Neoadjuvant chemotherapy plus radical cystectomy versus radical cystectomy alone in clinical T2 bladder cancer without hydronephrosis

Francesco Soria; Peter C Black; Adrian S Fairey; Michael S Cookson; Evan Y Yu; Wassim Kassouf; Marc A Dall'Era; Srikala S Sridhar; John S McGrath; Jonathan L Wright; Andrew C Thorpe; Todd M Morgan; Siamak Daneshmand; Jeff M Holzbeierlein; Trinity J Bivalacqua; Scott North; Daniel A Barocas; Yair Lotan; Petros Grivas; Andrew J Stephenson; Jay B Shah; Bas W van Rhijn; Philippe E Spiess; Shahrokh F Shariat; Paolo Gontero

doi:10.1111/bju.15289

Neoadjuvant chemotherapy plus radical cystectomy versus radical cystectomy alone in clinical T2 bladder cancer without hydronephrosis

BJU Int. 2021 Jul;128(1):79-87. doi: 10.1111/bju.15289. Epub 2020 Nov 21.

Authors

Francesco Soria¹, Peter C Black², Adrian S Fairey³, Michael S Cookson⁴, Evan Y Yu⁵, Wassim Kassouf⁶, Marc A Dall'Era⁷, Srikala S Sridhar⁸, John S McGrath⁹, Jonathan L Wright¹⁰, Andrew C Thorpe¹¹, Todd M Morgan¹², Siamak Daneshmand¹³, Jeff M Holzbeierlein¹⁴, Trinity J Bivalacqua¹⁵, Scott North^{16

17}, Daniel A Barocas¹⁸, Yair Lotan¹⁹, Petros Grivas^{5

20}, Andrew J Stephenson²¹, Jay B Shah^{22

23}, Bas W van Rhijn²⁴, Philippe E Spiess²⁵, Shahrokh F Shariat^{19

26

27

28

29

30}, Paolo Gontero¹

Affiliations

¹ Division of Urology, Department of Surgical Sciences, Torino School of Medicine, Torino, Italy.
² Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
³ University of Alberta, Edmonton, AB, Canada.
⁴ Department of Urology, University of Oklahoma College of Medicine, Oklahoma City, OK, USA.
⁵ Department of Medicine, Division of Oncology, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
⁶ Department of Surgery (Division of Urology), McGill University Health Center, Montreal, Canada.
⁷ Department of Urology, Davis Medical Center, University of California at Davis, Sacramento, CA, USA.
⁸ Princess Margaret Hospital, Toronto, ON, Canada.
⁹ Department of Surgery, Exeter Surgical Health Services Research Unit, Royal Devon and Exeter NHS Trust, Exeter, UK.
¹⁰ Department of Urology, University of Washington, Seattle, WA, USA.
¹¹ Department of Urology, Freeman Hospital, Newcastle Upon Tyne, UK.
¹² Department of Urology, University of Michigan Health System, Ann Arbor, MI, USA.
¹³ USC/Norris Comprehensive Cancer Center, Institute of Urology, University of Southern California, Los Angeles, CA, USA.
¹⁴ Department of Urology, University of Kansas Medical Center, Kansas City, KS, USA.
¹⁵ Department of Urology, The James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
¹⁶ Cross Cancer Institute, Edmonton, AB, Canada.
¹⁷ Department of Oncology, University of Alberta, Alberta, AB, Canada.
¹⁸ Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁹ Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
²⁰ Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
²¹ Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
²² Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.
²³ Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.
²⁴ Department of Urology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
²⁵ Department of Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
²⁶ Department of Urology, Weill Cornell Medical College, Presbyterian Hospital, New York, NY, USA.
²⁷ Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
²⁸ Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
²⁹ Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
³⁰ Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan.

PMID: 33152179
DOI: 10.1111/bju.15289

Abstract

Objectives: To assess the efficacy of neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in a retrospective multicentre cohort of patients with cT2N0M0 bladder cancer (BCa) without preoperative hydronephrosis.

Patients and methods: This was a propensity-based analysis of 619 patients. Of these, 316 were treated with NAC followed by RC and 303 with upfront RC. After multiple imputations, inverse probability of treatment weighting (IPTW) was used to account for potential selection bias. Multivariable logistic regression analysis was performed to evaluate the impact of NAC on pathological complete response and downstaging at RC, while IPTW-adjusted Kaplan-Meier curves and Cox regression models were built to evaluate the impact of NAC on overall survival (OS).

Results: After IPTW-adjusted analysis, standardised differences between groups were <15%. A complete response (pT0N0) at final pathology was achieved in 94 (30%) patients receiving NAC and nine (3%) undergoing upfront RC. Downstaging to non-muscle-invasive disease (<pT2N0M0) was observed in 174 (55%) patients after NAC and in 72 (24%) without NAC. On multivariable analysis, NAC was found to be an independent predictor of both pathological complete response and downstaging. No significant difference with respect to OS was observed between groups with a median follow-up of 18 months.

Conclusions: In patients with cT2N0 BCa and no preoperative hydronephrosis, NAC increased the rate of pathological complete response and downstaging.

Keywords: #BladderCancer; #blcsm; #uroonc; #utuc; bladder cancer; clinical T2; downstaging; hydronephrosis; neoadjuvant chemotherapy.

Publication types

Comparative Study
Multicenter Study

MeSH terms

Aged
Cohort Studies
Combined Modality Therapy
Cystectomy* / methods
Female
Humans
Hydronephrosis
Male
Middle Aged
Neoadjuvant Therapy*
Neoplasm Staging
Propensity Score
Retrospective Studies
Treatment Outcome
Urinary Bladder Neoplasms / drug therapy*
Urinary Bladder Neoplasms / pathology
Urinary Bladder Neoplasms / surgery*