By Daniel Spratt, MD, and Timur Mitin, MD, PhD
Prostate cancer is diagnosed in more than one million men worldwide each year. In countries with PSA screening, over 90% of cases are diagnosed when they are localized. The two most common treatments are radiation therapy and surgical removal of the prostate. One of the reasons men select surgery is the logistical barrier to undergo radiation therapy for eight to 10 weeks of daily, low-dose radiation therapy treatments (39 to 48 treatments). This can be a huge barrier for patients, especially those who are working, live a distance away, or have financial barriers to commute that often.
Fortunately, technology has improved over the past 30 years, and now there is increasing high-level evidence and guideline support to treat prostate cancer with many fewer treatments. This form of radiation therapy is often termed ultra or extreme hypofractionation, simply meaning fewer fractions of radiation therapy. More than 40 clinical trials have been published on this newer form of radiation therapy, including two large randomized trials. Nearly all the trials have used between four and seven fractions of radiation therapy, with the most common regimen being just five treatments. This is commonly termed stereotactic body radiation therapy (SBRT) or stereotactic ablative body radiotherapy (SABR).
To summarize the evidence of the >6,500 men who have been treated on trials using SABR, grade ≥3 toxicity is typically 0-2%, even with long-term follow-up, and appears to have equal or potentially superior tumor control when compared to conventional radiation therapy. Patients do not require anesthesia or any invasive procedure, as required with surgery or brachytherapy, and the logistical burden is minimal with just five outpatient treatment visits. Additionally, it costs less money to deliver SABR than conventional radiation therapy, uses less resources for departments, and is substantially more convenient for patients. For this reason, SABR is now considered “a” standard of care in National Comprehensive Cancer Network (NCCN) guidelines and used routinely in countries like the United States and Canada at centers capable of delivering the treatment. Recent estimates show 15-20% of patients who are treated with external beam radiation therapy receive it as SABR in the U.S.
Financial considerations unquestionably influence practice patterns, and radiation oncology is no exception. Historically, hypofractionation has been met with lukewarm enthusiasm among practices that bill per fraction. However, in the era of bundled payments that is rapidly approaching, fewer fractions may become more profitable as clinics will be able to treat a greater number of patients or reduce resource utilization. SBRT today in the U.S. is defined by insurance companies as a radiation treatment course with five or fewer fractions. Giving six fractions of the same radiation therapy plan means that the SBRT billing code no longer can be used, even if every single other aspect of the treatment was identical. Thus, six and seven fractions pays less than five fractions because of arbitrary billing code nomenclature. Next year, many centers will receive a set amount of reimbursement for a treatment course, no matter what the treatment is called. Widmark et al. have established a seven-fractions course of EBRT for men with both intermediate and high-risk prostate cancer as non-inferior to conventionally fractionated EBRT, with no rectal spacers and largely with 3-D planning. This regimen may indeed be the most cost-effective randomized trial-proven prostate-directed radiation therapy option for clinics to consider in the era of bundled payment.
We are all patiently waiting for the maturation and completion of Phase III trials, such as PACE-B and NRG GU005, respectively. If the results of these trials demonstrate similar efficacy and toxicity of SABR compared to older forms of radiation therapy at ≥5-years of follow-up, SABR will likely be deemed “the” standard of care for the treatment of localized prostate cancer. Other ongoing areas of investigation include the role of SABR for men with high-risk disease, and promising prospective data has been published from multiple groups demonstrating the safety and efficacy of this approach, even with simultaneous treatment of the pelvic lymph nodes. Finally, in Europe they are comparing SABR head-to-head to surgery. This will be a very informative trial to determine the difference in side effects and quality of life with modern non-invasive SABR compared to surgery.
The bottom-line: Prostate SBRT is here, and we anticipate it will only become increasingly utilized in the U.S. given the convergence of prospective and new level one evidence and financial incentives from the new bundled payment model. We anticipate that learning to safely deliver prostate SBRT will become very important in the not too distant future.
Daniel Spratt, MD, is an associate professor, Laurie Snow Endowed professor, associate chair for Research, and chair of the Genitourinary Clinical Research Division at the Rogel Cancer Center at University of Michigan.
Timur Mitin, MD, PhD, is an associate professor at Oregon Health and Science University. Dr. Mitin co-authored a recently published Red Journal article, SBRT for Localized Prostate Cancer: Is it Ready for Take-Off? on which this blogpost is based.