Randomized trial of concomitant hypofractionated IMRT boost versus conventional fractionated IMRT boost for localized high-risk prostate cancer (pHART2-RCT)

To report on the results of a phase II randomized trial of moderately hypofractionated (MH) versus conventionally fractionated (CF) radiotherapy to the prostate with elective nodal irradiation (ENI).This was a single-centre prospective phase II randomized study. Patients with high-risk disease (cT3, PSA >20 ng/mL, or Gleason score 8-10) were eligible. Patients were randomized to either MH using a simultaneous integrated boost (68 Gy in 25 fractions to prostate; 48 Gy to pelvis) or CF (46 Gy in 23 fractions with a sequential boost to the prostate of 32 Gy in 16 fractions), with long-term androgen deprivation therapy (ADT). The primary endpoint was grade ≥2 acute gastrointestinal (GI) and genitourinary (GU) toxicity (CTCAE v3.0). Secondary endpoints included late GI and GU toxicity, quality of life, and oncologic outcomes.180 patients enrolled: 90 were randomized to and received MH and 90 to CF. Median follow-up was 67.4 months. Seventy-five (41.7%) patients experienced a grade ≥2 acute GI and/or GU toxicity, including 34 (37.8%) in the MH and 41 (45.6%) in the CF arms, respectively (p=0.29). Late grade ≥2 GI (p=0.07) and GU (p=0.25) toxicity was not significantly different between arms, however, late grade ≥3 GI toxicity was worse in the MH group (p=0.01). There were no statistically significant quality of life differences between the two treatments. There were no statistically significant differences observed in cumulative incidence of biochemical failure (p=0.71) or distant metastasis (p=0.31), and overall survival (p=0.46).MH to the prostate and pelvis with ADT for men with high-risk localized prostate cancer was not significantly different than CF with regards to acute toxicity, quality of life and oncologic efficacy. However, late grade ≥3 late GI toxicity was more common in the MH arm.