Neopterin Levels Associated With Survival in Ovarian Cancer

Elevated levels of neopterin were found to be significantly associated with poorer survival outcomes in patients with ovarian cancer in a new study by the Austrian Gynecologic Oncology Group. The compound could be used as a prognostic marker in this malignancy.

Neopterin is produced by macrophages upon stimulation by interferon-gamma, meaning that elevated concentrations indicate a cellular innate immune response. “High levels have been found to be associated with disease activity and impaired prognosis in several neoplasms,” wrote study authors led by Christian Marth, MD, PhD, of the Medical University of Innsbruck, Austria.

The new study measured urinary neopterin levels at diagnosis and after primary treatment in 114 patients with ovarian cystadenomas and 223 with invasive ovarian cancer. Surviving patients were followed for a median of 161 months. The results of the study were published online ahead of print in Annals of Oncology.

Elevated levels of neopterin (defined as > 250 µmol/mol creatinine, to account for differences in urine density) were found less frequently in women with benign ovarian cystadenomas (24%) than in patients with malignant disease (58%).

On a univariate analysis, high neopterin levels both before and after therapy were significantly associated with both overall and progression-free survival (P < .001). FIGO stage, tumor grade, residual tumor after surgery, age, and histological tumor subtype were also associated with survival outcomes.

A multivariate analysis showed that pretreatment neopterin levels remained significantly predictive of overall survival. Patients with elevated neopterin had a relative risk of death of 5.2 (95% CI, 3.0–11.85; P < .05) compared to non-elevated levels. Residual tumor and age also remained predictive of overall survival.

Patients with normal neopterin levels both before and after therapy had the best prognosis, followed by patients with elevated levels that normalized post-treatment. Patients with elevated levels at both measurements fared worst.

A subgroup of 30 patients with surgically staged FIGO I or II ovarian cancer was then analyzed as a separate cohort. Three of these patients had elevated neopterin levels, and two of those died of the disease; in contrast, only two of 27 patients with normal pretreatment neopterin levels died (P = .004).

“Measurement of urine neopterin is a simple analysis that might allow adaption of follow-up examinations, especially for patients with persistently high neopterin levels who are at higher risk for disease progression,” the authors wrote. “Accordingly, neopterin could be an interesting biomarker deserving prospective investigation for selecting patients who may derive the greatest benefit from the costly bevacizumab maintenance therapy in frontline ovarian cancer treatment.”