Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer

Homayoun Zargar, Patrick N. Espiritu, Adrian S. Fairey, Laura S. Mertens, Colin P. Dinney, Maria C. Mir, Laura Maria Krabbe, Michael S. Cookson, Niels Erik Jacobsen, Nilay M. Gandhi, Joshua Griffin, Jeffrey S. Montgomery, Nikhil Vasdev, Evan Y. Yu, David Youssef, Evanguelos Xylinas, Nicholas J. Campain, Wassim Kassouf, Marc Dall'Era, Jo An Seah & 21 others Cesar E. Ercole, Simon Horenblas, Srikala S. Sridhar, John S. McGrath, Jonathan Aning, Shahrokh F. Shariat, Jonathan L. Wright, Andrew C. Thorpe, Todd M. Morgan, Jeff M. Holzbeierlein, Trinity J. Bivalacqua, Scott North, Daniel A. Barocas, Yair Lotan, Jorge A. Garcia, Andrew J. Stephenson, Jay B. Shah, Bas W. Van Rhijn, Siamak Daneshmand, Philippe E. Spiess, Peter C. Black

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

Background The efficacy of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (BCa) was established primarily with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), with complete response rates (pT0) as high as 38%. However, because of the comparable efficacy with better tolerability of gemcitabine and cisplatin (GC) in patients with metastatic disease, GC has become the most commonly used regimen in the neoadjuvant setting. Objective We aimed to assess real-world pathologic response rates to NAC with different regimens in a large, multicenter cohort. Design, setting, and participants Data were collected retrospectively at 19 centers on patients with clinical cT2-4aN0M0 urothelial carcinoma of the bladder who received at least three cycles of NAC, followed by radical cystectomy (RC), between 2000 and 2013. Intervention NAC and RC. Outcome measurements and statistical analysis The primary outcome was pathologic stage at cystectomy. Univariable and multivariable analyses were used to determine factors predictive of pT0N0 and ≤pT1N0 stages. Results and limitations Data were collected on 935 patients who met inclusion criteria. GC was used in the majority of the patients (n = 602; 64.4%), followed by MVAC (n = 183; 19.6%) and other regimens (n = 144; 15.4%). The rates of pT0N0 and ≤pT1N0 pathologic response were 22.7% and 40.8%, respectively. The rate of pT0N0 disease for patients receiving GC was 23.9%, compared with 24.5% for MVAC (p = 0.2). There was no difference between MVAC and GC in pT0N0 on multivariable analysis (odds ratio: 0.89 [95% confidence interval, 0.61-1.34]; p = 0.6). Conclusions Response rates to NAC were lower than those reported in prospective randomized trials, and we did not discern a difference between MVAC and GC. Without any evidence from randomized prospective trials, the best NAC regimen for invasive BCa remains to be determined. Patient summary There was no apparent difference in the response rates to the two most common presurgical chemotherapy regimens for patients with bladder cancer.

Original languageEnglish (US)
Pages (from-to)241-249
Number of pages9
JournalEuropean Urology
Volume67
Issue number2
DOIs
StatePublished - Feb 1 2015

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gemcitabine
Urinary Bladder Neoplasms
Cisplatin
Drug Therapy
Muscles
Vinblastine
Methotrexate
Doxorubicin
Cystectomy
Urinary Bladder
Odds Ratio
Confidence Intervals
Carcinoma

Keywords

  • Complete pathologic response
  • Cystectomy
  • GC
  • MVAC
  • Neoadjuvant chemotherapy
  • Partial pathologic response
  • Urothelial cancer

ASJC Scopus subject areas

  • Urology

Cite this

Zargar, H., Espiritu, P. N., Fairey, A. S., Mertens, L. S., Dinney, C. P., Mir, M. C., ... Black, P. C. (2015). Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer. European Urology, 67(2), 241-249. https://doi.org/10.1016/j.eururo.2014.09.007

Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer. / Zargar, Homayoun; Espiritu, Patrick N.; Fairey, Adrian S.; Mertens, Laura S.; Dinney, Colin P.; Mir, Maria C.; Krabbe, Laura Maria; Cookson, Michael S.; Jacobsen, Niels Erik; Gandhi, Nilay M.; Griffin, Joshua; Montgomery, Jeffrey S.; Vasdev, Nikhil; Yu, Evan Y.; Youssef, David; Xylinas, Evanguelos; Campain, Nicholas J.; Kassouf, Wassim; Dall'Era, Marc; Seah, Jo An; Ercole, Cesar E.; Horenblas, Simon; Sridhar, Srikala S.; McGrath, John S.; Aning, Jonathan; Shariat, Shahrokh F.; Wright, Jonathan L.; Thorpe, Andrew C.; Morgan, Todd M.; Holzbeierlein, Jeff M.; Bivalacqua, Trinity J.; North, Scott; Barocas, Daniel A.; Lotan, Yair; Garcia, Jorge A.; Stephenson, Andrew J.; Shah, Jay B.; Van Rhijn, Bas W.; Daneshmand, Siamak; Spiess, Philippe E.; Black, Peter C.

In: European Urology, Vol. 67, No. 2, 01.02.2015, p. 241-249.

Research output: Contribution to journalArticle

Zargar, H, Espiritu, PN, Fairey, AS, Mertens, LS, Dinney, CP, Mir, MC, Krabbe, LM, Cookson, MS, Jacobsen, NE, Gandhi, NM, Griffin, J, Montgomery, JS, Vasdev, N, Yu, EY, Youssef, D, Xylinas, E, Campain, NJ, Kassouf, W, Dall'Era, M, Seah, JA, Ercole, CE, Horenblas, S, Sridhar, SS, McGrath, JS, Aning, J, Shariat, SF, Wright, JL, Thorpe, AC, Morgan, TM, Holzbeierlein, JM, Bivalacqua, TJ, North, S, Barocas, DA, Lotan, Y, Garcia, JA, Stephenson, AJ, Shah, JB, Van Rhijn, BW, Daneshmand, S, Spiess, PE & Black, PC 2015, 'Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer', European Urology, vol. 67, no. 2, pp. 241-249. https://doi.org/10.1016/j.eururo.2014.09.007
Zargar H, Espiritu PN, Fairey AS, Mertens LS, Dinney CP, Mir MC et al. Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer. European Urology. 2015 Feb 1;67(2):241-249. https://doi.org/10.1016/j.eururo.2014.09.007
Zargar, Homayoun ; Espiritu, Patrick N. ; Fairey, Adrian S. ; Mertens, Laura S. ; Dinney, Colin P. ; Mir, Maria C. ; Krabbe, Laura Maria ; Cookson, Michael S. ; Jacobsen, Niels Erik ; Gandhi, Nilay M. ; Griffin, Joshua ; Montgomery, Jeffrey S. ; Vasdev, Nikhil ; Yu, Evan Y. ; Youssef, David ; Xylinas, Evanguelos ; Campain, Nicholas J. ; Kassouf, Wassim ; Dall'Era, Marc ; Seah, Jo An ; Ercole, Cesar E. ; Horenblas, Simon ; Sridhar, Srikala S. ; McGrath, John S. ; Aning, Jonathan ; Shariat, Shahrokh F. ; Wright, Jonathan L. ; Thorpe, Andrew C. ; Morgan, Todd M. ; Holzbeierlein, Jeff M. ; Bivalacqua, Trinity J. ; North, Scott ; Barocas, Daniel A. ; Lotan, Yair ; Garcia, Jorge A. ; Stephenson, Andrew J. ; Shah, Jay B. ; Van Rhijn, Bas W. ; Daneshmand, Siamak ; Spiess, Philippe E. ; Black, Peter C. / Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer. In: European Urology. 2015 ; Vol. 67, No. 2. pp. 241-249.
