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