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Risk-Based Assessment Of the Impact Of Intravesical Therapy on Recurrence-Free Survival Rate Following Resection of Suspected Low-grade, Non-muscle-invasive Bladder Cancer (NMIBC): A Southwest Oncology Groups (SWOG) S0337 Posthoc Analysis

  • Nicholas J. Corsi
    Affiliations
    Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation (VCORE), Henry Ford Hospital, Detroit, MI

    Wayne State University School of Medicine, Detroit, MI
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  • Edward M. Messing
    Affiliations
    Department of Urology, University of Rochester, Rochester, NY
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  • Akshay Sood
    Affiliations
    Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation (VCORE), Henry Ford Hospital, Detroit, MI

    Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX
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  • Jacob Keeley
    Affiliations
    Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation (VCORE), Henry Ford Hospital, Detroit, MI
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  • Chandler Bronkema
    Affiliations
    Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation (VCORE), Henry Ford Hospital, Detroit, MI

    Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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  • Nikola Rakic
    Affiliations
    Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation (VCORE), Henry Ford Hospital, Detroit, MI

    Department of Urology, Baylor College of Medicine, Houston, TX
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  • Marcus Jamil
    Affiliations
    Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation (VCORE), Henry Ford Hospital, Detroit, MI

    Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI
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  • Deepansh Dalela
    Affiliations
    Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation (VCORE), Henry Ford Hospital, Detroit, MI

    Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI
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  • Sohrab Arora
    Affiliations
    Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation (VCORE), Henry Ford Hospital, Detroit, MI

    Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI
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  • Austin J. Piontkowski
    Affiliations
    Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation (VCORE), Henry Ford Hospital, Detroit, MI

    Wayne State University School of Medicine, Detroit, MI
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  • Sami E. Majdalany
    Affiliations
    Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation (VCORE), Henry Ford Hospital, Detroit, MI
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  • Mohit Butaney
    Affiliations
    Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation (VCORE), Henry Ford Hospital, Detroit, MI
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  • Ivan Rakic
    Affiliations
    Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation (VCORE), Henry Ford Hospital, Detroit, MI

    Wayne State University School of Medicine, Detroit, MI
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  • Pin Li
    Affiliations
    Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation (VCORE), Henry Ford Hospital, Detroit, MI

    Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI
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  • Mani Menon
    Affiliations
    Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation (VCORE), Henry Ford Hospital, Detroit, MI

    Department of Urology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY
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  • Craig G. Rogers
    Affiliations
    Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation (VCORE), Henry Ford Hospital, Detroit, MI

    Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI
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  • Firas Abdollah
    Correspondence
    Address for correspondence: Firas Abdollah, MD, Vattikuti Urology Institute, Henry Ford Hospital, 2799 W. Grand Boulevard, Detroit, Michigan, USA 48202.
    Affiliations
    Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation (VCORE), Henry Ford Hospital, Detroit, MI

    Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI
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      Highlights

      • On posthoc analysis, intravesical chemotherapy (Gemcitabine) reduces the risk of nonmuscle invasive bladder cancer recurrence in suspected low-grade, stage Ta or T1 bladder cancer.
      • We propose regression-tree analysis generated non-muscle invasive bladder cancer risk groups. This risk stratification shows distinct oncological outcomes with Gemcitabine.
      • Regression tree analysis suggests older patients (≥ 57 years) with a single tumor maximally benefit from immediate postresection instillation of intravesical chemotherapy (Gemcitabine).

      Abstract

      Background

      Nonmuscle invasive bladder cancer (NMIBC) has an elevated risk of recurrence, and immediate postresection intravesical instillation of chemotherapy (IVC) significantly reduces the risk of recurrence. Questions remain about which subpopulation may maximally benefit from IVC. Our aim was to develop risk groups based on recurrence risk in NMIBC, and then evaluate the impact of a single, postoperative instillation of IVC on the subsequent risk of recurrence for each risk group.

      Material and Methods

      Using the SWOG S0337 trial cohort, we performed a posthoc analysis of 345 patients who were diagnosed with suspected low-grade NMIBC, underwent transurethral resection of the bladder tumor (TURBT), and received post-operative IVC (gemcitabine vs. saline). Using regression tree analysis, the regression tree stratified patients based on their risk of recurrence into low-risk – single tumor and aged < 57 years, intermediate-risk – single tumor and aged ≥ 57 years, and high-risk – multiple tumors. We used Cox proportional hazard models to test the impact of recurrence-free rate, and after adjustment to available covariates.

      Results

      Median age of the cohort was 66.5 (IQR: 59.7-75.8 years) with 85% of patients being males. Median overall follow-up time was 3.07 years (IQR: 0.75-4.01 years). When testing the impact of treatment in each risk group separately, we found that patients in the intermediate-risk treated with gemcitabine had a 24-month recurrence free rate of 77% (95% CI: 68%-86%) vs. 59% (95% CI: 49%-70%) in the saline group. This survival difference was confirmed on multivariable analysis (hazard ratio: 0.39, 95% CI: 23%-66%, P < 0.001). This group represented 53% of our cohort. Conversely, we did not observe a significant difference in recurrence-free survival among patients in the low- (P = 0.7) and high-risk (P = 0.4) groups.

      Conclusion

      Our findings indicate that older patients with a single tumor of suspected low-grade NMIBC at TURBT maximally benefit from immediate postresection IVC (gemcitabine).

      Key Words

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