For prostate cancer patients, intensity-modulated radiation therapy (IMRT) may offer better disease control than standard radiation therapy, but proton therapy won’t provide additional benefits, researchers found.
Men who had IMRT were less likely to need additional cancer therapy (RR 0.81, 95% CI 0.73 to 0.89), Ronald Chen, MD, MPH, of the University of North Carolina at Chapel Hill, and colleagues reported in the April 18 issue of the Journal of the American Medical Association.
They were also less likely to have gastrointestinal comorbidities (RR 0.91, 95% CI 0.86 to 0.96) and hip fractures (RR 0.78, 95% CI 0.65 to 0.93) than those who had conformal radiation therapy, although they were more likely to have erectile dysfunction (RR 1.12, 95% CI 1.03 to 1.20).
“Taken together, these results suggest that IMRT facilitated radiation dose escalation without compromising acceptable long-term morbidity,” they wrote.
Those who had proton therapy, on the other hand, didn’t gain any advantages over IMRT patients in terms of mortality or additional cancer therapy—but they did have a higher risk of gastrointestinal morbidity, the researchers found.
“Overall, our results do not clearly demonstrate a clinical benefit to support the recent increase in proton therapy use for prostate cancer,” they wrote.
What is Intensity-Modulated Radiation Therapy and how is it used?
Intensity-modulated radiation therapy (IMRT) is an advanced mode of high-precision radiotherapy that utilizes computer-controlled linear accelerators to deliver precise radiation doses to a malignant tumor or specific areas within the tumor. IMRT allows for the radiation dose to conform more precisely to the three-dimensional (3-D) shape of the tumor by modulating – or controlling – the intensity of the radiation beam in multiple small volumes. IMRT also allows higher radiation doses to be focused to regions within the tumor while minimizing the dose to surrounding normal critical structures. Treatment is carefully planned by using 3-D computed tomography (CT) or magnetic resonance (MRI) images of the patient in conjunction with computerized dose calculations to determine the dose intensity pattern that will best conform to the tumor shape. Typically, combinations of multiple intensity-modulated fields coming from different beam directions produce a custom tailored radiation dose that maximizes tumor dose while also minimizing the dose to adjacent normal tissues.
Because the ratio of normal tissue dose to tumor dose is reduced to a minimum with the IMRT approach, higher and more effective radiation doses can safely be delivered to tumors with fewer side effects compared with conventional radiotherapy techniques. IMRT also has the potential to reduce treatment toxicity, even when doses are not increased. Due to its complexity, IMRT does require slightly longer daily treatment times and additional planning and safety checks before the patient can start the treatment than conventional radiotherapy.
Currently, IMRT is being used most extensively to treat cancers of the prostate, head and neck, and central nervous system. IMRT has also been used in limited situations to treat breast, thyroid, lung, as well as in gastrointestinal, gynecologic malignancies and certain types of sarcomas. IMRT may also be beneficial for treating pediatric malignancies.
Radiation therapy, including IMRT, stops cancer cells from dividing and growing, thus slowing or stopping tumor growth. In many cases, radiation therapy is capable of killing all of the cancer cells, thus shrinking or eliminating tumors.
There’s been rapid adoption of newer radiation treatments for prostate cancer, including both IMRT and proton therapy—even though these technologies cost more, and researchers say the evidence backing their use is lacking.
IMRT was developed to deliver higher radiation doses to the prostate while sparing those to surrounding organs. Despite a lack of comparative data, there has been almost complete adoption of IMRT for prostate cancer, the researchers said.
It’s also unclear as to what advantages proton therapy could convey beyond IMRT, they noted, though the idea is also to minimize collateral radiation damage.
There are several ways IMRT differs from conventional radiation therapy:
– Employs a powerful, advanced software to plan a precise dose of radiation, based on tumor size, shape and location.
