The addition of androgen deprivation therapy (ADT) to external beam radiation therapy (RT) has been shown to prolong overall survival in men with intermediate or high-risk prostate cancer (PC) enrolled on several randomized controlled trials [
With regard to decreased metabolism, several investigators have shown that ADT causes a decrease in lean body mass with a concomitant increase in total body fat of up to ~10% [
Therefore, the purpose of this study was to use data from a prospective randomized trial in order to ascertain clinical factors at randomization associated with significant weight gain (≥10 pounds) following the completion of RT and ADT [
Between December 1, 1995, and April 15, 2001, 206 men were enrolled in a prospective randomized trial evaluating the impact on the survival of adding 6 months of combined ADT to ~70 Gy RT [
Following the completion of RT with or without 6 months of combined ADT, men were seen at approximately 6 months after randomization. At each followup, a digital rectal examination, serum PSA, and weight measurement were obtained. The scale used to measure patients at this 6-month followup was the same as at randomization and the difference in weight in pounds was ascertained and recorded between the two time-points.
Clinical characteristics at baseline were enumerated and compared across randomized treatment arms. For the continuous covariates of BMI, PSA, and age, the nonparametric Wilcoxon test [
The primary endpoint of this study was whether the patient gained ≥10 lbs by the 6-month follow-up point after randomization. Univariable and multivariable logistic regression [
The distribution of the 85 and 86 men, who underwent RT or RT and ADT, respectively, and experienced ≥10 lbs weight gain versus <10 lbs, 6 months following randomization, stratified by well-defined BMI cut-points for normal weight, overweight, and obese, was compared using Fisher’s exact test [
Table
Distribution and comparison of clinical factors at randomization of the study cohort stratified by randomized treatment arm.
Clinical factor | Treatment with RT |
Treatment with RT and AST |
|
---|---|---|---|
Median BMI (IQR) | 27.44 kg/m2 |
27.35 kg/m2 |
0.73 |
Median PSA (IQR) | 11.54 ng/mL |
10.85 ng/mL |
0.38 |
Median Age (IQR) | 73.36 |
72.12 |
0.11 |
T1 | 37 (44%) | 46 (53%) | 0.19 |
T2 | 48 (56%) | 40 (47%) | |
Gleason score 6 or less | 26 (31%) | 25 (29%) | 0.92 |
7 | 45 (53%) | 49 (57%) | |
8 to 10 | 14 (16%) | 12 (14%) | |
No or minimal cm | 65 (76%) | 65 (76%) | 0.89 |
Moderate to severe cm | 20 (24%) | 21 (24%) |
RT indicates radiotherapy; ADT: androgen deprivation therapy; BMI: body mass index; IQR: interquartile range; PSA: prostate-specific antigen; cm: comorbidity.
By the 6-month followup, 12 men were observed to have gained ≥10 lbs of which 10 (83%) were treated with RT and ADT, and 7 (70%) were obese at the time of randomization. For these 7 men, the median increase in BMI was 5.21% (range: 3.60%–6.37%). As shown in Table
Univariate and multivariate odds ratios for the risk of ≥10 lbs weight gain 6 months after randomization for each clinical factor.
Clinical factor | Number of men | Number of men who gained ≥10 lbs by EOT | Univariable analysis | Multivariable analysis | ||
---|---|---|---|---|---|---|
OR (95% CI) |
|
AOR (95% CI) |
|
|||
RT | 85 | 2 | 0.18 |
0.03 | 0.18 |
0.04 |
RT + AST | 86 | 10 | 1 (Ref) | — | 1 (Ref) | — |
BMI increase per kg/m2 | 171 | 12 | 1.18 |
0.01 | 1.15 |
0.04 |
PSA increase per ng/mL | 171 | 12 | 0.98 |
0.58 | 0.97 |
0.57 |
Age | 171 | 12 | 0.93 |
0.14 | 0.95 |
0.38 |
Gleason score 8 to 10 | 26 | 3 | 2.09 |
0.39 | 1.17 |
0.87 |
7 | 94 | 6 | 1.091 |
0.90 | 0.55 |
0.49 |
6 or less | 51 | 3 | 1 (Ref) | — | 1 (Ref) | — |
T2 | 88 | 8 | 1.98 |
0.28 | 1.99 |
0.33 |
T1 | 83 | 4 | 1 (Ref) | — | 1 (ref) | — |
Mod to Sev cm | 41 | 5 | 2.44 |
0.15 | 2.11 |
0.28 |
No or min cm | 130 | 7 | 1 (Ref) | — | 1 (Ref) | — |
RT indicates radiotherapy; ADT: androgen deprivation therapy; BMI: body mass index; PSA: prostate-specific antigen; cm: comorbidity; OR: odds ratio; CI: confidence interval; AOR: adjusted odds ratio; EOT: end of treatment.
Table
Distribution of weight gain 6 months following randomization, stratified by treatment received and body mass index.
RT only ( |
RT + ADT ( |
|||
---|---|---|---|---|
Weight change 6 months following randomization | ||||
<10 lbs ( |
≥10 lbs ( |
<10 lbs ( |
≥10 lbs ( |
|
BMI (range in kg/m2) | (Range −13 to +9; median −1 lb) | (Range 10 to 13; median +11.5 lbs) | (Range −11 to +8; median +1 lb) | (Range 10 to 17 lbs; median +11.25 lbs) |
Normal (18.5–24.9) | 17 (20%) | 1 (50%) | 22 (29%) | 2 (20%) |
Overweight (25.0–29.9) | 43 (52%) | 1 (50%) | 37 (49%) | 1 (10%) |
Obese (≥30.0) | 23 (28%) | 0 (0%) | 17 (22%) | 7 (70%) |
Fisher’s exact test |
Fisher’s exact test |
RT indicates radiotherapy; ADT: androgen deprivation therapy; BMI: body mass index.
In this study, we observed that men at highest risk of ≥10 lbs weight gain following RT and 6 months of ADT were those who were obese at the outset of treatment. Specifically, for every 1 unit increase in BMI, there was a 15% increase in the odds of gaining at least 10 pounds by the 6-month follow-up visit and the median increase in BMI was 5.21%. Given the established association of increased mortality with additional weight gain in obese men [
Several points require further clarification. First, weight gain in obese patients is known to reduce both quality of life (QoL) and longevity [
Specifically, ADT has been used in men with benign prostatic hyperplasia and low risk PC who are not candidates for brachytherapy due to pubic arch interference as determined at the time of volume study [
Therefore, ADT use should be discouraged in obese men with low- or favorable-intermediate risk PC. Moreover, future studies should employ a validated QoL metric [
A limitation of the current analysis is the relatively small event rate (
In conclusion, obese men are at increased risk for ≥10 lbs weight gain by the end of 6 months of ADT, prompting serious consideration to limiting or avoiding the use of ADT in these men with low- or favorable-intermediate risk PC where improvement in cancer control has not been observed but a shortened life expectancy from further weight gain may be expected.
The material presented in this paper is original research, has not been previously published, and has not been submitted for publication elsewhere while under consideration.
The authors declare that there is no conflict of interests regarding the publication of this paper.