Session Item

Randomized comparison of dose-escalated hypofractionated image guided intensity modulated radiotherapy (Hy-IGIM-RT) for localized prostate cancer (PC) with standard RT (StD-RT) with regard to toxicity.

In this phase 3 clinical trial conducted by five Italian centers, pts with low/intermediate risk PC (D’Amico classification) were randomized. Median age was 74 years (range 61-85), histologically confirmed stage was cT1a-cT2c cN0 cM0 PC, PSA ≤ 20 ng/mL, Gleason score ≤ 7 and ECOG  0-2. A web-based platform was used to randomly assign (1:1) pts. Low-risk pts received StD-RT (74Gy in 37 fractions) or Hy-IGIM-RT (54,3Gy in 15 fractions, 4 fractions per week). Intermediate risk pts received StD-RT (78Gy in 39 fractions) or Hy-IGIM-RT (57,3Gy in 15 fractions, 4 fractions per week) (Fig. 1).

Daily IGRT (mainly MVCT or CBCT) was systematically used in pts treated with Hy-IGIM-RT. The primary endpoint was to detect a 10% gain in 2-year relapse-free survival for pts who underwent Hy-IGIM-RT. Secondary endpoint was to evaluate the incidence of acute and late gastrointestinal (GI) and genitourinary (GU) toxicity in the two different treatment arms.

Toxicity was scored using the NCI Common Terminology Criteria for Adverse Events (CTCAE v4.0) focusing on 5 GI (proctitis, anal pain, hemorrhoids, fecal incontinence, diarrhea) and 3 GU categories (non-infective cystitis, urinary retention, urinary incontinence). Patients' self-assessment questionnaires were also used (EORTC QLQ-C30, IPSS score).

Between April 2013 and June 2020, 166 pts (83 per arms) were randomly assigned to StD-RT or Hy-IGIM-RT; 7 pts did not receive the planned treatment. Median FUP was 58 months (IQR 36-66). The most frequently reported acute toxicity was ≤ grade 2 (G2) non-infective cystitis, only one patient developed G4 urinary retention in the StD-RT group. No statistically significant differences emerged with chi-square test between the 4 dose levels.

Late toxicity was available in 154 pts (96,8%), taking together categories analyzed for GI and GU toxicity. At a median FUP of 4.5 years the cumulative incidences of G≥2 GI toxicity was 23.3%, 23.6%, 27% and 17% for 54,3Gy,57,3Gy,74Gy and 78Gy dose level arms, respectively. The GU≥G2 toxicity cumulative incidences were: 17%,18%,20%,13% for 54,3Gy,57,3Gy,74Gy and 78Gy dose level arms respectively. One patient developed G4 proctitis in the 57,3Gy dose level arm. A detailed description of G2 or worse acute and late toxicities is reported in Table 1. No statistically significant differences emerged with log-rank test between all subgroups.

Hy-IGIM-RT schedules, although applying higher biologically equivalent doses compared to those of previous randomized trials, resulted well tolerated without worsening acute and late toxicity in comparison with the StD-RT ones. If efficacy endpoints also indicate at least equivalence, the Hy-IGIM-RT schedules tested may be taken into consideration for the treatment of selected low and intermediate-risk PC pts.