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

David D'Andrea, Peter C. Black, Homayoun Zargar, Colin P. Dinney, Francesco Soria, Michael S. Cookson, Jeffrey S. Montgomery, Wassim Kassouf, Marc A. Dall'Era, Srikala S. Sridhar, John S. McGrath, Jonathan L. Wright, Andrew C. Thorpe, Jeff M. Holzbeierlein, Diego M. 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

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1 Scopus citations

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 languageEnglish (US)
Pages (from-to)70-76
Number of pages7
JournalJournal of Urology
Volume207
Issue number1
DOIs
StatePublished - Jan 1 2022
Externally publishedYes

Keywords

  • drug administration schedule
  • neoadjuvant therapy
  • survival
  • urinary bladder neoplasms

ASJC Scopus subject areas

  • Urology

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