FDA Grants Breakthrough Device Designation to GALAD Score for Early Diagnosis of HCC

The FDA has granted Breakthrough Device designation to GALAD score, a serum biomarker-based device that predicts the probability that patients with chronic liver disease will develop hepatocellular carcinoma.

The FDA has granted a breakthrough device designation to the GALAD score (Elecsys), a serum biomarker-based model that predicts the probability that patients with chronic liver disease will develop hepatocellular carcinoma (HCC).1

“HCC is the fourth leading cause of cancer-related death worldwide, with the highest burden of disease in East Asia and Africa. This high mortality is largely driven by most patients being detected at a late stage when curative therapies are no longer possible. Therefore, improving early HCC detection is a critical area of need,” said Amit Singal, MD, medical director of the Liver Tumor Program and clinical chief of pathology, UT Southwestern Medical Center, in a statement.

The GALAD score is calculated by combining gender and age with the results of 3 assays: α-fetoprotein (AFP), AFP isoform L3 (AFP-L3), and des-gamma-carboxy prothrombin (DCP).

In a recent study published inClinical Gastroenterology and Hepatology, the GALAD score was compared with individual serum AFP, AFP-L3, and DCP levels in patients with liver disease to determine which is better for detecting the chances of these patients developing HCC. The GALAD score was determined to be a superior biomarker for early diagnosis of HCC in patients with nonalcoholic steatohepatitis (NASH), a chronic liver disease.2

The study included 125 patients with NASH from 8 different centers in Germany. Patients’ AFP, AFP-L3, and DCP were compared with the GALAD score to identify the patients who did have HCC using corresponding area under the curve (AUC) analyses and receiver operating characteristic curves. The study also included a cohort of 389 patients with NASH who were followed for a median of 167 months in Japan.

The results show a significantly higher median of AFP, AFP-L3, DCP, and the GALAD score levels in patients with any stage of NASH-HCC compared with NASH control participants. Moderate sensitivity for detection of HCC at any stage were reached in common cutoffs of the individuals markers (AFP 56.8% cutoff, 10 ng/mL; AFPL3 56.8% cutoff, 10%; DCP 81.6% cutoff, 0.76 ng/mL) and the respective specificities were high (98.7%, 96.5%, and 87.88%). In an AUC analysis, the GALAD score demonstrated a significantly higher overall diagnostic performance than each individual biomarker (P<.0005). The investigators also identified an optimal cutoff of —1.334 (sensitivity, 91.2%; specificity, 90.9%) by the highest Youden index.

Among cases of early-stage HCC—defined as Barcelona Clinic Liver Cancer (BCLC) stage A, investigators analyzed each biomarker in isolation. In this analysis, the GALAD AUC for early detection of HCC was 0.92, which was a better score than AFP (P= .0021), AFP-L3 (P<.0001), and DCP (P>.5). Additionally, a sensitivity of 72.4% and a specificity of 95.2% were observed with the —0.63 cutoff. The newly calculated cutoff of –1.335, however, achieved a sensitivity of 86.2% and a specificity of 90.9%. When early HCC was defined using Milan criteria, the results were similar, showing a 68.0% sensitivity and 95.2% specificity at the common cutoff of –0.63. The Milan criteria reached 84.0% sensitivity and the specificity was 90.9% at the common cutoff of –1.334.

A subgroup analysis of patients with cirrhosis of the liver included 95 patients with HCC and 49 control subjects. An AUC of 0.93 was achieved for detecting HCC of any stage, which was superior to that observed with AFP (AUC, 0.79;P= .0003), AFP-L3 (AUC, 0.75; P<.0001), and DCP (0.83;P= .0033) individually. In participants with early cirrhotic HCC (n = 22), the AUC was 0.85 with a sensitivity of 68.2% and 91.8% specificity at a —0.63 cutoff.

Among patients with non-cirrhotic NASH (HCC, n = 30; control subjects, n = 182), GALAD achieved an AUC of 0.98 for the detection of HCC at any stage. The sensitivity in this analysis was 93.3% and the specificity was 96.1% at a cutoff of —0.63. In patients with early non-cirrhotic HCC (n = 7), the AUC achieved by GALAD was 0.94, with an 85.7% sensitivity and a 96.2% specificity at a –0.63 cutoff.

In the Japanese cohort, 7% of patients developed HCC after a median of 10.3 years (range, 3.1-21.3) from the start of surveillance. Of these 28 patients, GALAD scores were available for 26. The analysis showed significantly higher GALAD scores among 17 patients who developed HCC, who had more than 1 set of biomarkers before their diagnosis, which had a strong increase within a shorter time frame than other patients.

The study was limited by a low number of early-stage BCLC 0/A cases, which would have been the screening target group. But robust results were still observed in this subgroup of patients, study author Best et al noted.

The authors concluded from this study that the GALAD score is a superior serum marker for the detection of HCC in patients with NASH, independent of tumor cirrhosis. They also stated that GALAD should be investigated as a potential screening tool to detect resectable-stage HCC in a prospective study to determine a cutoff.

"We are excited about FDA’s recognition of the potential clinical benefit the Elecsys GALAD score could bring in diagnosing hepatocellular cancer at an early stage," said Thomas Schinecker, CEO of Roche Diagnostics, in a statement. "The combination of blood-based biomarkers with clinical algorithms has the potential to significantly reduce the mortality of [patients with] HCC as they can receive a more timely diagnosis and treatment."

References

  1. FDA grants Breakthrough Device Designation for Roche's Elecsys GALAD score to support earlier diagnosis of hepatocellular carcinoma [news release]. Basel, Switzerland: Roche; March 4, 2020. https://bit.ly/2PGMPVt. Accessed March 4, 2020.
  2. Best J, Bechmann LP, Sowa JP, et al. GALAD score detects early hepatocellular carcinoma in an international cohort of patients with nonalcoholic steatohepatitis.Clinical Gastroenterology and Hepatology.2020;18:728