Impact of sex on response to neoadjuvant chemotherapy in patients with bladder cancer

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

doi:10.1016/j.urolonc.2020.01.010

Impact of sex on response to neoadjuvant chemotherapy in patients with bladder cancer

David D'Andrea, Peter C. Black, Homayoun Zargar, Kamran Zargar-Shoshtari, Sonja Zehetmayer, Adrian S. Fairey, Laura S. Mertens, Colin P. Dinney, Maria C. Mir, Laura Maria Krabbe, Michael S. Cookson, Niels Erik Jacobsen, Jeffrey S. Montgomery, Nikhil Vasdev, Evan Y. Yu, Evanguelos Xylinas, Nicholas J. Campain, Wassim Kassouf, Marc A. Dall'Era, Jo An SeahCesar E. Ercole, Simon Horenblas, Srikala S. Sridhar, John S. McGrath, Jonathan Aning, Jonathan L. Wright, Andrew C. Thorpe, Todd M. Morgan, Jeffrey M. Holzbeierlein, Trinity J. Bivalacqua, Scott North, Daniel A. Barocas, Yair Lotan, Petros Grivas, Andrew J. Stephenson, Jay B. Shah, Bas W. van Rhijn, Siamak Daneshmand, Philippe E. Spiess, Shahrokh F. Shariat

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Abstract

Objective: To assess the effect of patient's sex on response to neoadjuvant chemotherapy (NAC) in patients with clinically nonmetastatic muscle-invasive bladder cancer (MIBC). Methods: Complete pathologic response, defined as ypT0N0 at radical cystectomy, and downstaging were evaluated using sex-adjusted univariable and multivariable logistic regression modeling. We used interaction terms to account for age of menopause and smoking status. The association of sex with overall survival and cancer-specific survival was evaluated using Cox regression analyses. Results: A total of 1,031 patients were included in the analysis, 227 (22%) of whom were female. Female patients had a higher rate of extravesical disease extension (P = 0.01). After the administration of NAC, ypT stage was equally distributed between sexes (P = 0.39). On multivariable logistic regression analyses, there was no difference between the sexes or age of menopause with regards to ypT0N0 rates or downstaging (all P > 0.5). On Cox regression analyses, sex was associated with neither overall survival (hazard ratio 1.04, 95% confidence interval 0.75–1.45, P = 0.81) nor cancer-specific survival (hazard ratio 1.06, 95% confidence interval 0.71–1.58, P = 0.77). Conclusion: Our study generates the hypothesis that NAC equalizes the preoperative disparity in pathologic stage between males and females suggesting a possible differential response between sexes. This might be the explanation underlying the comparable survival outcomes between sexes despite females presenting with more advanced tumor stage.

Original language	English
Journal	Urologic Oncology: Seminars and Original Investigations
Early online date	11 Feb 2020
DOIs	https://doi.org/10.1016/j.urolonc.2020.01.010
Publication status	E-pub ahead of print - 11 Feb 2020

Keywords

Bladder cancer
Neoadjuvant chemotherapy
Response
Sex

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UrologicOncology
© 2020 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/.
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D'Andrea, D., Black, P. C., Zargar, H., Zargar-Shoshtari, K., Zehetmayer, S., Fairey, A. S., Mertens, L. S., Dinney, C. P., Mir, M. C., Krabbe, L. M., Cookson, M. S., Jacobsen, N. E., Montgomery, J. S., Vasdev, N., Yu, E. Y., Xylinas, E., Campain, N. J., Kassouf, W., Dall'Era, M. A., ... Shariat, S. F. (2020). Impact of sex on response to neoadjuvant chemotherapy in patients with bladder cancer. Urologic Oncology: Seminars and Original Investigations. https://doi.org/10.1016/j.urolonc.2020.01.010

