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SAN FRANCISCO -- A modest hypofractionated radiotherapy protocol demonstrated non-inferiority to conventional treatment and can be considered a new standard of care in patients with low- and intermediate-risk prostate cancer, investigators concluded here.

Over a follow-up period of about 5 years, a 3-Gy schedule of 60 Gy in 20 fractions proved non-inferior to 74Gy in 37 fractions, with respect to biochemical failure/prostate cancer recurrence and overall survival. The schedules had similarly low rates of acute and late side effects, reported , at the Genitourinary Cancers Symposium.

"We believe that modified hypofractionation, using 60 Gy in 20 fractions delivered with high-quality radiotherapy, can now be recommended as a new standard of care in patients with this type of intermediate- and low-risk cancer," he said. "The low side-effect profile, in general, probably reflects the technique of radiotherapy and the strict use of dose constraint and quality assurance."

The findings come from the multicenter, randomized (Conventional or Hypofractionated High dose Intensity Modulated Radiotherapy in Prostate Cancer; CRUK/06/016) trial.

CHHip investigated two 3-Gy hypofractionated radiotherapy dose schedules in 3,216 men with T1b to T3N0M0 localized prostate cancer, following hormonal treatment for 3 to 6 months, which was optional in men with low-risk disease, defined as stage T1c/T2a and a Gleason score ≤6 and a serum prostate-specific antigen (PSA) level ≤10 ng/mL.

Patients enrolled in CHHip had a risk of seminal vesicle involvement ≤30% and a serum PSA value ≤30 ng/mL, and were randomized in a 1:1:1 fashion to standard radiotherapy delivered using 74 Gy in 37 fractions over 7.4 weeks or one of two experimental hypofractionated regimens: 60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3.8 weeks.

Toxicity was assessed before hormone therapy; before radiotherapy; weekly during radiotherapy; at weeks 10, 12 and 18; and then at 26 weeks and every 6 months for 5 years.

Median age of patients was 69 years; 73% had intermediate- risk, 15% had low-risk and 12% had high-risk prostate cancer; 62% had a Gleason score of 7 and 35% had a Gleason score ≤6 and 55% had stage T2 and 36% had stage T1 disease. Their median PSA level prior to hormone therapy was 10 ng/mL.

The 5-year progression-free survival was 88.3% in the 74-Gy arm, 90.6% in the 60-Gy arm, and 85.9% in the 57-Gy arm. The 60-Gy schedule met the non-inferiority criterion compared with the 74-Gy schedule (HR 0.84, 90% CI 0.68-1.03, P=0.004), but the 57-Gy schedule did not (HR 1.20, 90% CI 0.99-1.46, P=0.96).

Mortalities were 8.6%, 6.8%, and 8.1% in the standard, 60-Gy and 57-Gy arms, respectively, with no significant difference between the arms.

Compared with standard radiotherapy, bowel toxicity was worse for both hypofractionated schedules (P<0.001 in each arm). There was no significant difference in acute bladder or acute bowel toxicity between the hypofractionation schedules.

The hypofractionated schedule had favorable late-toxicity.

"The 60-Gy in 20 fractions was associated with a small increase in late bowel side effects compared to 57 Gy, but not compared to 74 Gy," said Dearnaley. The 2-year RTOG grade 2+ bowel toxicity was 5.4% in the 60-Gy arm and 4.4% in the 57-Gy arm (P=0.39), and the rates at 5 years were 5.2% and 3.9% (P=0.32), respectively.

The rates of grade 2+ bladder toxicity were 13.7% in the 60-Gy arm and 10.8% in the 57-Gy arm at 2 years (P=0.07), with corresponding 5-year rates 13.2% and 11.2% (P=0.35), respectively. Of note, bladder symptoms were less common at 2 years and 5 years compared with pretreatment, he said.

There was no difference between the three treatment groups in sexual dysfunction.

Hypofractionation may not necessarily be a superior treatment, but the data clearly establish that "modest hypofractionation regimens are noninferior for biochemical failure with modest to no change in toxicity," said invited discussant , of the Texas Center for Proton Therapy in Irving. "This is probably ready for prime time."

Hamstra added, "Questions that remain to be answered include, what is the correct regimen, should it be shorter, and how do we implement this in the United States?"

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