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Lack of effectiveness of postchemotherapy lymphadenectomy in bladder cancer patients with clinical evidence of metastatic pelvic or retroperitoneal lymph nodes only: A propensity score-based analysis

Lack of effectiveness of postchemotherapy lymphadenectomy in bladder cancer patients with clinical evidence of metastatic pelvic or retroperitoneal lymph nodes only: A propensity score-based analysis
Lack of effectiveness of postchemotherapy lymphadenectomy in bladder cancer patients with clinical evidence of metastatic pelvic or retroperitoneal lymph nodes only: A propensity score-based analysis

Background: Limited data is available on the role, and extent of, postchemotherapy lymphadenectomy (PC-LND) in patients with clinical evidence of pelvic (cN1-3) or retroperitoneal (RP) lymph node spread from urothelial bladder carcinoma. Objective: To compare the outcomes of operated versus nonoperated patients after first-line chemotherapy. Design, setting, and participants: Data from 34 centers was collected, totaling 522 patients, treated between January 2000 and June 2015. Criteria for patient selection were the following: bladder primary tumor, lymph node metastases (pelvic. ±. RP) only, first-line platinum-based chemotherapy given. Intervention: LND (with cystectomy) versus observation after first-line chemotherapy for metastatic urothelial bladder carcinoma. Outcome measures and statistical analysis: Overall survival (OS) was the primary endpoint. Multiple propensity score techniques were adopted, including 1:1 propensity score matching and inverse probability of treatment weighting. Additionally, the inverse probability of treatment weighting analysis was performed with the inclusion of the covariates, that is, with doubly robust estimation. Results and limitations: Overall, 242 (46.4%) patients received PC-LND and 280 (53.6%) observation after chemotherapy. There were 177 (33.9%) and 345 (66.1%) patients with either RP or pelvic LND only, respectively. Doubly robust estimation-adjusted comparison was not significant for improved OS for PC-LND (hazard ratio [HR]: 0.86, 95% confidence interval [CI]: 0.56-1.31, p = 0.479), confirmed by matched analysis (HR: 0.91, 95% CI: 0.60-1.36, p = 0.628). This was also observed in the RP subgroup (HR: 1.12, 95% CI: 0.68-1.84). The retrospective nature of the data and the heterogeneous patient population were the major limitations. Conclusions: Although there were substantial differences between the two groups, after accounting for major confounders we report a nonsignificant OS difference with PC-LND compared with observation only. These findings may be hypothesis-generating for future prospective trials. Patient summary: We found no differences in survival by adding postchemotherapy lymphadenectomy in patients with pelvic or retroperitoneal lymph node metastatic bladder cancer. The indication to perform postchemotherapy lymphadenectomy in the most suitable patients requires additional studies. In contemporary cohorts of patients with metastatic pelvic or retroperitoneal lymph nodes from bladder cancer, we found no survival benefit from postchemotherapy surgery versus observation in a retrospective study. Performing postchemotherapy lymphadenectomy remains investigational in patients with metastatic bladder cancer.

First-line chemotherapy, Postchemotherapy lymphadenectomy, Propensity-score, Urothelial carcinoma
Necchi, Andrea
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Mariani, Luigi
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Lo Vullo, Salvatore
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Yu, Evan Y.
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Woods, Michael E.
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Wong, Yu Ning
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Harshman, Lauren C.
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Alva, Ajjaj
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Sternberg, Cora N.
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Bamias, Aristotelis
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Grivas, Petros
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Koshkin, Vadim S.
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Roghmann, Florian
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Dobruch, Jakub
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Eigl, Bernie J.
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Nappi, Lucia
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Milowsky, Matthew I.
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Niegisch, Guenter
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Pal, Sumanta K.
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De Giorgi, Ugo
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Recine, Federica
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Vaishampayan, Ulka
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Berthold, Dominik D.
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Bowles, Daniel W.
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Baniel, Jack
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Theodore, Christine
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Ladoire, Sylvain
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Srinivas, Sandy
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Agarwal, Neeraj
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Crabb, Simon
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Sridhar, Srikala
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Golshayan, Ali Reza
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Ohlmann, Carsten
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Xylinas, Evanguelos
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Powles, Thomas
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Rosenberg, Johnathan E.
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Bellmunt, Joaquim
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van Rhijn, Bas
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Galsky, Matthew D.
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Hendricksen, Kees
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Necchi, Andrea
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Mariani, Luigi
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Lo Vullo, Salvatore
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Yu, Evan Y.
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Woods, Michael E.
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Wong, Yu Ning
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Harshman, Lauren C.
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Alva, Ajjaj
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Sternberg, Cora N.
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Bamias, Aristotelis
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Grivas, Petros
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Koshkin, Vadim S.
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Roghmann, Florian
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Dobruch, Jakub
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Eigl, Bernie J.
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Nappi, Lucia
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Milowsky, Matthew I.
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Niegisch, Guenter
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Pal, Sumanta K.
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De Giorgi, Ugo
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Recine, Federica
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Vaishampayan, Ulka
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Berthold, Dominik D.
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Bowles, Daniel W.
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Baniel, Jack
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Theodore, Christine
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Ladoire, Sylvain
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Srinivas, Sandy
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Agarwal, Neeraj
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Crabb, Simon
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Sridhar, Srikala
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Golshayan, Ali Reza
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Ohlmann, Carsten
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Xylinas, Evanguelos
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Powles, Thomas
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Rosenberg, Johnathan E.
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Bellmunt, Joaquim
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van Rhijn, Bas
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Galsky, Matthew D.
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Hendricksen, Kees
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Necchi, Andrea, Mariani, Luigi, Lo Vullo, Salvatore, Yu, Evan Y., Woods, Michael E., Wong, Yu Ning, Harshman, Lauren C., Alva, Ajjaj, Sternberg, Cora N., Bamias, Aristotelis, Grivas, Petros, Koshkin, Vadim S., Roghmann, Florian, Dobruch, Jakub, Eigl, Bernie J., Nappi, Lucia, Milowsky, Matthew I., Niegisch, Guenter, Pal, Sumanta K., De Giorgi, Ugo, Recine, Federica, Vaishampayan, Ulka, Berthold, Dominik D., Bowles, Daniel W., Baniel, Jack, Theodore, Christine, Ladoire, Sylvain, Srinivas, Sandy, Agarwal, Neeraj, Crabb, Simon, Sridhar, Srikala, Golshayan, Ali Reza, Ohlmann, Carsten, Xylinas, Evanguelos, Powles, Thomas, Rosenberg, Johnathan E., Bellmunt, Joaquim, van Rhijn, Bas, Galsky, Matthew D. and Hendricksen, Kees (2017) Lack of effectiveness of postchemotherapy lymphadenectomy in bladder cancer patients with clinical evidence of metastatic pelvic or retroperitoneal lymph nodes only: A propensity score-based analysis. European Urology Focus. (doi:10.1016/j.euf.2017.05.006).

