Palliative bladder radiotherapy: caveats in a changing landscape

Worldwide, bladder cancer is the ninth most common tumor (1). In muscle-invasive bladder cancer, the standard treatment consists of neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy (2,3). For patients who are considered unfit for surgery or who wish to attempt bladder-preservation, radiotherapy after maximal radical transurethral resection (TUR) represents a possible alternative. The addition of concomitant chemotherapy (whether mitomycine and 5-fluorouracil or cisplatin) to radiotherapy significantly improves outcome (4). With aggressive trimodality protocols (i.e., maximal TUR followed by concomitant chemoradiotherapy), survival rates similar those reported with radical cystectomy can be achieved (5). In addition to its use in the curative setting, radiotherapy can provide considerable palliation in patients with metastatic disease or patients who are not candidates for definitive therapy. Prolonged hematuria is a frequent and debilitating complication in patients with bladder cancer (6). The hemostatic effect of radiotherapy is wellestablished and its therapeutic onset is generally observed very quickly (7). Several mechanisms contribute to the hemostatic effect of radiotherapy, including increased adhesion of thrombocytes to the vascular endothelium, blood vessel fibrosis and to some extent, tumor regression. In a non-curative setting, hypofractionation is usually preferred, as it is cheaper and provides greater comfort to patients by decreasing the time spent traveling. However, toxicity can be pronounced when conventional palliative schedules (using multiple daily fractions of 3–4 Gy) are prescribed. This is especially true for bladder radiotherapy, because several critical organs at risk (OAR) are located very close to the target (e.g., small bowel, rectum) and the bladder itself appears to be very sensitive to radiation. To minimize this toxicity, alternative fractionation schedules have been developed using weekly fractions (8). The major advantage of the longer delay between fractions is the potential recovery of acute toxicity. Still, palliative bladder radiotherapy remains a treatment with considerable sideeffects and patient selection is of the utmost importance. Clearly, physicians are not very good at estimating survival in metastatic cancer patients, and bladder cancer is a particularly aggressive disease (9). Amin and colleagues performed a retrospective analysis from 2 British cancer centers (The Christie NHS Foundation Trust, Manchester and St James’s University Hospital, Leeds) on 241 patients treated with palliative bladder radiotherapy (10). Interestingly, the indication for the bladder irradiation was local disease control (65%) rather than hematuria (only 19%). Still, 18% of patients had deceased within 30 days after RT and 14% of patients could not even finish the planned radiation treatment. In all, one in four patients (25%) underwent “futile” palliative bladder Editorial Commentary