Outcomes of stage�II‑IV upper‑tract urothelial carcinoma and adjuvant chemotherapy for locally advanced cancer

Abstract

The present retrospective study aimed to examine the outcomes of stage II-IV upper-tract urothelial carcinoma (UTUC) and determine whether adjuvant chemotherapy is a beneficial treatment for patients with locally advanced UTUC (specifically, stage III-IV). The analysis included 126 patients with muscle-invasive UTUC who were treated between June 2003 and June 2012. All patients underwent laparoscopic or open nephroureterectomy and bladder cuff excision. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LRFS) were assessed. Outcomes were compared between groups of patients with stage II (high-stage localized) disease, stage III-IV (high-stage locally advanced) disease treated with chemotherapy, and stage III-IV disease not treated with chemotherapy. Among patients with high-stage locally advanced UTUC (stage III-IV), those who received adjuvant chemotherapy had significantly better rates of OS (67.1 vs. 33.7%; P=0.004), DFS (70.2 vs. 46.0%; P=0.030) and DMFS (86.3 vs. 65.2%; P=0.048) at 5-years compared with those who did not undergo adjuvant chemotherapy. However, there was no significant difference between the 5-year LRFS rates in these two groups (78.2 vs. 62.5%; P=0.525). Importantly, the survival curve of patients with high-stage UTUC who received adjuvant chemotherapy was similar to that of patients with low-stage UTUC who underwent surgery only. Multivariate analysis revealed that adjuvant chemotherapy was an independent risk factor for OS [without adjuvant chemotherapy vs. with adjuvant chemotherapy: Hazard ratio (HR), 0.29; 95% confidence interval (CI), 0.129-0.654; P=0.003] and DFS (without adjuvant chemotherapy vs. with adjuvant chemotherapy: HR, 0.381; 95% CI, 0.168-0.865; P=0.021). In conclusion, adjuvant chemotherapy may improve the outcome for patients with high-stage locally advanced UTUC.

Acidic Urine Is Associated With Poor Prognosis of Upper Tract Urothelial Carcinoma

“…Although UTUC is relatively uncommon compared with bladder cancer (5–10% of UCC) ( 3 ), a three- to four-fold higher rate of muscle invasion at diagnosis ( 4 ) leads to poor prognosis of patients. In fact, the 5-year survival rate is < 50% for patients with T2-T3 and < 10% for patients with T4 UTUC, which are substantially lower than the average survival rates in other cancers ( 5 ). Therefore, studies focused on identification and stratification of risk factors via orthogonal approaches, including genetic analysis and molecular subtyping to enhance survival outcomes ( 3 , 6 – 11 ).…”

Clinical Efficacy of Adjuvant Chemotherapy in Advanced Upper Tract Urothelial Carcinoma (pT3-T4): Real-World Data from the Taiwan Upper Tract Urothelial Carcinoma Collaboration Group

“…In 2017, Nakagawa et al reported that adjuvant chemotherapy improved CSS in a cohort of 109 patients with advanced-stage UTUC after RUN [13]. In 2019, Huang et al also demonstrated the therapeutic benefit of adjuvant chemotherapy in stage II-IV local UTUC [14].…”

“…In a previous study, carboplatin was a useful alternative solution when cisplatin was contraindicated and not at the expense of efficacy [18]. Chang et al also supported the efficacy of adjuvant chemotherapy with carboplatin in patients with advanced UTUC [14]. In contrast, Leow et al compared non-cisplatin-based or cisplatin-based adjuvant chemotherapy after RUN and found no survival benefit for non-cisplatin-based regimens [19].…”

Survival Impact of Nephroureterectomy for De Novo Stage IV Nonmetastatic and Metastatic Upper Tract Urothelial Carcinoma

“…NCCN guidelines either lack treatment recommendations for stage IV nmUTUC (T4N0M0, TanyN1-2M0) or recommend CT alone for mUTUC treatment ( 7 ). Although a few studies have reported the survival benefit of CT + NU for locally advanced UTUC compared with NU alone, few have analyzed this in patients with stage IV nmUTUC ( 6 , 9 , 15 – 17 ) or mUTUC ( 2 , 8 , 13 ). Our study demonstrated that compared with CT alone, their combination confers OS benefits to patients with stage IV nmUTUC or mUTUC.…”

“…Patients with UTUC have a lower OS than do those with bladder urothelial cancer (BUC) because >60% of patients with UTUC present with invasion at diagnosis, whereas only 15%–25% of patients with BUC present with invasion at diagnosis ( 3 , 4 ). Furthermore, the prognosis of patients with T4 UTUC is poor, with the 5-year OS being <10% ( 5 , 6 ).…”