Concomitant carcinoma in situ as an independent prognostic parameter for recurrence and survival in upper tract urothelial carcinoma: a multicenter analysis of 772 patients.

PURPOSE: The purpose of this study is to assess the association of concomitant carcinoma in situ (CIS) with disease recurrence and cancer-related death in a multi-institutional series of patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: We collected retrospectively the data of 772 patients treated with RNU and ipsilateral bladder cuff excision at 9 international institutions in Asia, Europe, and Northern America from 1987 to 2008. Surgical specimens were processed according to standard pathologic procedures at each institution. Univariable and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality. RESULTS: Concomitant CIS was present in 88 patients (11.4%); it was associated with more advanced pathologic stage, higher tumor grade, and presence of lymphovascular invasion (all P-values < 0.05). The five-year recurrence-free (RFS) and cancer-specific survival (CSS) estimates were 74.4 and 76.3%, respectively, in the absence of CIS compared with 56.4 and 59.9%, respectively, in the presence of CIS (P-values < 0.0001 for RFS and 0.002 for CSS, respectively). On multivariable Cox regression analyses, concomitant CIS was an independent predictor of both RFS (hazard ratio (HR): 1.9; P = 0.007) and CSS (HR: 1.7, P = 0.048). Similar findings were reconfirmed in subgroups analyses limited to T2, organ confined, and N0/Nx UTUC, or patients who did not receive adjuvant chemotherapy. CONCLUSIONS: Presence of concomitant CIS is an independent predictor of both RFS and CSS in patients treated with RNU for UTUC. This information may be useful in risk stratification of UTUC patients for follow-up and additional therapy.