@article{3c0354c097fb452d990928b71bc0253f,
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, {Colin P.} and Francesco Soria and Cookson, {Michael S.} and Montgomery, {Jeffrey S.} and Wassim Kassouf and Dall'Era, {Marc A.} and Sridhar, {Srikala S.} and McGrath, {John S.} and Wright, {Jonathan L.} and Thorpe, {Andrew C.} and Holzbeierlein, {Jeff M.} and Carri{\'o}n, {Diego M.} 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.}",
note = "Funding Information: Conflict of Interest: David D'Andrea: none. Peter C. Black: is a member of an advisory board or equivalent with a commercial organization for AbbVie, AstraZeneca, Astellas, Bayer, Biosyent, BMS, EMD-Serono, Ferring, Fergene, H3-Biomedicine, Janssen, Merck, Protara Therapeutics, QED Bioscience, Roche, Sanofi, Sesen Bio, TerSera; is a member of a Speakers bureau for AbbVie, Biosyent, Janssen, Ferring, TerSera, Pfizer; has received a grant(s) or an honorarium from a commercial organization form iProgen, Sanofi, Bayer; is currently participating in or has participated in a clinical trial within the past 2 years with Genentech, Janssen, BMS, Astellas, Sitka, MDx Health, AstraZeneca, Therelase, Pacific Edge; shares a patent with (but has received no royalties from) Decipher Biosciences. Homayoun Zargar: none. Colin P Dinney: none. Francesco Soria: none. Michael S. Cookson: is a consultant for Merck, Myovant Sciences, TExoRx Pharma. Jeffrey S. Montgomery: none. Wassim Kassouf: none. Marc A. Dall'Era: none. Srikala S. Sridhar: none. John S. McGrath: none. Jonathan L. Wright: none. Andrew C. Thorpe: none. Jeff M. Holzbeierlein: none. Diego M. Carri{\'o}n: none. Ettore Di Trapani: none. Trinity J. Bivalacqua: none. Scott North: none. Daniel A. Barocas: none. Yair Lotan: is a consultant for C2I genomics, Photocure, Astra-Zeneca, Merck, Feregene, Abbvie, Cleveland Diagnostics, Nucleix, Ambu, Seattle Genetics, Hitachi, Ferring, Verity Pharmaceuticals; is a researcher for Abbott, Cepheid, Pacific Edge, FKD, MDxHealth, Biocancell, GenomeDx, Storz. Petros Grivas: (in the last 3 years, unrelated to this study) has provided consulting to AstraZeneca, Bayer, Bristol Myers Squibb, Clovis Oncology, Dyania Health, Driver, EMD Serono, Exelixis, Foundation Medicine, Genentech/Roche, Genzyme, GlaxoSmithKline, Heron Therapeutics, Immunomedics, Infinity Pharmaceuticals, Janssen, Merck & Co., Mirati Therapeutics, Pfizer, QED Therapeutics, Regeneron Pharmaceuticals, Seattle Genetics, 4D Pharma PLC; his institution has received research funding from Bavarian Nordic, Bristol Myers Squibb, Clovis Oncology, Debiopharm, GlaxoSmithKline, Immunomedics, Kure It Cancer Research, Merck & Co., Mirati Therapeutics, Pfizer, QED Therapeutics. Andrew J. Stephenson: none. Bas W. van Rhijn: received consultancy fees from AstraZeneca, Ferring and QED Therapeutics. Siamak Daneshmand: none. Philippe E. Spiess: none. Shahrokh F. Shariat: received honoraria from Astellas, Astra Zeneca, Bayer, BMS, Cepheid, Ferring, Ipsen, Janssen, Lilly, MSD, Olympus, Pfizer, Pierre Fabre, Richard Wolf, Roche, Sanochemia, Sanofi, Takeda, Urogen; is consulting for Astellas, Astra Zeneca, Bayer, BMS, Cepheid, Ferring, Ipsen, Janssen, Lilly, MSD, Olympus, Pfizer, Pierre Fabre, Richard Wolf, Roche, Sanochemia, Sanofi, Takeda, Urogen; is a speaker for Astellas, Astra Zeneca, Bayer, BMS, Cepheid, Ferring, Ipsen, Janssen, Lilly, MSD, Olympus, Pfizer, Pierre Fabre, Richard Wolf, Roche, Sanochemia, Sanofi, Takeda, Urogen, Movember Foundation. Publisher Copyright: {\textcopyright} 2022 Lippincott Williams and Wilkins. All rights reserved.",
year = "2022",
month = jan,
day = "1",
doi = "10.1097/JU.0000000000002190",
language = "English (US)",
volume = "207",
pages = "70--76",
journal = "Journal of Urology",
issn = "0022-5347",
publisher = "Elsevier Inc.",
number = "1",
}