Record type: Article

Abstract

Background: Limited data is available on the role, and extent of, postchemotherapy lymphadenectomy (PC-LND) in patients with clinical evidence of pelvic (cN1-3) or retroperitoneal (RP) lymph node spread from urothelial bladder carcinoma. Objective: To compare the outcomes of operated versus nonoperated patients after first-line chemotherapy. Design, setting, and participants: Data from 34 centers was collected, totaling 522 patients, treated between January 2000 and June 2015. Criteria for patient selection were the following: bladder primary tumor, lymph node metastases (pelvic. ±. RP) only, first-line platinum-based chemotherapy given. Intervention: LND (with cystectomy) versus observation after first-line chemotherapy for metastatic urothelial bladder carcinoma. Outcome measures and statistical analysis: Overall survival (OS) was the primary endpoint. Multiple propensity score techniques were adopted, including 1:1 propensity score matching and inverse probability of treatment weighting. Additionally, the inverse probability of treatment weighting analysis was performed with the inclusion of the covariates, that is, with doubly robust estimation. Results and limitations: Overall, 242 (46.4%) patients received PC-LND and 280 (53.6%) observation after chemotherapy. There were 177 (33.9%) and 345 (66.1%) patients with either RP or pelvic LND only, respectively. Doubly robust estimation-adjusted comparison was not significant for improved OS for PC-LND (hazard ratio [HR]: 0.86, 95% confidence interval [CI]: 0.56-1.31, p = 0.479), confirmed by matched analysis (HR: 0.91, 95% CI: 0.60-1.36, p = 0.628). This was also observed in the RP subgroup (HR: 1.12, 95% CI: 0.68-1.84). The retrospective nature of the data and the heterogeneous patient population were the major limitations. Conclusions: Although there were substantial differences between the two groups, after accounting for major confounders we report a nonsignificant OS difference with PC-LND compared with observation only. These findings may be hypothesis-generating for future prospective trials. Patient summary: We found no differences in survival by adding postchemotherapy lymphadenectomy in patients with pelvic or retroperitoneal lymph node metastatic bladder cancer. The indication to perform postchemotherapy lymphadenectomy in the most suitable patients requires additional studies. In contemporary cohorts of patients with metastatic pelvic or retroperitoneal lymph nodes from bladder cancer, we found no survival benefit from postchemotherapy surgery versus observation in a retrospective study. Performing postchemotherapy lymphadenectomy remains investigational in patients with metastatic bladder cancer.

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Accepted/In Press date: 6 May 2017
e-pub ahead of print date: 3 June 2017
Keywords: First-line chemotherapy, Postchemotherapy lymphadenectomy, Propensity-score, Urothelial carcinoma

Identifiers

Local EPrints ID: 412142
URI: http://eprints.soton.ac.uk/id/eprint/412142
PURE UUID: 010a971e-8ea0-423e-ae5d-14ebb1b82cf8
ORCID for Simon Crabb: ORCID iD orcid.org/0000-0003-3521-9064

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Date deposited: 11 Jul 2017 16:31
Last modified: 16 Mar 2024 05:28

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Contributors

Author: Andrea Necchi
Author: Luigi Mariani
Author: Salvatore Lo Vullo
Author: Evan Y. Yu
Author: Michael E. Woods
Author: Yu Ning Wong
Author: Lauren C. Harshman
Author: Ajjaj Alva
Author: Cora N. Sternberg
Author: Aristotelis Bamias
Author: Petros Grivas
Author: Vadim S. Koshkin
Author: Florian Roghmann
Author: Jakub Dobruch
Author: Bernie J. Eigl
Author: Lucia Nappi
Author: Matthew I. Milowsky
Author: Guenter Niegisch
Author: Sumanta K. Pal
Author: Ugo De Giorgi
Author: Federica Recine
Author: Ulka Vaishampayan
Author: Dominik D. Berthold
Author: Daniel W. Bowles
Author: Jack Baniel
Author: Christine Theodore
Author: Sylvain Ladoire
Author: Sandy Srinivas
Author: Neeraj Agarwal
Author: Simon Crabb ORCID iD
Author: Srikala Sridhar
Author: Ali Reza Golshayan
Author: Carsten Ohlmann
Author: Evanguelos Xylinas
Author: Thomas Powles
Author: Johnathan E. Rosenberg
Author: Joaquim Bellmunt
Author: Bas van Rhijn
Author: Matthew D. Galsky
Author: Kees Hendricksen

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