Identifying the Optimal Number of Neoadjuvant Chemotherapy Cycles in Patients with Muscle-Invasive Bladder Cancer

David D'Andrea; Peter C. Black; Homayoun Zargar; C. P. Dinney; Francesco Soria; M. S. Cookson; Jeffrey S Montgomery; Wassim Kassouf; Marc A Dall'Era; Srikala S. Sridhar; John S McGrath; Jonathan  Wright; Andrew C. Thorpe; J. M. Holzbeierlein; Diego Carrión; Ettore Di Trapani; Trinity J Bivalacqua; Scott North; Daniel A Barocas; Yair Lotan; Petros Grivas; Andrew J Stephenson; Bas W van Rhijn; Siamak Daneshmand; Philippe E Spiess; Shahrokh F Shariat; Kamran Zargar-Shoshtari; Laura S Mertens; Adrian S Fairey; Maria C Mir; Laura-Maria Krabbe; Niels-Erik Jacobsen; Nikhil Vasdev; Evan Y Yu; Evanguelos Xylinas; Benjamin Pradere; Renate Pichler; Nicholas J Campain; J. A. Seah; C. E. Ercole; Simon Horenblas; J. Aning; Todd M Morgan; Jay B Shah; Marco Moschini

doi:10.1097/JU.0000000000002190

Identifying the Optimal Number of Neoadjuvant Chemotherapy Cycles in Patients with Muscle-Invasive Bladder Cancer

David D'Andrea, Peter C. Black, Homayoun Zargar, C. P. Dinney, Francesco Soria, M. S. Cookson, Jeffrey S Montgomery, Wassim Kassouf, Marc A Dall'Era, Srikala S. Sridhar, John S McGrath, Jonathan Wright, Andrew C. Thorpe, J. M. Holzbeierlein, Diego Carrión, Ettore Di Trapani, Trinity J Bivalacqua, Scott North, Daniel A Barocas, Yair LotanPetros Grivas, Andrew J Stephenson, Bas W van Rhijn, Siamak Daneshmand, Philippe E Spiess, Shahrokh F Shariat, Kamran Zargar-Shoshtari, Laura S Mertens, Adrian S Fairey, Maria C Mir, Laura-Maria Krabbe, Niels-Erik Jacobsen, Nikhil Vasdev, Evan Y Yu, Evanguelos Xylinas, Benjamin Pradere, Renate Pichler, Nicholas J Campain, J. A. Seah, C. E. Ercole, Simon Horenblas, J. Aning, Todd M Morgan, Jay B Shah, Marco Moschini

Research output: Contribution to journal › Article › peer-review

Abstract

Purpose:We investigated the pathological response rates and survival associated with 3 vs 4 cycles of cisplatin-based neoadjuvant chemotherapy (NAC) in patients with cT2-4N0M0 muscle invasive bladder cancer.Materials and Methods:In this cohort study we analyzed clinical data of 828 patients treated with NAC and radical cystectomy between 2000 and 2020. A total of 384 and 444 patients were treated with 3 and 4 cycles of NAC, respectively. Pathological objective response (pOR; ypT0-Ta-Tis-T1 N0), pathological complete response (pCR; ypT0 N0), cancer-specific survival and overall survival were investigated.Results:pOR and pCR were achieved in 378 (45%; 95% CI 42, 49) and 207 (25%; 95% CI 22, 28) patients, respectively. Patients treated with 4 cycles of NAC had higher pOR (49% vs 42%, p=0.03) and pCR (28% vs 21%, p=0.02) rates compared to those treated with 3 cycles. This effect was confirmed on multivariable logistic regression analysis (pOR OR 1.46 p=0.008, pCR OR 1.57, p=0.007). On multivariable Cox regression analysis, 4 cycles of NAC were significantly associated with overall survival (HR 0.68; 95% CI 0.49, 0.94; p=0.02) but not with cancer-specific survival (HR 0.72; 95% CI 0.50, 1.04; p=0.08).Conclusions:Four cycles of NAC achieved better pathological response and survival compared to 3 cycles. These findings may aid clinicians in counseling patients and serve as a benchmark for prospective trials. Prospective validation of these findings and assessment of cumulative toxicity derived from an increased number of cycles are needed.

