Role of Adjuvant Chemotherapy in Advanced Stage Upper Urinary Tract Urothelial Carcinoma after Radical Nephroureterectomy: Competing Risk Analysis after Propensity Score-Matching

Abstract

Objective: To determine whether adjuvant chemotherapy (ACH) influences cancer-specific mortality, bladder cancer-specific mortality, and other-cause mortality in patients with locally advanced upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU) through the use of competing risk analysis.Methods: Among 785 patients with UTUC who underwent RNU from 1994 through 2015, we analyzed 338 individuals with locally advanced UTUC (pathologic T3-T4 and/or positive lymph nodes) without distant metastases. Patients were classified into two groups according to receipt of ACH. We performed a 1:1 propensity score-matching analysis between the ACH and no ACH group. The study endpoints were UTUC- and other cause-specific survivals. The association of potential risk factors with outcome was tested with the Fine and Gray regression model.Results: During a median follow-up duration of 31.5 months, rates of UTUC- and other cause-mortalities were 32.9% (n = 79) and 8.7% (n = 21), respectively. Of note, there were no significant differences in overall survival between the observation and ACH groups according to the competing risks of death (UTUC and other causes of death). Multivariate analysis showed that only older age at surgery (≥ 65 years; hazard ratio [HR] = 1.73), multifocality (HR = 1.74), and tumor size (HR = 1.92) remained as poor predictors of UTUC-specific survival. Additionally, positive surgical margin was only identified as independent predictor of other causes of death (HR = 4.23).Conclusion: In summary, postoperative chemotherapy failed to improve UTUC- and other cause-specific survival rates, based on competing risk analysis after propensity score-matching.

Platinum-based adjuvant chemotherapy for upper tract urothelial carcinoma: a change of paradigm? A meta-analysis of aggregate data

“…Fifteen studies were retrospective and one study was a phase 3 RCT. One retrospective study classified patients into two groups according to nodal status [25]; for data analysis, we split this study into Kang pN- (pT3–4 and pN0) and Kang pN+ (patients with pT3–4 and/or pN 1-3). Overall, a total of 6275 patients who underwent RNU for UTUCs were included in the analysis.…”

“…Moreover, six retrospective studies that reported CSS were selected, including 1678 patients [19,21,22,24,25,27]. Even then, the pooled analysis showed that the administration of platinum-based AC was not superior in terms of CCS compared to observation alone in patients after radical surgery for UTUCs (pooled HR 0.87; 95% CI: 0.65–1.17) (Fig.…”

“…Of the 53 reports were retrieved for full-text evaluation. Only 16 studies met the inclusion criteria and were included in this systematic review [6,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Table 1 showed the characteristics of the included studies.…”

“…Risk of bias were moderate in 8 studies [18][19][20][21][22]24,26,27] and low in 7 studies [13][14][15][16][17]23,25]. The one RCT scored 3 in the Jadad scale [6] (Supplementary Materials Table S1, S2, Supplemental digital content 1, http://links.lww.…”

The prognostic impact of lymph node dissection for clinically node-negative upper urinary tract urothelial carcinoma in patients who are treated with radical nephroureterectomy

“…According to the NCCN guidelines, patients with pT2-4 and pN+ UTUC should consider postoperative AC [13]. Although some observational studies have reported inconsistent results regarding the effectiveness of AC [28][29][30][31][32], a recent systematic review showed that AC is associated with better metastasis-free survival (HR = 0.65, p<0.001) and CSS (HR = 0.66, p<0.001). The association between AC and OS is significant in patients with locally advanced UTUC [33].…”