Hypofractionated Dose-Escalated IMRT vs Conventionally Fractionated IMRT in Localized Prostate Cancer


Key Points

  • Cancer control was improved with dose-escalated moderately hypofractionated IMRT.
  • A nonsignificant increase in late grade 2 or 3 GI toxicity was observed in the hypofractionated IMRT group.

In a long-term follow-up of a phase III trial reported in the Journal of Clinical Oncology, Hoffman et al found that dose-escalated moderately hypofractionated intensity-modulated radiation therapy (HIMRT) improved disease control and reduced treatment duration vs conventionally fractionated IMRT (CIMRT) in localized prostate cancer.

Study Details

In the trial, 206 men in the as-treated population at The University of Texas MD Anderson Cancer Center were randomized between January 2001 and January 2010 to receive a dose-escalated moderate HIMRT regimen that delivered 72 Gy in 2.4 Gy fractions over 6 weeks (biologically equivalent to 85 Gy in 1.8 Gy fractions; n = 104) or a CIMRT regimen consisting of 75.6 Gy in 1.8 Gy fractions delivered over 8.4 weeks (n = 102). Failure was defined as prostate-specific antigen (PSA) failure (nadir plus 2 ng/mL) or initiation of salvage therapy. Most patients had cT1 disease (72%), Gleason score of 6 or 7 (99%), and PSA level ≤ 10 ng/mL (90%), and 24% were receiving androgen-deprivation therapy.  

Treatment Failure

Over a median follow-up of 8.5 years, treatment failure occurred in 10 patients in the HIMRT group vs 21 in the CIMRT group (P = .036). Of the 31 failures, 28 were PSA failures. The 5-, 8-, and 10-year cumulative incidence of failure was 8.2% vs 8.3%, 10.7% vs 15.4%, and 10.7% vs 23.7%. No prostate cancer deaths occurred. No significant difference in overall survival between groups was observed (P = .39), with 8- and 10-year rates of 90.0% vs 85.2% and 82.8% vs 76.1%.


There was a nonsignificant increase in late grade 2 or 3 gastrointestinal (GI) toxicity with HIMRT, with 8-year rates of 12.6% vs 5.0% (P = .08). The 8-year rate of such toxicity in the HIMRT group was 8.6% when the rectal volume receiving 65 Gy of HIMRT was ≤ 15%. Rectal bleeding accounted for 13 of 14 cases of grade 2 toxicity in the HIMRT group and each of 3 grade 3 events. The 8-year cumulative incidence of grade 2 or 3 late genitourinary (GU) toxicity was 15.1% vs 16.4% (P = .84). No grade 4 GI or GU late toxicity was observed.

The investigators concluded, “[C]ompared with CIMRT (75.6 in 1.8 Gy fractions), this dose-escalated moderate HIMRT regimen (72 Gy in 2.4 Gy fractions) shortened treatment duration while improving prostate cancer control. GU toxicity was similar. Although there was a nonsignificant increase in late grade 2 and 3 GI toxicity with dose-escalated hypofractionated treatment, the number of men who developed toxicity was small; all rectal bleeding resolved with treatment; and the risk of bleeding can be reduced by minimizing the proportion of rectum that receives high-dose radiation.”

The study was supported in part by a grant from the National Cancer Institute.

Karen E. Hoffman, MD, of The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.