ASTRO Issues First Clinical Practice Guideline on Radiation for Bladder Cancer

Published in Practical Radiation Oncology, the American Society for Radiation Oncology (ASTRO) has released its first standalone clinical practice guideline on radiation therapy (RT) for bladder cancer, addressing 4 key clinical questions spanning curative-intent bladder preservation through trimodal therapy (TMT), RT techniques and dose-fractionation, postoperative RT following cystectomy, and palliative and consolidative RT in metastatic disease.^1,2 The guideline was developed in collaboration with the American Society of Clinical Oncology (ASCO), the European Association of Urology (EAU), and the European Society for Radiotherapy and Oncology (ESTRO), and is endorsed by the EAU.

The task force was led by corresponding author Leslie K. Ballas, MD, professor in the Department of Radiation Oncology at Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute in Los Angeles, California, and senior author Jason A. Efstathiou, MD, DPhil, program director for the Genitourinary (GU) Radiation Oncology Program within the Mass General Brigham Cancer Institute, vice-chair for Faculty Enrichment in the Mass General Brigham Department of Radiation Oncology, and the Jenot W. and William U. Shipley professor of Radiation Oncology at Harvard Medical School.

What does the guideline recommend for bladder-preserving trimodal therapy?

For select patients with cT2-4aN0M0 muscle-invasive bladder cancer (MIBC), the guideline offers a strong recommendation that TMT is a recommended alternative to radical cystectomy (RC). TMT consists of maximal transurethral resection of bladder tumor (TURBT) followed by concurrent chemoradiation. The most favorable prognostic features include solitary tumors smaller than 7 cm, predominant urothelial carcinoma histology, and the absence of extensive carcinoma in situ or hydronephrosis.

The guideline also strongly recommends concurrent radiosensitizing systemic therapy during TMT, with chemotherapy preferred. Recommended regimens include cisplatin with or without 5-fluorouracil (5-FU), 5-FU plus mitomycin C, or low-dose gemcitabine. For patients at higher risk of distant metastatic progression, such as those with cT3-4 or N1-3 disease, neoadjuvant or induction systemic therapy before TMT is also strongly recommended. For patients with high-grade cT1N0M0 non–muscle-invasive bladder cancer (NMIBC) who experience T1 recurrence despite intravesical or systemic therapies and decline or are ineligible for cystectomy, TMT or enrollment in a clinical trial is conditionally recommended. A prospective trial (NCT00981656) in this population demonstrated a 3-year cystectomy-free rate of 88% with chemoradiation.³

What RT techniques and dose-fractionation does the guideline recommend?

For patients with intact, localized, or node-positive bladder cancer, intensity modulated radiation therapy (IMRT) with daily image guidance using cone-beam CT is strongly recommended to verify bladder volume and target localization. Whole bladder RT to full dose or a partial tumor boost are both recommended; elective pelvic nodal RT is conditionally recommended based on higher-risk clinical features, including cT3-4 disease, hydronephrosis, aggressive histologic subtypes, or lymphovascular invasion.

Recommended dose-fractionation regimens include moderately hypofractionated RT at 55 Gy in 20 fractions, or conventionally fractionated RT at 64 to 64.8 Gy in 32 to 36 fractions. A continuous RT course without a mid-treatment break is strongly recommended, superseding the historical practice of interim cystoscopy during an RT break. Dose escalation above 64 to 64.8 Gy is not recommended outside of a clinical trial.

The ongoing randomized controlled phase 3 ARCHER trial (NCT07097142) is evaluating adaptive 5-fraction ultrahypofractionated RT vs moderately hypofractionated RT, both with concurrent chemotherapy, in localized bladder cancer.⁴ Moreover, the ongoing SWOG/NRG 1806 trial (NCT03775265) is evaluating whether adding atezolizumab (Tecentriq) to standard chemoradiation improves outcomes in MIBC managed with bladder-preserving TMT.⁵ Adaptive RT techniques are conditionally recommended where standard planning cannot meet target coverage and organ-at-risk constraints.

