Randomized Trial of Hypofractionated, Dose-Escalated, Intensity-Modulated Radiation Therapy (IMRT) Versus Conventionally Fractionated IMRT for Localized Prostate Cancer

Abstract

Purpose: Hypofractionated radiotherapy delivers larger daily doses of radiation and may increase the biologically effective dose delivered to the prostate. We conducted a randomized trial testing the hypothesis that dose-escalated, moderately hypofractionated intensity-modulated radiation therapy (HIMRT) improves prostate cancer control compared with conventionally fractionated IMRT (CIMRT) for men with localized prostate cancer.

Patients and methods: Men were randomly assigned to 75.6 Gy in 1.8-Gy fractions delivered over 8.4 weeks (CIMRT) or 72 Gy in 2.4 Gy fractions delivered over 6 weeks (HIMRT, biologically equivalent to 85 Gy in 1.8-Gy fractions assuming prostate cancer α-to-β ratio of 1.5). Failure was defined as prostate-specific antigen (PSA) failure (nadir plus 2 ng/mL) or initiation of salvage therapy. Modified Radiation Therapy Oncology Group criteria were used to grade late (≥ 90 days after completion of radiotherapy) GI and genitourinary toxicity.

Results: Most of the 206 men (72%) had cT1, Gleason score 6 or 7 (99%), and PSA level ≤ 10 ng/mL (90%) disease. Androgen deprivation therapy was received by 24%. With a median follow-up of 8.5 years, men treated with HIMRT experienced fewer treatment failures (n = 10) than men treated with CIMRT (n = 21; P = .036). The 8-year failure rate was 10.7% (95% CI, 5.8% to 19.1%) with HIMRT and 15.4% (95% CI, 9.1% to 25.4%) with CIMRT. There was no difference in overall survival ( P = .39). There was a nonsignificant increase in late grade 2 or 3 GI toxicity with HIMRT (8-year 5.0% v 12.6%; P = .08). However, GI toxicity was only 8.6% when rectal volume receiving 65 Gy of HIMRT was ≤ 15%. Late genitourinary toxicity was similar ( P = .84). There was no grade 4 toxicity.

Conclusion: The results of this randomized trial demonstrate superior cancer control for men with localized prostate cancer who receive dose-escalated moderately hypofractionation radiotherapy while shortening treatment duration.

Fig 1.

CONSORT diagram. ADT, androgen deprivation therapy; CIMRT, conventional intensity modulated radiation therapy; HIMRT, hypofractionated intensity modulated radiation therapy; RT, radiation therapy.

Fig 2.

Cumulative incidence of treatment failure after CIMRT or HIMRT for (A) all patients, (B) men who did not receive androgen deprivation therapy, and (C) men with prostate-specific antigen concentration ≤ 10 ng/mL. CIMRT, conventional intensity modulated radiation therapy; HIMRT, hypofractionated intensity modulated radiation therapy; RT, radiation therapy.

Fig 3.

Overall survival for men who received CIMRT or HIMRT. CIMRT, conventional intensity modulated radiation therapy; HIMRT, hypofractionated intensity modulated radiation therapy; RT, radiation therapy.

Fig 4.

(A) Grade 2 or 3 late GI (grade 2a) and (B) genitourinary (grade 2b) toxicity in men who received CIMRT or HIMRT. CIMRT, conventional intensity modulated radiation therapy; HIMRT, hypofractionated intensity modulated radiation therapy; RT, radiation therapy.

Fig A1.

Grade 2 or 3 late GI toxicity in men who received HIMRT stratified by volume of rectum receiving 65 Gy ≤ 15% versus > 15%. HIMRT, hypofractionated intensity modulated radiation therapy; RT, radiation therapy.