Pattern and risk factors of local recurrence after nephroureterectomy for upper tract urothelial carcinoma

Abstract

Purpose: This study aims to identify predictive local recurrence risk factors and site-specific local recurrence pattern of upper tract urothelial carcinoma (UTUC) with different primary tumor locations.

Methods: Three hundred and eighty-nine UTUC patients with radical nephroureterectomy were included in this study. Univariate and multivariate Cox proportional hazards regressions were performed to measure the risk of local recurrence. We also mapped the position of local recurrence sites stratified by primary tumor locations.

Results: A total of 73 patients (18.7%) developed local recurrence within a median follow-up of 41 months (range, 3-80 months). For patients with local recurrence, the median interval of local recurrence was 9 months. Ureter tumor, multifocality, T stage, G grade, lymph node metastasis (LNM), lymph node dissection (LND), and lymph vascular invasion (LVI) were all significantly associated with increased local recurrence by univariable analyses (P < 0.05). Only multifocality, T3-4, G3, and LNM remained independent predictors of increased local recurrence by multivariable analyses. Adjuvant radiotherapy could reduce the local recurrence (HR = 0.177; 95% CI 0.064-0.493, P = 0.001). Patients with local recurrence had poorer cancer-specific survival (4-year cancer-specific survival rate 36 ± 7.5% vs 88.4 ± 2.2%, P = 0.000). We evaluated local recurrence pattern stratified by tumor locations. Para-aortic lymph node region was the most common recurrence area for all the patients. Left-sided UTUC had more than 70% recurrent lymph nodes in the left para-aortic region (LPA). For right-sided UTUC patients, recurrent para-aortic lymph nodes distributed in the LPA (33.3%), aortocaval (AC) (41.5%), and right paracaval (RPC) (25.2%) regions. Recurrence in the internal and external iliac regions was only found in the distal ureter group (P < 0.05). Renal pelvic fossa recurrence was only found in renal pelvic tumor (22.2%, P = 0.007). The ureter tumor bed recurrence rate was higher for ureter patients (P = 0.001).

Conclusions: Multifocality, T3-4, G3, and LNM are predictors of higher local recurrence rate of UTUC. Adjuvant radiotherapy can reduce local recurrence rate. Local recurrence patterns are different according to primary tumor locations.

Keywords: Local recurrence; Primary tumor location; Risk factor; Upper tract urothelial carcinoma.

Fig. 1

The Kaplan-Meier survival curves of local recurrence-free survival stratified by T stage (a), G grade (b), multifocality (c); radiation therapy (RT) (d); lymph node status (e); cancer specific-free survival stratified by local recurrence (LR) (f)

Fig. 2

Recurrence lymph node distribution map stratified by primary tumor location. a Recurrence lymph nodes of pelvic tumor. b Recurrence lymph nodes of proximal ureter tumor. c Recurrence lymph nodes of middle ureter tumor. d Recurrence lymph nodes of distal ureter tumor (red, artery; blue, vein)

Fig. 3

Recurrence lymph node distribution ratio stratified by primary tumor site. a Recurrence lymph node distribution ratio of left UTUC patients. b Recurrence lymph node distribution ratio of right UTUC patients (red, left para-aortic; yellow, aortocaval; blue, right paracaval)