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Association of Preoperative Plasma Levels of Insulin-Like Growth Factor I and Insulin-Like Growth Factor Binding Proteins-2 and -3 With Prostate Cancer Invasion, Progression, and Metastasis

From the Baylor Prostate Center and Male Reproductive Medicine and Surgery, the Scott Department of Urology and Department of Molecular and Cellular Biology, Department of Pathology, Baylor College of Medicine, and The Methodist Hospital, Houston, TX; and the Department of Urology and Department of Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY.

Address reprint requests to Kevin Mark Slawin, MD, Scott Department of Urology, Baylor College of Medicine, 6560 Fannin St, Ste 2100, Houston, TX 77030; email: kslawin{at}www.urol.bcm.tmc.edu

PURPOSE: We tested the hypothesis that preoperative plasma levels of insulin-like growth factor (IGF) binding protein (BP)-2 or IGFBP-3 would predict cancer stage and prognosis in patients undergoing radical prostatectomy.

MATERIAL AND METHODS: Plasma levels of IGF-I, IGFBP-2, and IGFBP-3 were measured preoperatively in 120 consecutive patients who underwent radical prostatectomy for clinically localized disease, postoperatively in 51 of these patients, in 44 healthy men, in 19 patients with metastases to regional lymph nodes, and in 10 patients with bone metastases.

RESULTS: Plasma IGFBP-3 levels were lowest in patients with bone metastases (P .043). IGFBP-2 levels were elevated in prostate cancer patients compared with healthy subjects (P .006). However, within the group of prostatectomy patients, preoperative plasma IGFBP-2 levels were lower in patients with advanced disease (P .033), were inversely correlated with prostatic tumor volume (P = .037), and declined after prostate removal (P = .044). Lower preoperative IGFBP-2 and IGFBP-3 levels and biopsy Gleason score were independent predictors of biochemical progression (P = .043, P = .040, and P = .020, respectively). In patients with disease progression, preoperative plasma IGFBP-3 levels were lower in those with aggressive than in those with nonaggressive failure (P = .042).

CONCLUSION: Elevation of plasma IGFBP-2 levels in prostate cancer patients apparently is due to increased release directly from the prostate. For patients with clinically localized prostate cancer, preoperative plasma IGFBP-2 levels are inversely associated with biologically aggressive disease and disease progression. Preoperative plasma IGFBP-3 levels were decreased in patients with prostate cancer metastases and were an independent predictor of biochemical progression after surgery, presumably because of an association with occult metastatic disease present at the time of radical prostatectomy.

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