Efficacy of radiotherapy combined with systemic therapy for retroperitoneal lymph node metastasis in upper tract urothelial carcinoma(UTUC) patients after radical nephroureterectomy.

BACKGROUND: Retroperitoneal lymph node metastasis (rLNM) of upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU) represents a distinct metastatic state. Due to the unclear efficacy and side effects of radiotherapy in the treatment of these patients.This study aimed to assess the efficacy and adverse effects of radiotherapy combined with systemic therapy in rLNM patients after RNU. METHODS: A total of 114 UTUC patients with retroperitoneal LNM after RNU were prospectively enrolled database with retroperitoneal LNM after RNU. Patients were classified by initial treatment type: (1) radiation therapy, (2) systemic therapy or (3) combination therapy. Cox proportional hazard models were used to assess the factors associated with progression free survival (PFS) and overall survival (OS). Survival curves for each group were generated and compared via the Kaplan‒Meier method. RESULTS: A total of 114 rLNM patients with a median recurrence-free interval of 8 months after surgery (range: 1-108) were analyzed. During the median follow-up of 22 months (range: 3-81 months), 60 patients (58.8%) developed distant metastases. The para-aortic region was the most frequent site of recurrence. The recurrence rate in this region was significantly higher in patients with renal pelvic and proximal ureteral tumors (UTUCs) than in those with middle and distal UTUCs (P = 0.046). The common iliac region was the second most common recurrence site. Compared with renal pelvic tumors, ureteral tumors were more likely to recur in the common iliac region (P = 0.001). We delineated the radiotherapy clinical target volume (CTV) on the basis of primary tumor site; only 3 patients developed in-field recurrence during follow-up.The 2-year PFS rates for the combination therapy, radiation therapy and systemic therapy groups were 65.7%, 21.1% and 20.2%, respectively (P < 0.001). The 2-year OS rates for the combination therapy, radiation therapy and systemic therapy groups were 87.9%, 48.1% and 45.6%, respectively (P < 0.001). Multivariate analysis revealed that combination therapy,radiotherapy beginning within 3 months after recurrence and maintenance therapy after radiation were independent predictors of PFS. Maintenance therapy after radiation and distant metastasis were significant predictors of OS. Among 55 patients, 1 patient (1.8%) experienced acute grade 3 adverse events during combination therapy. CONCLUSIONS: Systemic therapy and radiotherapy improved PFS compared with either therapy type alone in rLNM UTUC patients.The majority of patients experiencing only grade 1-2 gastrointestinal reactions.