– Delivers prostate cancer radiation in sculpted doses that match the exact 3D geometrical shape of the tumor, including concave and complex shapes.
– Adjusts the intensity of radiation beams across the treatment area as needed with laser accuracy.
Because of its greater degree of accuracy, IMRT may be a treatment option if you have reached the maximum allowable dose of prostate cancer radiation therapy and have a recurrent tumor in the treated area.
Several groups have called for comparative effectiveness research of the therapies because of the large number of men with the disease and because the trend toward expensive, unproven therapies is likely to continue, the researchers said. The use of IMRT versus conformal radiation therapy, for instance, increased from 0.15% in 2000 to 95.9% in 2008.
For their comparisons, the researchers looked at data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database from 2000 through 2009 for patients with nonmetastatic prostate cancer.
Proton therapy wasn’t associated with any improvements over IMRT in terms of urinary incontinence, erectile dysfunction, hip fractures, or the receipt of additional cancer therapy—and appeared to carry a higher risk of gastrointestinal problems.
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A propensity score-matched comparison showed IMRT patients had a lower rate of gastrointestinal morbidity (RR 0.66, 95% CI 0.55 to 0.79).
They concluded that the results suggest IMRT is associated with fewer comorbidities—with the exception of erectile dysfunction—than standard radiation therapy, and that proton therapy doesn’t offer any additional benefits.
The study was limited by its use of claims data, which are subject to reporting bias, although the researchers noted that a comparative trial between IMRT and proton therapy would require many years to provide results and the SEER-Medicare data represent “an important data source with an established methodology for comparative effectiveness research.”
Prostate Cancer Information: External Radiation Treatment
Newer forms of radiation treatment work to escalate tumor dose and minimize toxicity to healthy surrounding tissue. Advanced radiotherapy techniques include three-dimensional conformal radiotherapy (3D-CRT), intensity modulated beam radiation therapy (IMRT), image-guided radiation therapy (IGRT), intra-operative radiation therapy (IORT), proton beam radiation therapy (PBRT), tomotherapy, systemic radiation therapy, radioimmunotherapy (RIT), and hypofractionated radiation therapy.
What is Radiation Therapy for Prostate Cancer?
There are three ways radiation may be delivered to prostate cancer patients: by a machine outside the body (external beam radiation therapy), by placing radioactive materials inside the body (internal radiation therapy or brachytherapy), and by ingesting radioactive substances (systemic radiation therapy). External therapy has been in practice longer than brachytherapy. This treatment is often referred to as radiotherapy. EBRT has been so commonly used that EBRT and radiation therapy are sometimes used interchangeably.
ProCure Treatment Centers, a group of centers that offers proton beam therapy, sent a statement to reporters calling attention to several studies “that evaluate actual patient experience rather than stats from a database” and contradict the findings by Chen and colleagues.
The statement said these studies show that gastrointestinal and other side effects are “consistently less or essentially comparable” with IMRT.
Louis Potters, MD, chair of radiation medicine at North Shore University Hospital and Long Island Jewish Medical Center in N.Y., who was not involved in the study, said in a statement that it’s “good to see that this study affirms the use IMRT to reduce side effects and to reduce the risk of additional therapy.”
“Patients have a propensity toward ‘new’ and ‘expensive’ care, and while the role of proton beam therapy still requires more study, these results significantly question [its] value for prostate cancer,” he added.
Potters also lamented the fact that brachytherapy for prostate cancer wasn’t included in the analysis, even though the data is “at least as good, if not better, than for IMRT.”
The study was supported by the Agency for Healthcare Research and Quality and the National Institute of Nursing Research.
The researchers reported relationships with Degarelix and GlaxoSmithKline.
Primary source: Journal of the American Medical Association
Source reference: Sheets NC, et al “Intensity-modulated radiation therapy, proton therapy, or conformal radiation therapy and morbidity and disease control in localized prostate cancer” JAMA 2012; 307(15): 1611-1620.
