July 2011

SBRT for Prostate Cancer
By Beth W. Orenstein
Radiology Today
Vol. 12 No. 7 P. 24

While early results appear promising, critics in radiation oncology say longer-term data are needed before widely offering the treatment to men.

When Accuray’s CyberKnife Robotic Radiosurgery System was introduced in the 1990s, facilities acquired it mostly as an alternative for treating head, neck, and spinal tumors—tumors that would otherwise be difficult, if not impossible, to reach. In 2001, the FDA cleared the CyberKnife system to treat tumors anywhere in the body. Since then, many facilities are offering it as an alternative treatment for other cancers, including of the lung, breast, liver, and prostate, which is the second leading cancer killer among men.

Prostate cancer strikes more than 186,000 men in America each year and kills more than 28,000. CyberKnife treatment—called stereotactic body radiation therapy (SBRT)—is a high-dose radiation treatment. Physicians inject tiny gold fiducial markers into the prostate to help target the beams. The robotic arm swivels around the patient, shooting beams of radiation from multiple angles into the target.

Advocates believe SBRT will revolutionize prostate cancer treatment and that it is a better option because less healthy tissue is affected by the treatment; treatment can be completed in four or five days vs. six to eight weeks; and the treatment is just as effective as external beam radiation therapy or seed implants.

“I believe that CyberKnife treatment is as good, if not better, than conventional treatments for prostate cancer based on low PSA [prostate-specific antigen] levels and low recurrence that we are seeing today and … that it’s only five days makes it even better,” says Alan Katz, MD, of Flushing Radiation Oncology CyberKnife Center in Flushing, N.Y.

A multicenter study of 41 patients (at UCLA and in Naples, Fla., presented in the January 10 issue of the online journal Radiation Oncology) found 93% of patients treated with the CyberKnife system had no cancer recurrence at a median follow-up of five years. The authors indicated the rate compared favorably with results obtained with other treatment modalities, including surgery and conventional radiation therapy.

However, some in the medical community are concerned that finances, not efficacy, is motivating CyberKnife centers to expand the surgery to include prostate cancer treatment, claiming that not enough evidence has been accumulated to show SBRT is even an equivalent treatment.

“The idea of the treatment for patients with low-risk prostate cancer is great,” says Gerald Chodak, MD, a former practicing urologist who writes for Medscape on prostate issues. “If you could treat someone in five days vs. eight weeks and get comparable outcomes, that would be great. But there’s absolutely no proof yet that long-term outcomes are going to be the same.”

The five-year data that were recently presented are positive, Chodak says, but five years is not long-term and until the long-term data are available, he wouldn’t recommend offering SBRT as an option for patients with prostate cancer, which one man in six will get in his lifetime.

Chodak also fears that “money is driving this more than anything else.” Facilities are investing millions in CyberKnife machines and may be expanding to prostate treatments largely to get more use out of them, he says.

Katz has treated more than 700 prostate cancer patients with the CyberKnife system—more than anyone else in the world, he says. While he doesn’t have as much five-year data as the authors of the Radiation Oncology study, he has hundreds of patients with four-year data that he presented at the annual American Society of Radiology Oncology (ASTRO) meeting last year. He has been accepted to present his updated data at the ASTRO 2011 meeting in October.

“What we’re seeing,” he says, “is that if you treat with CyberKnife … you can get control rates that are better than standard IMRT [intensity-modulated radiation therapy] at four-year follow-up.”

The CyberKnife system delivers roughly quadruple the usual dose of radiation per day and about one-half as much total compared with a standard course of IMRT. “If you’re going to give large doses, you want to give it accurately and want the dose to be conformal, to hug the prostate, and to give as little as possible to surrounding healthy structures,” Katz says. “Using the CyberKnife, we’ve been able to accomplish both.”

Katz says he doesn’t necessarily need 10-year data to be convinced CyberKnife is a valuable alternative. “This is because data from the use of radioactive seeds shows that low PSA nadirs are an excellent predictor of 10- to 15-year outcomes. Why wouldn’t the results be applicable to other forms of radiation such as SBRT? Our four-year data shows median PSA nadirs of 0.1 following treatment with CyberKnife; that’s lower than levels following IMRT. To me, that’s a good indicator that we will have positive long-term outcomes.”

PSA levels are important for various reasons, Katz notes. One reason is if a patient’s PSA level goes up, it could prompt additional biopsies and treatments, he says.

If SBRT can achieve similar results but the treatments require only 45 minutes per day for four or five days—rather than spread over six to eight weeks—that alone makes it a better alternative for men, especially those in their 50s and 60s who are more likely to be working and have less time to devote to the longer course of treatment, Katz says.

Katz’s research has shown that about 80% of CyberKnife patients retain sexual potency, which is higher than with other treatments, and that urinary and bowel side effects are also very mild. “These are very important considerations when patients weigh their treatment options,” Katz says. Side effects of radiation treatment can include incontinence, bleeding, problems urinating, and impotence.

Katz also says CyberKnife treatment costs less than conventional radiation treatments. So the argument that radiation oncologists are pushing it to make money is hollow, he says.

