Prognostic value of CA 125 and neopterin in women with ovarian cancer undergoing second-look laparotomy

LETTERS TO THE EDITORS Prognostic value of CA 125 and neopterin in women with ovarian cancer undergoing second-look laparotomy To the Editors: We have read the article by Hunter et al. (Hunter V.I, Daly L, Helms M, et al. The prognostic significance of CA 125 half-life in patients with ovarian cancer who have received primary chemotherapy after surgical cytoreduction. AYI J Ollsnl GVKECOI. 1990; 163: 1164-7) describing prolonged overall survival in patients with CA 125 half-life <20 days. The authors pointed out that after negative second-look procedures, "eight individuals whose serum CA 125 value normalized by 65 days after initial operation appeared to have improved survival." On the basis of a recent investigation, I we would like to extend the discussion raised by the authors. We have determined serum concentrations ofCA 125 and urine levels of neopterin immediately before sec(md-Iook laparotomy in 72 women with ovarian cancer. Neopterin is a sensitive marker of cell-mediated immune activation." One-year survival rates (mean ± SE) after surgical reexploration were associated (p < 0.000 I) with concentrations of CA 125 (93% ± 4% in women with CA 125 values <35 U I Ill\; 47% ± 13% in women with higher CA 125 values) as well as neopterin (88% ± 5(k· in women with neopterin values <235 f.Lmollmol creatinine; 270/c ± 13% in women with higher neopterin values). Multivariate analysis was done to assess whether both predictors were independent of the surgical findings at second look, and separate survival curves were obtained by subdividing the group according to secondlook outcome. CA 125 serum levels showed a stronger direct correlation than neopterin with the surgical findings at the procedure but biled to reach joint significance in addition to sUI'gical outcome. In contrast, a significant correlation of raised neopterin levels with more unfavorable p"ognosis was found in patients with no evidence of disease and in those with residual tumors < I cm. Women with tumors> I cm unifonnly had poor prognoses, as did patients with low versus high neopterin levels. Identification of patients with negative second-look laparotomies who are at higher risk of disease progression would be helpful in ovarian cancer follow-up. Our results suggest that CA 125 provides an excellent predictor of the findings at second-look operation but does not provide predictive information for further follow-up in addition to the surgical outcome. In contrast, neopterin concentrations (which show a weaker correlation with the outcome of second look) do provide independent prognostic information and may be used to define risk groups. Our results are compatible with the background of both markers: whereas CA 125 is a classic tumor marker, neopterin is an indicator of

cell-mediated immune activation and thus contributes information about a mechanism different from instantaneous tumor progression. Lotlwi C. Fuith, lHD Allgemeines (jtfent/ir:iJes Kmnhenhaus del' BanllhiTzigell Briidn. Abteilungfiir Frauellheilkunde lIIld Geburtshilfe. Ester/ulZYlfr. 26, A-70()() Eisenstadt, Austria

Dietmar Fuchs, PhD, Gilbert Reilmegger, DSr;, anri Hellllut Wachter, PhD Institut fi'ir A1edizillische Chemie Ulld Biochemie, Ulli,l. fllllsbnlck. Fritz Preg! Str. 3, A-6020 Innsinur:/i. Austria

REFERENCES I. Fuith Le, Dapunt O. Hetzel H, Reibnegger G, Wachter H. Second-look operation in women with ovarian cancer. I. Concentrations of neopterin in urine and CA 125 in serum at second-look laparotomy: their relationship with subsequent prognosis. TUlJlor Diagn Ther 1990; II: 147-51. 2. Wachter H. Fuchs D, Hausen A, Reibnegger G, Werner ER. Neopterin as a marker for activation of cellular immunity: immunologic basis and clinical application. Adv Clin Chern 1990;27:HI-141.

Response declined

Free /3-protein studies need confirmation To the Editors: I was impressed by the article of Macri et al. (MacriJN, Kasturi RV, Krantz DA, et al. Maternal serum Down syndrome screening: Free f3-protein is a more effective marker than human chorionic gonadotropin. AM J OIlSTET GYJ\ECOL 1990; 163: 1248-53). However, the following month an advertisement appeared in my mail over the senior author's signature and from his commercial laboratory. It extolled free f3-protein as a "patent pending scientific discovery" that "is the most accurate and reliable biochemical marker for Down's syndrome screening," citing this article by Macri et al. The JOURI\AL asks potential authors about conMict of interest, and this appears to be an example of significant "commercial association of the author." In my view, the findings of Macri et al. should be quickly confirmed by an independent investigator. Robert C. Goodlin, MD Department of Health and Hospitals. Cit, and COUllt, of Denvl'l'. 777 Bannock St., Denver, CO 80204-451J7

Reply To the Editors: Dr. Goodlin is aware that it is conventional

in clinical investigation to subject an original scientific discovery to retrospective studies, to publish these findings after peer review, and thereafter to undertake prospective studies. A careful reading of what Goodlin refers to as "an advertisement" reveals that it is actually a letter calling for participation in a prospective study. The letter states: "The discovery has been reduced to

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