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Tumor downstaging as an intermediate endpoint to assess the activity of neoadjuvant systemic therapy in patients with muscle-invasive bladder cancer

Tumor downstaging as an intermediate endpoint to assess the activity of neoadjuvant systemic therapy in patients with muscle-invasive bladder cancer
Tumor downstaging as an intermediate endpoint to assess the activity of neoadjuvant systemic therapy in patients with muscle-invasive bladder cancer

Background: Achieving a pathologic complete response (pCR) with neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC) has been associated with improved overall survival (OS). This study was aimed at evaluating the impact of pathologic downstaging (pDS; ie, a pT stage at least 1 stage lower than the pre-NAC cT stage) on the OS of patients with MIBC treated with NAC. Methods: The Retrospective International Study of Cancers of the Urothelial Tract (RISC) and the National Cancer Database (NCDB) were queried for cT2-4N0M0 patients treated with NAC. A multivariable Cox model including either pDS or pCR was generated. A nested model was built to evaluate the added value of pDS (excluding patients achieving a pCR) to a model including pCR alone. C indices were computed to assess discrimination. NCDB was used for validation. The treatment effect of NAC versus cystectomy alone in achieving pDS was estimated through an inverse probability–weighted regression adjustment. Results: Overall, 189 and 2010 patients from the RISC and NCDB cohorts, respectively, were included; pDS and pCR were achieved by 33% and 35% and by 20% and 15% in RISC and NCDB, respectively. In both data sets, pDS and pCR were associated with better OS and C indices. Adding pDS excluding pCR to the model with pCR fit the data better (likelihood ratio, P =.019 for RISC and P <.001 for NCDB), and it yielded better discrimination (incremental C index, 4.2 for RISC and 1.6 for NCDB). The treatment effect of NAC in achieving pDS was 2.07-fold (P <.001) in comparison with cystectomy alone. Conclusions: A decrease of at least 1 stage from the cT stage to the pT stage is associated with improved OS in patients with MIBC treated with NAC.

bladder cancer, neoadjuvant chemotherapy, overall survival, radical cystectomy, urothelial cancer
0008-543X
3155-3163
Martini, Alberto
503a1ef3-d4c6-47a3-8ae0-f6ddc62567ff
Jia, Rachel
80910243-5852-4124-a474-3e766f1b7b11
Ferket, Bart S.
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Waingankar, Nikhil
b968a6c3-b11f-41dc-ab05-3f7b2f47dde0
Plimack, Elizabeth R.
1813cdc7-c75c-4161-834c-6dc10354c973
Crabb, Simon J.
bcd1b566-7677-4f81-8429-3ab0e85f8373
Harshman, Lauren C.
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Yu, Evan Y.
929df91d-9197-40a1-9260-fe52652fa93e
Powles, Thomas
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Rosenberg, Jonathan E.
b9e011ca-9408-4366-baea-5f487a246938
Pal, Sumanta K.
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Vaishampayan, Ulka N.
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Necchi, Andrea
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Wiklund, N. Peter
b11bc515-a3d9-4ef5-8a5b-02ef59ac45bc
Mehrazin, Reza
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Mazumdar, Madhu
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Sfakianos, John P.
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Galsky, Matthew D.
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Martini, Alberto
503a1ef3-d4c6-47a3-8ae0-f6ddc62567ff
Jia, Rachel
80910243-5852-4124-a474-3e766f1b7b11
Ferket, Bart S.
9c0f120c-0830-4ece-b6a0-faed80d5fb3f
Waingankar, Nikhil
b968a6c3-b11f-41dc-ab05-3f7b2f47dde0
Plimack, Elizabeth R.
1813cdc7-c75c-4161-834c-6dc10354c973
Crabb, Simon J.
bcd1b566-7677-4f81-8429-3ab0e85f8373
Harshman, Lauren C.
65c2410e-23a7-49e4-b2ac-05409f320222
Yu, Evan Y.
929df91d-9197-40a1-9260-fe52652fa93e
Powles, Thomas
55539b87-1c5e-45ae-9e07-5b2232c2236c
Rosenberg, Jonathan E.
b9e011ca-9408-4366-baea-5f487a246938
Pal, Sumanta K.
62b6ea1e-83c1-4ba7-a37a-c813fe15b55c
Vaishampayan, Ulka N.
d2d140dc-26fc-457b-8c20-86e41271a02f
Necchi, Andrea
fb44790a-f8fe-43b6-ad82-72cf5b9107d6
Wiklund, N. Peter
b11bc515-a3d9-4ef5-8a5b-02ef59ac45bc
Mehrazin, Reza
346663ab-56d0-4f98-a8d2-3ac099b5ea18
Mazumdar, Madhu
ce856c50-0b95-4be2-a3a6-a1e8e7f1ce84
Sfakianos, John P.
3b996d87-a2c4-43fe-bd00-728860229c84
Galsky, Matthew D.
57bcde2a-bfea-490b-8a09-8ee8e28563da

