Session Item

Local recurrences after radiotherapy for prostate cancer often originate at the location of the macroscopic tumour(s). Since prostate cancer cells are known to be sensitive to high fraction doses, hypofractionated whole gland stereotactic body radiotherapy (SBRT) in conjunction with a simultaneous ablative microboost to the macroscopic tumour(s) within the prostate could be a way to cope with local failure. We investigated the safety of this treatment strategy in the hypo-FLAME trial.

Patients with intermediate or high risk prostate cancer were enrolled in a multicenter, prospective phase II trial. All patients were treated with extreme hypofractionated doses of 35 Gy in 5 weekly fractions to the whole prostate gland with an integrated boost up to 50 Gy to the multiparametric MRI-defined tumour(s). If the dose constraints to the normal tissue were at risk, these were prioritised over the aimed boost dose. The primary endpoint of the trial was treatment related acute toxicity measured by the CTCAE v4.0.

Between April 2016 and December 2018, 100 men were treated in four academic centres. All patients were followed for a minimum of 6 months. At baseline, median age of the included patients was 73 years (range, 57‐84 years), median PSA level was 10.8 ng/mL (range, 3.0‐29.0 ng/mL) and 75.0% of the patients were classified as having high risk prostate cancer according to the EAU risk classification. Additionally, 44% was staged clinical tumour category cT3a. The median mean dose delivered to the visible tumour nodule(s) on multiparametric MRI was 44.7 Gy. The aimed dose of 50 Gy was in most cases not achieved, due to normal tissue constraints. No grade ≥3 acute genitourinary (GU) or gastrointestinal (GI) toxicity was observed. The acute (90 days after start of treatment) cumulative  grade 2 GU and GI toxicity rates  were 34.0% and 5.0%, respectively. The prevalence of grade 2 GU toxicity increased during treatment and reached a maximum at the end of treatment (25.5%). Thereafter, the prevalence of GU toxicity declined to 11.4%, 90 days after starting the radiation treatment. The prevalence of grade 2 GI toxicity did not exceed 5% at any time (Figure 1).

The phase II hypo-FLAME trial showed that a focal SBRT boost to the macroscopic tumour(s) in addition to whole gland prostate SBRT is associated with acceptable acute GU and GI toxicity. Furthermore, besides the potential benefit in tumour control by focal boosting and extreme hypofractionation, the associated reduction in fraction number is attractive to both patients and radiation oncology departments.