ADT for Prostate Cancer May Increase Death Risk in Black Men

Nick Mulcahy

August 17, 2016

Black men had a 77% higher risk for death from all causes compared with men of other races when treated with a short-term course of androgen deprivation therapy (ADT) for "favorable-risk" prostate cancer before receiving radiation, a retrospective study has found.

"Physicians should consider reserving the use of ADT in African American men for high-risk prostate cancer and consider avoiding it in favorable-risk disease," said lead author Konstantin A. Kovtun, MD, a resident in radiation oncology at Brigham and Women's Hospital in Boston, Massachusetts, in an email to Medscape Medical News.

Favorable-risk refers to low-risk and favorable-intermediate risk prostate cancer.

The advice is obvious and sensible. ADT plus radiotherapy is not recommended for any man in this setting — regardless of skin color — because it does not improve survival, point out the study authors.

But now there is evidence that this nonrecommended treatment may be especially ill advised for black men.

"When African-American men were exposed to an average of only four months of hormone therapy, primarily used to make the prostate small enough for brachytherapy, they suffered from higher mortality rates due to causes other than prostate cancer than non-African American men," Dr Kovtun further explained in a press statement.

The new study was published online August 4 in Cancer.

The team analyzed the medical records of 7252 men from the Chicago Prostate Cancer Center who had low- or favorable-intermediate–risk prostate cancer and were treated with brachytherapy between 1997 and 2013, including 20% who were also treated with ADT.

After a median follow-up of 8 years, 869 men (12.0%) died: 48 (5.52%) of prostate cancer and 821 (94.48%) of other causes.

There was a significant association between black race and an increased risk for all-cause mortality (adjusted hazard ratio [aHR], 1.77; 95% confidence interval [CI], 1.06 - 2.94; P =.028).

The authors point out that major clinical trials have failed to show that ADT plus radiation therapy improves survival in these favorable-risk patients. This would include the Radiation Therapy Oncology Group 94-08 study, as reported by Medscape Medical News. Furthermore, these patients might now be candidates for active surveillance.

Dr Kovtun and colleagues also explain that ADT plus radiation therapy is, however, a standard of care in higher-risk prostate cancer (unfavorable intermediate risk and high risk) on the basis of multiple randomized clinical trials.

Still, even among these men with more advanced cancers, the recommended use of ADT is tricky because of its potential side effects, including cardiotoxicities, suggest the authors.

To illustrate this point, the team cites a recent study that found, among men with unfavorable-risk prostate cancer who also had moderate to severe comorbidity, ADT use was associated with significantly shorter survival because of increased risk for fatal myocardial infarction (JAMA. 2015;314:1291-1293).

Despite all of the above, use of ADT in American black men with favorable-risk disease has some intuitive appeals, the authors say. They are more likely than white counterparts to harbor occult high-grade/stage prostate cancer. The hope is that ADT would attack hidden and dangerous disease in some men and thus extend life in such cases.

Because of this complex tableau, Dr Kovtun and colleagues initiated their new study to find out what has gone on when black men with good-risk disease received ADT before radiotherapy.

These authors should be "applauded" for investigating these circumstances, said an expert not involved with the study.

The "study highlights the importance of tailoring therapeutic interventions to individual patients," said Claire Brady, MD, a medical oncologist at Cork University Hospital in Ireland, who was approached for comment.

"Incredible gains" have been made in improving prostate cancer survival via treatment, she said. However, over time, as the "margin of benefit has become smaller," Dr Brady said, "the risk of doing more harm than good significantly increases."

"This study emphasizes the importance of taking into consideration the risk of an individual's co-morbid risk factors," she told Medscape Medical News in an email.

No Problem Among Men Not Treated with ADT

As noted above, there was a significant association between black race and an increased risk for all-cause mortality.

The same was also true for other-cause mortality (aHR, 1.86; 95% CI, 1.08 - 3.19; P = .024) among black men vs nonblack men who received ADT.

Importantly, this association between black race and mortality was not found among the men who were not treated with ADT (aHR for all-cause mortality, 1.33 [95% CI, 0.93 - 1.91; P = .12]; aHR for other-cause mortality, 1.39 [95% CI, 0.96 - 2.02; P = .08]).

These multivariate analyses adjusted for the age at brachytherapy, year of brachytherapy, cardiometabolic comorbidity status (history of myocardial infarction, heart failure, or diabetes), risk group, and ADT treatment propensity score.

The authors highlight the fact that the median follow-up for black men receiving ADT was significantly shorter than that for nonblack men (6.12 vs 9.62 years). Thus, there was less time for black men receiving ADT to acquire mortality events, yet a significant association with an increased risk for mortality was observed anyway.

So, a question arises: Why are black men at risk for death from ADT treatment?

Comorbidities are a likely answer because the black men in the study were more likely to have significant cardiometabolic comorbidity. However, the authors adjusted for cardiometabolic comorbidity in their multivariate analysis.

Thus, the authors conclude that "cardiometabolic comorbidity alone does not appear to be sufficient to explain the significant increase" in mortality risk.

The team speculates that other factors, such as noncardiometabolic comorbidity, socioeconomic status, and health insurance status, may have affected the results.

But, as with many studies that are not prospective, randomized clinical trials, the researchers conclude that more study is needed to both confirm the findings and further understand what drives the problem at hand.

The authors and Dr Brady have disclosed no relevant financial relationships.

Cancer. Published online August 4, 2016. Abstract

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