Original language	English
Pages (from-to)	70-76
Number of pages	7
Journal	AUA Journal of Urology
Volume	207
Issue number	1
Early online date	27 Aug 2021
DOIs	https://doi.org/10.1097/JU.0000000000002190
Publication status	Published - 1 Jan 2022

Keywords

drug administration schedule
neoadjuvant therapy
survival
urinary bladder neoplasms

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D'Andrea, D., Black, P. C., Zargar, H., Dinney, C. P., Soria, F., Cookson, M. S., Montgomery, J. S., Kassouf, W., Dall'Era, M. A., Sridhar, S. S., McGrath, J. S., Wright, J., Thorpe, A. C., Holzbeierlein, J. M., Carrión, D., Di Trapani, E., Bivalacqua, T. J., North, S., Barocas, D. A., ... Moschini, M. (2022). Identifying the Optimal Number of Neoadjuvant Chemotherapy Cycles in Patients with Muscle-Invasive Bladder Cancer. AUA Journal of Urology, 207(1), 70-76. https://doi.org/10.1097/JU.0000000000002190

@article{0986db00638948f1a9dbad3759e84534,

title = "Identifying the Optimal Number of Neoadjuvant Chemotherapy Cycles in Patients with Muscle-Invasive Bladder Cancer",

abstract = "Purpose:We investigated the pathological response rates and survival associated with 3 vs 4 cycles of cisplatin-based neoadjuvant chemotherapy (NAC) in patients with cT2-4N0M0 muscle invasive bladder cancer.Materials and Methods:In this cohort study we analyzed clinical data of 828 patients treated with NAC and radical cystectomy between 2000 and 2020. A total of 384 and 444 patients were treated with 3 and 4 cycles of NAC, respectively. Pathological objective response (pOR; ypT0-Ta-Tis-T1 N0), pathological complete response (pCR; ypT0 N0), cancer-specific survival and overall survival were investigated.Results:pOR and pCR were achieved in 378 (45%; 95% CI 42, 49) and 207 (25%; 95% CI 22, 28) patients, respectively. Patients treated with 4 cycles of NAC had higher pOR (49% vs 42%, p=0.03) and pCR (28% vs 21%, p=0.02) rates compared to those treated with 3 cycles. This effect was confirmed on multivariable logistic regression analysis (pOR OR 1.46 p=0.008, pCR OR 1.57, p=0.007). On multivariable Cox regression analysis, 4 cycles of NAC were significantly associated with overall survival (HR 0.68; 95% CI 0.49, 0.94; p=0.02) but not with cancer-specific survival (HR 0.72; 95% CI 0.50, 1.04; p=0.08).Conclusions:Four cycles of NAC achieved better pathological response and survival compared to 3 cycles. These findings may aid clinicians in counseling patients and serve as a benchmark for prospective trials. Prospective validation of these findings and assessment of cumulative toxicity derived from an increased number of cycles are needed.",

keywords = "drug administration schedule, neoadjuvant therapy, survival, urinary bladder neoplasms",

