Adjuvant chemotherapy after radical nephroureterectomy does not improve survival in patients with upper tract urothelial carcinoma: A joint study by the European Association of Urology-Young Academic Urologists and the Upper Tract Urothelial Carcinoma Collaboration

Andrea Necchi, Salvatore Lo Vullo, Luigi Mariani, Marco Moschini, Kees Hendricksen, Michael Rink, Roman Sosnowski, Jakub Dobruch, Jay D. Raman, Christopher G. Wood, Vitaly Margulis, Morgan Roupret, Alberto Briganti, Francesco Montorsi, Evanguelos Xylinas, Shahrokh F. Shariat

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Abstract

Objective: To analyse the outcomes of adjuvant chemotherapy vs observation in a multicentre cohort of patients with upper tract urothelial carcinoma (UTUC) in order to clarify whether such patients benefit from adjuvant chemotherapy after radical nephroureterectomy (RNU). Patients and Methods: Data from 15 centres were collected for a total of 1544 patients, treated between 2000 and 2015. Criteria for patient selection included pT2-4N0/x stage, or lymph node-positive disease, and prior RNU. The standardized difference approach was used to compare subgroup characteristics. Overall survival (OS) was the primary endpoint. The primary analysis used 1:1 propensity score matching, with inverse probability of treatment weighting in addition to this in the secondary analysis. The latter was also performed with the inclusion of covariates, i.e. with 'doubly robust' estimation. A 6-month landmark analysis was performed to exclude early events. Results: A total of 312 patients received adjuvant chemotherapy and 1232 underwent observation. Despite differences between the two groups, the standardized difference was generally <10% after matching. In the matched analysis no difference was observed in OS between adjuvant chemotherapy and observation (hazard ratio [HR] 1.14, 95% confidence inverval [CI] 0.91-1.43; P = 0.268). In the doubly robust estimate-adjusted comparison, adjuvant chemotherapy was significantly associated with shorter OS (HR 1.26, 95% CI 1.02-1.54; P = 0.032). Similar findings were confirmed in subgroup analyses stratified by pathological stage, and after landmark analysis. Results should be interpreted with consideration given to the inherent limitations of retrospective studies. Conclusion: Adjuvant chemotherapy did not improve OS compared with observation in the present study. These results contribute to the uncertainties regarding postoperative chemotherapy in UTUC, and suggest dedicated prospective trials, new more potent therapies, and the identification of enhanced patient selection criteria are required.

Original languageEnglish (US)
JournalBJU International
DOIs
StateAccepted/In press - 2017

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Adjuvant Chemotherapy
Carcinoma
Survival
Observation
Patient Selection
Propensity Score
Uncertainty
Urologists
Retrospective Studies
Lymph Nodes
Drug Therapy
Therapeutics

Keywords

  • Adjuvant chemotherapy
  • Nephroureterectomy
  • Propensity scores
  • Upper tract
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Urology

Cite this

Adjuvant chemotherapy after radical nephroureterectomy does not improve survival in patients with upper tract urothelial carcinoma : A joint study by the European Association of Urology-Young Academic Urologists and the Upper Tract Urothelial Carcinoma Collaboration. / Necchi, Andrea; Lo Vullo, Salvatore; Mariani, Luigi; Moschini, Marco; Hendricksen, Kees; Rink, Michael; Sosnowski, Roman; Dobruch, Jakub; Raman, Jay D.; Wood, Christopher G.; Margulis, Vitaly; Roupret, Morgan; Briganti, Alberto; Montorsi, Francesco; Xylinas, Evanguelos; Shariat, Shahrokh F.

In: BJU International, 2017.

Research output: Contribution to journalArticle

Necchi, Andrea ; Lo Vullo, Salvatore ; Mariani, Luigi ; Moschini, Marco ; Hendricksen, Kees ; Rink, Michael ; Sosnowski, Roman ; Dobruch, Jakub ; Raman, Jay D. ; Wood, Christopher G. ; Margulis, Vitaly ; Roupret, Morgan ; Briganti, Alberto ; Montorsi, Francesco ; Xylinas, Evanguelos ; Shariat, Shahrokh F. / Adjuvant chemotherapy after radical nephroureterectomy does not improve survival in patients with upper tract urothelial carcinoma : A joint study by the European Association of Urology-Young Academic Urologists and the Upper Tract Urothelial Carcinoma Collaboration. In: BJU International. 2017.
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abstract = "Objective: To analyse the outcomes of adjuvant chemotherapy vs observation in a multicentre cohort of patients with upper tract urothelial carcinoma (UTUC) in order to clarify whether such patients benefit from adjuvant chemotherapy after radical nephroureterectomy (RNU). Patients and Methods: Data from 15 centres were collected for a total of 1544 patients, treated between 2000 and 2015. Criteria for patient selection included pT2-4N0/x stage, or lymph node-positive disease, and prior RNU. The standardized difference approach was used to compare subgroup characteristics. Overall survival (OS) was the primary endpoint. The primary analysis used 1:1 propensity score matching, with inverse probability of treatment weighting in addition to this in the secondary analysis. The latter was also performed with the inclusion of covariates, i.e. with 'doubly robust' estimation. A 6-month landmark analysis was performed to exclude early events. Results: A total of 312 patients received adjuvant chemotherapy and 1232 underwent observation. Despite differences between the two groups, the standardized difference was generally <10{\%} after matching. In the matched analysis no difference was observed in OS between adjuvant chemotherapy and observation (hazard ratio [HR] 1.14, 95{\%} confidence inverval [CI] 0.91-1.43; P = 0.268). In the doubly robust estimate-adjusted comparison, adjuvant chemotherapy was significantly associated with shorter OS (HR 1.26, 95{\%} CI 1.02-1.54; P = 0.032). Similar findings were confirmed in subgroup analyses stratified by pathological stage, and after landmark analysis. Results should be interpreted with consideration given to the inherent limitations of retrospective studies. Conclusion: Adjuvant chemotherapy did not improve OS compared with observation in the present study. These results contribute to the uncertainties regarding postoperative chemotherapy in UTUC, and suggest dedicated prospective trials, new more potent therapies, and the identification of enhanced patient selection criteria are required.",
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author = "Andrea Necchi and {Lo Vullo}, Salvatore and Luigi Mariani and Marco Moschini and Kees Hendricksen and Michael Rink and Roman Sosnowski and Jakub Dobruch and Raman, {Jay D.} and Wood, {Christopher G.} and Vitaly Margulis and Morgan Roupret and Alberto Briganti and Francesco Montorsi and Evanguelos Xylinas and Shariat, {Shahrokh F.}",
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TY - JOUR

