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Clinical Trial
. 2024 Dec;42(34):4095-4102.
doi: 10.1200/JCO.23.02510. Epub 2024 Sep 3.

Bladder-Preserving Trimodality Treatment for High-Grade T1 Bladder Cancer: Results From Phase II Protocol NRG Oncology/RTOG 0926

Douglas M Dahl  1 , Joseph P Rodgers  2 , William U Shipley  2 , M Dror Michaelson  2 , Chin-Lee Wu  2 , William Parker  3 , Ashesh B Jani  4 , Fabio L Cury  3 , Richard S Hudes  5 , Jeff M Michalski  6 , Alan C Hartford  7 , Daniel Song  8 , Deborah E Citrin  9 , Theodore G Karrison  2 , Howard M Sandler  10 , Felix Y Feng  11 , Jason A Efstathiou  1
Affiliations
Clinical Trial

Bladder-Preserving Trimodality Treatment for High-Grade T1 Bladder Cancer: Results From Phase II Protocol NRG Oncology/RTOG 0926

Douglas M Dahl et al. J Clin Oncol. 2024 Dec.

Abstract

Purpose: To investigate the use of radiation with radiosensitizing chemotherapy following repeated transurethral resection (trimodality therapy) as an alternative to radical cystectomy in T1 bladder cancer which has failed Bacillus Calmette-Guerin (BCG).

Patients and methods: Patients with recurrent T1 bladders who had failed BCG and were recommended to undergo cystectomy were treated with trimodality therapy. The primary end point was 3-year freedom from cystectomy. Secondary end points were distant metastasis at 3 and 5 years, local recurrence, disease-specific and overall survival (OS), and safety.

Results: This single-arm phase II study enrolled 37 patients. Efficacy and safety were evaluated in 34 patients after three exclusions. The median follow-up was 5.1 years. The 3-year freedom from cystectomy rate was 88% (lower one-sided 97.5% confidence limit [CI], 72%), meeting the primary study goal. OS at 3 and 5 years was 69% (95% CI, 54 to 85) and 56% (95% CI, 39 to 74), respectively. The distant metastasis rates at 3 and 5 years were 12% (95% CI, 4 to 26) and 19% (95% CI, 7 to 34), respectively. Eight patients died due to urothelial cancer, 12 exhibited local recurrence at 3 years (cumulative incidence: 32%; 95% CI, 17 to 48), 18 experienced grade 3 adverse events, mostly hematological, and one developed grade 4 neutropenia.

Conclusion: Trimodality therapy is an effective potential alternative to radical cystectomy for recurrent high-grade T1 urothelial cancer of the bladder. At 3 years, 88% of the patients remained free of cystectomy.

Trial registration: ClinicalTrials.gov NCT00981656.

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Conflict of interest statement

Conflict of interests:

Drs. Dahl, Hudes, Jani, Michaelson, Michalski, Song, and Rodgers declare no conflicts of interest.

Since the initial planning of the work, the authors declare NCI Employment and funding for clinical research, along with sponsored travel to the ASTRO 2022 annual meetings in the past 36 months.

Dr. Cury declares grants or contracts from Boston Scientific and Sanofi, Payment, or honoraria in the past 36 months for lectures, presentations, support for attending meetings and/or travel from Varian, Participation on a Data Safety Monitoring Board, or Advisory Board with Abbvie, Bayer, Sanofi, as part of the educational grant Boston Scientific.

Dr. Efstathiou declares consulting fees for Blue Earth Diagnostics, Boston Scientific, AstraZeneca, Genentech, Payment, and Honoraria from IBA in the past 36 months; Participation in Data Safety Monitoring or Advisory Board, Merck, Roivant Pharma, Myovant Sciences, Janssen, Bayer Healthcare, Progenics Pharmaceuticals, Pfizer, Gilead, Lantheus, Blue Earth Diagnostics; and Board membership (unpaid) in the Massachusetts Prostate Cancer Coalition (MPCC), American College of Radiation Oncology (ACRO), and Radiation Oncology Institute (ROI).

Dr. Feng declares a 36-month relationship with the following companies: Janssen Oncology, Astellas Pharma, Serimmune, Foundation Medicine, Exact Sciences, Bristol-Myers Squibb, Varian Medical Systems (termed), Novartis, Roivant (termed), Myovant Sciences (termed), Bayer, BlueStar Genomics, Artera, Tempus, Genentech (termed), and Artera (role: medical advisor). Additionally, Dr. Feng received stock options from the following companies to serve on their advisory boards: Artera, BlueStar Genomics, and SerImmune.

Dr. Hartford declares that Dartmouth Health, as an employer, provided support for attending meetings associated with clinical and administrative responsibilities in the past 36 months, primarily including the ASTRO Annual Meetings and the NRG-Oncology bi-annual meetings; ASTRO has covered travel and meeting expenses for attendance at the Annual Meetings of the American College of Radiology (ACR), where Dr. Hartford has represented ASTRO on the ACR Council; Additionally, Dr. Hartford serves as an alternate representing NHMS at the House of Delegates of the American Medical Association (AMA), with meeting/travel expenses covered for biannual AMA meetings, starting in June 2022, on the NHMS Council (its governing body); Furthermore, Dr. Hartford acts as a representative for NHMS to the AMA-House of Delegates, currently serving as President of CARROS, the ACR Chapter representing radiation oncologists nationwide to the Council of the ACR. Leadership of American Society for Radiation Oncology (ASTRO).

Dr. Karrison declares that the NCI provided salary support since the initial planning of the work.

Dr. Parker declares that, McGill University provided salary support since the initial planning and has covered travel expenses for the past 36 months.

Dr. Sandler declares being a member of the Clinical Trial Steering Committee at Janssen and the Board of Directors at ASTRO within the past 36 months.

Dr Shipley declares having stocks with Pfizer in the past 36 months.

Dr. Wu declares receiving consulting fees (<$10,000 per year) from OrigiMed Co., Ltd. and from Conrad Trosch & Kemmy, P.A. (for expert review) in 2023. Additionally, Dr. Wu holds stocks (<1% of the company) with GoPath Diagnostics, LLC.

Figures

Figure 1.
Figure 1.
Kaplan–Meier estimates of overall survival (a), cumulative incidence estimates of distant metastasis (b), disease-specific survival (c), local recurrence (d), and recurrence-free survival (e)
Figure 2.
Figure 2.
Cumulative incidence of first grade 3+ adverse event
See this image and copyright information in PMC

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