BACKGROUND: The literature on upper tract urothelial carcinoma (UTUC) has been limited to small, single center studies. A large series of patients treated with radical nephroureterectomy for UTUC were studied, and variables associated with poor prognosis were identified.METHODS: Data on 1363 patients treated with radical nephroureterectomy at 12 academic centers were collected. All pathologic slides were re‐reviewed by genitourinary pathologists according to strict criteria.RESULTS: Pathologic review revealed renal pelvis location (64%), necrosis (21.6%), lymphovascular invasion (LVI) (24.8%), concomitant carcinoma in situ (28.7%), and high‐grade disease (63.7%). A total of 590 patients (43.3%) underwent concurrent, lymphadenectomy and 135 (9.9%) were lymph node (LN) ‐positive. Over a mean follow‐up of 51 months, 379 (28%) patients experienced disease recurrence outside of the bladder and 313 (23%) died of UTUC. The 5‐year recurrence‐free and cancer‐specific survival probabilities (±SD) were 69% ± 1% and 73% ± 1%, respectively. On multivariate analysis, high tumor grade (hazards ratio [HR]: 2.0, P < .001), advancing pathologic T stage (P‐for‐trend <.001), LN metastases (HR: 1.8, P < .001), infiltrative growth pattern (HR: 1.5, P < .001), and LVI (HR: 1.2, P = .041) were associated with disease recurrence. Similarly, patient age (HR: 1.1, P = .001), high tumor grade (HR: 1.7, P = .001), increasing pathologic T stage (P‐for‐trend <.001), LN metastases (HR: 1.7, P < .001), sessile architecture (HR: 1.5, P = .002), and LVI (HR: 1.4, P = .02) were independently associated with cancer‐specific survival.CONCLUSIONS: Radical nephroureterectomy provided durable local control and cancer‐specific survival in patients with localized UTUC. Pathologic tumor grade, T stage, LN status, tumor architecture, and LVI were important prognostic variables associated with oncologic outcomes, which could potentially be used to select patients for adjuvant systemic therapy. Cancer 2009. © 2009 American Cancer Society.

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.