Increased Radiation Dose With Hypofractionated vs Conventional Radiation Therapy Does Not Improve Biochemical/Clinical Failure Rate in Prostate Cancer
In a study reported in the Journal of Clinical Oncology, Alan Pollack, MD, PhD, of University of Miami Miller School of Medicine, and colleagues compared escalated radiation dose using hypofractionated vs conventional fractionation intensity-modulated radiation therapy in men with favorable- to high-risk prostate cancer. They found that hypofractionated intensity-modulated radiation therapy did not improve the rate of biochemical or clinical disease failure. However, there were no differences in late toxicities between groups, and patients on the hypofractionation regimen required 12 fewer daily radiotherapy treatments.
Study Details
Between June 2002 and May 2006, 303 men with favorable- to high-risk prostate cancer were randomly assigned to receive 76 Gy in 38 fractions at 2.0 Gy per fraction (conventional fractionation intensity-modulated radiation therapy; n = 152) or 70.2 Gy in 26 fractions at 2.7 Gy per fraction (hypofractionated intensity-modulated radiation therapy; n = 151), with the hypofractionation regimen being estimated to be equivalent to 84.4 Gy in 2.0 Gy fractions. High-risk patients received long-term androgen deprivation therapy and some intermediate-risk patients received short-term androgen deprivation therapy.
The primary endpoint was the cumulative incidence of biochemical or clinical disease failure. Clinical failure included local failure (local progression or prostate biopsy proof of disease with rising prostate-specific antigen [PSA]) or regional/distant metastasis (radiographic or pathologic). A modification of the ASTRO (American Society for Radiation Oncology) definition of biochemical failure (ie, three consecutive PSA rises) was used. Results were also analyzed using the biochemical failure definition of nadir plus 2 ng/mL.
The conventional fractionation and hypofractionation groups were well balanced for age (mean, 67 years in both), T category (T2 in 51% and 47%), Gleason score (6 in 34% and 35%, 7 in 47% in both), pretreatment PSA level (< 10 ng/mL in 65% and 63%), pretreatment biopsy percentage positive tissue (> 20% in 72% and 68%), and risk group/planned duration of androgen deprivation therapy (intermediate/none in 53% and 55%, intermediate/short-term in 13% and 10%, and high/long-term in 33.5% and 35%).
Biochemical or Clinical Disease Failure Outcomes
After median follow-up of 68.4 months, 5-year rates of biochemical or clinical disease failure were 21.4% for conventional fractionation vs 23.3% for hypofractionation (P = .745). Results were similar using the strict ASTRO biochemical failure definition and the nadir plus 2 ng/mL definition. There was no difference between groups in local failure (3 vs 5 patients, P = .5) or distant failure (6 vs 8 patients, P = .6). There was also no difference in prostate cancer–specific mortality (P = .407), death resulting from other causes (P = .513), or overall survival (P = .335).
On multivariable analysis of biochemical or clinical disease failure, treatment arm was not significant, whereas T category, Gleason score, initial PSA, and duration of androgen deprivation therapy (nadir plus 2 ng/mL definition only) were significant. On separate testing, risk group and planned length of androgen deprivation therapy were not significant.
Late Toxicity
There were no statistically significant differences in late gastrointestinal or genitourinary toxicity between groups. However, in multivariate subgroup analysis of late grade ≥ 2 genitourinary adverse events, pretreatment International Prostate Symptom Score > 12 in the hypofractionation group, but not the conventional fractionation group, was associated with significantly increased risk of such toxicity (hazard ratio = 2.54, P = .001).
The investigators concluded, “The hypofractionation regimen did not result in a significant reduction in [biochemical or clinical disease failure]; however, it is delivered in 2.5 fewer weeks. Men with compromised urinary function before treatment may not be ideal candidates for this approach.”
The study was supported by National Cancer Institute and Florida Biomed Bankhead Coley grants.
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