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Clinical Restaging and Tumor Sequencing are Inaccurate Indicators of Response to Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer.
Becker, Russell E N; Meyer, Alexa R; Brant, Aaron; Reese, Adam C; Biles, Michael J; Harris, Kelly T; Netto, George; Matoso, Andres; Hoffman-Censits, Jean; Hahn, Noah M; Choi, Woonyoung; McConkey, David; Pierorazio, Phillip M; Johnson, Michael H; Schoenberg, Mark P; Kates, Max R; Baras, Alex; Bivalacqua, Trinity J.
Afiliação
  • Becker REN; The Greenberg Bladder Cancer Institute & James Buchanan Brady Urological Institute, Johns Hopkins Medicine, Baltimore, MD, USA. Electronic address: rbecker@jhmi.edu.
  • Meyer AR; The Greenberg Bladder Cancer Institute & James Buchanan Brady Urological Institute, Johns Hopkins Medicine, Baltimore, MD, USA.
  • Brant A; Department of Urology, Weill Cornell Medicine, New York, NY, USA.
  • Reese AC; Department of Urology, Temple Health, Philadelphia, PA, USA.
  • Biles MJ; The Greenberg Bladder Cancer Institute & James Buchanan Brady Urological Institute, Johns Hopkins Medicine, Baltimore, MD, USA.
  • Harris KT; The Greenberg Bladder Cancer Institute & James Buchanan Brady Urological Institute, Johns Hopkins Medicine, Baltimore, MD, USA.
  • Netto G; Department of Urology, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Matoso A; The Greenberg Bladder Cancer Institute & James Buchanan Brady Urological Institute, Johns Hopkins Medicine, Baltimore, MD, USA.
  • Hoffman-Censits J; The Greenberg Bladder Cancer Institute & James Buchanan Brady Urological Institute, Johns Hopkins Medicine, Baltimore, MD, USA.
  • Hahn NM; The Greenberg Bladder Cancer Institute & James Buchanan Brady Urological Institute, Johns Hopkins Medicine, Baltimore, MD, USA.
  • Choi W; The Greenberg Bladder Cancer Institute & James Buchanan Brady Urological Institute, Johns Hopkins Medicine, Baltimore, MD, USA.
  • McConkey D; The Greenberg Bladder Cancer Institute & James Buchanan Brady Urological Institute, Johns Hopkins Medicine, Baltimore, MD, USA.
  • Pierorazio PM; The Greenberg Bladder Cancer Institute & James Buchanan Brady Urological Institute, Johns Hopkins Medicine, Baltimore, MD, USA.
  • Johnson MH; The Greenberg Bladder Cancer Institute & James Buchanan Brady Urological Institute, Johns Hopkins Medicine, Baltimore, MD, USA.
  • Schoenberg MP; Department of Urology, Montefiore Medical Center, Bronx, NY, USA.
  • Kates MR; The Greenberg Bladder Cancer Institute & James Buchanan Brady Urological Institute, Johns Hopkins Medicine, Baltimore, MD, USA.
  • Baras A; The Greenberg Bladder Cancer Institute & James Buchanan Brady Urological Institute, Johns Hopkins Medicine, Baltimore, MD, USA.
  • Bivalacqua TJ; The Greenberg Bladder Cancer Institute & James Buchanan Brady Urological Institute, Johns Hopkins Medicine, Baltimore, MD, USA.
Eur Urol ; 79(3): 364-371, 2021 03.
Article em En | MEDLINE | ID: mdl-32814637
ABSTRACT

BACKGROUND:

Standard of care for patients with muscle-invasive bladder cancer (MIBC) includes neoadjuvant cisplatin-based chemotherapy (NAC) followed by consolidative therapy with either chemoradiation or radical cystectomy (RC). Some patients experience robust pathologic responses to NAC, and these have been reported to associate with somatic mutations in specific gene pathways including DNA damage response genes.

OBJECTIVE:

To evaluate the ability of post-NAC clinical restaging, with or without tumor sequencing, to predict final RC pathologic staging. DESIGN, SETTING, AND

PARTICIPANTS:

We reviewed our institutional review board-approved institutional database to identify patients with MIBC who underwent NAC followed by RC from 2003 to 2016. Following NAC prior to RC, cystoscopy was performed routinely, with resection of residual visible tumor and/or tumor base (transurethral resection [TUR]). For patients with pre-NAC tumor tissue available, tumor sequencing was performed. Outcome measurements and statistical

analysis:

Clinical restaging and tumor sequencing were evaluated for their ability to predict the final pathologic stage accurately at RC using chi-square or Fisher's exact test. RESULTS AND

LIMITATIONS:

A total of 114 patients underwent restaging TUR following NAC and prior to RC. The diagnostic accuracy of post-NAC clinical restaging including TUR was poor, with 32% of patients being downstaged falsely when compared with their final RC pathology. Forty-nine patients had sequencing of pre-NAC tumor tissue, of whom 32 showed at least one mutation of interest. However, NAC responses and rates of false downstaging did not differ significantly according to tumor mutation status.

CONCLUSIONS:

This study highlights the inaccuracy of post-NAC clinical restaging TUR with or without adjunctive tumor mutation analysis, to assess pathologic residual disease accurately. Caution must be taken when performing post-NAC restaging, especially when considering conservative management strategies such as active surveillance on this basis. Patient

summary:

Several groups are evaluating whether certain patients, whose bladder cancer responds well to upfront chemotherapy, may be able to forego cystectomy safely. We demonstrate that currently available staging tools and tumor DNA sequencing cannot identify such patients reliably and accurately.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Bexiga Urinária / Terapia Neoadjuvante Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Bexiga Urinária / Terapia Neoadjuvante Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article