Scanning the Horizon: Advances in Radiation Treatment for Prostate Cancer

After James Levy finished his high-dose-rate (HDR) brachytherapy to treat his localized prostate cancer, he celebrated by getting a tattoo that included the StandUp2Cancer logo, the date his treatment ended and the word “radioactive.” It was his way of acknowledging his successful treatment with this relatively new approach.

“I’m a big fan of HDR brachytherapy,” says Levy, of Richmond, Va. “I went in Friday and was back at work on Monday. There was nothing to it.”

HDR brachytherapy, which involves placing strong sources of radioactivity in or near the cancerous tissue for a few minutes and then removing them, joins other, more established forms of radiation as a treatment option.

These techniques include one other type of brachytherapy and many forms of external beam radiation therapy (EBRT), which sends beams of radiation into the prostate from outside the body. In addition, for men whose prostate cancer has metastasized to the bone, a fairly new radiopharmaceutical is available. These approaches give patients a variety of choices if they select radiation treatment as either a first-line or follow-up therapy.

The common variable that internal and external radiation share is their increasing ability to deliver higher doses to the prostate while reducing exposure to nearby healthy tissues. Nonetheless, the treatments can cause side effects, including temporary fatigue or later development of permanent urinary incontinence, bowel problems and erectile dysfunction, among others.

For Levy, 57, who completed treatment about a year ago, side effects have not been an issue. “I’ve had none of the common long-term effects, like incontinence, erectile dysfunction or bowel issues,” says Levy. This is likely because of HDR’s ability to direct radiation specifically at the tumor and avoid nearby tissue and organs — and its short duration.

To treat his localized prostate cancer, James Levy chose high-dose-rate brachytherapy, and has not experienced any long-term side effects. [Photo by Liza Bishop, VCU Massey Cancer Center]

While that outcome is compelling, HDR may not be right for everyone. In fact, sifting through possibilities to arrive at the best radiation option for each patient can be challenging, says James B. Yu, a radiation oncologist at Yale University School of Medicine in New Haven, Conn. The decision, he says, is as individual as the man and his cancer.

“It depends on what you’re looking at — cure rates or complications,” he says. “Patients care about some complications more than others, such as erectile dysfunction, so the choice of treatment is intensely personal.”

Questions about the relative value of newer radiation methods may, in particular, give men pause.

For instance, in administering EBRT, “Physicians are looking at shortening the number of radiation treatments by increasing the dose per treatment,” Yu explains. He says there continues to be concern that giving more intense radiation treatments, even if there aren’t as many, could be more toxic overall. Adding to the confusion is that current research is mixed, highlighting “the complexity of comparing these treatments and saying that one is better than the other.”

When is Radiation Appropriate?

Yu urges patients to learn as much as they can about the pros and cons of various treatments before making a decision, and to discuss any questions they might have with their health care providers. Levy agrees, adding that “the Internet makes it possible to become really well-informed.”For men with localized prostate cancer (meaning it hasn’t spread outside the gland), often the first step after diagnosis is choosing between active surveillance (particularly for lower-grade tumors, as indicated by the level of prostate-specific antigen [PSA] in a man’s blood and the Gleason score doctors use to describe aggressiveness); surgery to remove the prostate gland (called a radical prostatectomy), or radiation therapy. If a man has localized prostate cancer and plans to undergo treatment, he should know that surgery and radiation are considered equally effective when it comes to preventing the advancement of the disease, according to the American Cancer Society (ACS).

One option for men with locally advanced prostate cancer (in which lymph nodes or other nearby tissues are involved) is radiation therapy plus hormonal therapy, which several studies have shown is more effective at fighting the cancer than hormonal therapy alone. In addition, men with this condition and a higher risk of recurrence should be informed that radiation therapy after a radical prostatectomy decreases their risk of cancer recurrence or progression, according to national guidelines issued in May 2013. Issued jointly by the American Society for Radiation Oncology and the American Urological Association, the guidelines also state that doctors should offer “salvage radiotherapy” to patients whose PSA levels rise, or who have a local recurrence after prostatectomy but show no evidence of distant metastases.