@article{bdd00d2f6dfa4c47af1afa49cb9cba3f,

title = "Impact of sex on response to neoadjuvant chemotherapy in patients with bladder cancer",

abstract = "Objective: To assess the effect of patient's sex on response to neoadjuvant chemotherapy (NAC) in patients with clinically nonmetastatic muscle-invasive bladder cancer (MIBC). Methods: Complete pathologic response, defined as ypT0N0 at radical cystectomy, and downstaging were evaluated using sex-adjusted univariable and multivariable logistic regression modeling. We used interaction terms to account for age of menopause and smoking status. The association of sex with overall survival and cancer-specific survival was evaluated using Cox regression analyses. Results: A total of 1,031 patients were included in the analysis, 227 (22%) of whom were female. Female patients had a higher rate of extravesical disease extension (P = 0.01). After the administration of NAC, ypT stage was equally distributed between sexes (P = 0.39). On multivariable logistic regression analyses, there was no difference between the sexes or age of menopause with regards to ypT0N0 rates or downstaging (all P > 0.5). On Cox regression analyses, sex was associated with neither overall survival (hazard ratio 1.04, 95% confidence interval 0.75–1.45, P = 0.81) nor cancer-specific survival (hazard ratio 1.06, 95% confidence interval 0.71–1.58, P = 0.77). Conclusion: Our study generates the hypothesis that NAC equalizes the preoperative disparity in pathologic stage between males and females suggesting a possible differential response between sexes. This might be the explanation underlying the comparable survival outcomes between sexes despite females presenting with more advanced tumor stage.",

keywords = "Bladder cancer, Neoadjuvant chemotherapy, Response, Sex",

author = "David D'Andrea and Black, {Peter C.} and Homayoun Zargar and Kamran Zargar-Shoshtari and Sonja Zehetmayer 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 Montgomery, {Jeffrey S.} and Nikhil Vasdev and Yu, {Evan Y.} and Evanguelos Xylinas and Campain, {Nicholas J.} and Wassim Kassouf and Dall'Era, {Marc A.} and Seah, {Jo An} and Ercole, {Cesar E.} and Simon Horenblas and Sridhar, {Srikala S.} and McGrath, {John S.} and Jonathan Aning and Wright, {Jonathan L.} and Thorpe, {Andrew C.} and Morgan, {Todd M.} and Holzbeierlein, {Jeffrey M.} and Bivalacqua, {Trinity J.} and Scott North and Barocas, {Daniel A.} and Yair Lotan and Petros Grivas and Stephenson, {Andrew J.} and Shah, {Jay B.} and {van Rhijn}, {Bas W.} and Siamak Daneshmand and Spiess, {Philippe E.} and Shariat, {Shahrokh F.}",

note = "{\textcopyright} 2020 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/.",

year = "2020",

month = feb,

day = "11",

doi = "10.1016/j.urolonc.2020.01.010",

language = "English",

journal = "Urologic Oncology",

issn = "1078-1439",

publisher = "Elsevier",

}

D'Andrea, D, Black, PC, Zargar, H, Zargar-Shoshtari, K, Zehetmayer, S, Fairey, AS, Mertens, LS, Dinney, CP, Mir, MC, Krabbe, LM, Cookson, MS, Jacobsen, NE, Montgomery, JS, Vasdev, N, Yu, EY, Xylinas, E, Campain, NJ, Kassouf, W, Dall'Era, MA, Seah, JA, Ercole, CE, Horenblas, S, Sridhar, SS, McGrath, JS, Aning, J, Wright, JL, Thorpe, AC, Morgan, TM, Holzbeierlein, JM, Bivalacqua, TJ, North, S, Barocas, DA, Lotan, Y, Grivas, P, Stephenson, AJ, Shah, JB, van Rhijn, BW, Daneshmand, S, Spiess, PE & Shariat, SF 2020, 'Impact of sex on response to neoadjuvant chemotherapy in patients with bladder cancer', Urologic Oncology: Seminars and Original Investigations. https://doi.org/10.1016/j.urolonc.2020.01.010

TY - JOUR

T1 - Impact of sex on response to neoadjuvant chemotherapy in patients with bladder cancer

AU - D'Andrea, David

AU - Black, Peter C.

AU - Zargar, Homayoun

AU - Zargar-Shoshtari, Kamran

AU - Zehetmayer, Sonja

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 - Montgomery, Jeffrey S.

AU - Vasdev, Nikhil

AU - Yu, Evan Y.

AU - Xylinas, Evanguelos

AU - Campain, Nicholas J.

AU - Kassouf, Wassim

AU - Dall'Era, Marc A.

