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Adjuvant radiation therapy for locally advanced bladder cancer: A safe and promising emerging treatment option

Recurrence after radical cystectomy for patients with cT3-4N0-N+ disease is relatively high, with approximately one third developing local-regional failure as the initial site of relapse.1-4 Chemotherapy given neoadjuvantly or adjuvantly can reduce rates of distant disease but has not been shown to reduce rates of local-regional relapse in this patient population.5,6

Adjuvant immunotherapy has been shown to improve disease-free survival in the Ambassador and CheckMate 274 trials but the impact of immunotherapy on local-regional control has not been reported.7,8 Local failures are rarely salvageable since the absence of the bladder combined with the proximity of small bowel to gross disease often precludes definitive dose salvage radiation. Morbidity and mortality from these recurrences is high, with only 1 out of 80 patients surviving more than 5 years in a large retrospective series.9 Adjuvant radiation therapy has been proposed as a way to reduce the risk of localregional recurrence and has been the standard-of-care in Egypt and parts of the Middle East based on the results of randomized trials first conducted in the 1980s and 1990’s that demonstrated improved DFS with adjuvant RT vs. observation in a majority squamous cell carcinoma patient population.10 Interest in adjuvant radiation in other parts of the world had been dampened due to toxicity concerns from the early experience using 2-D radiation techniques and doubts as to whether urothelial carcinoma patients would benefit.

Brian C. Baumann MD1,2 Jason A. Efstathiou, MD, DPhil3

  1. Springfield Clinic, Department of Radiation Oncology, Springfield, IL
  2. University of Pennsylvania, Department of Radiation Oncology, Philadelphia, PA
  3. Massachusetts General Hospital, Department of Radiation Oncology, Boston, MA
References:

  1. Christodouleas JP, Baumann BC, He J, Hwang WT, Tucker KN, Bekelman JE, et al. Optimizing bladder cancer locoregional failure risk stratification after radical cystectomy using SWOG 8710. Cancer. 2014;120:1272-80.
  2. Baumann BC, Guzzo TJ, He J, Keefe SM, Tucker K, Bekelman JE, et al. A novel risk stratification to predict local-regional failures in urothelial carcinoma of the bladder after radical cystectomy. Int J Radiat Oncol Biol Phys. 2013;85:81-8.
  3. Reddy AV, Pariser JJ, Pearce SM, Weichselbaum RR, Smith ND, Steinberg GD, et al. Patterns of Failure After Radical Cystectomy for pT3-4 Bladder Cancer: Implications for Adjuvant Radiation Therapy. Int J Radiat Oncol Biol Phys. 2016;94:1031-9.
  4. Murthy V, Manjali J, Bakshi G, Prakash G, Pal M, Joshi A, et al. Locoregional recurrence after cystectomy in muscle-invasive bladder cancer: Implications of adjuvant radiotherapy. Urol Oncol. 2021;In press.
  5. Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003;349:859-66.
  6. Herr HW, Faulkner JR, Grossman HB, Natale RB, deVere White R, Sarosdy MF, et al. Surgical factors influence bladder cancer outcomes: a cooperative group report. J Clin Oncol. 2004;22:2781-9.
  7. Apolo AB, Ballman KV, Sonpavde G, Berg S, Kim WY, Parikh R, et al. Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma. N Engl J Med. 2024.
  8. Bajorin DF, Witjes JA, Gschwend JE, Schenker M, Valderrama BP, Tomita Y, et al. Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N Engl J Med. 2021;384:2102-14.
  9. Baumann BC, Guzzo TJ, He J, Vaughn DJ, Keefe SM, Vapiwala N, et al. Bladder cancer patterns of pelvic failure: implications for adjuvant radiation therapy. Int J Radiat Oncol Biol Phys. 2013;85:363-9.
  10. Baumann BC, Zaghloul MS, Sargos P, Murthy V. Adjuvant and Neoadjuvant Radiation Therapy for Locally Advanced Bladder Cancer. Clin Oncol (R Coll Radiol). 2021;33:391-9.
Source: Brian C. Baumann, Jason A. Efstathiou. Adjuvant radiation therapy for locally advanced bladder cancer: A safe and promising emerging treatment option. International Journal of Radiation Oncology, Biology, Physics. 2024. DOI: https://doi.org/10.1016/j.ijrobp.2024.09.042.