Secondary Logo

Journal Logo

Proton Boost Cuts Risk of Prostate Cancer Recurrence in Low- and Intermediate-Risk Patients with Minimal Side Effects

Laino, Charlene

doi: 10.1097/01.COT.0000365664.41061.78

CHICAGO— A boost of proton-beam therapy may prevent prostate cancer recurrence in low- and intermediate-risk patients, suggests a study of nearly 400 men presented here at the American Society for Radiation Oncology (ASTRO) Annual Meeting.

“This first-of-its-kind study provides evidence of the benefits of giving high-dose proton-beam radiation doses to low- and intermediate-risk prostate cancer patients. It is safe, effective, and has minimal side effects,” said lead researcher Carl J. Rossi Jr., MD, Associate Professor of Radiation Medicine at Loma Linda University in California.

The study, known as Proton Radiation Oncology Group/American College of Radiology 95-09, was designed to determine whether giving an extra boost of proton-beam therapy after a standard course of radiation would improve outcomes.

“We've known for decades that the ability to destroy prostate cancer cells depends on the dose. The higher the dose, the greater the chance of success, but also the greater risk of side effects,” Dr. Rossi said.

“We asked the question, can we give a higher dose to the prostate by using a proton beam, improving the chance of success without compromising safety.”

The proton-beam accelerator more precisely delivers radiation to the target than conventional photon-beam radiotherapy does, he explained. The properties of protons allow radiation oncologists to deliver a more homogenous dose to the tumor, while reducing radiation to surrounding tissue.

In the study reported by NANCY P

In the study reported by NANCY P

“The delivery method is critical. With proton-beam therapy, we have exquisite control over where the radiation goes. We can design the field so the vast majority of radiation goes right to the target, which lets us increase the dose by several orders of magnitude, compared with conventional photon x-rays.”

Back to Top | Article Outline

Boost Benefits Low-Risk Patients

To be eligible for the new trial, men had to have Stage T1b-2b disease and a PSA level of 15 ng/mL or less.

The 393 participants all received 50.4 Gy of 3-D conformal photon radiotherapy, and were then randomized to receive either a 19.8 Gy or 28.8 Gy boost of proton radiotherapy to the prostate. “In other words, one group received a conventional 70 Gy dose of radiation and the other group received a total 79 Gy, or high-dose radiation,” Dr. Rossi said.

Of the total, 227 patients (58%) were classified as being at low risk for recurrence, based on Gleason scores, PSA levels, and disease stage. Another 144 (37%) were classified as intermediate-risk, and 17 (5%) were classified as high-risk patients.

After 10 years of treatment, 6.1% of low-risk men treated with high-dose radiotherapy suffered a biochemical recurrence, compared with 29.0% of low-risk men receiving conventional-dose radiotherapy. The difference was highly statistically significant, with a p value of 0.0001, Dr. Rossi said.

Among the intermediate-risk men, the 10-year biochemical failure rate was 28.6% for the high-dose group vs 37.0% for the conventional-dose group. The difference trended in favor of the arm that received the extra proton boost.

Overall survival rates were similar among the two groups: 83.4% for the high-dose arm and 78.4% for the conventional-dose group. Noting the trend toward improved survival rates in the arm that got the extra boost, Dr. Rossi said that might change with longer follow-up.

Eleven percent of patients in the conventional-dose group required subsequent androgen-deprivation therapy to prevent recurrences vs 6% in the high-dose group.

“High-dose conformal therapy was associated with about a 50% reduction in the chance of receiving subsequent androgen-deprivation therapy,” Dr. Rossi said.

Back to Top | Article Outline

Side Effects

About 2% of patients in both groups had late urinary or rectal complications of Grade 3 or higher. “Dose escalation was achieved without any significant increase in Grade 3 or higher gastrointestinal or genitourinary toxicities,” Dr. Rossi said.



A second study presented at the meeting confirmed the safety of the technique. The researchers followed 212 men enrolled in one of three prospective trials of proton therapy for at least one year.

“Fewer than one percent of patients suffered Grade 3 genitourinary side effects, and less than one-half of one percent suffered Grade 3 GI toxicities,” said Nancy P. Mendenhall, MD, Professor of Radiation Oncology at the University of Florida, adding that most of the patients who did had pretreatment conditions that might have predicted for these side effects.

Back to Top | Article Outline

Still Hotly Debated

Based on conversations with oncologists attending the meeting, though, despite the positive findings of both studies the role of proton-beam therapy in the future treatment of prostate cancer patients is still a hot topic of debate.

Dr. Rossi said he believes that proton-beam therapy will become the radiation treatment of choice for prostate cancer over the next decade. The bottom line, he said, is that “high-dose conformal radiation therapy delivered via a conformal proton-beam boost conveys a long-term advantage in terms of reducing the rate of biochemical failure for patients with low- and intermediate-risk prostate cancer.”

Said Farzan Siddiqui, MD, PhD, a radiation oncologist at Henry Ford Hospital in Detroit, who was not involved with either of the studies: “The Holy Grail of radiation oncology is to deliver more radiation to the target and spare healthy tissues and organs, and this is the promise we are seeing with proton therapy.”

But Alan Pollack, MD, PhD, Chair of Radiation Oncology at the University of Miami, said, “Many of us do not think proton-beam therapy will be the standard in the future.”

Noting that it is very expensive, he said that it does not offer “real advantages in terms of control and side effects,” compared with conventional forms of radiation.

Currently, only about six medical centers in the United States, including Loma Linda and the University of Florida, have proton therapy capabilities, but several other facilities are opening up in the near future, Dr. Mendenhall said.

While the treatment can be expensive—up to 50% more than conventional radiation therapy—she said she expects costs to come down as availability rises.

Dr. Siddiqui agreed and pointed to laptop computers as a case in point. “When those computers were first on the market, they cost around $5,000. But [now years later] you can get devices that are more compact and much more powerful for about $200.”

ASTRO 2009–2010 President Anthony L. Zietman, MD, the Jenot W. and William U. Shipley Professor of Radiation Oncology at Harvard Medical School, said he remains unsure about what the role of proton beam therapy will become.

“It is very expensive, but that could change. On other hand, we don't have long-term data on side effects, and most complications of radiation don't show up until years down the line. Also, there are other ways to deliver extra radiation beside proton beams. We're just going have to wait and see.”

There is also the role in other cancers to consider, said William M. Mendenhall, MD, Professor of Radiation Oncology at the University of Florida and Dr. Nancy's Mendenhall's husband.

He told OT that he thinks proton-beam therapy will prove useful for pediatric patients with solid brain or skull-based tumors, where targeted delivery of radiation is essential.

© 2009 Lippincott Williams & Wilkins, Inc.
Home  Clinical Resource Center
Current Issue       Search OT
Archives Get OT Enews
Blogs Email us!