Novel Hormone-Radiation Therapy Approaches

Radiation therapy (RT) used in combination with hormonal approaches continues to be a viable strategy for treating localized, high-risk prostate cancer patients even though many clinicians are not employing it, said Howard M. Sandler, MD.

Sandler is chair in Cancer Therapeutics and professor and chair of the Department of Radiation Oncology at Cedars-Sinai Medical Center in Los Angeles, California. He also is a member of the Research Strategy Committee of the Radiation Therapy Oncology Group, a national clinical cooperative funded by the National Cancer Institute.

During his presentation, Sandler cited a recent National Cancer Institute of Canada study as a “bold trial” that posed important questions about whether or not advances in hormonal therapy have made RT less relevant (abstract CRA4504 from J Clin Oncol. 2010;28 [suppl 18]).

“It goes to the very heart of radiation oncology,” Sandler said. “It asks in a randomized trial: Does what we do for a living make a difference?”

After 7 years, the study found that high-risk patients treated with continuous androgen deprivation therapy (ADT) plus RT showed an overall survival advantage of 74% versus 68% for those who had been treated with ADT alone. “The curves were pretty much together until about 5 years and then they split apart,” he said.

Sandler said other studies support the use of RT but that clinicians are turning to primary ADT.

Cooperberg et al analyzed data from the CaPSURE registry for 10,808 men diagnosed between 1990 and 2007; they found the use of primary ADT had risen to 29.1% by 2004-2007 while the use of eternal-beam radiation declined to 10.9%. Additionally, the study found the use of adjuvant radiation after radical prostatectomy “is relatively uncommon among high-risk men” while a growing proportion of these patients receive ADT (World J Urol. 2008;26:211-218).

“It is kind of shocking to me that when you go all across the country that’s what people are getting,” Sandler said.

“Primary hormonal therapy really should be used sparingly in these patients,” contended Sandler, adding clinicians probably should add radiation if they do choose ADT. “It’s not a trivial effect adding radiation to these patients. The magnitude of benefit is on the order of radical prostatectomy for localized prostate cancer. ”

Major Trial to Yield Significant Results

For intermediate-risk patients, Sandler anticipates important results from the a large phase 3 trial comparing short-term ADT prior to and during RT with RT alone; the results are scheduled to be reported in The New England Journal of Medicine within several months. Sandler, who is a coauthor, believes the RTOG 94-08 study is the largest ever conducted for localized prostate cancer patients.

He said the study showed that the addition of short-term hormone therapy to RT improved overall survival to 62% versus 57% for RT alone. He said the results are impressive, particularly considering that the hormonal therapy was given for a total of 4 months (2 months before and during RT).

Intermediate-risk patients, who comprised 1068 of the 1979 patients participating in the trial, benefited the most from the combination therapy, Sandler said, although he said he further divides patients who fall into this group into lower- and higher-risk categories.

“The trend was improved in the high-risk group but it was only 226 patients here so there’s a wide confidence interval,” he said. “In the subset analysis, the only group that benefitted was the intermediate-risk group of patients. The more important part is that low-risk patients did not benefit from the hormonal therapy.”

Low-risk patients were defined as those with a Gleason score ≤6 with prostate-specific antigen (PSA) ≤10 and not T2b; intermediate-risk was defined as Gleason 7 or Gleason ≤6 and either PSA 10 to 20 or T2b; and high-risk was defined as a Gleason score of 8 to 10.