In the first trial ever to randomly assign patients to extreme hypofractionation, primary radiation therapy delivered in just seven treatments had the same effectiveness and safety as 39 treatments.
The top-line results of the HYPO-RT-PC randomized clinical trial were presented at a meeting of the European Society for Radiotherapy and Oncology (ESTRO). There was an earlier report on toxicity. Between 2005 and 2015, they enrolled 1,200 intermediate- and high-risk patients at 12 centers in Sweden and Denmark to receive either:
- Conventional fractionation: 78 Gy in 39 fractions
- SBRT (stereotactic body radiation therapy): 42.7 Gy in 7 fractions
The biologically effective dose is 19 percent higher for SBRT in terms of cancer control. The biologically effective doses are equivalent in terms of toxicity.
The patients were all intermediate to high risk, defined as:
- Stage T1c to T3a
- PSA > 10 ng/ml
- Gleason score ≥ 7
Most of the patients (80 percent) were treated with a technology called three-dimensional conformal radiation therapy (3D-CRT), which is seldom used in treatment of prostate cancer with 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 percent in both arms of the study.
They also reported updated late-toxicity results. By 6 years after treatment:
- Grade 2+ urinary toxicity was 3.5 percent for conventional fractionation, and 2.5% for SBRT — no significant difference.
- Grade 2+ rectal toxicity was 2.3 percent for conventional fractionation, and 1.2 percent 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 moderate 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, will probably not be as thrilled.