Proton Therapy Boost Reduces Prostate Cancer Recurrence

Nick Mulcahy

November 10, 2009

November 10, 2009 (Chicago, Illinois) — Proton-beam therapy will replace conventional radiation in the curative treatment of cancer in the next 10 to 15 years, said one enthusiastic proponent of the technology during a press conference here at the American Society for Radiation Oncology (ASTRO) 51st Annual Meeting.

Dr. Carl Rossi (Courtesy of ASTRO)

The proponent is Carl Rossi, MD, from Loma Linda University in California, which is 1 of 6 institutions in the United States with a proton-beam accelerator. Dr. Rossi explained that the protons allow for more precise delivery of radiation to a target than conventional radiotherapy. Proton-beam therapy reduces the amount of normal tissue that is affected by treatment, he said. Dr. Rossi said that his prediction about proton therapy echoes that of another prominent radiation oncologist, Herman Suit, MD, from Massachusetts General Hospital in Boston.

Will proton beam therapy be the standard in the future? Many of us think not.

"This is a hot topic of debate," said another ASTRO presenter, Alan Pollack, MD. "Will proton-beam therapy be the standard in the future? Many of us think not," he said, when asked about the therapy by Medscape Oncology. "We are not seeing clinical superiority with it," said Dr. Pollack, who is from the University of Miami in Florida, which does not have a proton-beam accelerator.

Skepticism about the use of proton-beam therapy for treating prostate cancer was also expressed in several comments in response to a Medscape blog on the topic earlier this year.

"Proton beam is phenomenally expensive," said Anthony Zietman, MD, the incoming president of ASTRO and a clinician at Massachusetts General Hospital, which has a proton-beam accelerator. "It's hard to justify because we are not seeing clinical superiority. But that may change," Dr. Zietman added.

Boost vs Extra Boost Study in Prostate Cancer

The clinical superiority of receiving an extra boost of proton therapy can be seen in a study of 393 men with localized prostate cancer being studied at Loma Linda and Massachusetts General Hospital, suggested Dr. Rossi.

The new study, known as Proton Radiation Oncology Group/American College of Radiology 95-09, set out to test the hypothesis that increasing radiation dose above conventional levels for men with localized prostate cancer will improve outcomes, he said.

The patients were randomized to 2 groups, both of which received 50 Gy of 3-D conformal photons and a 20 Gy boost of proton therapy. In addition, 1 group received an extra boost of proton therapy (9 Gy). Thus, there was a group that received a conventional dose of radiation (70Gy) and one that received high-dose radiation (79 Gy).

At 10 years, among low-risk men, 6% of the men treated with high-dose radiotherapy had biochemical recurrence, as did 29% of those receiving conventional-dose radiotherapy (P = .0001).

At 10 years, among intermediate-risk men, 37% of the high-dose group had biochemical recurrence, as did 45% of the conventional-dose group (P = .0581).

We are seeing a trend toward improved overall survival in the proton beam boost group.

"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," concluded Dr. Rossi at his presentation.

However, there was no significant difference in overall survival, which was a secondary outcome in the study, between the high-dose and conventional-dose groups (83.4% vs 78.4%; = .41), said Dr. Rossi. Nevertheless, that might change, he suggested. "We are seeing a trend toward improved overall survival in the boost group."

No Increase in Grade 3 or Higher Toxicities

The new study required that participants have clinical stage T1b-2b disease and a prostate-specific antigen level of 15 ng/mL or less. Enrollment ended in 1999.

The median follow-up for surviving patients was 8.9 years. There were 227 low-risk (58%), 144 intermediate-risk (37%), and 17 high-risk (4%) patients.

As noted above, the 2 randomized groups received identical treatments, with 1 exception: one group (n = 196) received an extra proton boost and the other group (n = 197) did not.

Eleven percent of the patients subsequently required androgen deprivation for recurrence in the conventional-dose group, as did 6% in the high-dose group (P = 0.047). "High-dose conformal therapy was associated with about a 50% reduction in the chance of receiving subsequent androgen-deprivation therapy," summarized Dr. Rossi.

A total of 2.1% of patients in both groups experienced late urinary or rectal toxicity of at least grade 3. "This conformal dose escalation was achieved without any associated increase in grade 3 and above [gastrointestinal/genitourinary] morbidity," said Dr. Rossi.

The cumulative incidence of any grade 2 or more late toxicity was 39.4% and 29.4% for the high-dose and conventional-dose groups, respectively (P = .045).

Quality-of-life studies, undertaken in parallel with this study, have shown similar levels of satisfaction with bowel and urinary function in both groups, said Dr. Rossi.

The researchers have disclosed no relevant financial relationships.

American Society for Radiation Oncology (ASTRO) 51st Annual Meeting: Abstract 22. Presented November 2, 2009.


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