Martini, Alberto, Jia, Rachel, Ferket, Bart S., Waingankar, Nikhil, Plimack, Elizabeth R., Crabb, Simon J., Harshman, Lauren C., Yu, Evan Y., Powles, Thomas, Rosenberg, Jonathan E., Pal, Sumanta K., Vaishampayan, Ulka N., Necchi, Andrea, Wiklund, N. Peter, Mehrazin, Reza, Mazumdar, Madhu, Sfakianos, John P. and Galsky, Matthew D. (2019) Tumor downstaging as an intermediate endpoint to assess the activity of neoadjuvant systemic therapy in patients with muscle-invasive bladder cancer. Cancer, 125 (18), 3155-3163. (doi:10.1002/cncr.32169).

Record type: Article

Abstract

Background: Achieving a pathologic complete response (pCR) with neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC) has been associated with improved overall survival (OS). This study was aimed at evaluating the impact of pathologic downstaging (pDS; ie, a pT stage at least 1 stage lower than the pre-NAC cT stage) on the OS of patients with MIBC treated with NAC. Methods: The Retrospective International Study of Cancers of the Urothelial Tract (RISC) and the National Cancer Database (NCDB) were queried for cT2-4N0M0 patients treated with NAC. A multivariable Cox model including either pDS or pCR was generated. A nested model was built to evaluate the added value of pDS (excluding patients achieving a pCR) to a model including pCR alone. C indices were computed to assess discrimination. NCDB was used for validation. The treatment effect of NAC versus cystectomy alone in achieving pDS was estimated through an inverse probability–weighted regression adjustment. Results: Overall, 189 and 2010 patients from the RISC and NCDB cohorts, respectively, were included; pDS and pCR were achieved by 33% and 35% and by 20% and 15% in RISC and NCDB, respectively. In both data sets, pDS and pCR were associated with better OS and C indices. Adding pDS excluding pCR to the model with pCR fit the data better (likelihood ratio, P =.019 for RISC and P <.001 for NCDB), and it yielded better discrimination (incremental C index, 4.2 for RISC and 1.6 for NCDB). The treatment effect of NAC in achieving pDS was 2.07-fold (P <.001) in comparison with cystectomy alone. Conclusions: A decrease of at least 1 stage from the cT stage to the pT stage is associated with improved OS in patients with MIBC treated with NAC.

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More information

Accepted/In Press date: 24 February 2019
e-pub ahead of print date: 31 May 2019
Published date: 15 September 2019
Keywords: bladder cancer, neoadjuvant chemotherapy, overall survival, radical cystectomy, urothelial cancer

Identifiers

Local EPrints ID: 433937
URI: http://eprints.soton.ac.uk/id/eprint/433937
ISSN: 0008-543X
PURE UUID: 4e764409-9378-4520-9156-a892b768022e
ORCID for Simon J. Crabb: ORCID iD orcid.org/0000-0003-3521-9064

Catalogue record

Date deposited: 06 Sep 2019 16:30
Last modified: 16 Mar 2024 03:32

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Contributors

Author: Alberto Martini
Author: Rachel Jia
Author: Bart S. Ferket
Author: Nikhil Waingankar
Author: Elizabeth R. Plimack
Author: Simon J. Crabb ORCID iD
Author: Lauren C. Harshman
Author: Evan Y. Yu
Author: Thomas Powles
Author: Jonathan E. Rosenberg
Author: Sumanta K. Pal
Author: Ulka N. Vaishampayan
Author: Andrea Necchi
Author: N. Peter Wiklund
Author: Reza Mehrazin
Author: Madhu Mazumdar
Author: John P. Sfakianos
Author: Matthew D. Galsky

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