Diabetes and mortality in men with locally advanced prostate cancer: RTOG 92-02.
OBJECTIVE
Diabetes is associated with lower risk of prostate cancer. Most men with diabetes are obese, and obesity is associated with greater prostate cancer mortality. Whether diabetes influences outcomes after prostate cancer diagnosis is unknown.


METHODS
We assessed the relationship between prevalent diabetes and mortality using data from Radiation Therapy Oncology Group Protocol 92-02, a large randomized trial of men (N = 1,554) treated with radiation therapy and short-term versus long-term adjuvant goserelin for locally advanced prostate cancer. Regression and proportional hazard models were performed to evaluate relationships between prevalent diabetes and all-cause mortality, prostate cancer mortality, and non-prostate cancer mortality. Covariates included age, race, tumor stage, Gleason score, prostate-specific antigen, weight, and treatment arm.


RESULTS
There were a total of 765 deaths; 210 (27%) were attributed to prostate cancer. In univariate analyses, prevalent diabetes was associated with greater all-cause mortality and non-prostate cancer mortality but not prostate cancer mortality. After controlling for other covariates, prevalent diabetes remained significantly associated with greater all-cause mortality and non-prostate cancer mortality (hazard ratio [HR] = 2.12; 95% CI, 1.69 to 2.66; P < .0001) but not prostate cancer mortality (HR = 0.80; 95% CI, 0.51 to 1.25; P = .34). In contrast, weight was associated with greater prostate cancer mortality (HR = 1.77; 95% CI, 1.22 to 2.55; P = .002) but not all-cause or non-prostate cancer mortality.


CONCLUSIONS
Weight but not prevalent diabetes is associated with greater prostate cancer mortality in men receiving combined modality treatment for locally advanced disease. These observations suggest that the association between obesity and greater prostate cancer mortality is mediated by mechanism(s) other than the characteristic metabolic alterations of diabetes.
Smith
Matthew R
MR
Department of Radiation Oncology, Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA 02114, USA. smith.matthew@mgh.harvard.edu
Bae
Kyounghwa
K
Efstathiou
Jason A
JA
Hanks
Gerald E
GE
Pilepich
Miljenko V
MV
Sandler
Howard M
HM
Shipley
William U
WU
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000401:mortality*; D017273:Goserelin / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011878:Radiotherapy
D018931:Antineoplastic Agents, Hormonal; D017273:Goserelin
Cancer. 2006 Aug 1;107(3):631-9
16802288
J Clin Epidemiol. 2004 Oct;57(10):1096-103
15528061
J Clin Oncol. 2003 Nov 1;21(21):3972-8
14581419
Cancer Causes Control. 2005 Sep;16(7):789-97
16132789
Eur J Cancer. 2005 Dec;41(18):2887-95
16243513
Diabetes Care. 2007 Jan;30 Suppl 1:S42-7
17192378
Nat Genet. 2007 Aug;39(8):977-83
17603485
JAMA. 2005 Sep 14;294(10):1255-9
16160134
Ann Intern Med. 2007 Aug 7;147(3):149-55
17576993
J Clin Oncol. 2006 Sep 20;24(27):4448-56
16983113
J Natl Cancer Inst. 2007 Dec 5;99(23):1793-800
18042933
J Urol. 2005 Sep;174(3):919-22
16093988
Clin Cancer Res. 2005 Oct 1;11(19 Pt 1):6889-94
16203779
Epidemiol Rev. 2007;29:88-97
17478439
Cancer Epidemiol Biomarkers Prev. 2006 Nov;15(11):2056-62
17119028
Diabetes Care. 2006 Jun;29(6):1263-8
16732006
J Clin Oncol. 2004 Feb 1;22(3):439-45
14691120
Cancer. 2007 Dec 15;110(12):2691-9
17999404
J Chronic Dis. 1974 Sep;27(7-8):365-75
4612056
Diabetes Care. 1998 Jul;21(7):1138-45
9653609
J Clin Oncol. 2004 Feb 1;22(3):446-53
14691122
Obes Res. 1998 Sep;6 Suppl 2:51S-209S
9813653