First randomized clinical trial of SBRT

In the first trial ever to randomly assign patients to extreme hypofractionation, primary radiation therapy delivered in just 7 treatments had the same effectiveness and safety as 39 treatments.

The results of the HYPO-RT-PC randomized clinical trial were published in The Lancet. There was an earlier report on toxicity. Details of the trial specs are available here. Between 2005 and 2015, they enrolled 1200 intermediate- and high-risk patients at 12 centers in Sweden and Denmark to receive either:

1. Conventional fractionation: 78 Gy in 39 fractions
2. SBRT (stereotactic body radiation therapy): 42.7 Gy in 7 fractions

The biologically effective dose is 19% higher for SBRT in terms of cancer control. The biologically effective doses are equivalent in terms of toxicity.

The patients were all intermediate (89%) to high risk (11%), defined as:

1. Stage T1c-T3a
2. PSA> 10 ng/ml 
3. Gleason score ≥7

80% of the men were treated with a technology called three-dimensional conformal radiation therapy (3D-CRT), which is seldom used for prostate cancer external beam therapy anymore at major tertiary care centers. It is never used for SBRT in the US because it is considered not precise enough, and too toxic. SBRT is usually delivered in 4 or 5 fractions in the US. CyberKnife and VMAT are the most common technologies in use, and use of sophisticated image guidance throughout each treatment is a common practice.

With follow-up of 1,180 patients for 5 years, they report biochemical recurrence-free survival of 84% in both arms of the study.

They also reported updated late-toxicity results. By 5 years after treatment:

• Grade 2+ urinary toxicity was 5% for conventional fractionation, 5% for SBRT - no significant difference.
• Grade 2+ rectal toxicity was 4% for conventional fractionation, 1% for SBRT - no significant difference.

Up until now, we've only had reports from clinical trials using SBRT (like this one) or conventional fractionation (like this one), and it could have been reasonably argued that SBRT results looked good because of selection bias. With this study, we now have Level 1 evidence of non-inferiority. This will not be surprising to those of us who have followed the randomized clinical trials of moderately hypofractionation vs. conventional fractionation (see this link). This will be hailed as a victory for patients who no longer have to endure and pay the high cost of 8 weeks of treatments. radiation oncologists, who are reimbursed by the number of treatments they deliver, probably will not be as thrilled.