Palliative bladder EBRT

• Bladder carcinoma.

• Disease causing or likely to cause local symptoms such as: haematuria, irritable bladder, dysuria, pain or urethral obstruction.

• Patients not suitable for curative therapy e.g. too frail, disease stage too advanced.

Cautions

• Previous high dose radiation to the pelvis.

• Direct invasion of the vagina, sigmoid colon or rectum, on imaging.

• Inflammatory bowel disease and/or history of adhesions/bowel obstruction.

• Non-rheumatoid collagen vascular disorders.

• Cardiac implantable electronic devices (CIEDs).

• Pre-treatment cystoscopy may be useful.

• FBC/renal function may be considered.

• Consider a referral to palliative care services.

• Anxiety and depression are common in patients with cancer. A referral to a psychosocial practitioner should be considered.

Prescription notes

• In patients with poor performance or more advanced disease, consider the use of shorter fractionation schedules.

• Publication of results are pending from the randomised multicentre trial (HYBRID) which evaluated hypofractionated bladder radiation therapy, 36 Gy in 6 fractions delivered 1 fraction per week, with or without image-guided adaptive planning.^rr

• Consider adaptive radiation therapy (ART), particularly in the setting of higher prescription  doses.^r

Margin ranges have been agreed by the Radiation Oncology reference committee and reflect safe clinical practice.

Target volume notes

• If daily soft tissue image guidance is available, reduced margins may be considered to reduce small bowel dose.

• A smaller margin may be used for involved nodes.

• Currently there are no guidelines for dose constraints when giving hypofractionated short-course radiation therapy. However, it is reasonable to aim to treat as small a volume of small bowel as necessary to ensure adequate PTV coverage. 

Target verification recommendations reflect the minimum imaging required for the safe delivery of this protocol.

Target verification notes

• When PTV margins <1 cm, daily soft tissue imaging is recommended.

Efficacy

The key evidence supporting the use of this protocol comes from the Medical Research Council (MRC) randomised trial by Duchesne et al. for the palliation of local symptoms from muscle invasive bladder cancer.^r Between 1992 and 1997, 500 patients were randomised to receive 35 Gy in 10 fractions (n = 248) or 21 Gy in 3 fractions (n = 252); median survival was was 7.5 months. For both arms, the estimated survival was 77% at 3 months, 35% at 1 year and 19% at 2 years, respectively. Similar survival results were reported by Jose et al.^r Symptomatic improvement was achieved in 68% of patients (71% for 35 Gy, 64% for 21 Gy) with no significant difference seen between groups. At 3 months, haematuria was alleviated in 88%, frequency in 82%, dysuria in 72% and nocturia in 64% of patients when data was pooled from both treatment arms. The median time to deterioration of one or more bladder-related symptoms from the commencement of radiation therapy was 9 months (6 months from the 3-month assessment). For those that benefited from radiation therapy, approximately 70% had deterioration in bladder-related symptoms at 12 months.

A group from the UK Institute of Cancer Research treated 55 patients with T2-T4a, Nx-2, M0-1 bladder cancer, who were not suitable for radical treatment.^r In this phase II study, a 'plan of the day' approach was used to deliver 36 Gy in 6 fractions (1 fraction per week). The median patient age was 86 years (range 68-97 years). Cumulative incidence of local progression at 1-year was 7% (95% CI:2-17%). Overall survival at 1-year was 63% (95% CI:48-74%). A higher biologically equivalent total dose was used than other commonly used radiation therapy regimens in the non-radical setting. Hypofractionation and feasibility of an online cone beam CT (CBCT) adaptive protocol to treat non-curative bladder cancer patients is being further evaluated in a phase III study, results are pending.^r

A study conducted in the UK by the Christie NHS Foundation Trust, retrospectively reviewed patients treated for palliative bladder cancer between 2014 and 2017.^r Ali et al. found one quarter of patients treated either did not complete their treatment or died within 30 days of treatment. The study used the Adult Comorbidity Evaluation [ACE]-27 score, performance status (PS ≤2 and PS ≥3), and stage, and found significant differences in survival based on these groupings. The authors stated the benefits of palliative radiation therapy may be delayed for up to 3 months, whereas side effects occur earlier and resolve within 4-6 weeks. The authors concluded that radiation treatment is futile if patients are unlikely to live longer than 30 days after the completion of radiation therapy, as these patients are unlikely to receive maximal treatment benefit, but may experience treatment-related side effects.

Dose and fractionation regimens for palliative radiation therapy to provide rapid relief of pain or haematuria in patients with advanced bladder cancer should be tailored to a patient's life expectancy and performance status.^r

Toxicity

A summary of the most clinically significant toxicities associated with this protocol are included in the table below:

• A group from the UK Institute of Cancer Research treated 55 patients with T2-T4a, Nx-2, M0-1 bladder cancer, who were not suitable for radical treatment.^r Grade 3 acute toxicity was reported as 18% for genitourinary toxicity, and 4% for gastrointestinal toxicity. Any grade 3 or greater late toxicity at 6 and 12 months was reported as 6.5% and 4.3% of patients, respectively.