Long-term Results of Hypofractionated Radiotherapy with Intra-Prostatic Boosts in Men with Intermediate- and High-risk Prostate Cancer: A Phase II trial

Abstract

AimIn the conventionally fractionated phase III FLAME prostate trial, focal boosts improved local control and biochemical disease-free survival (bDFS). We explored the toxicity and effectiveness of a moderately hypofractionated schedule with focal boosts. Material and Method[REDACTED] is a phase II single-arm non-randomised trial for intermediate-to very high-risk localised prostate cancer patients with bulky tumour volumes. Multi-parametric MRI and 18F-choline PET-CT scans were used for staging and boost volume definition. Patients were treated with 60Gy in 20 fractions with a boost dose up to 68Gy. Five patients with positive lymph nodes on the PET CT scan received radiotherapy to pelvic lymph nodes (45Gy to elective nodes, boosted up to 50Gy to involved nodes). Primary outcomes were acute (≤18 weeks) and late urinary and gastrointestinal toxicity prospectively recorded up to 5 years with Common Terminology Criteria for Adverse Events v4 (CTCAE). Secondary outcomes were biochemical or clinical progression, metastasis-free survival (MFS), and overall survival (OS). Results61 patients completed radiotherapy with hormone therapy (range: 6 – 36 months). Cumulative acute and late gastrointestinal toxicity was low at 6.6% and 5.0% respectively. Cumulative acute and late urinary toxicity was 49.2% and 30.1% respectively; the prevalence reduced to 5.9% at 5 years. At 5-years: 6 patients had biochemical progression (bDFS: 88.5%; 95% CI: 80.2-97.6%), the MFS was 82.4% (95% CI: 73.0-92.9%), 5 patients died (OS: 91.2%; 95% CI: 84.1-98.9%), one with prostate cancer. The prostate, boost, nodal planning volumes and the organs at risk (rectum, bowel, urethra, and bladder) met the optimal protocol dose constraints. There was a trend to increased urinary toxicity with increasing urethral (RR: 1.95, 95% CI: 0.73-5.22, p = 0.18), but not bladder dose. ConclusionFocal boosts with a 20 fraction hypofractionated prostate radiotherapy schedule are associated with an acceptable risk of gastrointestinal and urinary toxicity and achieve good cancer control. ClinicalTrials.gov identifierNCT02125175.