T1 - Adjuvant chemotherapy after radical nephroureterectomy does not improve survival in patients with upper tract urothelial carcinoma

T2 - A joint study by the European Association of Urology-Young Academic Urologists and the Upper Tract Urothelial Carcinoma Collaboration

AU - Necchi, Andrea

AU - Lo Vullo, Salvatore

AU - Mariani, Luigi

AU - Moschini, Marco

AU - Hendricksen, Kees

AU - Rink, Michael

AU - Sosnowski, Roman

AU - Dobruch, Jakub

AU - Raman, Jay D.

AU - Wood, Christopher G.

AU - Margulis, Vitaly

AU - Roupret, Morgan

AU - Briganti, Alberto

AU - Montorsi, Francesco

AU - Xylinas, Evanguelos

AU - Shariat, Shahrokh F.

PY - 2017

Y1 - 2017

N2 - Objective: To analyse the outcomes of adjuvant chemotherapy vs observation in a multicentre cohort of patients with upper tract urothelial carcinoma (UTUC) in order to clarify whether such patients benefit from adjuvant chemotherapy after radical nephroureterectomy (RNU). Patients and Methods: Data from 15 centres were collected for a total of 1544 patients, treated between 2000 and 2015. Criteria for patient selection included pT2-4N0/x stage, or lymph node-positive disease, and prior RNU. The standardized difference approach was used to compare subgroup characteristics. Overall survival (OS) was the primary endpoint. The primary analysis used 1:1 propensity score matching, with inverse probability of treatment weighting in addition to this in the secondary analysis. The latter was also performed with the inclusion of covariates, i.e. with 'doubly robust' estimation. A 6-month landmark analysis was performed to exclude early events. Results: A total of 312 patients received adjuvant chemotherapy and 1232 underwent observation. Despite differences between the two groups, the standardized difference was generally <10% after matching. In the matched analysis no difference was observed in OS between adjuvant chemotherapy and observation (hazard ratio [HR] 1.14, 95% confidence inverval [CI] 0.91-1.43; P = 0.268). In the doubly robust estimate-adjusted comparison, adjuvant chemotherapy was significantly associated with shorter OS (HR 1.26, 95% CI 1.02-1.54; P = 0.032). Similar findings were confirmed in subgroup analyses stratified by pathological stage, and after landmark analysis. Results should be interpreted with consideration given to the inherent limitations of retrospective studies. Conclusion: Adjuvant chemotherapy did not improve OS compared with observation in the present study. These results contribute to the uncertainties regarding postoperative chemotherapy in UTUC, and suggest dedicated prospective trials, new more potent therapies, and the identification of enhanced patient selection criteria are required.

AB - Objective: To analyse the outcomes of adjuvant chemotherapy vs observation in a multicentre cohort of patients with upper tract urothelial carcinoma (UTUC) in order to clarify whether such patients benefit from adjuvant chemotherapy after radical nephroureterectomy (RNU). Patients and Methods: Data from 15 centres were collected for a total of 1544 patients, treated between 2000 and 2015. Criteria for patient selection included pT2-4N0/x stage, or lymph node-positive disease, and prior RNU. The standardized difference approach was used to compare subgroup characteristics. Overall survival (OS) was the primary endpoint. The primary analysis used 1:1 propensity score matching, with inverse probability of treatment weighting in addition to this in the secondary analysis. The latter was also performed with the inclusion of covariates, i.e. with 'doubly robust' estimation. A 6-month landmark analysis was performed to exclude early events. Results: A total of 312 patients received adjuvant chemotherapy and 1232 underwent observation. Despite differences between the two groups, the standardized difference was generally <10% after matching. In the matched analysis no difference was observed in OS between adjuvant chemotherapy and observation (hazard ratio [HR] 1.14, 95% confidence inverval [CI] 0.91-1.43; P = 0.268). In the doubly robust estimate-adjusted comparison, adjuvant chemotherapy was significantly associated with shorter OS (HR 1.26, 95% CI 1.02-1.54; P = 0.032). Similar findings were confirmed in subgroup analyses stratified by pathological stage, and after landmark analysis. Results should be interpreted with consideration given to the inherent limitations of retrospective studies. Conclusion: Adjuvant chemotherapy did not improve OS compared with observation in the present study. These results contribute to the uncertainties regarding postoperative chemotherapy in UTUC, and suggest dedicated prospective trials, new more potent therapies, and the identification of enhanced patient selection criteria are required.

KW - Adjuvant chemotherapy

KW - Nephroureterectomy

KW - Propensity scores

KW - Upper tract

KW - Urothelial carcinoma

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DO - 10.1111/bju.14020

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