Multicenter Evaluation of Neoadjuvant and Induction Gemcitabine-Carboplatin versus Gemcitabine-Cisplatin Followed by Radical Cystectomy for Muscle-Invasive Bladder Cancer

Sarah MH Einerhand; Anna J Black; Homayoun Zargar; Adrian S. Fairey; Colin P Dinney; Maria C Mir; Laura-Maria Krabbe; Michael S. Cookson; Niels-Erik Jacobson; Jeffrey S Montgomery; Nikhil Vasdev; Evan Y Yu; Evanguelos Xylinas; Wassim Kassouf; Marc A. Dall’Era; Srikala S. Sridhar; Jonathan 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; Petros Grivas; Jorge A Garcia; Andrew J Stephenson; Jay B Shah; Simak Daneshmand; Kamran Zargar-Shoshtari; P. E. Spiess; Bas W van Rhijn; Peter C. Black; L. S. Mertens

doi:10.1007/s00345-022-04160-7

Multicenter Evaluation of Neoadjuvant and Induction Gemcitabine-Carboplatin versus Gemcitabine-Cisplatin Followed by Radical Cystectomy for Muscle-Invasive Bladder Cancer

Sarah MH Einerhand, Anna J Black, Homayoun Zargar, Adrian S. Fairey, Colin P Dinney, Maria C Mir, Laura-Maria Krabbe, Michael S. Cookson, Niels-Erik Jacobson, Jeffrey S Montgomery, Nikhil Vasdev, Evan Y Yu, Evanguelos Xylinas, Wassim Kassouf, Marc A. Dall’Era, Srikala S. Sridhar, Jonathan S McGrath, Jonathan Aning, Shahrokh F Shariat, Jonathan L. WrightAndrew C. Thorpe, Todd M Morgan, Jeff M. Holzbeierlein, Trinity J Bivalacqua, Scott North, Daniel A. Barocas, Yair Lotan, Petros Grivas, Jorge A Garcia, Andrew J Stephenson, Jay B Shah, Simak Daneshmand, Kamran Zargar-Shoshtari, P. E. Spiess, Bas W van Rhijn, Peter C. Black, L. S. Mertens

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Abstract

PurposeCisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin-ineligible. The aim of this study was to compare clinical outcomes after ≥3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis). Methods We identified 1865 patients treated at 19 centers between 2000 and 2013. Patients were included if they had received ≥3 cycles of neoadjuvant (cT2-4aN0M0) or induction (cTanyN+M0) gem-carbo or gem-cis followed by RC. Results We included 747 patients treated with gem-carbo (n=147) or gem-cis (n=600). Patients treated with gem carbo had a higher Charlson Comorbidity Index (p=0.016) and more clinically node-positive disease (32% 88 versus 20%; p=0.013). The complete pathological response (pCR; ypT0N0) rate did not significantly differ between gem-carbo and gem-cis (20.7% versus 22.1%; p=0.73). Chemotherapeutic regimen was not significantly associated with pCR (OR: 0.99 [95%CI, 0.61-1.59]; p=0.96), overall survival (OS) (HR: 1.20 91 [95%CI, 0.85-1.67]; p=0.31), or cancer-specific survival (CSS) (HR: 1.35 [95%CI, 0.93-1.96]; p=0.11). Median OS of patients treated with gem-carbo and gem-cis was 28.6 months (95%CI 18.1-39.1) and 45.1 months (95%CI 32.7-57.6)(p=0.18), respectively. Median CSS of patients treated with gem-carbo and gem-cis was 28.8 months (95%CI 9.8-47.8) and 71.0 months (95%CI median not reached)(p=0.02), respectively. Subanalyses of the neoadjuvant and induction setting did not show significant survival differences. 4 Conclusion Our results show that a subset of cisplatin-ineligible patients with MIBC achieve pCR on gem-carbo and that survival outcomes seem comparable to gem-cis provided patients are able to receive ≥3 cycles and undergo RC.

Original language	English
Journal	World Journal of Urology
DOIs	https://doi.org/10.1007/s00345-022-04160-7
Publication status	Published - 28 Sept 2022

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© 2022 Springer Nature Switzerland AG. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1007/s00345-022-04160-7
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Einerhand, S. MH., Black, A. J., Zargar, H., Fairey, A. S., Dinney, C. P., Mir, M. C., Krabbe, L.-M., Cookson, M. S., Jacobson, N.-E., Montgomery, J. S., Vasdev, N., Yu, E. Y., Xylinas, E., Kassouf, W., Dall’Era, M. A., Sridhar, S. S., McGrath, J. S., Aning, J., Shariat, S. F., ... Mertens, L. S. (2022). Multicenter Evaluation of Neoadjuvant and Induction Gemcitabine-Carboplatin versus Gemcitabine-Cisplatin Followed by Radical Cystectomy for Muscle-Invasive Bladder Cancer. World Journal of Urology. https://doi.org/10.1007/s00345-022-04160-7