Many Types of EBRT

In 2015, the National Comprehensive Cancer Network (NCCN) issued new guidelines for patients. These guidelines recommend EBRT as a staple of treatment for men with various stages of the disease: as a first-line treatment for those at low risk for developing metastatic disease and who are expected to live 10 years after diagnosis; as a first-line or adjuvant therapy for many categories of men at intermediate risk, and for many groups of men with high-risk disease.Most radiation options fall under the umbrella of EBRT, which is typically administered over a seven- to nine-week period, according to the ACS. Among EBRT therapies, intensity modulated radiation therapy (IMRT) is the most common and has been adopted extensively over the past 15 years. This approach uses a machine that moves around the patient, shaping the beams and aiming them from several angles. In this way, the dose of radiation can be adjusted, directing higher doses to the places where there are cancerous cells.

Other high-tech options include three-dimensional conformal radiation therapy (3D-CRT), image-guided radiation therapy and intensity-modulated arc therapy. The shared element among these therapies is a careful mapping of the exact size, shape and location of the prostate gland and tumor using imaging tests, such as computed tomography and magnetic resonance imaging scans or X-rays. This information helps doctors determine precisely where to aim higher and lower doses of radiation for maximum effectiveness and minimum side effects. One recent comparative study showed that IMRT offers a disease-control advantage over 3D-CRT.

Stereotactic body radiation therapy (SBRT), which is often referred to by the names of the machines that administer the radiation, including CyberKnife, Gamma Knife and X-Knife, is a form of EBRT that delivers large doses of radiation to the prostate. Although the benefit of SBRT is that its entire treatment course is days and not several weeks, some studies have shown side effects to be worse with this form of therapy.

Another promising, yet controversial, form of EBRT is proton beam therapy, which aims protons (the heavy, positive parts of atoms) at tumors and releases their energy after traveling a specific distance, thereby causing less damage to tissues they pass through. Although research is inconclusive about whether proton therapy reduces sexual complications, one study did find that men aged 60 or younger treated with this modality experienced little sexual dysfunction; in comparison with the findings of other studies cited in the paper, the amount of dysfunction was comparable to that in populations treated with EBRT in general, but better than that in men treated with prostatectomy.

LDR AND HDR Brachytherapy Round Out Options

But other research has suggested limited advantages of proton therapy. A 2012 study comparing IMRT with proton therapy found that the newer therapy was no more effective in getting cancer in check. In addition, experts warn that proton beam therapy is not only more expensive than other forms of radiation (primarily due to costly machinery), but also might not be the best choice to treat prostate cancer because “critical structures, such as the rectum and urethra, will still get radiation no matter how perfect your particle is,” Yu explains.Men with early stage, slow-growing tumors who would prefer fewer radiation treatments — or even just a single treatment — might be candidates for traditional brachytherapy, which places radioactive seeds directly, and permanently, into the prostate gland during a short surgical procedure. Radiation is then delivered slowly, for months, at a low-dose rate (LDR); eventually, the seeds lose their radioactivity.

HDR brachytherapy, a newer approach, is administered through temporary catheters, in which a high-activity source is placed for just minutes to deliver HDR radiation.

[Photo by Liza Bishop, VCU Massey Cancer Center]

Experts have placed some caveats on these treatments. Current guidelines from the NCCN recommend that brachytherapy as a standalone treatment be limited to low-risk or intermediate-risk cases. And for now, HDR is usually reserved for cancers that are progressing.

“Only when you need to deliver a big radiobiological punch — like when the disease is aggressive — do you go with HDR, typically not for early-stage prostate cancer,” says Dorin Todor, director of the brachytherapy program at Virginia Commonwealth University’s Massey Cancer Center in Richmond. “I think this is where brachytherapy combined with EBRT really shines.

These rules of thumb may be changing, though. According to Todor, “There are ongoing clinical trials trying to prove the equivalence between LDR treatments and one large fraction of HDR for early-stage prostate cancer. Both have the advantage of being a ‘one-stop shop,’ but during HDR, radiation is delivered for only 10 to 15 minutes, as opposed to months or years.”

Radiation can also be delivered directly to bone metastases via radiopharmaceuticals — drugs that contain radioactive elements — in patients with advanced prostate cancer. These drugs are a particularly useful approach when multiple areas of bone are involved. They can shrink painful lesions and improve quality of life with less exposure to normal tissue.

In May 2013, the U.S. Food and Drug Administration approved Xofigo (radium-223) to treat bone metastases, and a study published in July 2013 in The New England Journal of Medicine showed that those receiving Xofigo had improved median overall survival (14.9 months) compared with those on placebo (11.3 months).

Although there are many radiation treatment options, with the guidelines continuing to evolve, Levy is pleased that he chose HDR brachytherapy for his localized tumor.

“I didn’t want to take any chances,” he says. “Two days of treatment meant that I would likely not have any problems down the road.”