Does Proton Beam Therapy for Prostate Cancer Live Up to Its Promise?

Men diagnosed with prostate cancer are faced with an array of prostate treatment options. Proton beam therapy—a form of external beam radiation therapy—is the latest choice now available in the United States. But it’s a controversial option as well, with some critics suggesting that its popularity may be driven by advertising rather than by sound scientific evidence of benefit over other therapies.

Indeed, advertisements aimed directly at men with prostate cancer often promote proton beam therapy as a cutting-edge alternative treatment. While proton beams may sound like something out of science fiction, in reality, this therapy has been a part of cancer care for more than a half century, used to treat cancers of the brain, head and neck, spine, and eye.

Early on, much of that care was provided in research settings. But with the opening of the first hospital-based proton therapy center in 1990—and promising early results in men with prostate cancer—interest in proton beam therapy has taken off.

As of mid-2016, 20 medical centers in the United States were offering proton beam therapy, and 16 more facilities are under construction or in planning. In spite of the building boom, however, it may surprise you to learn that doctors are not yet sure whether proton beam therapy will live up to its promise—particularly when it comes to adverse effects.

Protons vs. photons

Proton beam therapy is a variation on conventional radiation therapy for prostate cancer. Conventional radiation therapy uses X-rays (also called photons) to destroy tumors. Proton beam therapy, as its name indicates, uses protons to irradiate, or kill, cancer cells. However, protons (positively charged atoms) have certain unique qualities that set them apart from X-rays. And those features allow doctors to target proton beams with greater precision.

Think of the difference between X-rays and protons this way: Imagine that an X-ray is a bullet that enters the body, strikes a tumor, and then exits the body through the other side. Throughout this process, the X-ray releases energy, damaging healthy and malignant tissue alike.

By contrast, doctors can calculate how deep in the body they want a proton beam to fire. That means a proton beam doesn’t exit the body, so it delivers most of its energy in the tumor.

In theory, this pinpoint-targeting ability should make proton beam therapy less likely than conventional radiation treatments to damage healthy tissue in the vicinity of a tumor—damage that can result in side effects such as erectile dysfunction, incontinence, and serious gastrointestinal problems such as bleeding and ulcers.

But few prostate cancer patients receive conventional radiation treatments these days. Over the last decade or so, a more refined version of conventional radiation known as intensity-modulated radiation therapy (IMRT) has become by far the most common method for using X-rays to eradicate prostate tumors. IMRT uses computers to produce three-dimensional images of tumors. Doctors then use these images to irradiate a tumor from many different angles.

Like proton beam therapy, IMRT was designed to limit damage to healthy neighboring tissues. But is one method better than the other at accomplishing this?

How they stack up

Studies have shown that when it comes to eliminating tumors and treating prostate cancer, proton beam therapy works about as well as IMRT. However, relatively little research has been conducted comparing the safety profiles of proton beam therapy and IMRT. One recent study, reported in the Journal of the American Medical Association (JAMA), is helping to provide much-needed clarity.

For the study, investigators analyzed Medicare claims data from nearly 13,000 men treated with radiation for nonmetastatic prostate cancer (that is, cancer that had not spread beyond the prostate) between 2000 and 2009. The men had been treated with conventional radiation, IMRT, or proton beam therapy.

The investigators reported that IMRT was associated with fewer adverse gastrointestinal effects and fewer hip fractures than conventional radiation, but more erectile dysfunction. Overall, there was no significant difference between proton beam therapy and IMRT—with one major exception. Men treated with IMRT were 34 percent less likely than those who had proton beam therapy to develop gastrointestinal problems after their treatments.

This seems to confirm results from an earlier study showing that men undergoing proton therapy had significantly higher rates of gastrointestinal bleeding and ulceration than those receiving other types of radiation.

Why pay more?

Proton beam therapy is significantly more expensive to perform than IMRT (though both are costly procedures). One study found that treating a prostate cancer patient in his 60s or 70s with proton beam therapy costs about $64,000, on average, compared with $39,000 for IMRT. (Medicare and health insurance plans usually cover either treatment, but some insurance companies no longer offer coverage for proton therapy.)

But the JAMA findings raise an important question: All else being equal, if proton beam therapy is more likely than IMRT to produce adverse gastrointestinal effects, why pay the additional cost? Patients aren’t the only ones with a vested interest. Insurers (including Medicare) and hospital administrators have a stake as well.

Setting up a proton beam clinic requires a major investment of space and money. The massive machines that produce protons, known as cyclotrons, cost millions of dollars to build. While proton beam therapy has a role in treating many different forms of cancer, many hospitals that devote resources to these clinics assume that a good number of their patients will be men with prostate cancer. If that assumption is wrong, will they be able to recoup their costs? And if proton beam therapy offers no advantage over a less expensive prostate cancer therapy, why should insurers pay for it?

The only way to demonstrate which treatment is truly associated with a lower risk of side effects is to conduct a large head-to-head clinical trial. Fortunately, such a trial is underway.

Researchers are in the midst of a study that will eventually include more than 400 men with prostate cancer who will receive proton beam therapy or IMRT. The research team will follow the men for several years and track whether they develop side effects, including bowel problems, urinary difficulties, or erectile dysfunction.

By the end of this important trial, which is expected to end in 2018, with data presented soon afterward, doctors should have a better idea about whether proton beam therapy and IMRT live up to the promise of protecting healthy tissue and preventing side effects. For now, however, there is no evidence to support claims that proton beam therapy provides improved cancer-free or quality-of-life outcomes when compared with less expensive alternatives like IMRT and surgery.

What to do in the meantime? “When patients ask about proton beam therapy, I tell them there is no good evidence that protons are any better than photons in curing prostate cancer,” says Phuoc T. Tran, M.D., Ph.D., clinical director of radiation oncology and molecular radiation sciences at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center.

“I always tell patients that if you live near a proton center and your insurance covers the cost of treatment, sure, go for it," Trans says. "On the other hand, I would never recommend that a patient relocate to go to a proton center for prostate cancer treatment. It’s simply not worth the effort or expense.”