Neoadjuvant chemotherapy with dose dense MVAC is associated with improved survival after radical cystectomy compared to other cytotoxic regimens: A tertiary center experience

<h4>Introduction</h4> Neoadjuvant chemotherapy has become standard of care for cisplatin-eligible patients with muscle-invasive bladder cancer qualified to radical cystectomy, providing a modest increase in 5-year overall survival rate. Several regimens are being employed for neoadjuvant...

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Autores principales:	Artur Lemiński, Krystian Kaczmarek, Tomasz Byrski, Marcin Słojewski
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/10173fc408eb4d47a9ea677e37015541
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spelling	oai:doaj.org-article:10173fc408eb4d47a9ea677e370155412021-11-11T07:14:47ZNeoadjuvant chemotherapy with dose dense MVAC is associated with improved survival after radical cystectomy compared to other cytotoxic regimens: A tertiary center experience1932-6203https://doaj.org/article/10173fc408eb4d47a9ea677e370155412021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8565719/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Introduction</h4> Neoadjuvant chemotherapy has become standard of care for cisplatin-eligible patients with muscle-invasive bladder cancer qualified to radical cystectomy, providing a modest increase in 5-year overall survival rate. Several regimens are being employed for neoadjuvant treatment, largely because of their efficacy in metastatic setting. There is however a scarcity of evidence on the optimal cytotoxic regimen for neoadjuvant chemotherapy. <h4>Objectives</h4> We evaluated the efficacy of different protocols of neoadjuvant chemotherapy amongst patients who underwent radical cystectomy at our institution. <h4>Methods</h4> This is a single-center, retrospective, observational study including a cohort of 220 patients who underwent radical cystectomy between 2014 and 2020. The neoadjuvant chemotherapy cohort included 79 patients and was compared to the cohort of historical controls including 141 patients operated prior to routine administration of neoadjuvant chemotherapy and those who opted for upfront surgery. <h4>Results</h4> Administration of neoadjuvant chemotherapy decreased the risk of overall and cancer-specific mortality HR = 0.625 (95% CI 0.414–0.944), p = 0.025 and HR = 0.579 (95% CI 0.348–0.964), p = 0.036. Rates of downstaging, complete responses, lymph node metastasis, extravesical extension and positive surgical margins significantly favored neoadjuvant chemotherapy. Out of cytotoxic regimens, dose-dense MVAC and gemcitabine-cisplatin were similarly efficacious providing 46.9% and 50% of downstaging to <ypT2N0 respectively, including 30.6% and 25% of complete remissions. However, only dose-dense MVAC was associated with reduction of all-cause and cancer specific mortality risk HR = 0.385 (95% CI 0.214–0.691) p = 0.001 and HR = 0.336 (95% CI 0.160–0.703), p = 0.004 respectively. <h4>Conclusions</h4> Our study implies that neoadjuvant chemotherapy with subsequent radical cystectomy provides significant improvement over upfront surgery in locoregional control and long-term prognosis of muscle-invasive bladder cancer. The urologic community should strive to maximize utilization of neoadjuvant chemotherapy, yet further research, including randomized control trials, is needed to validate superiority of dose-dense MVAC as the preferred regimen for cisplatin-eligible patients.Artur LemińskiKrystian KaczmarekTomasz ByrskiMarcin SłojewskiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Artur Lemiński Krystian Kaczmarek Tomasz Byrski Marcin Słojewski Neoadjuvant chemotherapy with dose dense MVAC is associated with improved survival after radical cystectomy compared to other cytotoxic regimens: A tertiary center experience