When does the guideline recommend adjuvant RT after cystectomy?

For patients with urothelial carcinoma who have (y)pT3-4 or (y)pN+ disease or positive margins following RC, adjuvant RT is conditionally recommended for locoregional control, a recommendation supported by evidence from 3 randomized controlled trials (RCTs) demonstrating clinically meaningful and statistically significant improvements in local control. Target volumes should routinely include the cystectomy bed and pelvic lymph nodes.

The recommended dose is 44 Gy to 50.4 Gy in 22 to 28 fractions; for positive margins, a simultaneous integrated boost (SIB) to up to 56 Gy may be added when anatomically feasible. IMRT with daily cone-beam CT imaging is strongly recommended. The guideline notes that a neobladder reconstruction is not a contraindication to adjuvant RT. Initiating adjuvant RT within 2 to 3 months of RC, or within 8 weeks of completing adjuvant chemotherapy, is strongly recommended, with a delay of up to 4 months acceptable in patients with neobladders working to achieve continence.

What does the guideline recommend for palliation and metastatic bladder cancer?

For patients with high-burden metastatic and locally symptomatic bladder cancer, or locoregional disease managed with noncurative intent, bladder-directed RT for local control and/or palliation is strongly recommended. Palliative dose-fractionation options include 21 Gy in 3 fractions given on alternate days, 34.5 Gy to 36 Gy in 6 weekly fractions, or shorter schedules such as a single fraction of 6 Gy to 8 Gy, 20 Gy in 5 fractions, or 30 Gy in 10 fractions.

For patients with low-burden metastatic disease, defined as 5 metastatic sites or fewer, who respond to systemic therapy, bladder-directed consolidative RT is conditionally recommended. Ablative, metastasis-directed RT for oligometastatic or oligoprogressive disease is also conditionally recommended based on limited but growing evidence. Conversely, consolidative bladder RT is not recommended for asymptomatic patients with high-burden metastatic disease, defined as 5 or more metastases.

What health disparities concerns does the guideline identify?

The guideline dedicates a section to health disparities in bladder cancer care, noting that patients who are Black with MIBC are less likely to receive definitive curative-intent treatment including cystectomy or chemoradiation. Geographic factors further compound inequities, with rural populations experiencing higher mortality and reduced access to specialized cancer centers. The guideline emphasizes expanding access to high-volume centers and multidisciplinary clinics, as well as increasing enrollment of underrepresented populations in clinical trials evaluating bladder-preserving and surgical therapies.

References

1. Ballas LK, Solanki AA, Baumann BC, et al. Radiation therapy for bladder cancer: an ASTRO clinical practice guideline. Pract Radiat Oncol. Published online September 15, 2026. doi:10.1016/j.prro.2026.09.001
2. ASTRO issues its first clinical guideline on radiation therapy for bladder cancer. News release. ASTRO. September 16, 2026. Accessed September 17, 2026. https://tinyurl.com/mwdte9cm
3. Dahl DM, Rodgers JP, Shipley WU, et al. Bladder-preserving trimodality treatment for high-grade T1 bladder cancer: results from phase II protocol NRG Oncology/RTOG 0926. J Clin Oncol. 2024;42(34):4095-4102. doi:10.1200/JCO.23.02510
4. NRG GU015: adaptive ultrahypofractionated versus moderately hypofractionated radiotherapy with concurrent chemotherapy for localized bladder cancer. ClinicalTrials.gov. Updated August 18, 2026. Accessed September 17, 2026. https://tinyurl.com/7cdmhdvr
5. Chemoradiotherapy with or without atezolizumab in treating patients with localized muscle invasive bladder cancer. ClinicalTrials.gov. Updated August 28, 2026. Accessed September 17, 2026. https://tinyurl.com/5b9xmczh