The Association between Lymph Node Dissection and Survival in Lymph Node-Negative Upper Urinary Tract Urothelial Cancer

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Abstract

The benefit of lymph node dissection (LND) during radical nephroureterectomy (RNU) in lymph node (LN)-negative (cN0/pN0) UTUC remains controversial. We aimed to assess the association between LND and its extent and survival in LN-negative UTUC. The Surveillance, Epidemiology, and End Results database was searched to identify patients with non-metastatic chemotherapy-naïve cN0/pNx or pN0 UTUC who underwent RNU +/− LND between 2004 and 2019. Overall, 4649 patients with cN0/pNx or pN0 UTUC were analyzed, including 909 (19.55%) individuals who had LND. Among them, only in 368 patients (7.92%) was LND extended to at least four LNs, and the remaining 541 patients (11.64%) have had < four LNs removed. In the whole cohort, LND contributed to better cancer-specific survival (CSS) and overall survival (OS). Furthermore, a propensity score-matched analysis adjusted for confounders confirmed that improved CSS and OS was achieved only when ≥ four LNs had been removed, especially in muscle-invasive UTUC. A multivariable analysis further confirmed an association between the extent of LND and CSS. To conclude, adequate LND during RNU was associated with improved OS and CSS in LN-negative UTUC, particularly in muscle-invasive stage. This underscores that a sufficient LN yield is required to reveal a therapeutic benefit in patients undergoing RNU.

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Most cited references 29

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European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2020 Update

Morgan Rouprêt, Marko Babjuk, Maximilian Burger … (2020)

The European Association of Urology (EAU) Guidelines Panel on Upper Urinary Tract Urothelial Carcinoma (UTUC) has prepared updated guidelines to aid clinicians in the current evidence-based management of UTUC and to incorporate recommendations into clinical practice.

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Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial

Alison Birtle, Mark Damone Johnson, John Chester … (2020)

Summary Background Urothelial carcinomas of the upper urinary tract (UTUCs) are rare, with poorer stage-for-stage prognosis than urothelial carcinomas of the urinary bladder. No international consensus exists on the benefit of adjuvant chemotherapy for patients with UTUCs after nephroureterectomy with curative intent. The POUT (Peri-Operative chemotherapy versus sUrveillance in upper Tract urothelial cancer) trial aimed to assess the efficacy of systemic platinum-based chemotherapy in patients with UTUCs. Methods We did a phase 3, open-label, randomised controlled trial at 71 hospitals in the UK. We recruited patients with UTUC after nephroureterectomy staged as either pT2–T4 pN0–N3 M0 or pTany N1–3 M0. We randomly allocated participants centrally (1:1) to either surveillance or four 21-day cycles of chemotherapy, using a minimisation algorithm with a random element. Chemotherapy was either cisplatin (70 mg/m2) or carboplatin (area under the curve [AUC]4·5/AUC5, for glomerular filtration rate <50 mL/min only) administered intravenously on day 1 and gemcitabine (1000 mg/m2) administered intravenously on days 1 and 8; chemotherapy was initiated within 90 days of surgery. Follow-up included standard cystoscopic, radiological, and clinical assessments. The primary endpoint was disease-free survival analysed by intention to treat with a Peto-Haybittle stopping rule for (in)efficacy. The trial is registered with ClinicalTrials.gov, NCT01993979. A preplanned interim analysis met the efficacy criterion for early closure after recruitment of 261 participants. Findings Between June 19, 2012, and Nov 8, 2017, we enrolled 261 participants from 57 of 71 open study sites. 132 patients were assigned chemotherapy and 129 surveillance. One participant allocated chemotherapy withdrew consent for data use after randomisation and was excluded from analyses. Adjuvant chemotherapy significantly improved disease-free survival (hazard ratio 0·45, 95% CI 0·30–0·68; p=0·0001) at a median follow-up of 30·3 months (IQR 18·0–47·5). 3-year event-free estimates were 71% (95% CI 61–78) and 46% (36–56) for chemotherapy and surveillance, respectively. 55 (44%) of 126 participants who started chemotherapy had acute grade 3 or worse treatment-emergent adverse events, which accorded with frequently reported events for the chemotherapy regimen. Five (4%) of 129 patients managed by surveillance had acute grade 3 or worse emergent adverse events. No treatment-related deaths were reported. Interpretation Gemcitabine–platinum combination chemotherapy initiated within 90 days after nephroureterectomy significantly improved disease-free survival in patients with locally advanced UTUC. Adjuvant platinum-based chemotherapy should be considered a new standard of care after nephroureterectomy for this patient population. Funding Cancer Research UK.

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Potential Benefit of Lymph Node Dissection During Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review by the European Association of Urology Guidelines Panel on Non–muscle-invasive Bladder Cancer

Jose Dominguez-Escrig, Benoit Peyronnet, Thomas Seisen … (2017)

The oncological efficacy of routine lymphadenectomy (lymph node dissection [LND]) at the time of radical nephroureterectomy (RNU) remains controversial.

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Author and article information

Journal

Journal ID (publisher-id): CANCCT

Title: Cancers

Abbreviated Title: Cancers

Publisher: MDPI AG

ISSN (Electronic): 2072-6694

Publication date Created: September 2023

Publication date (Electronic): September 21 2023

Volume: 15

Issue: 18

Page: 4660

Article

DOI: 10.3390/cancers15184660

SO-VID: c57c4052-97df-4698-8d63-72bd2876cfbc

License:

https://creativecommons.org/licenses/by/4.0/

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