Campus & Community

Study predicts risk of prostate cancer death:

7 min read

Who will be alive 10 years after treatment?

Anthony D'Amico and Kemal
Anthony D'Amico (right) works with Kemal Tuncali to adjust computer-controlled dose of radiation treatment being given to a prostate cancer patient. (Staff photo by Kris Snibbe)

I underwent radiation treatment for prostate cancer in 1996, so I was startled to come across a recent report that predicts who among men like myself would still be alive after 10 years.

The report was published in the Dec. 1 issue of the Journal of Clinical Oncology. Was there a chart or graph that would quickly tell me I have less than four years to live?

Nah. Things are never that simple. The article describes how researchers at Brigham and Women’s Hospital and Dana Farber Cancer Institute, both Harvard-affiliated hospitals in Boston, followed 381 people like me to “identify predictors of time to prostate specific death following external radiation therapy.” (The memory came to mind of lying on a hard table every weekday for seven weeks and taking the trivia quiz taped to the ceiling while the device that shoots the beam was rotated around me.)

“The results of this study give us a better understanding of what form of treatment will extend a patient’s life to a point where he’s more likely to die from causes other than prostate cancer,” says Anthony D’Amico, leader of the research and an associate professor of radiation oncology at Harvard Medical School.

He and his colleagues divided the men into three groups: high, intermediate, and low risk of prostate cancer death. The first thing they checked was the amount of PSA, or prostate-specific antigen, in the men’s blood. The body secretes excess amounts of this protein in response to prostate cancer. The higher its level, the more cancer is present. It was the level of PSA in my blood that trigged the digital examination and biopsy that found my cancer.

After treatment, by radiation or surgery, doctors closely monitor PSA levels. Experience has shown that men whose PSA levels rise rapidly do a lot worse than others. D’Amico and his team found that a doubling of PSA scores in one year or less is almost a sure predictor of death for those who received external radiation. Of 18 men in his study who showed such a rise, 17 (95 percent) of them died because the cancer spread to their bones.

I didn’t have to check my medical records; I keep my PSA numbers in my head. My levels gradually dropped after the radiation and have stayed comfortably low for the past six years.

Aggressive treatment needed

D’Amico believes his group’s findings will have a major impact on patient treatment and future research. For men like me, the findings are reassuring. Those whose PSA doubles in less than a year require quick, aggressive intervention. The same, of course, is true for men who have not yet been treated.

This death marker could also change the way research on prostate cancer treatments is done. At present, trials of drugs and other unproven therapies compare the results in men who receive a treatment with those who don’t.

“It now takes 10-15 years to run such prostate cancer trials,” D’Amico points out. “Using a short doubling time for PSA, instead of death, as an end point, we would have the answer in five years.”

Risk ratings

PSA doubling held true not only for high-risk men, who came into radiation treatment with a PSA score greater than 20, but for low-risk patients with PSAs of 10 or less. I went into treatment with a score of 5.4.

There also are other signals involved in the forecast.

When pathologists look closely at prostate cells in a microscope they assign them a so-called Gleason rating, a measure of how aggressively the cancer is growing. Gleason numbers of 8 or more put men into the high-risk category, 6 or less ranks you low. I read those numbers with relief; my Gleason score was 6.

Finally, risk is rated by the feel of the tumor during a digital exam. A big tumor on both sides of the prostate is bad news. Small tumors on one or both sides signal low risk. I had a small tumor on the right side. I was batting a thousand in the game of life and death.

Of the 381 men followed by the researchers, almost half (45 percent) of those at high-risk died of their prostate cancer within 10 years. About a quarter (27 percent) died from heart disease, stroke, complications of diabetes, or other causes. This observation is particularly important, given the competing causes of mortality expected in these men – whose median age at the time of diagnoses was 73.

The risk of dying of prostate cancer for men in the intermediate-risk group drops to 6 percent. For those in the low-risk group, the risk is zero! I went out for a long walk after reading that result. I walked very carefully. The risk was zero for prostate cancer only, not for getting hit by a car.

D’Amico was not as happy as I am about the results. The way he sees it, “If you’re in the high-risk group, external beam therapy was essentially inadequate. Now we treat such men with a combination of higher radiation doses and hormones. Our goal is to extend a man’s life to the point where he’s more likely to die with prostate cancer than from it.”

Salvage with hormones

The study also provided more insight into treating men with rapidly rising PSA. Hormones can add years to a man’s life, but when is the best time to give them? The therapy involves side effects that some will tell you are worse than the cancer. Doctors, therefore, want to wait until bone scans show the cancer has spread to a man’s bones. However, many patients want help before the pain starts. If their cancer is spreading, they want to do what they can right away.

Evidence from those in the study who received this so-called “salvage therapy” show clearly that starting hormone therapy before cancer spreads to the bones prolongs survival longer than waiting. “This is the first good evidence to support giving hormonal therapy early when PSA rises rapidly after radiation treatment,” D’Amico points out. “What we have yet to determine is the best type of anti-testosterone drugs to use and the duration of treatment.”

Of approximately 200,000 men diagnosed with prostate cancer each year, about half choose to have their prostate gland removed by surgery. Roughly 40 percent opt for external beam radiation with or without the implantation of tiny radiation-emitting seeds. The new study’s findings thus apply to as many as 80,000 patients. Whether they fall into high-, intermediate-, or low-risk categories, if their PSA doubles within a year after radiation treatment, these men are strong candidates for immediate hormone therapy.

What about those who choose surgery? D’Amico has already begun to collect data on more than 19,000 men to determine if those who had surgery will also benefit from immediate treatment with anti-testosterone drugs.

When informed that they have prostate cancer, about 10 percent of men decide to do nothing. That strategy is known as “watchful waiting,” hoping your cancer will not be aggressive enough to put you into the high-risk group and that your PSA will not double in a year or less.

The “watchful waiting” choice had appealed to me. I couldn’t decide whether to have surgery or undergo long weeks of radiation. Doing nothing sounded good.

D’Amico and his colleagues advised against that option. “If you take a low-risk man and remove his prostate gland, 92 percent of the time we find significant cancer,” D’Amico notes. “Only 8 percent may have something small enough to be watched, and we can’t determine who fits into that 8 percent with the means we now possess.” I was in the 92 percent.

D’Amico’s words forcefully brought home an old gag that watchful waiters tell about one of their group who jumped off a 20-story building. “How do you feel?” Some asked him as he fell past the 10th story. “All right – so far,” he answered.