@article{130fa278cb5f413997107726776792e3,

title = "Multicenter Evaluation of Neoadjuvant and Induction Gemcitabine-Carboplatin versus Gemcitabine-Cisplatin Followed by Radical Cystectomy for Muscle-Invasive Bladder Cancer",

abstract = "PurposeCisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin-ineligible. The aim of this study was to compare clinical outcomes after ≥3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis). Methods We identified 1865 patients treated at 19 centers between 2000 and 2013. Patients were included if they had received ≥3 cycles of neoadjuvant (cT2-4aN0M0) or induction (cTanyN+M0) gem-carbo or gem-cis followed by RC. Results We included 747 patients treated with gem-carbo (n=147) or gem-cis (n=600). Patients treated with gem carbo had a higher Charlson Comorbidity Index (p=0.016) and more clinically node-positive disease (32% 88 versus 20%; p=0.013). The complete pathological response (pCR; ypT0N0) rate did not significantly differ between gem-carbo and gem-cis (20.7% versus 22.1%; p=0.73). Chemotherapeutic regimen was not significantly associated with pCR (OR: 0.99 [95%CI, 0.61-1.59]; p=0.96), overall survival (OS) (HR: 1.20 91 [95%CI, 0.85-1.67]; p=0.31), or cancer-specific survival (CSS) (HR: 1.35 [95%CI, 0.93-1.96]; p=0.11). Median OS of patients treated with gem-carbo and gem-cis was 28.6 months (95%CI 18.1-39.1) and 45.1 months (95%CI 32.7-57.6)(p=0.18), respectively. Median CSS of patients treated with gem-carbo and gem-cis was 28.8 months (95%CI 9.8-47.8) and 71.0 months (95%CI median not reached)(p=0.02), respectively. Subanalyses of the neoadjuvant and induction setting did not show significant survival differences. 4 Conclusion Our results show that a subset of cisplatin-ineligible patients with MIBC achieve pCR on gem-carbo and that survival outcomes seem comparable to gem-cis provided patients are able to receive ≥3 cycles and undergo RC.",

author = "Einerhand, {Sarah MH} and Black, {Anna J} and Homayoun Zargar and Fairey, {Adrian S.} and Dinney, {Colin P} and Mir, {Maria C} and Laura-Maria Krabbe and Cookson, {Michael S.} and Niels-Erik Jacobson and Montgomery, {Jeffrey S} and Nikhil Vasdev and Yu, {Evan Y} and Evanguelos Xylinas and Wassim Kassouf and Dall{\textquoteright}Era, {Marc A.} and Sridhar, {Srikala S.} and McGrath, {Jonathan 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 Petros Grivas and Garcia, {Jorge A} and Stephenson, {Andrew J} and Shah, {Jay B} and Simak Daneshmand and Kamran Zargar-Shoshtari and Spiess, {P. E.} and {van Rhijn}, {Bas W} and Black, {Peter C.} and Mertens, {L. S.}",

note = "{\textcopyright} 2022 Springer Nature Switzerland AG. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1007/s00345-022-04160-7",

year = "2022",

month = sep,

day = "28",

doi = "10.1007/s00345-022-04160-7",

language = "English",

journal = "World Journal of Urology",

issn = "0724-4983",

publisher = "Springer Nature",

}

Einerhand, SMH, Black, AJ, Zargar, H, Fairey, AS, Dinney, CP, Mir, MC, Krabbe, L-M, Cookson, MS, Jacobson, N-E, Montgomery, JS, Vasdev, N, Yu, EY, Xylinas, E, Kassouf, W, Dall’Era, MA, Sridhar, SS, McGrath, JS, Aning, J, Shariat, SF, Wright, JL, Thorpe, AC, Morgan, TM, Holzbeierlein, JM, Bivalacqua, TJ, North, S, Barocas, DA, Lotan, Y, Grivas, P, Garcia, JA, Stephenson, AJ, Shah, JB, Daneshmand, S, Zargar-Shoshtari, K, Spiess, PE, van Rhijn, BW, Black, PC & Mertens, LS 2022, 'Multicenter Evaluation of Neoadjuvant and Induction Gemcitabine-Carboplatin versus Gemcitabine-Cisplatin Followed by Radical Cystectomy for Muscle-Invasive Bladder Cancer', World Journal of Urology. https://doi.org/10.1007/s00345-022-04160-7

TY - JOUR

T1 - Multicenter Evaluation of Neoadjuvant and Induction Gemcitabine-Carboplatin versus Gemcitabine-Cisplatin Followed by Radical Cystectomy for Muscle-Invasive Bladder Cancer

AU - Einerhand, Sarah MH

AU - Black, Anna J

AU - Zargar, Homayoun

AU - Fairey, Adrian S.