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abstract = "Background The efficacy of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (BCa) was established primarily with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), with complete response rates (pT0) as high as 38{\%}. However, because of the comparable efficacy with better tolerability of gemcitabine and cisplatin (GC) in patients with metastatic disease, GC has become the most commonly used regimen in the neoadjuvant setting. Objective We aimed to assess real-world pathologic response rates to NAC with different regimens in a large, multicenter cohort. Design, setting, and participants Data were collected retrospectively at 19 centers on patients with clinical cT2-4aN0M0 urothelial carcinoma of the bladder who received at least three cycles of NAC, followed by radical cystectomy (RC), between 2000 and 2013. Intervention NAC and RC. Outcome measurements and statistical analysis The primary outcome was pathologic stage at cystectomy. Univariable and multivariable analyses were used to determine factors predictive of pT0N0 and ≤pT1N0 stages. Results and limitations Data were collected on 935 patients who met inclusion criteria. GC was used in the majority of the patients (n = 602; 64.4{\%}), followed by MVAC (n = 183; 19.6{\%}) and other regimens (n = 144; 15.4{\%}). The rates of pT0N0 and ≤pT1N0 pathologic response were 22.7{\%} and 40.8{\%}, respectively. The rate of pT0N0 disease for patients receiving GC was 23.9{\%}, compared with 24.5{\%} for MVAC (p = 0.2). There was no difference between MVAC and GC in pT0N0 on multivariable analysis (odds ratio: 0.89 [95{\%} confidence interval, 0.61-1.34]; p = 0.6). Conclusions Response rates to NAC were lower than those reported in prospective randomized trials, and we did not discern a difference between MVAC and GC. Without any evidence from randomized prospective trials, the best NAC regimen for invasive BCa remains to be determined. Patient summary There was no apparent difference in the response rates to the two most common presurgical chemotherapy regimens for patients with bladder cancer.",
keywords = "Complete pathologic response, Cystectomy, GC, MVAC, Neoadjuvant chemotherapy, Partial pathologic response, Urothelial cancer",
author = "Homayoun Zargar and Espiritu, {Patrick N.} and Fairey, {Adrian S.} and Mertens, {Laura S.} and Dinney, {Colin P.} and Mir, {Maria C.} and Krabbe, {Laura Maria} and Cookson, {Michael S.} and Jacobsen, {Niels Erik} and Gandhi, {Nilay M.} and Joshua Griffin and Montgomery, {Jeffrey S.} and Nikhil Vasdev and Yu, {Evan Y.} and David Youssef and Evanguelos Xylinas and Campain, {Nicholas J.} and Wassim Kassouf and Marc Dall'Era and Seah, {Jo An} and Ercole, {Cesar E.} and Simon Horenblas and Sridhar, {Srikala S.} and McGrath, {John S.} and Jonathan Aning and Shariat, {Shahrokh F.} and Wright, {Jonathan L.} and Thorpe, {Andrew C.} and Morgan, {Todd M.} and Holzbeierlein, {Jeff M.} and Bivalacqua, {Trinity J.} and Scott North and Barocas, {Daniel A.} and Yair Lotan and Garcia, {Jorge A.} and Stephenson, {Andrew J.} and Shah, {Jay B.} and {Van Rhijn}, {Bas W.} and Siamak Daneshmand and Spiess, {Philippe E.} and Black, {Peter C.}",
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TY - JOUR

