Matrix metalloproteinases (MMPs) are known to promote tumor development and to facilitate the spread of invasive cancers. Two recent publications conclude that high MMP levels in the urine of patients with bladder malignancy indicate advanced disease and poorer prognosis.

A team from Denmark and The Netherlands studied the levels of MMP-9 in the urine of 188 patients diagnosed with bladder cancer. Voided samples were collected and frozen prior to surgery. A commercially available immunocapture assay kit was used to measure MMP-9 in thawed aliquots.

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During 15 years of follow-up 175 patients died. Construction of a Kaplan–Meier survival plot revealed that poor patient survival was predicted by increasing levels of MMP-9 in preoperative urine. An elevated concentration of MMP-9 was an independent prognostic marker of death.

In their paper, published in Acta Oncologica, lead author Birgitte Offersen and her colleagues outline the wide-ranging potential of such a noninvasive test. Applications could include optimizing staging to better direct choice of therapy, evaluating patient response to treatment, early detection of relapse, and reducing the need for follow-up cystoscopy.

Tibor Szarvas and co-workers, based in Germany and Hungary, share this enthusiasm for MMP-based prognosis in bladder carcinoma. These investigators focused on MMP-7, comparing levels in the voided urine of 132 patients and 96 controls.

There was no difference in the concentration of urinary MMP-7 between the control group and patients with localized disease. In stark contrast, a fourfold increase in MMP-7 level was detected in the urine of participants with metastatic malignancy. The sensitivity and specificity of the enzyme-linked immunosorbent assay for differentiating between patients with metastatic and localized carcinoma were 82% and 78%, respectively, at an MMP-7 threshold of 6.9 ng/ml.

“One-third of patients diagnosed with muscle-invasive bladder cancer have undetected metastasis at the time of surgical treatment” comments Szarvas. The potential utility of incorporating noninvasive MMP testing into everyday clinical decision-making is, therefore, great.