AU - Dinney, Colin P

AU - Mir, Maria C

AU - Krabbe, Laura-Maria

AU - Cookson, Michael S.

AU - Jacobson, Niels-Erik

AU - Montgomery, Jeffrey S

AU - Vasdev, Nikhil

AU - Yu, Evan Y

AU - Xylinas, Evanguelos

AU - Kassouf, Wassim

AU - Dall’Era, Marc A.

AU - Sridhar, Srikala S.

AU - McGrath, Jonathan 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 - Grivas, Petros

AU - Garcia, Jorge A

AU - Stephenson, Andrew J

AU - Shah, Jay B

AU - Daneshmand, Simak

AU - Zargar-Shoshtari, Kamran

AU - Spiess, P. E.

AU - van Rhijn, Bas W

AU - Black, Peter C.

AU - Mertens, L. S.

PY - 2022/9/28

Y1 - 2022/9/28

N2 - PurposeCisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin-ineligible. The aim of this study was to compare clinical outcomes after ≥3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis). Methods We identified 1865 patients treated at 19 centers between 2000 and 2013. Patients were included if they had received ≥3 cycles of neoadjuvant (cT2-4aN0M0) or induction (cTanyN+M0) gem-carbo or gem-cis followed by RC. Results We included 747 patients treated with gem-carbo (n=147) or gem-cis (n=600). Patients treated with gem carbo had a higher Charlson Comorbidity Index (p=0.016) and more clinically node-positive disease (32% 88 versus 20%; p=0.013). The complete pathological response (pCR; ypT0N0) rate did not significantly differ between gem-carbo and gem-cis (20.7% versus 22.1%; p=0.73). Chemotherapeutic regimen was not significantly associated with pCR (OR: 0.99 [95%CI, 0.61-1.59]; p=0.96), overall survival (OS) (HR: 1.20 91 [95%CI, 0.85-1.67]; p=0.31), or cancer-specific survival (CSS) (HR: 1.35 [95%CI, 0.93-1.96]; p=0.11). Median OS of patients treated with gem-carbo and gem-cis was 28.6 months (95%CI 18.1-39.1) and 45.1 months (95%CI 32.7-57.6)(p=0.18), respectively. Median CSS of patients treated with gem-carbo and gem-cis was 28.8 months (95%CI 9.8-47.8) and 71.0 months (95%CI median not reached)(p=0.02), respectively. Subanalyses of the neoadjuvant and induction setting did not show significant survival differences. 4 Conclusion Our results show that a subset of cisplatin-ineligible patients with MIBC achieve pCR on gem-carbo and that survival outcomes seem comparable to gem-cis provided patients are able to receive ≥3 cycles and undergo RC.

AB - PurposeCisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin-ineligible. The aim of this study was to compare clinical outcomes after ≥3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis). Methods We identified 1865 patients treated at 19 centers between 2000 and 2013. Patients were included if they had received ≥3 cycles of neoadjuvant (cT2-4aN0M0) or induction (cTanyN+M0) gem-carbo or gem-cis followed by RC. Results We included 747 patients treated with gem-carbo (n=147) or gem-cis (n=600). Patients treated with gem carbo had a higher Charlson Comorbidity Index (p=0.016) and more clinically node-positive disease (32% 88 versus 20%; p=0.013). The complete pathological response (pCR; ypT0N0) rate did not significantly differ between gem-carbo and gem-cis (20.7% versus 22.1%; p=0.73). Chemotherapeutic regimen was not significantly associated with pCR (OR: 0.99 [95%CI, 0.61-1.59]; p=0.96), overall survival (OS) (HR: 1.20 91 [95%CI, 0.85-1.67]; p=0.31), or cancer-specific survival (CSS) (HR: 1.35 [95%CI, 0.93-1.96]; p=0.11). Median OS of patients treated with gem-carbo and gem-cis was 28.6 months (95%CI 18.1-39.1) and 45.1 months (95%CI 32.7-57.6)(p=0.18), respectively. Median CSS of patients treated with gem-carbo and gem-cis was 28.8 months (95%CI 9.8-47.8) and 71.0 months (95%CI median not reached)(p=0.02), respectively. Subanalyses of the neoadjuvant and induction setting did not show significant survival differences. 4 Conclusion Our results show that a subset of cisplatin-ineligible patients with MIBC achieve pCR on gem-carbo and that survival outcomes seem comparable to gem-cis provided patients are able to receive ≥3 cycles and undergo RC.

U2 - 10.1007/s00345-022-04160-7

DO - 10.1007/s00345-022-04160-7

M3 - Article

SN - 0724-4983

JO - World Journal of Urology

JF - World Journal of Urology

ER -

Multicenter Evaluation of Neoadjuvant and Induction Gemcitabine-Carboplatin versus Gemcitabine-Cisplatin Followed by Radical Cystectomy for Muscle-Invasive Bladder Cancer

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