“If treatments are much cheaper, you can’t just let someone say this is about money,” he says.

Citing Medicare’s 2011 global number, Katz points out that CyberKnife treatment in a hospital setting averages $21,917, while treatment with IMRT in a hospital costs on average $26,806. Medicare and private insurers in many parts of the country cover the cost of the treatment; however, some insurers have taken a wait-and-see attitude and do not.

Dwight Heron, MD, FACRO, chairman of the department of radiation oncology at the University of Pittsburgh Medical Center (UPMC) Shadyside, an early adopter of the CyberKnife system, finds the recently released five-year data for prostate cancer encouraging.

“The five-year data says to us the outcomes are not inferior to the other modalities and indeed are superior to some,” he says. “It offers us encouraging data that this shorter course is no worse in toxicity and certainly no worse in outcomes, and that’s really good news.”

Heron says he would like to see seven- to 10-year data on the effectiveness of CyberKnife for prostate cancer, especially because prostate cancer is typically slow growing, but believes the information will eventually come.

“I think it’s only a matter of time before that data emerges as well,” he says.

 If the outcomes are equal, he adds, many men may prefer CyberKnife because it requires only a week of their time. “Lots of men tell me they’re professionals—lawyers or businessmen—and they can’t afford to be away for eight weeks of treatment,” he says. When he presents them with their treatment options, “That’s a conversation we often have.” Also, he says, if the treatment is quicker, it means the side effects of the radiation may resolve more quickly, which is important to many patients, especially those who are still working.

However, Chodak, author of the book Winning the Battle Against Prostate Cancer, who recently had a urology practice in Chicago and now spends his winters in Florida and summers in Indiana, believes the five-year data on CyberKnife for prostate cancer are being made to seem better than they are.

“The short-term outcomes are being interpreted as a predictor for long-term outcomes,” he says, “and you can’t legitimately make that leap.”

Chodak provides an example of why short-term outcomes are not reliable predictors of long-term outcomes: A randomized study done in Australia and New Zealand looked at men with early-stage prostate cancer and compared those who were treated with radiation alone with those who had radiation and hormone therapy for three months and those who had radiation and hormone therapy for six months.

“They found that those who had six months of hormone therapy had a higher survival than the other two groups,” Chodak says, “but those getting only three months of hormones had a similar PSA recurrence rate and metastatic rate as those getting longer therapy. If only the PSA data was considered, the wrong conclusion would be reached, namely that three months is as good as six months of hormone therapy.”

Chodak says he’s surprised the five-year study did not include information about the impact of SBRT on sexual function. (CyberKnife proponents say the information wasn’t included because it wasn’t the focus of the report and that these data will be in future studies.)

Chodak says he can see the potential benefits for patients in terms of convenience, as the CyberKnife treatment takes much less time than standard radiotherapy. Still, he says, he’s not convinced the data are there for physicians to be able to tell patients it is a comparable treatment. “Five years of results in a series of 41 patients treated for low-risk disease means very little,” he says.

It’s possible, he says, that because prostate cancer is slow growing, many of these men don’t need to be treated at all. Long-term survival is the outcome that matters the most, he says, particularly for men with low-risk prostate cancer. He believes it’s too soon for prostate cancer patients to be offered CyberKnife as a treatment option.

Rohit Inamdar, a senior medical physicist and senior associate in the Applied Solutions Group at the ECRI Institute in Plymouth Meeting, Pa., a nonprofit organization that evaluates medical products and processes, agrees with Chodak that the clinical evidence on the use of the CyberKnife for prostate cancer is “a little early … and a little weak. It’s still developing and cannot stand on its feet.”

Inamdar is also concerned about the financial issues. Some physicians might be presenting CyberKnife as an option for their patients because they’ve invested $5 million in the equipment and can’t afford to have it sit idle, he says.

“One fear I have is that it’s like a hammer looking for the nails,” Inamdar says. “If you paid $5 million for it and you’re paying for staff, now you have to put it to use.”

However, Inamdar says the controversy that’s been brewing over the use of CyberKnife for prostate cancer may be out of proportion to its use. While the use of the CyberKnife for prostate cancer has received a lot of media attention recently, its use is not as widespread as the stories make it seem, he explains.

“A couple months ago, there was a survey done by the University of California in San Diego. It was sent to 1,600 radiation oncologists and 550 responded. Most said they were using it to treat lung cancers (90%), spine tumors (68%), and liver tumors (55%). Only 8% reported using it to treat prostate cancer,” he says. “There’s all this media hype over the use of CyberKnife for prostate cancer, but what are facilities actually doing? The numbers using it to treat prostate is actually very small—less than 10%.”

Although watchful waiting is an alternative treatment for low-risk cancers, many men want to treat their prostate cancer, Inamdar says. At most radiation therapy facilities, he says breast cancer and prostate cancer are the bread and butter.

“But,” he adds, “it seems as though in the SBRT world, it’s a little different.”

— Beth W. Orenstein is a freelance medical writer based in Northampton, Pa. She is a frequent contributor to Radiology Today.