Adding Hormone Therapy to Radiation Helps Survival Of High Risk Prostate Cancer Patients
28 October 1998. Prostate cancer patients receiving radiotherapy who are at a high risk of dying of the disease have an increased survival rate if they take hormonal therapies for longer than average periods, according to a study conducted by a University of California San Francisco prostate cancer expert.      Mac Roach, III, MD, UCSF associate professor of radiation oncology and medicine, presented his findings October 28, 1998 in Phoenix, Arizona at the annual meeting of the American Society of Therapeutic Radiation Oncology (ASTRO).
     "Our study showed a 20 percent increase in survival after eight years for high risk prostate cancer patients who continued to receive hormonal therapy in conjunction with radiotherapy compared to those who received radiotherapy alone," Roach said. "This is the first study to suggest that some prostate cancer patients may need to take hormonal therapy for as long as breast cancer patients typically do in order to reach the maximum effect of the treatment."
      He noted that prostate and breast cancer are similar diseases because both are hormone dependent. In prostate cancer, the male's androgens or sex hormones, such as testosterone, act as a "catalyst" in governing the functions of the prostate and prostate cancer cells. In animal models, depriving tumors of hormones has been shown to weaken cancer cells, making them more sensitive to radiation, Roach said.
      During the study, researchers found that high risk patients who received radiotherapy alone had a 34 percent chance of dying of prostate cancer after the first five years of treatment. In contrast, those who received hormonal therapy along with radiotherapy had a 19 percent chance of dying of the disease.
      Roach said that prostate cancer patients frequently take hormone therapies for approximately four months. Recent American studies have administered the drug to men in clinical trials for two years, and in European studies, for three years.
      In the study, 2,464 men with an average age of 69 years were analyzed to assess the effects of short and long-term hormonal therapy on a patient's survival rate compared to that of a patient who only received radiotherapy. Short-term therapy was administered to men for two to four months before and during radiotherapy and long-term therapy for generally two years or longer. All men in the study had clinically localized prostate cancer, meaning that the disease had not spread to other parts of the body but was biologically advanced.
      Study participants were categorized into four risk groups that Roach developed in an earlier study. Men in group one and two were considered to be at a low risk of dying of prostate cancer, and groups three and four were considered to be at a high risk.
      Roach reported the effects of short and long-term hormonal therapy received in conjunction with radiotherapy on the four groups up to a twelve year period. During the trial, 1,557 patients were treated with radiotherapy alone while 907 received either short or long-term hormonal therapy. Men in the high risk groups (three and four) who received hormonal therapy in addition to radiotherapy were reported as having a 20 percent higher survival rate compared to those who only received radiotherapy after eight years of treatment. Roach also reported that the survival of high risk patients who do not respond well to radiotherapy was enhanced if they started to take hormone therapy early, rather than later, in their treatment regimen.
      Roach found that patients with early stages of prostate cancer and a low Gleason score, a grading system that measures the deviation of cancer cells from normal cells based upon their appearance, should also take hormonal therapies if their PSA level was 20 ng/ml or more.
      In his previous study, Roach predicted the effects of radiotherapy alone on the survival rate of men in the four risk groups at five, ten and 15 years following treatment. These patients were treated for prostate cancer with radiotherapy alone in clinical trials from 1975-1992. The four groups are based on the largest collection of prostate cancer patients, derived from the Radiation Oncology Therapy Group database.
      A patient's risk was determined by his Gleason score and tumor and pathologic lymph node status. Group one had a Gleason score (GS) of 2 to 6; group two GS of 6 to 7; group three GS of 7 to 10; and group four GS of 8 to 10.
      "These four groups provide an effective way of determining how long patients are likely to survive prostate cancer and who will benefit from what types of treatment," Roach said. "Without this information, it is difficult to provide an informed consent to a patient and for them to make the best treatment decisions."
      Informed consent is a required part of the consultation given to men with prostate cancer prior to the initiation of any treatment. For some, so-called "watchful waiting" may be appropriate, while for others, aggressive treatment should be considered, he said.
      The risk stratification system provides practical information for men diagnosed with prostate cancer, Roach said. For instance, a man belonging to a low risk group may seriously consider "watchful waiting," particularly if he is older than 70 years of age, because his risk of dying of prostate cancer is 3 percent or less. Such a patient would be three of four times more likely to die of another condition other than prostate cancer, such as a heart attack.
      In contrast, he said, a man belonging to risk group four has a much higher risk of dying of prostate cancer than a man in group one and therefore should consider aggressive therapy.
      Based on his most recent data, Roach said that radiotherapy in conjunction with long-term hormone therapy is the most effective treatment for high risk, group three and four men. Roach's current research also demonstrated that the Gleason score and tumor staging, a digital rectal exam that defines the status of a tumor, are the most effective determinants for predicting the survival of men with prostate cancer, rather than the commonly used PSA test.
      Although this test is sufficient in determining treatment failure, it is not, as is widely believed, the most effective predictor of survival of men with localized prostate cancer.
      Unfortunately, though, the Gleason score is not included in the current disease staging system and many pathologists are not able to correctly interpret scores, Roach said. He added that a greater emphasis needs to be placed on guaranteeing that the Gleason score is used accurately to manage patients.
     Roach said that his risk stratification system allows simple and routine pre-treatment tests, (tumor stage and Gleason Score) to precisely predict a patient's likelihood of dying of prostate cancer.

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