Association of tumor necrosis with pathological features and clinical outcome in 754 patients undergoing radical nephroureterectomy for upper tract urothelial carcinoma: an international validation study

Purpose: Tumor necrosis is associated with a poor oncological outcome in patients with upper tract urothelial carcinoma and other malignancies. We validated the association of tumor necrosis with pathological features and clinical outcomes in a large international cohort of patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.

Material and methods: This retrospective study included 754 patients treated with radical nephroureterectomy at a total of 9 centers. Tumor necrosis was scored as greater than 10% of tumor area based on microscopic evaluation.

Results: Tumor necrosis was present in 165 specimens (21.9%). The prevalence of tumor necrosis increased with advancing pathological stage, including 7%, 10.6% and 50% for T1, T2 and T3-4, respectively (p <0.001). Tumor necrosis was associated with features of aggressive upper tract urothelial carcinoma, such as high grade, lymph node metastasis, lymphovascular invasion, sessile tumor architecture and concomitant carcinoma in situ (p <0.002). Median followup in censored patients was 40 months (IQR 18 to 75). On univariate Cox regression analysis tumor necrosis was significantly associated with disease recurrence and cancer specific mortality (HR 2.4 and 2.7, p <0.001). However, on multivariate Cox regression analysis including patient age, stage, grade, lymph node status, lymphovascular invasion and adjuvant chemotherapy tumor necrosis was not associated with disease recurrence (HR 1.1, p = 0.49) or cancer specific mortality (HR 1.1, p = 0.51). Excluding 63 patients who received adjuvant chemotherapy and/or 49 with positive lymph nodes did not substantially change these results.

Conclusions: In this large, multicenter international study tumor necrosis was associated with pathological features of biologically aggressive upper tract urothelial carcinoma. However, tumor necrosis was not an independent predictor of clinical outcomes.