Defects in DNA Repair Genes Confer Improved Long-term Survival after Cisplatin-based Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer

Benjamin Miron, Jean H. Hoffman-Censits, Fern Anari, John O'Neill, Daniel M. Geynisman, Matthew R. Zibelman, Alexander Kutikov, Rosalia Viterbo, Richard E. Greenberg, David Chen, Costas D. Lallas, Edouard J. Trabulsi, R. Katherine Alpaugh, Essel Dulaimi, Erica A. Golemis, Robert Uzzo, Eric A. Ross, Elizabeth R. Plimack

Research output: Contribution to journalArticlepeer-review

Abstract

Cisplatin-based neoadjuvant chemotherapy (NAC) has demonstrated an overall survival (OS) benefit in muscle-invasive bladder cancer (MIBC). However, only a subset of patients (25-50%) have a pathologic complete response at cystectomy. Using a cohort of 58 patients from two phase 2 trials, our group previously reported that mutations in the ATM, RB1, and FANCC genes correlate with complete response to cisplatin-based NAC, and consequently improve OS and disease-specific survival (DSS). These trials enrolled patients with T2-4 (N0 or N1) MIBC and treated them with accelerated/dose-dense NAC with methotrexate, vinblastine, adriamycin, and cisplatin, or gemcitabine and cisplatin, with a plan for curative cystectomy. Updated long-term follow-up (median 74 mo) shows that significantly greater OS and DSS was maintained for patients with ATM, RB1, or FANCC mutations. The 5-yr survival rate for patients with at least one mutation was 85%, compared to 45% for patients without a mutation. On the basis of the associations with response and long-term OS and DSS, we propose that these alterations may be useful as predictive biomarkers to allow clinicians to prioritize patients who are most likely to benefit from NAC before radical cystectomy. PATIENT SUMMARY: In this report we looked at outcomes for patients with muscle-invasive bladder cancer treated with cisplatin-based chemotherapy before surgery (neoadjuvant) who had mutations in a set of DNA damage repair genes (ATM, RB1, FANCC) compared to those who did not. We found that patients who had at least one mutation in one of these genes survived longer after receiving cisplatin chemotherapy before surgery than patients who did not.

Original languageEnglish (US)
Pages (from-to)544-547
Number of pages4
JournalEuropean Urology Oncology
Volume3
Issue number4
DOIs
StatePublished - Aug 1 2020

Keywords

  • Biomarkers
  • Bladder cancer
  • Chemotherapy
  • Cisplatin
  • DNA damage repair
  • Neoadjuvant

ASJC Scopus subject areas

  • Surgery
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Urology

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