The GALAD scoring algorithm based on AFP, AFP-L3, and DCP significantly improves detection of BCLC early stage hepatocellular carcinoma

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of death in cirrhotic patients worldwide. The detection rate for early stage HCC remains low despite screening programs. Thus, the majority of HCC cases are detected at advanced tumor stages with limited treatment options. To facilitate earlier diagnosis, this study aims to validate the added benefit of the combination of AFP, the novel biomarkers AFP-L3, DCP, and an associated novel diagnostic algorithm called GALAD.

Material and methods: Between 2007 and 2008 and from 2010 to 2012, 285 patients newly diagnosed with HCC and 402 control patients suffering from chronic liver disease were enrolled. AFP, AFP-L3, and DCP were measured using the µTASWako i30 automated immunoanalyzer. The diagnostic performance of biomarkers was measured as single parameters and in a logistic regression model. Furthermore, a diagnostic algorithm (GALAD) based on gender, age, and the biomarkers mentioned above was validated.

Results: AFP, AFP-L3, and DCP showed comparable sensitivities and specifities for HCC detection. The combination of all biomarkers had the highest sensitivity with decreased specificity. In contrast, utilization of the biomarker-based GALAD score resulted in a superior specificity of 93.3 % and sensitivity of 85.6 %. In the scenario of BCLC 0/A stage HCC, the GALAD algorithm provided the highest overall AUROC with 0.9242, which was superior to any other marker combination.

Conclusions: We could demonstrate in our cohort the superior detection of early stage HCC with the combined use of the respective biomarkers and in particular GALAD even in AFP-negative tumors.

Zusammenfassung

Hintergrund: Das hepatozelluläre Karzinom (HCC) zählt weltweit zu den häufigsten Todesursachen bei Patienten mit Leberzirrhose. Die HCC-Detektion in frühen Stadien ist weiterhin zu selten, weshalb nur bei einem Bruchteil der Patienten kurativ intendierte Therapien durchführbar sind. Das Ziel dieser großen monozentrischen Studie ist die Optimierung der HCC-Frühdetektion mittels additivem Einsatz der neuen Biomarker AFP-L3 und DCP zusätzlich zur AFP-Bestimmung im neuen Diagnosealgorithmus GALAD.

Material und Methoden: Von 2007 bis 2008 sowie von 2010 bis 2012 wurden sowohl 285 Patienten mit der Erstdiagnose eines HCCs als auch 402 Patienten mit chronischen Lebererkrankungen in diese Studie eingeschlossen. Die Bestimmung von AFP, AFP-L3 und DCP erfolgte mit dem automatisierten µTASWako-i30-Immunoanalyzer. Die Leistungsfähigkeit der Biomarker wurde sowohl für Einzelparameter als auch im logistischen Regressionsmodell getestet. Zudem wurde der Diagnosealgorithmus GALAD validiert, der unter Einbeziehung von Geschlecht, Alter und der genannten Biomarker berechnet wird.

Ergebnisse: Einzeln erzielten AFP, AFP-L3 und DCP jeweils vergleichbare Sensitivitäten und Spezifitäten in der HCC-Detektion. Die höchste Sensitivität wurde in der Kombination aller drei Marker erzielt bei allerdings verminderter Spezifität. Im Gegensatz dazu zeigte der GALAD-Score eine deutlich überlegene Spezifität von 93,3 % bei einer Sensitivität von 85,6 %. Bei HCC-Frühstadien (BCLC 0/A) konnte GALAD eine AUROC von 0,9242 erzielen und war auch in dieser Subgruppe allen o. g. Markern und -kombinationen signifikant überlegen.

Schlussfolgerung: Für unsere Kohorte konnten wir demonstrieren, dass der kombinierte Einsatz der o. g. Biomarker und insbesondere der GALAD-Score die HCC-Detektion insbesondere in Frühstadien selbst bei AFP-negativen Tumoren signifikant verbessern konnte.

Schlüsselwörter

hepatozelluläres Karzinom - HCC - diagnostische serologische Tests - Prognosemodelle - Tumormarker - AFP - AFP-L3 - DCP - GALAD - BALAD-2

Key words

hepatocellular carcinoma - HCC - diagnostic serological tests - prognostic models - tumor marker - AFP - AFP-L3 - DCP - GALAD - BALAD-2

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