Obesity and Prostate Cancer Mortality

Abstract & Commentary

By William B. Ershler, MD, Editor

Synopsis: In a review of a large, multicenter trial of radiation and androgen deprivation therapy for men with locally advanced prostate cancer, patients with BMI of >25 but < than 30, or >30 were found to have a higher rate of prostate-cancer specific mortality. This prospective data is in agreement with previously published population studies indicating a higher death rate from prostate cancer in obese individuals.

Source: Efstathiou JA, et al. Obesity and mortality in men with locally advanced prostate cancer: Analysis of RTOG 85-31. Cancer. 2007;110:2691-2699.

Approximately one third of American menare obese1 and although the extent to which obesity contributes to development of prostate cancer remains unresolved,2-4 there have been reports of an association of high BMI with features of more aggressive disease.5, 6 Yet, survival after radical prostatectomy may be unaffected by BMI.7 It is not clear, however, if BMI affects outcomes for those receiving radiation or androgen deprivation therapy. In the current report, Efstathiou and colleagues present data from the Radiation Therapy Oncology Group (RTOG) addressing the question of whether BMI is associated with prostate cancer-specific mortality (PCSM) among men treated on RTOG protocol 85-31.

This Phase III trial, conducted between the years 1987 and 1992, randomized patients with locally-advanced prostate cancer to RT (external beam) followed by androgen deprivation therapy (ADT) either in the adjuvant setting or at the time of recurrence. For ADT, patients were administered goserelin (gonadotropin-releasing hormone [GnRH] agonist) 3.6 mg subcutaneously each month. For those in the adjuvant treatment arm the goserelin was started during the last week of RT. For those in the non-adjuvant group, goserelin treatment was initiated at the first sign of recurrence. For both arms, the monthly treatments were continued indefinitely or until sign of disease progression. For the 788 (of a total of 945), enrolled patients for whom height and weight data were available, Cox regression analyses were performed to evaluate possible associations between BMI and all cause (ACM) and prostate cancer-specific mortality (PCSM). Examined covariates included age, race, treatment arm, history of prostatectomy, nodal involvement, Gleason score, clinical stage and BMI.

The 5-year PCSM rate for men with BMI <25 kg/m2 was 6.5%, compared with 13.1% and 12.2% in men with BMI >25 to <30 and BMI >30, respectively (P = 0.005). In multivariate analysis, greater BMI was significantly associated with higher PCSM (for BMI >25 to <30, hazard ratio [HR] 1.53, 95% confidence interval [CI], 1.02-2.27, P = 0.04; for BMI >30, HR 1.64, 95% CI, 1.01-2.66, P = 0.04). Of note, non prostate cancer-specific mortality and all cause mortality were not different among the three BMI groups.

Commentary

The long-term data from this large, multicenter trial are quite compelling and indicate that a greater baseline BMI is independently associated with higher cancer specific mortality in men with prostate cancer. This supports conclusions made from epidemiological studies from both Europe8 and the United States9 that indicate a greater risk of dying from prostate cancer in obese men. Potential explanatory mechanisms include the greater difficulty in staging as well as delivering external beam radiotherapy to obese individuals. Certainly, to the extent that more extensive disease is more difficult to recognize and thereby results in under-staging, the finding might be a technical artifact. However, obesity alone is associated with hormonal and metabolic alterations, such as elevated estradiol, reduced testosterone, insulin resistance, elevated insulin like growth factors as well as elevated leptin and reduced adiponectin levels, all of which have been associated with more aggressive prostate cancers or other negative prostate cancer outcomes. Furthermore, despite lower testosterone levels at baseline, ADT has been shown to be less effective in obese men.10

Thus, baseline BMI is independently associated with higher cancer-specific mortality in patients with locally-advanced prostate cancer. Additional studies would be required to determine whether deliberate weight reduction after prostate cancer diagnosis would modify the negative influence of obesity at time of diagnosis.

References

1. Ogden CL, et al. Prevalence of overweight and obesity in the United States, 1999-2004. JAMA. 2006;295(13):1549-1555.

2. Engeland A, et al. Height, body mass index, and prostate cancer: a follow-up of 950000 Norwegian men. Br J Cancer. 2003;89(7):1237-1242.

3. Giovannucci E, et al. Body mass index and risk of prostate cancer in U.S. health professionals. J Natl Cancer Inst. 2003;95(16):1240-1244.

4. Presti JC, Jr., et al. Lower body mass index is associated with a higher prostate cancer detection rate and less favorable pathological features in a biopsy population. J Urol. 2004;171(6 Pt 1):2199-2202.

5. Amling CL, et al. Pathologic variables and recurrence rates as related to obesity and race in men with prostate cancer undergoing radical prostatectomy. J Clin Oncol. 2004;22(3):439-445.

6. Kane CJ, et al. Obesity and prostate cancer clinical risk factors at presentation: data from CaPSURE. J Urol. 2005;173(3):732-736.

7. Siddiqui SA, et al. Obesity and survival after radical prostatectomy: A 10-year prospective cohort study. Cancer. 2006;107(3):521-529.

8. Andersson SO, et al. Body size and prostate cancer: a 20-year follow-up study among 135006 Swedish construction workers. J Natl Cancer Inst. 1997;89(5):385-389.

9. Calle EE, et al. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625-1638.

10. Smith MR. Obesity and sex steroids during gonadotropin-releasing hormone agonist treatment for prostate cancer. Clin Cancer Res. 2007;13(1):241-245.