Survival effect of perioperative systemic chemotherapy on overall mortality in locally advanced and/or positive regional lymph node non-metastatic urothelial carcinoma of the upper urinary tract
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To analyze the potential survival benefit of perioperative chemotherapy (CHT) in patients treated with nephroureterectomy (NU) for non-metastatic locally advanced upper tract urothelial carcinoma.
Within the Surveillance, Epidemiology, and End Results database (2004–2014), we identified 1286 patients with T3 or T4, N 0–3 M0 UTUC. Kaplan–Meier plots, as well as multivariable Cox regression models (MCRMs) relying on inverse probability after treatment weighting (IPTW) and landmark analyses, were used to test the effect of CHT vs no CHT on overall mortality (OM) in the overall population (n =1286), as well as after stratification according to lymph node invasion (LNI).
Overall, 37.4% patients received CHT. The CHT rate was higher with LNI (62.2% vs 35.2%, p < 0.001). In MCRMs, testing for OM in the overall population, CHT was associated with lower rates of OM (HR 0.71, CI 0.58–0.87; p = 0.001). Similarly, in MCRMs testing for OM in patients with LNI, CHT achieved independent predictor status for lower OM (HR 0.61, CI 0.48–0.78; p < 0.001). Conversely, in MCRMs testing for OM in patients without LNI, no CHT effect was recorded (HR 0.72, CI 0.52–1.01; p = 0.05). All results were confirmed after IPTW adjustment and in landmark analyses.
Our results represent a contemporary North American report indicating lower OM after CHT for patients with locally advanced non-metastatic upper tract urothelial carcinoma, specifically in patients with T3–T4, N1–N3, M0 disease. Validation of the current and of the previous study is required within a randomized prospective design.
KeywordsUpper urinary tract Urothelial carcinoma Positive lymph nodes SEER Chemotherapy
Protocol/project development: SN, FP, EM, PIK. Data collection or management: SN, FP, EM, PIK, ZT. Data analysis: SN, FP, EM, PIK, ZT. Manuscript writing/editing: SN, FAM, SFS, DS, FS, EM, SL, AB, LC and PIK.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Compliance with ethical standards
Sebastiano Nazzani certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (e.g., employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: none.
Conflict of interest
The authors declare that they have no competing interests.
We affirm that all authors have complied with the principles of the World Journal of Urology regarding ethical responsibilities of authors and compliance with ethical standards.
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