Obesity and Mortality in Men with Locally Advanced Prostate Cancer
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An analysis of RTOG 85-31 patients suggests that increased body mass index (BMI) is associated with increased prostate cancer specific mortality (PCSM). The report appears in the online version of Cancer and is authored by Dr. Efstathiou and collaborators.
Greater BMI is associated with more aggressive higher-grade prostate cancer (CaP) and increase biochemical recurrence rates after radical prostatectomy. There is less data published regarding radiotherapy (XRT). This study sought to analyze the relationship between BMI and PCSM in a large cohort of patients treated with XRT on the RTOG 85-31 trial. RTOG 85-31 was a phase III trial comparing the XRT with indefinite androgen deprivation therapy (ADT) begun during the last week of XRT, to XRT alone with ADT initiated at the time of disease recurrence. Participants had evidence of locally advanced disease, clinical stage T3, or evidence of regional lymph node metastasis. Stage T4 tumors were not included and patients needed a Karnofsky performance status >60%. Total XRT dose was 65-70Gy. PCSM was defined as death from CaP or protocol treatment. All cause mortality (ACM) was death from any cause. Univariate and multivariate analysis was performed, the latter including age, race, centrally reviewed Gleason score, clinical stage, nodal metastasis, prior prostatectomy, treatment arm, and BMI.
Patients were enrolled between 1987 and 1992. Arm I was immediate ADT and included 477 patients while Arm II was ADT at time of progression and included 468 men. Of these, 788 (83%) had BMI data available and comprise the dataset for this analysis. Median BMI was 26.6 kg/m2, 241 men (31%) were of normal weight, 402 (51%) as overweight, and 145 (18%) as obese. With median followup of 8.1 years, a total of 476 deaths occurred of which 169 were CaP related. Men in Arm I (immediate ADT) had a PCSM of 8.5% versus 13.6% for Arm II (delayed ADT). ACM was 23.8% for Arm I and 29.1% for Arm II. In multivariable analysis, a greater BMI was significantly associated with higher PCSM, adjusted HR=1.52 for overweight and HR=1.64 for obese men. The 5 year PCSM for normal weight men was 6.5% compared with 13.1% for overweight men and 12.2% for obese men. Other variables also associated with increased PCSM were Arm II, no history of prostatectomy, presence of lymph node metastasis, and Gleason score 7-10 CaP. BMI was not associated with non-PCSM or ACM.
The authors discuss that obesity is associated with higher estradiol, lower testosterone, and lower sex hormone-binding globulin levels and this may predispose to more aggressive disease. In addition, Obesity is correlated with insulin resistance and diabetes and it is appreciated that insulin-like growth factors IGFs may promote prostate cancer progression.
Reference:
Cancer. ePub: November 12, 2007
Efstathiou JA, Bae K, Shipley WU, Hanks GE, Pilepich MV, Sandler HM, Smith MR
Reported by Christopher P. Evans, MD, a Contributing Editor with UroToday.
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