By Chris Berrie
BARCELONA -- November 30, 2009 -- Hypofractionation radiotherapy is superior to conventional fractionation radiotherapy for patients with high-risk prostate cancer, with no differences in acute and late toxicities, according to researchers presenting at the 2nd European Multidisciplinary Meeting on Urological Cancers (EMUC).
Although there have been 2 previous randomised trials on hypofractionation, both of these trials "did not provide any conclusive evidence because they were performed before studies suggesting the low alpha:beta ratio for prostate cancer," explained principal investigator Stefano Arcangeli, MD, Regina Elena National Cancer Institute, Rome, Italy, speaking here on November 27.
The objective of this randomised, phase 3 study was to compare the efficacy of conventional fractionation radiotherapy (CFR) of 80 Gy/40 fractions/8 weeks with hypofractionation radiotherapy (HFR) of 62 Gy/20 fractions/5 weeks, 4 fractions per week, in treatment of patients with high-risk prostate cancer.
A total of 168 patients with high-risk prostate cancer were randomised to receive CFR (n = 83) or HFR (n = 85) schedules of 3-dimensional conformal radiotherapy to the prostate and seminal vesicles.
All patients had previously received a 9-month course of total androgen blockade, with radiotherapy started 2 months after its initiation.
Biochemical failure was determined according to the nadir + 2 ng/mL Phoenix definition, with acute toxicity according to the European Organisation for Research and Treatment of Cancer/Radiation Therapy Oncology Group scoring system, and late toxicity according to the Subjective, Objective, Medical Management and Analytical Evaluation of Injury/Late Effects on Normal Tissue clinical scale.
Across the 2 treatment groups, there were no baseline differences in mean patient age, Gleason score, T stage, or pretreatment prostate-specific antigen (iPSA) levels.
At a median follow-up of 35 months (CFR) and 32 months (HFR), the 3-year rates of freedom from biochemical failure were significantly greater for those on the HFR schedule (87%) compared with those on the CFR schedule (79%; P = .035). Dr. Arcangeli noted that, for the very high-risk patients -- those with iPSA >20 ng/mL, Gleason score >8 or T stage >2c -- this benefit of the HFR schedule was further increased versus the CFR schedule (88% vs 76%, respectively; P = .014).
In the acute toxicity assessment, there were no significant differences between HFR and CFR for either urinary (G2+G3: 47% vs 40%; P = .45) or rectal (G2+G3: 35% vs 21%; P = .07) toxicity. Similarly, the 3-year incidence of complications were not significantly different between the HFR and CFR groups; grade 2 or higher gastrointestinal late complications were 17% vs 14%, respectively (P = .57) and genitourinary late complications were 16% vs 11%, respectively (P = .10).
"The results are showing us that hypofractionation is clearly better than conventional fractionation, with no increase in late toxicity ... and the higher the risk for the patient, the better the results with hypofractionation," Dr. Arcangeli summarised.
"This confirms the radiobiological assumption that the alpha:beta ratio for prostate cancer is low, so it is a cancer that is very sensitive to low dose per fraction," he added.
EMUC was co-organised by the European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), and the European Society for Therapeutic Radiology and Oncology (ESTRO).
[Presentation titles: Hypofractionation vs Conventional Fractionation Radiotherapy in Patients With High Risk Prostate Cancer: Early Results of a Phase III Randomized Study. Abstract P001.
and
Hypofractionation vs Conventional Fractionation Radiotherapy in Patients With High Risk Prostate Cancer: Analysis of Acute and Late Toxicity. Abstract P048]
E-Mail this DGDispatch to a colleague
