One of the major themes of the ASTRO Annual Meeting and also a major point of discussion, in general, in recent years has been a greater move toward the use of hypofractionated radiation techniques for early-stage prostate cancer. The rationale is that due to the biologic nature of most prostate cancers which tend to be slower growing than other malignancies giving fewer treatments at higher doses can potentially be just as effective as a standard, multiweek course of radiation therapy.

The benefit of hypofractionated radiation therapy is that it can be more convenient and less costly than traditional radiotherapy. However, the long-term toxicity results of this strategy have not been well studied until recently. Several studies have come out that look at moderately hypofractionated radiation therapy, but we havent seen much in the way of extremely hypofractionated radiation therapy. This treatment platform is usually administered over the course of five to seven appointments, whereas conventionally radiotherapy can take up to 44 appointments to fully administer.

This study by Widmark and colleagues found that early adverse events in patients assigned to extremely hypofractionated radiotherapy were slightly worse compared with standard fractionation. However, after 2 years, the adverse event profiles were essentially similar. It will be interesting to see the late adverse event profiles after 5 or more years of follow-up.

However, the current results suggest that extreme hypofractionation is well-tolerated and could potentially serve as a viable alternative to conventional fractionation regimens for prostate cancer.

Two trials at this year’s ASTRO Annual Meeting add evidence in support of the use of hypofractionation in the treatment of prostate cancer. Hypofractionation — where fewer fractions, but larger individual fractions of radiation are given — has the theoretical benefit of delivering effective cancer treatment quicker than conventionally fractionated intensity-modulated radiation therapy (IMRT). The question has remained, though, whether this treatment is as effective, and safe, as conventional high-dose IMRT. More and more studies from large randomized prospective clinical trials — like the CHHiP trial from the United Kingdom, the HYPRO trial from the Netherlands, and the Fox Chase trial from the United States — have all supported the safety and efficacy of hypofractionated radiation therapy for the treatment of men with prostate cancer.

Now, two more studies add weight to this argument. In the HYPO-RT-PC trial — a randomized multi-institutional phase 3 trial from Scandinavia — Widmark and colleagues presented the results of highly accelerated extreme hypofractionation, or seven fractions of 6.1 Gy each compared with 39 fractions of 2 Gy each. Researchers randomly assigned 1,200 men with tumor stages of T1c to T3a, PSA levels of 20 or below, and one or two of three risk factors: stage T3a, a Gleason tumor score of 7 or higher, or a PSA level greater than 10.

Men who received extremely hypofractionated radiation in seven treatments experienced similar side effects two years following treatment as those who received conventional radiation in 39 treatments. Rates of physician-reported grade 2 or worse toxicities at 2 years following treatment did not differ significantly between treatment arms. Importantly, this study included patient-reported outcomes at 2 years following treatment, which also did not differ significantly between treatment groups for overall bother from urinary, bowel or sexual function symptoms.

In another trial presented at ASTRO, Bruner and colleagues reported quality-of-life results from NRG/RTOG 05-14 for men with low-risk early-stage prostate cancer. Last year, the clinical and biochemical results were reported and demonstrated no difference between the two arms (73.8 Gy in 41 fractions over 8.2 weeks or 70 Gy in 28 fractions over 5.6 weeks).

Researchers assessed health-related quality-of-life outcomes using the Expanded Prostate Cancer Index Composite test. At baseline and 6 months, there was no difference between the two treatment groups for the four domains — bowel, bladder, sexual and hormonal. At 12 months, the hypofractionated group of men experienced a decline in the bowel domain, but they did not consider it clinically significant.

These two large randomized prospective clinical trials add support to the expanded use of hypofractionated radiation therapy in men with all stages of prostate cancer. The treatment is efficacious and safe compared with conventionally fractionated IMRT and should be considered another standard treatment that is also more convenient for the patient.

Reference:

Bruner DW, et al. Abstract 4.