M-A Rowlands, JMP Holly, F Hamdy, J Phillips, L Goodwin, G Marsden, D Gunnell, J Donovan, DE Neal, RM Martin
Cancer Causes Control
CONTEXT: Many studies have reported associations of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with prostate cancer development, but none have investigated their association with fatal progression of prostate cancer. OBJECTIVE: We investigated associations of circulating IGF-I, IGF-II, IGFBP-2 and IGFBP-3 with all-cause and prostate cancer mortality in men with clinically identified prostate cancer, stratified by whether localised (stage T1 or T2) or advanced (T3, T4, N1 or M1) at diagnosis. DESIGN, SETTING AND PARTICIPANTS: UK hospital-based cohort study of 396 men with prostate cancer, diagnosed between 1990 and 2008, with mean follow-up of 3.7 years. MAIN OUTCOME MEASURES: All-cause and prostate cancer-specific mortality. RESULTS: In men with advanced cancer, there was some evidence that IGF-I was positively associated (HR 1.20; 95% CI: 0.96, 1.49; p = 0.11) and IGFBP-3 was inversely associated (HR 0.84; 95% CI: 0.70, 1.01; p = 0.07) with all-cause mortality after controlling for age, treatment status, smoking, prostate-specific antigen and Gleason grade at diagnosis. There was some evidence that IGF-I was positively associated with prostate cancer mortality in advanced cases (HR 1.23; 95% CI: 0.94, 1.62; p = 0.13). In advanced cancers, associations of IGF-I with all-cause (HR 1.68; 95% CI: 1.28, 2.23; p < 0.001) and prostate cancer-specific (HR 1.59; 95% CI: 1.11, 2.28; p = 0.01) mortality strengthened (and were conventionally statistically significant) after further controlling for IGFBP-3. CONCLUSIONS: Measures of IGF-I and IGFBP-3 may have potential as prognostic markers in predicting risk of death in men with advanced prostate cancer. Large, prospective studies with repeat IGFs and IGFBPs are now required.