author = "David D'Andrea and Black, {Peter C.} and Homayoun Zargar and Dinney, {C. P.} and Francesco Soria and Cookson, {M. S.} and Montgomery, {Jeffrey S} and Wassim Kassouf and Dall'Era, {Marc A} and Sridhar, {Srikala S.} and McGrath, {John S} and Jonathan Wright and Thorpe, {Andrew C.} and Holzbeierlein, {J. M.} and Diego Carri{\'o}n and {Di Trapani}, Ettore and Bivalacqua, {Trinity J} and Scott North and Barocas, {Daniel A} and Yair Lotan and Petros Grivas and Stephenson, {Andrew J} and {van Rhijn}, {Bas W} and Siamak Daneshmand and Spiess, {Philippe E} and Shariat, {Shahrokh F} and Kamran Zargar-Shoshtari and Mertens, {Laura S} and Fairey, {Adrian S} and Mir, {Maria C} and Laura-Maria Krabbe and Niels-Erik Jacobsen and Nikhil Vasdev and Yu, {Evan Y} and Evanguelos Xylinas and Benjamin Pradere and Renate Pichler and Campain, {Nicholas J} and Seah, {J. A.} and Ercole, {C. E.} and Simon Horenblas and J. Aning and Morgan, {Todd M} and Shah, {Jay B} and Marco Moschini",

note = "{\textcopyright} 2021 by American Urological Association Education and Research, Inc.",

year = "2022",

month = jan,

day = "1",

doi = "10.1097/JU.0000000000002190",

language = "English",

volume = "207",

pages = "70--76",

journal = "AUA Journal of Urology",

publisher = "American Urological Association (AUA)",

number = "1",

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D'Andrea, D, Black, PC, Zargar, H, Dinney, CP, Soria, F, Cookson, MS, Montgomery, JS, Kassouf, W, Dall'Era, MA, Sridhar, SS, McGrath, JS, Wright, J, Thorpe, AC, Holzbeierlein, JM, Carrión, D, Di Trapani, E, Bivalacqua, TJ, North, S, Barocas, DA, Lotan, Y, Grivas, P, Stephenson, AJ, van Rhijn, BW, Daneshmand, S, Spiess, PE, Shariat, SF, Zargar-Shoshtari, K, Mertens, LS, Fairey, AS, Mir, MC, Krabbe, L-M, Jacobsen, N-E, Vasdev, N, Yu, EY, Xylinas, E, Pradere, B, Pichler, R, Campain, NJ, Seah, JA, Ercole, CE, Horenblas, S, Aning, J, Morgan, TM, Shah, JB & Moschini, M 2022, 'Identifying the Optimal Number of Neoadjuvant Chemotherapy Cycles in Patients with Muscle-Invasive Bladder Cancer', AUA Journal of Urology, vol. 207, no. 1, pp. 70-76. https://doi.org/10.1097/JU.0000000000002190

TY - JOUR

T1 - Identifying the Optimal Number of Neoadjuvant Chemotherapy Cycles in Patients with Muscle-Invasive Bladder Cancer

AU - D'Andrea, David

AU - Black, Peter C.

AU - Zargar, Homayoun

AU - Dinney, C. P.

AU - Soria, Francesco

AU - Cookson, M. S.

AU - Montgomery, Jeffrey S

AU - Kassouf, Wassim

AU - Dall'Era, Marc A

AU - Sridhar, Srikala S.

AU - McGrath, John S

AU - Wright, Jonathan

AU - Thorpe, Andrew C.

AU - Holzbeierlein, J. M.

AU - Carrión, Diego

AU - Di Trapani, Ettore

AU - Bivalacqua, Trinity J

AU - North, Scott

AU - Barocas, Daniel A

AU - Lotan, Yair

AU - Grivas, Petros

AU - Stephenson, Andrew J

AU - van Rhijn, Bas W

AU - Daneshmand, Siamak

AU - Spiess, Philippe E

AU - Shariat, Shahrokh F

AU - Zargar-Shoshtari, Kamran

AU - Mertens, Laura S

AU - Fairey, Adrian S

AU - Mir, Maria C

AU - Krabbe, Laura-Maria

AU - Jacobsen, Niels-Erik

AU - Vasdev, Nikhil

AU - Yu, Evan Y

AU - Xylinas, Evanguelos

AU - Pradere, Benjamin

AU - Pichler, Renate

AU - Campain, Nicholas J

AU - Seah, J. A.

AU - Ercole, C. E.

AU - Horenblas, Simon

AU - Aning, J.

