For patients with high-risk, locally bulky prostate cancer, an intra-prostatic boost to tumour volumes (dose-painting) offers a risk-adapted dose escalation. We evaluated the feasibility of hypofractionated dose-painting radiotherapy and the associated toxicity. The possibility to streamline a radiobiologically optimised planning protocol was also investigated.

Twenty-eight patients were treated using a dose-painting approach; boost volumes were identified with functional magnetic resonance imaging scans. The prostate dose outside the boost volume was 60 Gy in 20 fractions, and the maximum integrated boost dose was set to 68 Gy, provided that the dose constraints to the organs at risk could be fulfilled. Rotational intensity-modulated radiotherapy was used with daily image guidance and fiducial markers.

The boost dose was escalated to 68 Gy for 25 patients (median dose 69 Gy, range 68-70 Gy); for three patients the boost dose was 67 Gy, due to the proximity of the urethra and/or the rectum. The mean normal tissue complication probability for rectal bleeding was 4.7% (range 3.4-5.8%) and was 3.5% for faecal incontinence (range 2.3-5.0%). At a median follow-up of 38 months (range 32-45) there was no grade 3 toxicity. Two patients developed grade 2 genitourinary toxicity (7.1%) and none developed grade 2 gastrointestinal toxicity. The mean prostate-specific antigen (PSA) for 23 patients who had stopped the adjuvant hormone therapy with a normal testosterone was 0.27 ng/ml (0.02-0.72) at follow-up; two patients have suppressed PSA and testosterone after stopping 3 year adjuvant hormone and three patients have relapsed (one pelvic node, two PSA only) at 36, 12 and 42 months, respectively.

A hypofractionated radiotherapy schedule, 60 Gy in 20 fractions with intra-prostatic boost dose of 68 Gy, can be achieved without exceeding dose constraints for organs at risk. Hypofractionated dose-painting escalated radiotherapy has an acceptable safety profile. The same planning protocol was used in a phase II single-arm trial (BIOPROP20: ClinicalTrials.gov identifier NCT02125175) and will further be used in a large phase III randomised trial (PIVOTALboost): patients will be randomised standard radiotherapy (60 Gy in 20 fractions) with or without lymph node radiotherapy versus dose-painting radiotherapy with or without lymph node radiotherapy; the trial will be opened for recruitment in summer 2017.