ASTRO 2021: RTOG 0926: Phase II Protocol Stage T1 Bladder Cancer to Evaluate Selective Bladder Preserving Treatment by Radiation Therapy Concurrent with Radiosensitizing Chemo Following a Thorough Transurethral Surgical Re-Staging

(UroToday.com) The 2021 American Society for Radiation Oncology (ASTRO) Hybrid Annual Meeting included a presentation by Dr. Jason Efstathiou discussing results of the NRG Oncology/RTOG 0926 trial. This trial assessed selective bladder preserving treatment by radiation therapy concurrent with radiosensitizing chemotherapy following a thorough restaging TURBT.

 Bladder-sparing trimodal therapy is a well-established alternative to radical cystectomy for >=T2 bladder cancer. T1 high-grade (grade 3) bladder urothelial carcinoma recurs despite resection and intra-vesical therapy, with a substantial rate of progression to invasive and metastatic disease (35.5% mortality rate, median follow-up of 2 years [1]).

 For the NRG Oncology/RTOG 0926 trial, patients were included if they had recurrent high-grade non-muscle invasive bladder cancer for whom the next step is radical cystectomy. The specific protocol included maximal TURBT followed by chemoradiotherapy (61.2 Gy in 34 fractions) with radio-sensitizing cisplatin or mitomycin/5-FU chemotherapy. There were 37 patients enrolled, of which 34 were evaluable; the median age was 74 years, 91.2% were male and 94.1% were white. The primary endpoint for this trial was freedom from cystectomy at 3 years, and secondary endpoints were as follows:

  • Freedom from cystectomy at 5 years
  • Distant disease at 3 and 5 years
  • Local recurrence
  • Overall survival
  • Adverse events and AUA symptom scores at baseline and at 3 years

At 3 years, 88% of patients were free from cystectomy (lower, one-sided 97.5% CI 70%). For the patients that underwent radical cystectomy, three patients had recurrent CIS and one patient had T1 disease as their indication to proceed with surgery. The 3- and 5-year overall survival rates were 69% and 53%, respectively: 

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The cumulative incidence of distant metastasis at 3 and 5-years was 12% and 20%, respectively:

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There were 8 patients that died of disease (23.5%), with the following cumulative incidence curve for disease specific mortality:

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With regards to adverse events, 20 patients (59%) had grade 3 adverse events, including anemia, gastrointestinal events, UTI, lymphopenia, hematuria, and metabolic/nutritional events. There were two Grade 4 adverse events (neutropenia). The mean AUA symptom score was 9.8 at baseline and 12.0 at 3 years of follow-up 

Dr. Efstathiou concluded his presentation of the NRG Oncology/RTOG 0926 trial with the following take-home messages:

  • Recurrent grade 3, T1 bladder cancer has a high rate of progression of disease
  • Trimodal therapy preserved a functional bladder in 88% of these patients for whom the next clinical step was radical cystectomy, which was significantly greater than the null hypothesis rate of 60%
  • CIS was the reason for cystectomy in 3 of 4 patients
  • Treatment was well-tolerated in this elderly patient population
  • Maximal resection, radiotherapy with radiosensitizing chemotherapy is an effective management strategy for T1 urothelial carcinoma of the bladder in those who have recurred despite intra-vesical therapy


Presented by: Jason Efstathiou, MD, DPhil, Director, Genitourinary Service, Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, MA 

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 American Society for Radiation Oncology (ASTRO) Hybrid Annual Meeting, Sat, Oct 23 – Wed, Oct 27, 2021

References:

  1. Fritsche HM, Burger M, Svatek RS, et al. Characteristics and outcomes of patients with clinical T1 grade 3 urothelial carcinoma treated with radical cystectomy: results from an international cohort. Eur Urol. 2010 Feb;57(2):300-309.

 

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