HORMONE THERAPY FOR INTERMEDIATE RISK PROSTATE CANCER UNDERGOING RADIOTHERAPY

March 4, 2010 — The results of a landmark study often represent the definitive word clinically.

For the landmark Radiation Therapy Oncology Group (RTOG) 94-08 study, which evaluated short-term hormone therapy (4 months) in men with prostate cancer who undergo radiation therapy, this is and is not the case.

The study found that administering hormones to men with low-risk prostate cancer is not necessary.

This is the definitive word.

And it was reported as such by Medscape Oncology at the 2009 annual meeting of the American Society for Radiation Oncology (ASTRO).

However, the ROTG investigators found a different result in men with intermediate-risk prostate cancer: short-term hormone therapy offered a survival benefit.

But this benefit is not the definitive word.

Why? In part because the study was not originally designed to evaluate intermediate-risk men. But also because the radiation dose and techniques used in the study, which was started in 1994, are now dated, said Christopher Jones, MD, one of the study's principal investigators.

In short, newer approaches to radiation now in practice throughout the United States might make the hormone therapy unnecessary in intermediate-risk men as well, summarized Dr. Jones, who is a partner at Radiological Associates of Sacramento in California.

Dr. Jones is presenting the data from the study again at the 2010 Genitourinary Cancers Symposium (GUCS) in San Francisco, California.

The data are the same as those presented at ASTRO, said Dr. Jones, speaking at press conference preceding the GUCS meeting.

However, unlike at ASTRO, where the findings in low-risk men were emphasized, Dr. Jones is highlighting the results in intermediate-risk men at GUCS.

At ASTRO, Dr. Jones reported that the overall survival rate at 8 years for intermediate-risk patients treated with hormones plus radiation therapy was 72%, compared with 66% for intermediate-risk patients treated with radiation therapy alone (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.02 - 1.49).

However, uncertainty about the value of the results in intermediate-risk men led to less-than-emphatic clinical advice during the GUCS press conference.

"I'd probably add hormone therapy to patients with intermediate risk," said Dr. Jones.

"I think many clinicians will add 4 months of hormone therapy in intermediate-risk patients," added Nicholas J. Vogelzang, MD, chair and medical director of the Developmental Therapeutics Committee of US Oncology, who moderated the GUCS press conference.

The definitive word on intermediate-risk men will come from another currently ongoing study, RTOG 08-15, said Dr. Jones.

In the meantime, clinicians can be reassured there is now some evidence in this setting, explained Dr. Vogelzang.

"This is the first evidence that hormone therapy adds benefit to radiation in these patients," he said, referring to Dr. Jones's study and intermediate-risk men.

Intermediate Risk Defined

In this study of 1979 patients with early-stage prostate cancer, intermediate-risk disease was defined as having T1b-T2b carcinoma of the prostate with a prostate-specific antigen (PSA) score of 20 or less.

About 54% of patients in the study had this stage of disease.

Originally, the study was designed to evaluate the treatment of men with low-risk prostate cancer only, but the definition of low risk evolved as the study got underway, Dr. Jones said at ASTRO.

"When we started this study in 1994, all of these patients were considered low risk," he said at the time. As PSA testing matured as a tool, it became clear that the study group could be further defined. "With the advent of PSA screening, we were able to further refine low- and intermediate-risk patients," he added.

Overall Findings

After median follow-ups of 8.4 years in the hormone-therapy-plus-radiation group (n = 987) and 8.1 years in the radiation-only group (n = 992), the study met its primary end point by documenting the fact that 51% of the patients who received hormone therapy plus radiation were still alive at 12 years, compared with 46% of those who received radiation alone.

A 66.6 Gy radiation dose was delivered to the prostate, and the techniques used were consistent with the standard of care in 1994, said Dr. Jones.

Total androgen suppression was achieved with flutamide 250 mg twice daily and either goserelin 3.6 mg once a month or leuprolide 7.5 mg once a month, he added. The hormone therapy lasted 4 months, and was started 2 months prior to the initiation of radiation.

Dr. Jones and his coinvestigators found that the subgroup of men with low-risk disease (35% of patients in the study) did not benefit from the addition of hormone therapy.

The disease-specific survival rate at 8 years for low-risk patients treated with hormones and radiation therapy was 98%, compared with 99% for low-risk patients treated with radiation therapy alone (HR, 1.07; 95% CI, 0.83 - 1.39), Dr. Jones reported at ASTRO.

"Low-risk patients do not need to undergo the toxicities of hormone therapy," said Dr. Jones at ASTRO.

GUCS is cosponsored by the American Society for Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

Dr. Jones has disclosed no relevant financial relationships. Dr. Vogelzang reports being a consultant or advisor to Allos Therapeutics, Ambit, Amgen, Bayer, Celgene, Genentech, Keryx, Novartis, Onyx, Pfizer, Wilex, Honoraria, Amgen, ArQule, Bayer, Clinical Care Options, Cougar Biotechnology, Genentech, Imedex, Lippincott, Williams and Wilkins, Novartis, Onyx, Pfizer, and Wyeth; he also reports receiving research funding from Argos Therapeutics, ArQule, AstraZeneca, Cougar Biotechnology, Endocyte, GlaxoSmithKline, Keryx, Medarex, Novartis, Pfizer, Wilex.

2010 Genitourinary Cancers Symposium (GUCS): Abstract 6. Presented March 5, 2010.