New ASTRO Guidelines for Radiation Therapy in Bladder Cancer

Endorsement of Trimodal Therapy for Muscle-Invasive Disease

The guidelines endorse trimodal therapy as a curative alternative to cystectomy for select patients with muscle-invasive bladder cancer. Trimodal therapy consists of maximal transurethral tumor resection followed by chemoradiation. The document provides detailed scenarios for this approach, along with practical tips on doses, fractionation schedules, treatment fields, radiosensitization, image-guided techniques, and surveillance. For regional node-positive disease, the recommendations distinguish between cN1M0 and cN2-3M0 tumors. The organization strongly recommends trimodal therapy or radical cystectomy for cN1M0 cancer. For cN2-3M0 tumors, the recommendation is conditional, applying only if the cancer has stabilized or responded to neovadjvant or induction systemic therapy. Task force chair Jason Efstathiou noted that the practical message is to reassess cN2-3M0 patients for suitability after systemic therapy, with specific attention to response, disease extent, and patient fitness.

Expanding Radiation Use in Non-Muscle Invasive and Post-Surgical Scenarios

The advice extends beyond muscle-invasive disease to include patients with recurrent, high-grade non-muscle invasive bladder cancer staged as cT1N0M0. Jason Efstathiou described this conditional recommendation as potentially surprising, noting it applies only to patients who have exhausted or cannot access other treatments and who decline or are not candidates for cystectomy. This recommendation is based largely on encouraging results from a 37-patient single-arm study, and Efstathiou emphasized that it should not be interpreted as a general recommendation for radiation in non-muscle invasive bladder cancer. For patients who undergo cystectomies, the guidelines conditionally recommend radiation to reduce local recurrence in those with pT3-4 tumors or high-risk features such as positive lymph nodes or surgical margins. Treatment fields typically include the tumor bed and involved nodes. The presence of a reconstructed neobladder is not a contraindication to adjuvant radiation, provided patients recover urinary continence first. While randomized trials show improved local control with adjuvant radiotherapy, an overall survival benefit has only been demonstrated in retrospective studies.

Integration with Immunotherapy and Management of Metastatic Disease

Integrating postsurgical radiation with adjuvant immunotherapy remains an open question. The guidelines conditionally recommend radiation before or during immunotherapy based on expert opinion, though giving radiation first may be preferable due to limited safety data for concurrent treatment. Because adjuvant immunotherapy can continue for up to a year, delaying radiation until it is complete is generally not feasible. For metastatic disease treated with noncurative intent, the guidelines strongly recommend palliative radiation to symptomatic metastases. The task force also conditionally recommends radioablation of metastatic sites when there are five or fewer. Radiation to the bladder is also strongly recommended for patients with more than five metastatic sites who have localized symptoms, as well as for local or locoregional disease treated with noncurative intent.