Study: Primary ADT Not Effective in Localized Prostate Cancer

Patients with localized prostate cancer treated with primary androgen deprivation therapy (ADT) without radiation therapy or surgery derived no survival benefit, according to the results of a large study.

Patients with localized prostate cancer treated with primary androgen deprivation therapy (ADT) without radiation therapy or surgery derived no survival benefit, according to the results of a large study published in the Journal of Clinical Oncology.

“Our main conclusion is that primary ADT does not seem to be an effective strategy as an alternative to no therapy among men diagnosed with clinically localized prostate cancer who are not receiving curative-intent therapy,” concluded the authors.

Arnold L. Potosky, PhD, of the Lombardi Comprehensive Cancer Center at Georgetown University in Washington, DC, and colleagues retrospectively analyzed cancer registry data from three integrated health plans of 15,170 men diagnosed between 1995 and 2008 who were not treated with curative therapy and were followed up with until 2010. Almost 23% of the men (3,435) received primary ADT; 11,735 had no ADT in the first 12 months, but 17% received it after 12 months. The ADT group had more comorbidities compared with the non-ADT group.

The men in the study who received ADT were generally older and had worse prognosis factors, such as higher baseline prostate-specific antigen (PSA) levels, a Gleason score of greater than 7, and greater than or equal to T2b disease at the time of diagnosis. Fifty-eight percent of the men in the initial ADT group were defined as high risk by the American Urological Association (AUA), compared with 18% in the non-ADT group.

Primary ADT was associated with neither a risk of all-cause mortality (hazard ratio [HR] = 1.04) nor prostate cancer–specific mortality (HR = 1.03) after the data were adjusted for sociodemographic and clinical characteristics. Forty-nine percent of the men in the ADT group died during follow-up compared with 28% in the non-ADT group, but the difference was not statistically significant after adjusting for different variables (HR = 1.04). There was also no difference in prostate cancer–specific mortality (13% in the ADT group compared with 5% in the non-ADT group [HR = 1.03]).

Men in the ADT group had increased risk of cardiovascular death (13% vs 8%, respectively), but this difference was not statistically significant after adjustments for patient factors (HR = 1.11).

Primary ADT was associated with decreased risk of all-cause mortality only among the subgroup of men with an AUA criteria–defined high risk of cancer progression (HR = 0.88; P = .02), though this did not translate to a decreased prostate cancer–specific mortality risk. “The observed benefit was relatively small and should not be taken as definitive, given the limitations of our data and the possibility of a spurious finding,” stated the authors in their discussion.

“In the high-risk localized prostate cancer setting, the study showed that there may be some positive benefit, but at this point, because this is a retrospective study, this should not change clinical practice at all,” said A. Oliver Sartor, MD, professor of cancer research in the department of medicine at Tulane University and the medical director of Tulane Cancer Center in New Orleans.

ADT is effective as a palliative treatment for men with metastatic prostate cancer and can even improve survival in specific cases, including as an adjuvant therapy for patients with lymph node–positive disease who have had a prostatectomy and lymphadenectomy or those who are intermediate or high risk who are receiving radiation therapy. But, according to Potosky and his coauthors, ADT use as a primary monotherapy for localized prostate cancer has seen an uptick among men who opt not to have a prostatectomy or receive radiation and also for men who have biochemical recurrence after a potentially curative treatment. Based on two published studies, as many as 40% of men with localized prostate cancer had received this treatment as an initial way to manage their disease between 1998 and 2002. ADT treatment has declined in recent years but is still in use.

ADT is associated with adverse events that include loss of muscle strength, anemia, impaired cognitive function, bone loss or fractures, coronary heart disease, insulin sensitivity, and diabetes mellitus. In 2010, manufacturers of ADT-injectable agents added a warning label to the products that stated they may have risks of coronary heart disease and diabetes.

In the current study, ADT included gonadotropin-releasing hormone analogues, such as leuprolide, goserelin, and triptorelin, or gonadotropin-releasing hormone antagonists, such as abarelix and degarelix. The antagonists could be administered with or without an oral antiandrogen, such as flutamide, bicalutamide, and nilutamide.

Previous studies assessing the impact of primary ADT for localized prostate cancer had mixed results, from no benefit and potential harm, to a possible benefit, but the studies included mostly older men and used analyses that may not be applicable to clinical practice.

“No current guidelines recommend that ADT monotherapy be given to patients with localized prostate cancer,” said Dr. Sartor. “The bottom line is that using ADT alone in this setting is not current practice and is not recommended. I am hard-pressed to find a reason why this treatment has persisted despite no evidence to support its use.”

Dr. Sartor did note that there are randomized studies that show that the addition of hormonal therapy to radiotherapy clearly benefits men with intermediate- or high-risk localized prostate cancer.