description	<h4>Introduction</h4> Neoadjuvant chemotherapy has become standard of care for cisplatin-eligible patients with muscle-invasive bladder cancer qualified to radical cystectomy, providing a modest increase in 5-year overall survival rate. Several regimens are being employed for neoadjuvant treatment, largely because of their efficacy in metastatic setting. There is however a scarcity of evidence on the optimal cytotoxic regimen for neoadjuvant chemotherapy. <h4>Objectives</h4> We evaluated the efficacy of different protocols of neoadjuvant chemotherapy amongst patients who underwent radical cystectomy at our institution. <h4>Methods</h4> This is a single-center, retrospective, observational study including a cohort of 220 patients who underwent radical cystectomy between 2014 and 2020. The neoadjuvant chemotherapy cohort included 79 patients and was compared to the cohort of historical controls including 141 patients operated prior to routine administration of neoadjuvant chemotherapy and those who opted for upfront surgery. <h4>Results</h4> Administration of neoadjuvant chemotherapy decreased the risk of overall and cancer-specific mortality HR = 0.625 (95% CI 0.414–0.944), p = 0.025 and HR = 0.579 (95% CI 0.348–0.964), p = 0.036. Rates of downstaging, complete responses, lymph node metastasis, extravesical extension and positive surgical margins significantly favored neoadjuvant chemotherapy. Out of cytotoxic regimens, dose-dense MVAC and gemcitabine-cisplatin were similarly efficacious providing 46.9% and 50% of downstaging to <ypT2N0 respectively, including 30.6% and 25% of complete remissions. However, only dose-dense MVAC was associated with reduction of all-cause and cancer specific mortality risk HR = 0.385 (95% CI 0.214–0.691) p = 0.001 and HR = 0.336 (95% CI 0.160–0.703), p = 0.004 respectively. <h4>Conclusions</h4> Our study implies that neoadjuvant chemotherapy with subsequent radical cystectomy provides significant improvement over upfront surgery in locoregional control and long-term prognosis of muscle-invasive bladder cancer. The urologic community should strive to maximize utilization of neoadjuvant chemotherapy, yet further research, including randomized control trials, is needed to validate superiority of dose-dense MVAC as the preferred regimen for cisplatin-eligible patients.
format	article
author	Artur Lemiński Krystian Kaczmarek Tomasz Byrski Marcin Słojewski
author_facet	Artur Lemiński Krystian Kaczmarek Tomasz Byrski Marcin Słojewski
author_sort	Artur Lemiński
title	Neoadjuvant chemotherapy with dose dense MVAC is associated with improved survival after radical cystectomy compared to other cytotoxic regimens: A tertiary center experience
title_short	Neoadjuvant chemotherapy with dose dense MVAC is associated with improved survival after radical cystectomy compared to other cytotoxic regimens: A tertiary center experience
title_full	Neoadjuvant chemotherapy with dose dense MVAC is associated with improved survival after radical cystectomy compared to other cytotoxic regimens: A tertiary center experience
title_fullStr	Neoadjuvant chemotherapy with dose dense MVAC is associated with improved survival after radical cystectomy compared to other cytotoxic regimens: A tertiary center experience
title_full_unstemmed	Neoadjuvant chemotherapy with dose dense MVAC is associated with improved survival after radical cystectomy compared to other cytotoxic regimens: A tertiary center experience
title_sort	neoadjuvant chemotherapy with dose dense mvac is associated with improved survival after radical cystectomy compared to other cytotoxic regimens: a tertiary center experience
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/10173fc408eb4d47a9ea677e37015541
work_keys_str_mv	AT arturleminski neoadjuvantchemotherapywithdosedensemvacisassociatedwithimprovedsurvivalafterradicalcystectomycomparedtoothercytotoxicregimensatertiarycenterexperience AT krystiankaczmarek neoadjuvantchemotherapywithdosedensemvacisassociatedwithimprovedsurvivalafterradicalcystectomycomparedtoothercytotoxicregimensatertiarycenterexperience AT tomaszbyrski neoadjuvantchemotherapywithdosedensemvacisassociatedwithimprovedsurvivalafterradicalcystectomycomparedtoothercytotoxicregimensatertiarycenterexperience AT marcinsłojewski neoadjuvantchemotherapywithdosedensemvacisassociatedwithimprovedsurvivalafterradicalcystectomycomparedtoothercytotoxicregimensatertiarycenterexperience
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Neoadjuvant chemotherapy with dose dense MVAC is associated with improved survival after radical cystectomy compared to other cytotoxic regimens: A tertiary center experience

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