T1 - Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer

AU - Zargar, Homayoun

AU - Espiritu, Patrick N.

AU - Fairey, Adrian S.

AU - Mertens, Laura S.

AU - Dinney, Colin P.

AU - Mir, Maria C.

AU - Krabbe, Laura Maria

AU - Cookson, Michael S.

AU - Jacobsen, Niels Erik

AU - Gandhi, Nilay M.

AU - Griffin, Joshua

AU - Montgomery, Jeffrey S.

AU - Vasdev, Nikhil

AU - Yu, Evan Y.

AU - Youssef, David

AU - Xylinas, Evanguelos

AU - Campain, Nicholas J.

AU - Kassouf, Wassim

AU - Dall'Era, Marc

AU - Seah, Jo An

AU - Ercole, Cesar E.

AU - Horenblas, Simon

AU - Sridhar, Srikala S.

AU - McGrath, John S.

AU - Aning, Jonathan

AU - Shariat, Shahrokh F.

AU - Wright, Jonathan L.

AU - Thorpe, Andrew C.

AU - Morgan, Todd M.

AU - Holzbeierlein, Jeff M.

AU - Bivalacqua, Trinity J.

AU - North, Scott

AU - Barocas, Daniel A.

AU - Lotan, Yair

AU - Garcia, Jorge A.

AU - Stephenson, Andrew J.

AU - Shah, Jay B.

AU - Van Rhijn, Bas W.

AU - Daneshmand, Siamak

AU - Spiess, Philippe E.

AU - Black, Peter C.

PY - 2015/2/1

Y1 - 2015/2/1

N2 - Background The efficacy of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (BCa) was established primarily with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), with complete response rates (pT0) as high as 38%. However, because of the comparable efficacy with better tolerability of gemcitabine and cisplatin (GC) in patients with metastatic disease, GC has become the most commonly used regimen in the neoadjuvant setting. Objective We aimed to assess real-world pathologic response rates to NAC with different regimens in a large, multicenter cohort. Design, setting, and participants Data were collected retrospectively at 19 centers on patients with clinical cT2-4aN0M0 urothelial carcinoma of the bladder who received at least three cycles of NAC, followed by radical cystectomy (RC), between 2000 and 2013. Intervention NAC and RC. Outcome measurements and statistical analysis The primary outcome was pathologic stage at cystectomy. Univariable and multivariable analyses were used to determine factors predictive of pT0N0 and ≤pT1N0 stages. Results and limitations Data were collected on 935 patients who met inclusion criteria. GC was used in the majority of the patients (n = 602; 64.4%), followed by MVAC (n = 183; 19.6%) and other regimens (n = 144; 15.4%). The rates of pT0N0 and ≤pT1N0 pathologic response were 22.7% and 40.8%, respectively. The rate of pT0N0 disease for patients receiving GC was 23.9%, compared with 24.5% for MVAC (p = 0.2). There was no difference between MVAC and GC in pT0N0 on multivariable analysis (odds ratio: 0.89 [95% confidence interval, 0.61-1.34]; p = 0.6). Conclusions Response rates to NAC were lower than those reported in prospective randomized trials, and we did not discern a difference between MVAC and GC. Without any evidence from randomized prospective trials, the best NAC regimen for invasive BCa remains to be determined. Patient summary There was no apparent difference in the response rates to the two most common presurgical chemotherapy regimens for patients with bladder cancer.

AB - Background The efficacy of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (BCa) was established primarily with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), with complete response rates (pT0) as high as 38%. However, because of the comparable efficacy with better tolerability of gemcitabine and cisplatin (GC) in patients with metastatic disease, GC has become the most commonly used regimen in the neoadjuvant setting. Objective We aimed to assess real-world pathologic response rates to NAC with different regimens in a large, multicenter cohort. Design, setting, and participants Data were collected retrospectively at 19 centers on patients with clinical cT2-4aN0M0 urothelial carcinoma of the bladder who received at least three cycles of NAC, followed by radical cystectomy (RC), between 2000 and 2013. Intervention NAC and RC. Outcome measurements and statistical analysis The primary outcome was pathologic stage at cystectomy. Univariable and multivariable analyses were used to determine factors predictive of pT0N0 and ≤pT1N0 stages. Results and limitations Data were collected on 935 patients who met inclusion criteria. GC was used in the majority of the patients (n = 602; 64.4%), followed by MVAC (n = 183; 19.6%) and other regimens (n = 144; 15.4%). The rates of pT0N0 and ≤pT1N0 pathologic response were 22.7% and 40.8%, respectively. The rate of pT0N0 disease for patients receiving GC was 23.9%, compared with 24.5% for MVAC (p = 0.2). There was no difference between MVAC and GC in pT0N0 on multivariable analysis (odds ratio: 0.89 [95% confidence interval, 0.61-1.34]; p = 0.6). Conclusions Response rates to NAC were lower than those reported in prospective randomized trials, and we did not discern a difference between MVAC and GC. Without any evidence from randomized prospective trials, the best NAC regimen for invasive BCa remains to be determined. Patient summary There was no apparent difference in the response rates to the two most common presurgical chemotherapy regimens for patients with bladder cancer.

KW - Complete pathologic response

KW - Cystectomy

KW - GC

KW - MVAC

KW - Neoadjuvant chemotherapy

KW - Partial pathologic response

KW - Urothelial cancer

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