Adjuvant chemotherapy improves survival of patients with high-risk upper urinary tract urothelial carcinoma: a propensity score-matched analysis

Abstract

BackgroundThe purposes of this study were to determine whether adjuvant chemotherapy (AC) improved the prognosis of patients with high-risk upper urinary tract urothelial carcinoma (UTUC)and to identify the patients who benefited from AC.MethodsAmong a multi-center database of 1014 patients who underwent RNU for UTUC, 344 patients with ≥ pT3 or the presence of lymphovascular invasion (LVI) were included. Cancer-specific survival (CSS) estimates were calculated by the Kaplan-Meier method, and groups were compared by the log-rank test. Each patient’s probability of receiving AC depending on the covariates in each group was estimated by logistic regression models. Propensity score matching was used to adjust the confounding factors for selecting patients for AC, and log-rank tests were applied to these propensity score-matched cohorts. Cox proportional hazards regression modeling was used to identify the variables with significant interaction with AC. Variables included age, pT category, LVI, tumor grade, ECOG performance status and low sodium or hemoglobin score, which we reported to be a prognostic factor of UTUC.ResultsOf the 344 patients, 241 (70%) had received RNU only and 103 (30%) had received RNU+AC. The median follow-up period was 32 (range 1–184) months. Overall, AC did not improve CSS (P = 0.12). After propensity score matching, the 5-year CSS was 69.0% in patients with RNU+AC versus 58.9% in patients with RNU alone (P = 0.030). Subgroup analyses of survival were performed to identify the patients who benefitted from AC. Subgroups of patients with low preoperative serum sodium (≤ 140 mEq/ml) or hemoglobin levels below the normal limit benefitted from AC (HR 0.34, 95% CI 0.15–0.61, P = 0.001). In the subgroup of patients with normal sodium and normal hemoglobin levels, 5-year CSS was 77.7% in patients with RNU+AC versus 80.2% in patients with RNU alone (P = 0.84). In contrast, in the subgroup of patients with low sodium or low hemoglobin levels, 5-year CSS was 71.0% in patients with RNU+AC versus 38.5% in patients with RNU alone (P < 0.001).ConclusionsHigh-risk UTUC patients, especially subgroups of patients with lower sodium and hemoglobin levels, could benefit from AC after RNU.

<p>The Significance of Preoperative Serum Sodium and Hemoglobin in Outcomes of Upper Tract Urothelial Carcinoma: Multi-Center Analysis Between China and the United States</p>

“… 10 Meanwhile, previous multi-center studies also indicated that low preoperative serum sodium was associated with poor prognosis. 15 , 16 These findings were in accordance with our results. In the present study, the cut-off value of preoperative serum sodium was set at the median value of 140 mEq/L, which was in accordance with previous studies.…”

“…In the present study, the cut-off value of preoperative serum sodium was set at the median value of 140 mEq/L, which was in accordance with previous studies. 15,16 Preoperative low serum sodium value was related to the presence of LVI and independently predicted a worse OS in the entire cohort.…”

“…Our findings validate those in previous studies that preoperative anemia was associated with unfavorable pathological factors and poor oncologic outcomes. [11][12][13][14]16 A low sodium level within the normal range is unlikely to cause poor outcomes in UTUC patients. The mechanisms responsible for decreased serum sodium and the association between preoperative sodium level below the median value and poorer outcomes remain unknown.…”

“…Studies of UTUC focusing on clinical significance of serum markers including sodium 10 and serum hemoglobin 11 – 14 provide evidence that these two factors might be associated with worse prognosis. 15 , 16 However, these studies are limited by sample size, in addition to differences between ethnic groups.…”

Validation of Hyponatremia as a Prognostic Predictor in Multiregional Upper Tract Urothelial Carcinoma

“…Compared to patients without hyponatremia, our results showed that hyponatremic UTUC patients had a similar trend for worse outcomes in cases receiving adjuvant chemotherapy (p = 0.097 and 0.036 for CSS and OS, respectively). Interestingly, a study mentioned that the benefit of adjuvant chemotherapy in UTUC is significant in Japanese patients who had low sodium or hemoglobin concentration but not in those had normal levels [28]. However, the effect of adjuvant chemotherapy was similar in patients with and without hyponatremia in this cohort.…”