A recent Yale study may help to improve treatment of prostate cancer in the future.
The study, carried out by several members of the Yale School of Medicine’s Department of Therapeutic Radiology, shows the potential downside of using hormone therapy to treat prostate-cancer patients with a history of heart attacks. According to Nataniel Lester-Coll, one of the study’s co-authors, men with prostate cancer are generally divided into three categories: low-, intermediate- and high-risk patients. While low-risk patients usually do not receive therapy, most intermediate- and high-risk patients receive hormone therapy in addition to radiation therapy. The study found that while most intermediate-risk patients benefit from hormone therapy, intermediate-risk men with a history of heart problems experience either harm or no benefit from this treatment.
“When you factor the unwanted side effects [of hormone therapy] in addition to the fact that there’s a very marginal gain in cancer control when you have a very significant competing risk of death, such as cardiac death, there just isn’t any particular benefit,” Lester-Coll said.
To evaluate the effects of hormone therapy, the researchers started with data from a prominent European study, EORTC 22991. The study, which was associated with Grenoble University in France, split intermediate-risk patients into two groups: one that received both types of therapy and another that received only radiation therapy. Scientists then assessed differences in survival rates between the groups. From this data, researchers at Yale created a computational model with added parameters — the most prominent of which was heart-attack history — that they used to generate survival outcomes for different groups of men between 50 and 70 years old.
“We set about the study because we knew that medical decision making is more complicated than a yes or no decision,” said James Yu ’99 MED ’14, an associate professor of therapeutic radiology and another co-author of the study.
The results of the study show that all groups either benefited or experienced no harm from hormone therapy except men with a history of heart attacks, who on average lost 0.3 to 0.4 quality-adjusted life years — a measure of both quantity and quality of life, with one quality-adjusted life year representing one year in perfect health.
According to the researchers, this result can be attributed to multiple different factors, and hormone therapy itself could be part the problem. This method, which is also known as androgen-deprivation therapy, works by blocking the release of testosterone-producing hormones, since prostate cancer is driven by testosterone. Hormone therapy can magnify the effects of cardiac problems, Lester-Coll said.
“There’s a body of literature that suggests that men who have low levels of circulating testosterone may have an increased risk of dying from a heart attack,” Lester-Coll said. “Additionally, for men who have had heart attacks, overall life expectancy is much less than it is for someone who has optimal cardiac health.”
Additionally, the side effects of hormone therapy can vary between patients, causing significant differences in life quality.
Yu noted that although some men experience only minor symptoms throughout the treatment, others experience negative side effects such as hot flashes, sluggishness and loss of libido.
Researchers said they hope the study will provide more clarity and guidelines to oncologists treating men with prostate cancer.
According to Yu, one of the biggest difficulties about hormone therapy use is deciding when a person will benefit from the treatment.
“Hopefully we can illuminate this for patients and caregivers who are trying to figure out whether androgen-deprivation therapy is worthwhile to them,” Yu said.
The Yale study also adds more nuance to the results of the European study.
Lester-Coll said the EORTC trial published this year is important because it shows that there is a substantial benefit to treating men with intermediate-risk disease with six months of hormone therapy. However, he added that the Yale study shows that although this is probably true for most men with intermediate risk, it may not be so for all of them.
The study is currently under a second review, and has yet to be published, but Lester-Coll has presented it to the American Society for Radiation Oncology.
The American Cancer Society has estimated that 180,890 new cases of prostate cancer will be diagnosed in 2016.