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Urinary VEGF and MMP Levels As Predictive Markers of 1-Year Progression-Free Survival in Cancer Patients Treated With Radiation Therapy: A Longitudinal Study of Protein Kinetics Throughout Tumor Progression and Therapy

From the Radiation Oncology Branch, Radiation Oncology Sciences Program, and Biometric Research Branch, Division of Cancer Treatment and Diagnosis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD; Department of Surgery, Harvard Medical School; and Vascular Biology Program and the Department of Surgery, Children's Hospital, Boston, MA.

Address reprint requests to Kevin Camphausen, MD, Radiation Oncology Branch, Radiation Oncology Sciences Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Dr, Building 10, Room B3/B69, Bethesda, MD, 20892-1002; e-mail: Camphauk{at}mail.nih.gov

PURPOSE: To determine the predictive value of urinary levels of two angiogenic factors, vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMPs), in a longitudinal study to determine their correlation with 1-year progression-free survival in patients with cancer.

PATIENTS AND METHODS: VEGF and MMP levels were measured in the urine of 65 cancer patients at first evaluation, during therapy, and at follow-up (n = 242); normalized by creatinine levels; and compared with 16 healthy controls. The correlation of initial levels and trends of VEGF and MMPs with 1-year progression-free survival was assessed using two-sample tests and stepwise logistic regression.

RESULTS: Urinary VEGF levels at presentation were different between patients with local-regional cancer and normal controls, and between patients with metastatic prostate cancer and local-regional disease (P = .04 and .01, respectively). Similar results were found with MMP measurement (P = .03 and .0001, respectively). Of those patients subsequently treated with radiation, VEGF levels at presentation between patients with no evidence of disease (NED) after radiation and those who had persistent or recurrent disease after radiotherapy were also different (P = .039). The comparison between angiogenic factor levels taken at least 1 month postradiotherapy and the last level taken during treatment was the strongest predictor of patient 1-year progression-free survival (P = .004). Similarly, the overall MMP trend was also significantly associated with 1-year progression-free survival, as was the individual MMP-2 trend (P = .004 and .001, respectively). Stepwise logistic regression revealed that the VEGF trend comparing postradiation levels with last level taken during treatment was an independent predictor of progression-free survival (P = .02).

CONCLUSION: This small exploratory study suggests that the angiogenic urinary trends of VEGF and MMPs may be useful predictive markers for progression-free survival in cancer patients after the completion of radiotherapy.

M.A.M. was supported in part by Global Medical Products Inc.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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