper Tract Urothelial Carcinoma

Eiji Kikuchi, Vitaly Margulis, Pierre I. Karakiewicz, Marco Roscigno, Shuji Mikami, Yair Lotan, Mesut Remzi, Christian Bolenz, Cord Langner, Alon Weizer, Francesco Montorsi, Karim Bensalah, Theresa M. Koppie, Mario I. Fernández, Jay D. Raman, Wassim Kassouf, Christopher G. Wood, Nazareno Suardi, Mototsugu Oya, Shahrokh F. Shariat

From Keio University School of Medicine, Tokyo, Japan; The University of Texas M. D. Anderson Cancer Center, Houston; University of Texas Southwestern Dallas, Dallas, TX; University of Michigan, Ann Arbor, MI; University of California Davis, Sacramento, CA; Cornell University, New York, NY; University of Montreal; McGill University, Montreal, Quebec, Canada; Vita-Salute University, Milan, Italy; University of Vienna, Vienna; Medical University Graz, Graz, Austria; University Medical Center Mannheim, Mannheim, Germany; University of Rennes, Rennes, France; and the Clinica Alemana, Santiago de Chile, Chile.

Corresponding author: Shahrokh F. Shariat, MD, Division of Urology/Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Box 27, New York, NY 10065; e-mail: shariats{at}mskcc.org.

Purpose To assess the association of lymphovascular invasion (LVI) with cancer recurrence and survival in a large international series of patients treated with radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC).

Patients and Methods Data were collected on 1,453 patients treated with RNU at 13 academic centers and combined into a relational database. Pathologic slides were rereviewed by genitourinary pathologists according to strict criteria. LVI was defined as presence of tumor cells within an endothelium-lined space.

Results LVI was observed in 349 patients (24%). Proportion of LVI increased with advancing tumor stage, high tumor grade, presence of tumor necrosis, sessile tumor architecture, and presence of lymph node metastasis (all P < .001). LVI was an independent predictor of disease recurrence and survival (P < .001 for both). Addition of LVI to the base model (comprising pathologic stage, grade, and lymph node status) marginally improved its predictive accuracy for both disease recurrence and survival (1.1%, P = .03; and 1.7%, P < .001, respectively). In patients with negative lymph nodes and those in whom a lymphadenectomy was not performed (n = 1,313), addition of LVI to the base model improved the predictive accuracy of the base model for both disease recurrence and survival by 3% (P < .001 for both). In contrast, LVI was not associated with disease recurrence or survival in node-positive patients (n = 140).

Conclusion LVI was an independent predictor of clinical outcomes in nonmetastatic patients who underwent RNU for UTUC. Assessment of LVI may help identify patients who could benefit from multimodal therapy after RNU. After confirmation, LVI should be included in staging of UTUC.

Both E.K. and S.F.S. contributed equally to this work.

S.F.S. is partially supported by a T32 training grant from the National Institutes of Health (T32CA082088); P.I.K. is partially supported by the University of Montreal Health Center Urology Associated, Fonds de la Recherche en Santé du Québéc, the University of Montreal, Department of Surgery and the University of Montreal Health Center (CHUM) Foundation; V.M. is partially supported by American Urological Association Foundation; and C.G.W. is partially supported by Grant No. R01CA104505 from the National Cancer Institute.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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