ADT for Prostate Cancer May Lead to Rapid, Significant Weight Gain

New data show that most prostate cancer patients who receive androgen-deprivation therapy (ADT) after radical prostatectomy gain a significant amount of weight within a year of starting treatment. ADT therapy has long been a mainstay treatment for recurrent or metastatic prostate cancer and is increasingly used to treat men with localized disease.

“This rising utilization of ADT warrants a closer examination of the side effects of therapy, which include metabolic changes that potentially contribute to an increased incidence of diabetes and perhaps other comorbidities,” said Howard S. Kim, MD, with Duke University School of Medicine in Durham, North Carolina, and colleagues.

For their study, the investigators examined weight change in 132 men on ADT, defined as either a bilateral orchidectomy or gonadotropin- releasing hormone (GnRH) agonist therapy, from 1 year before therapy to 2 years afterwards. The men were enrolled in the Shared Equal Access Regional Cancer Hospital (SEARCH) database and had undergone a radical prostatectomy between 1988 and 2009 at four Veterans Affairs Medical Centers.

Previous research has shown that men undergoing ADT for 1 year tend to experience a significant loss in muscle and bone mass and a gain in fat mass, leading to overall weight gain, Kim and associates noted. However, there has been a paucity of information about the natural history of weight change in men on ADT, with studies to date focusing mostly on a short time frame immediately after the start of ADT. Additional information about demographic, clinical, and pathological characteristics is also needed so that clinicians can identify the men who are most likely to experience a weight change.

Overall, 92 (70%) men gained weight while 35 (26%) men lost weight and 5 (4%) men remained at the same weight. So-called “weight-gainers” gained a mean of 4.2 kg, and “weight-losers” lost a mean of 2.4 kg. The mean weight gain for the entire cohort was 2.2 kg (P <.001), which is equivalent to 2.4% of their body weight.

"This rising utilization of ADT warrants a closer examination of the side effects of therapy, which include metabolic changes that potentially contribute to an increased incidence of diabetes and perhaps other comorbidities.” —Howard S. Kim, MD

Kim and associates said that their finding of a mean 2.2-kg weight gain is in line with an earlier prospective study. However, while the earlier study included primarily white men, 42% of men in the present study were black and 8% were from other races.

Further analysis in 84 (64%) men whose weight was recorded in the year prior to ADT therapy and during the second year of ADT use revealed that most of the weight gain occurred in the first year after ADT therapy was begun. Their mean overall weight gain was 2.1 kg during the first year (P <.001) with no change in the second year. No demographic, clinical, or pathological factor was able to predict the direction of weight change.

Kim and colleagues cautioned that the study’s retrospective nature means that the findings are “inherently subject to human error, and therefore variation in reporting.” Also, the database used in the analysis lacked specific information on body composition, including fat mass, abdominal versus limb obesity, muscle mass, and bone mineral density. As a result, the researchers measured weight change as a surrogate for metabolic change.

In addition, the results may be skewed by the fact that men in the SEARCH registry may have been healthier and younger than the typical prostate cancer patient. In fact, they noted that “it might have been interesting to analyze weight change in a population of men who are generally older and less fit, as these patients might respond differently to ADT.”

However, despite potential study limitations, the authors said that their findings argue in favor of a prospective analysis of the natural history of weight change in men receiving ADT.

Kim HS, Moreira DN, Smith MR, et al. A natural history of weight change in men with prostate cancer on androgen-deprivation therapy (ADT): results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database [Published online ahead of print September 22, 2010]. BJU Int. 2011. Mar;107(6):924-928. doi: 10.1111/j.1464-410X.2010.09679.x.