David C. Beyer, MD
Cancer Centers of Northern Arizona Healthcare
Why is this article contemporary?
As genitourinary radiation oncologists, we live in exciting times. The options and alternatives for managing prostate cancer with radiation have significantly expanded beyond a historical choice between external beam and brachytherapy. The therapeutic regimens we have at our disposal allow for many more technical options and diverse schedules with differing radiobiologic underpinnings.
More-accelerated fractionation schedules may represent a significant advance for our patients. The data thus far is promising. Much of these data for hypofractionation (17-28 fractions) and for stereotactic body radiation therapy (SBRT) are highlighted by Shah et al in this review article.
Left unanswered are many questions of personalization. We regularly use a variety of measures (stage, grade, prostate-specific antigen, urinary function, anatomy, etc) to help our patients select the best treatment. Which patient is best served by conventional fractionation, hypofractionation, or SBRT? Today, this remains an important unanswered question. But for now, we do know that these various treatment schedules have moved from the pure research setting into routine clinical practice worldwide, and this timely review provides the background for future work.
With improvements in technology allowing for highly conformal radiotherapy to be delivered in conjunction with three-dimensional online image guidance, renewed interest in hypofractionated radiotherapy for prostate cancer has emerged. Multiple randomized trials comparing standard fractionation and hypofractionation when treating the prostate +/- seminal vesicles have been performed with comparable clinical outcomes and toxicity, making it a standard of care of option in appropriately selected patients despite limited long-term (> 10 year) outcomes. Limited data are available supporting hypofractionation in post-prostatectomy and whole-pelvis settings. Stereotactic body radiation therapy (SBRT), as a form of extreme hypofractionation, has been evaluated in multiple prospective trials allowing for the completion of treatment in 5 fractions. Despite limited data comparing SBRT to standard or hypofractionated radiotherapy with regards to long-term clinical outcomes and toxicity profiles, the data are promising and appropriately selected patients can be offered such an approach off-protocol.
Prostate cancer represents the most common non-cutaneous cancer among men in the United States, with an annual incidence of 220,000 cases/year.1
Multiple treatment options exist for men based on patient and disease factors, with radiation therapy representing a treatment option for men with low- and intermediate-risk disease and a preferred treatment option in conjunction with androgen deprivation for high-risk disease.2
One major concern regarding external beam radiation therapy is the duration of treatment, with external beam radiation therapy often exceeding 7 weeks. This represents not only a major time commitment, but also increases the cost of therapy for the patient due to time lost and travel costs.3,4
Therefore, a growing focus on shorter course regimens such as hypofractionated (> 2.0 Gy/fraction) and stereotactic body radiotherapy (SBRT)—5 fractions or less, has emerged.5
While a switch from standard doses per fraction (1.8-2.0 Gy/fraction) to higher doses may seem to be a significant treatment paradigm change, this represents a continuation of research and treatment techniques that have been developed over the past several decades. Previously, radiobiologic studies have documented a low alpha/beta ratio (1.5) for prostate cancer, suggesting a benefit in the therapeutic ratio with increased biochemical control probability in comparison with toxicity to surrounding normal organs with larger doses per fraction (moderate hypofractionation).6
This strategy was initially employed with high dose rate (HDR) brachytherapy as the technique allowed for the highly conformal dose distributions necessary to limit doses to at-risk organs.7