AU - Morgan, Todd M

AU - Shah, Jay B

AU - Moschini, Marco

PY - 2022/1/1

Y1 - 2022/1/1

N2 - Purpose:We investigated the pathological response rates and survival associated with 3 vs 4 cycles of cisplatin-based neoadjuvant chemotherapy (NAC) in patients with cT2-4N0M0 muscle invasive bladder cancer.Materials and Methods:In this cohort study we analyzed clinical data of 828 patients treated with NAC and radical cystectomy between 2000 and 2020. A total of 384 and 444 patients were treated with 3 and 4 cycles of NAC, respectively. Pathological objective response (pOR; ypT0-Ta-Tis-T1 N0), pathological complete response (pCR; ypT0 N0), cancer-specific survival and overall survival were investigated.Results:pOR and pCR were achieved in 378 (45%; 95% CI 42, 49) and 207 (25%; 95% CI 22, 28) patients, respectively. Patients treated with 4 cycles of NAC had higher pOR (49% vs 42%, p=0.03) and pCR (28% vs 21%, p=0.02) rates compared to those treated with 3 cycles. This effect was confirmed on multivariable logistic regression analysis (pOR OR 1.46 p=0.008, pCR OR 1.57, p=0.007). On multivariable Cox regression analysis, 4 cycles of NAC were significantly associated with overall survival (HR 0.68; 95% CI 0.49, 0.94; p=0.02) but not with cancer-specific survival (HR 0.72; 95% CI 0.50, 1.04; p=0.08).Conclusions:Four cycles of NAC achieved better pathological response and survival compared to 3 cycles. These findings may aid clinicians in counseling patients and serve as a benchmark for prospective trials. Prospective validation of these findings and assessment of cumulative toxicity derived from an increased number of cycles are needed.

AB - Purpose:We investigated the pathological response rates and survival associated with 3 vs 4 cycles of cisplatin-based neoadjuvant chemotherapy (NAC) in patients with cT2-4N0M0 muscle invasive bladder cancer.Materials and Methods:In this cohort study we analyzed clinical data of 828 patients treated with NAC and radical cystectomy between 2000 and 2020. A total of 384 and 444 patients were treated with 3 and 4 cycles of NAC, respectively. Pathological objective response (pOR; ypT0-Ta-Tis-T1 N0), pathological complete response (pCR; ypT0 N0), cancer-specific survival and overall survival were investigated.Results:pOR and pCR were achieved in 378 (45%; 95% CI 42, 49) and 207 (25%; 95% CI 22, 28) patients, respectively. Patients treated with 4 cycles of NAC had higher pOR (49% vs 42%, p=0.03) and pCR (28% vs 21%, p=0.02) rates compared to those treated with 3 cycles. This effect was confirmed on multivariable logistic regression analysis (pOR OR 1.46 p=0.008, pCR OR 1.57, p=0.007). On multivariable Cox regression analysis, 4 cycles of NAC were significantly associated with overall survival (HR 0.68; 95% CI 0.49, 0.94; p=0.02) but not with cancer-specific survival (HR 0.72; 95% CI 0.50, 1.04; p=0.08).Conclusions:Four cycles of NAC achieved better pathological response and survival compared to 3 cycles. These findings may aid clinicians in counseling patients and serve as a benchmark for prospective trials. Prospective validation of these findings and assessment of cumulative toxicity derived from an increased number of cycles are needed.

KW - drug administration schedule

KW - neoadjuvant therapy

KW - survival

KW - urinary bladder neoplasms

UR - http://www.scopus.com/inward/record.url?scp=85121914585&partnerID=8YFLogxK

U2 - 10.1097/JU.0000000000002190

DO - 10.1097/JU.0000000000002190

M3 - Article

VL - 207

SP - 70

EP - 76

JO - AUA Journal of Urology

JF - AUA Journal of Urology

IS - 1

ER -

Identifying the Optimal Number of Neoadjuvant Chemotherapy Cycles in Patients with Muscle-Invasive Bladder Cancer

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