Hormoontherapie bij mannen met prostaatkanker en geschiedenis van hartklachten lopen twee keer zo groot risico op vroegtijdig overlijden. Artikel geplaatst 12 september 2009

12 september 2009: Bron; Medscape

Een nieuwe grootschalige retroprospectieve studie heeft uitgewezen dat patienten met prostaatkanker en een geschiedenis van hartklachten een twee keer zo groot risico lopen op vroegtijdig overlijden als ze een hormoonkuur volgen. Mannen met prostaatkanker en geen geschiedenis van hartklachten hadden geen groter risico op overlijden door de hormoonkuren. De onderzoekers merken op dat het zinvol lijkt vantevoren mannen te screnen op hartklachten voordat hormoontherapie wordt voorgeschreven. U zou natuurlijk ook gewoon PC-Spes of prostasol kunnen gebruiken.

September 1, 2009 — In localized or locally advanced prostate cancer, the use of neoadjuvant hormone therapy was associated with a nearly 2-fold risk for death in men who also had a history of coronary artery disease.

This finding comes from a retrospective study of 5077 men who were treated with brachytherapy for their cancer, 30% of whom received neoadjuvant hormone therapy for a median treatment duration of 4 months.

The hormone therapy consisted of both a luteinizing hormone-releasing hormone agonist (leuprolide or goserelin) and a nonsteroidal antiandrogen (bicalutamide or flutamide).

On the bright side of the data, there was no increase in all-cause mortality among men treated with hormone therapy who had either no cardiovascular comorbidity or a single coronary artery disease risk factor, such as diabetes mellitus, hypercholesterolemia, or hypertension. Smoking and a family history of heart disease were not evaluated as risk factors.

The study was published in the August 26 issue of the Journal of the American Medical Association.

In an interview with Medscape Oncology, the study's lead author stressed that only 5% of the men in the study — a "small subgroup" — had coronary artery disease (congestive heart failure or past heart attack).

"Our results suggest that for these men, either hormonal therapy not be used in the treatment of their prostate cancer or their underlying heart disease be addressed by a primary-care physician and/or a cardiologist before they are considered for hormonal therapy," said Akash Nanda, MD, PhD, from Brigham and Women's Hospital and the Dana-Farber Cancer Institute in Boston, Massachusetts.

This study should heighten awareness about the potential for harm with neoadjuvant hormone therapy in select men.

Dr. Nanda acknowledged that it is not known if treatment for heart disease would improve outcome. "The study does not address whether or not treatment for coronary artery disease potentially changes the risk for these patients," he said.

Dr. Nanda and his coauthors concluded that "this study should heighten awareness about the potential for harm with neoadjuvant hormone therapy in select men."

Study Details

Several clinical trials have shown that adding hormonal therapy to radiation therapy in the treatment of aggressive prostate cancer leads to an increase in survival, observed Dr. Nanda. However, a recent analysis (JAMA. 2008:299:289-295) indicated that "this may not be the case for men with coexisting illnesses," according to Dr. Nanda. The purpose of the new study was to identify comorbidities that might affect survival.

To that end, the investigators looked at 5077 men with clinical stage T1 to T3 N0 M0 prostate cancer treated between 1997 and 2006 at the Chicago Prostate Cancer Center, a community practice in Westmont, Illinois. Men were referred to this center on the basis of their interest in or candidacy for brachytherapy.

Among the men, 2653 (52.3%) had no history of a cardiovascular comorbidity, 2168 (42.7%) had a coronary artery disease risk factor, and 256 (5%) had coronary artery disease. The median age of the men was 69.5 years, and 555 (10.9%) had received supplemental external-beam radiation.

Most of the men in the study (70%) did not receive neoadjuvant hormone therapy and served as comparators for the men who did.

Neoadjuvant hormone therapy use was not significantly associated with an increased risk for all-cause mortality in men with no comorbidity (9.6% vs 6.7%; adjusted hazard ratio , 0.97; 95% confidence interval , 0.72 - 1.32; P = .86) or a single coronary artery disease risk factor (10.7% vs 7.0%; adjusted HR, 1.04; 95% CI, 0.75 - 1.43; P = .82) after median follow-ups of 5.0 and 4.4 years, respectively.

However, for men with coronary artery disease, the therapy was significantly associated with an increased risk for all-cause mortality (26.3% vs 11.2%; adjusted HR, 1.96; 95% CI, 1.04 - 3.71; P = .04). These men had a median follow-up of 5.1 years.

In arriving at these findings, the investigators adjusted for age, treatment year, supplemental external-beam radiation therapy, treatment propensity score, and known prostate cancer prognostic factors (such as Gleason score).

The authors also noted that, in other research in different settings, hormone therapy has been associated with a variety of adverse effects, including increased risk for cardiovascular death.

More on Clinical Significance

Dr. Nanda and his colleagues recommend that, in men with favorable-risk prostate cancer and a history of coronary artery disease, alternative strategies to brachytherapy and hormone therapy be considered. These include active surveillance, treatment with external-beam radiation alone, and prostatectomy. In such men, hormone therapy is not really needed to "maximize outcome" anyway, explained Dr. Nanda. Instead, hormone therapy is used to reduce the size of the gland, ensuring that brachytherapy is not obstructed by the arch of the pubic bone.

Hormone therapy is needed to maximize outcome.

However, in men with unfavorable-risk prostate cancer, hormone therapy offers a survival benefit. "This is a tougher decision because hormone therapy is needed to maximize outcome," said Dr. Nanda. The risks and benefits of hormone therapy must be balanced; as noted above, appropriate medical evaluation or treatment is needed before hormone therapy is used in this setting, Dr. Nanda said.

Dr. Nanda also pointed out that the findings were limited to brachytherapy and, as a result, not necessarily generalizable to men with prostate cancer who are treated with external-beam radiation. "Other investigators will want to validate these findings in other settings," he said.

The authors also note that the duration and extent of hormone therapy are variables in need of study. "Men with locally advanced prostate cancer are frequently treated with 2 to 3 years of hormone therapy in combination with external-beam radiation therapy," they write.

The researchers have disclosed no relevant financial relationships.

JAMA. 2009;302:866-873.

hartklachten, prostaatkanker, hormoontherapie