Safety of Adjuvant Radiotherapy after Radical Cystectomy for High-Risk Muscle-Invasive Bladder Cancer – Expert Commentary

Muscle-invasive bladder cancer (MIBC) is associated with a high risk of developing pelvic recurrence. Although adjuvant external beam radiotherapy (EBRT) decreases the risk of local recurrence, it has been associated with severe toxicity. Previous trials that assessed toxicity applied older techniques of delivering EBRT. It is unclear if modern techniques of EBRT delivery, combining highly conformal EBRT and daily image guidance, could have a better safety profile.

A recent phase II clinical trial published by Fonteyne et al. in European Urology Focus investigated the safety of adjuvant EBRT for patients with high-risk MIBC who have undergone radical cystectomy. The investigators recruited 92 patients from August 2014 till October 2020. Of whom, 20 patients were excluded mainly due to having metastatic disease on screening PET/CT scans. The remaining 72 patients fulfilled the inclusion criteria. M0-MIBC patients treated with radical cystectomy and extended pelvic lymph node dissection who had one or more high-risk features, including stage pT3-MIBC with lymphovascular invasion on pathological examination, stage pT4-MIBC, fewer than ten lymph nodes removed, presence positive lymph nodes, or positive surgical margins were included.

The investigators observed severe (acute grade ≥3) gastrointestinal (GI) toxicity in 6% (n=4) of patients, which fell below the predefined threshold of >25%, and acute grade ≥2 GI toxicity in 61% (n=44), a high but transient incidence. In addition, Urinary toxicity was evaluated in 17 patients with a neobladder. Only 18% (n=3) of these patients had grade 3 urinary toxicity.

These results confirm that adjuvant EBRT for MIBC is feasible and safe, even for patients with a neobladder. The limitations of this trial were the nonrandomized study design and the relatively short follow-up duration of only two years. Further phase III randomized controlled trials are needed to confirm the role of adjuvant radio(chemo)therapy for high-risk bladder cancer to improve the outcome of patients with high-risk MIBC.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York

Reference:

  1. Fonteyne V, Dirix P, Van Praet C, Berghen C, Albersen M, Junius S, et al. Adjuvant Radiotherapy After Radical Cystectomy for Patients with High-risk Muscle-invasive Bladder Cancer: Results of a Multicentric Phase II Trial. Eur Urol Focus. 2021 Dec 7. doi: 10.1016/j.euf.2021.11.004. PMID: 34893458.
  2. Zaghloul MS, Awwad HK, Akoush HH, Omar S, Soliman O, Attar I. Postoperative radiotherapy of carcinoma in bilharzial bladder: Improved disease free survival through improving local control. Int J Radiat Oncol. 1992 Jan;23(3):511–7.

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