AU - Seah, Jo An

AU - Ercole, Cesar E.

AU - Horenblas, Simon

AU - Sridhar, Srikala S.

AU - McGrath, John S.

AU - Aning, Jonathan

AU - Wright, Jonathan L.

AU - Thorpe, Andrew C.

AU - Morgan, Todd M.

AU - Holzbeierlein, Jeffrey M.

AU - Bivalacqua, Trinity J.

AU - North, Scott

AU - Barocas, Daniel A.

AU - Lotan, Yair

AU - Grivas, Petros

AU - Stephenson, Andrew J.

AU - Shah, Jay B.

AU - van Rhijn, Bas W.

AU - Daneshmand, Siamak

AU - Spiess, Philippe E.

AU - Shariat, Shahrokh F.

N1 - © 2020 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/.

PY - 2020/2/11

Y1 - 2020/2/11

N2 - Objective: To assess the effect of patient's sex on response to neoadjuvant chemotherapy (NAC) in patients with clinically nonmetastatic muscle-invasive bladder cancer (MIBC). Methods: Complete pathologic response, defined as ypT0N0 at radical cystectomy, and downstaging were evaluated using sex-adjusted univariable and multivariable logistic regression modeling. We used interaction terms to account for age of menopause and smoking status. The association of sex with overall survival and cancer-specific survival was evaluated using Cox regression analyses. Results: A total of 1,031 patients were included in the analysis, 227 (22%) of whom were female. Female patients had a higher rate of extravesical disease extension (P = 0.01). After the administration of NAC, ypT stage was equally distributed between sexes (P = 0.39). On multivariable logistic regression analyses, there was no difference between the sexes or age of menopause with regards to ypT0N0 rates or downstaging (all P > 0.5). On Cox regression analyses, sex was associated with neither overall survival (hazard ratio 1.04, 95% confidence interval 0.75–1.45, P = 0.81) nor cancer-specific survival (hazard ratio 1.06, 95% confidence interval 0.71–1.58, P = 0.77). Conclusion: Our study generates the hypothesis that NAC equalizes the preoperative disparity in pathologic stage between males and females suggesting a possible differential response between sexes. This might be the explanation underlying the comparable survival outcomes between sexes despite females presenting with more advanced tumor stage.

AB - Objective: To assess the effect of patient's sex on response to neoadjuvant chemotherapy (NAC) in patients with clinically nonmetastatic muscle-invasive bladder cancer (MIBC). Methods: Complete pathologic response, defined as ypT0N0 at radical cystectomy, and downstaging were evaluated using sex-adjusted univariable and multivariable logistic regression modeling. We used interaction terms to account for age of menopause and smoking status. The association of sex with overall survival and cancer-specific survival was evaluated using Cox regression analyses. Results: A total of 1,031 patients were included in the analysis, 227 (22%) of whom were female. Female patients had a higher rate of extravesical disease extension (P = 0.01). After the administration of NAC, ypT stage was equally distributed between sexes (P = 0.39). On multivariable logistic regression analyses, there was no difference between the sexes or age of menopause with regards to ypT0N0 rates or downstaging (all P > 0.5). On Cox regression analyses, sex was associated with neither overall survival (hazard ratio 1.04, 95% confidence interval 0.75–1.45, P = 0.81) nor cancer-specific survival (hazard ratio 1.06, 95% confidence interval 0.71–1.58, P = 0.77). Conclusion: Our study generates the hypothesis that NAC equalizes the preoperative disparity in pathologic stage between males and females suggesting a possible differential response between sexes. This might be the explanation underlying the comparable survival outcomes between sexes despite females presenting with more advanced tumor stage.

KW - Bladder cancer

KW - Neoadjuvant chemotherapy

KW - Response

KW - Sex

UR - http://www.scopus.com/inward/record.url?scp=85079152713&partnerID=8YFLogxK

U2 - 10.1016/j.urolonc.2020.01.010

DO - 10.1016/j.urolonc.2020.01.010

M3 - Article

AN - SCOPUS:85079152713

JO - Urologic Oncology

JF - Urologic Oncology

SN - 1078-1439

ER -

Impact of sex on response to neoadjuvant chemotherapy in patients with bladder cancer

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