Korean J Radiol.  2020 Apr;21(4):402-412. 10.3348/kjr.2019.0538.

Preoperative Prediction for Early Recurrence Can Be as Accurate as Postoperative Assessment in Single Hepatocellular Carcinoma Patients

• Cha DI
• Jang KM
• Kim SH
• Kim YK
• Kim H
• Ahn SH

• KMID: 2471806
• DOI: http://doi.org/10.3348/kjr.2019.0538

Abstract

OBJECTIVE
To evaluate the performance of predicting early recurrence using preoperative factors only in comparison with using both pre-/postoperative factors.
MATERIALS AND METHODS
We retrospectively reviewed 549 patients who had undergone curative resection for single hepatcellular carcinoma (HCC) within Milan criteria. Multivariable analysis was performed to identify pre-/postoperative high-risk factors of early recurrence after hepatic resection for HCC. Two prediction models for early HCC recurrence determined by stepwise variable selection methods based on Akaike information criterion were built, either based on preoperative factors alone or both pre-/postoperative factors. Area under the curve (AUC) for each receiver operating characteristic curve of the two models was calculated, and the two curves were compared for non-inferiority testing. The predictive models of early HCC recurrence were internally validated by bootstrap resampling method.
RESULTS
Multivariable analysis on preoperative factors alone identified aspartate aminotransferase/platelet ratio index (OR, 1.632; 95% CI, 1.056-2.522; p = 0.027), tumor size (OR, 1.025; 95% CI, 0.002-1.049; p = 0.031), arterial rim enhancement of the tumor (OR, 2.350; 95% CI, 1.297-4.260; p = 0.005), and presence of nonhypervascular hepatobiliary hypointense nodules (OR, 1.983; 95% CI, 1.049-3.750; p = 0.035) on gadoxetic acid-enhanced magnetic resonance imaging as significant factors. After adding postoperative histopathologic factors, presence of microvascular invasion (OR, 1.868; 95% CI, 1.155-3.022; p = 0.011) became an additional significant factor, while tumor size became insignificant (p = 0.119). Comparison of the AUCs of the two models showed that the prediction model built on preoperative factors alone was not inferior to that including both pre-/postoperative factors {AUC for preoperative factors only, 0.673 (95% confidence interval [CI], 0.623-0.723) vs. AUC after adding postoperative factors, 0.691 (95% CI, 0.639-0.744); p = 0.0013}. Bootstrap resampling method showed that both the models were valid.
CONCLUSION
Risk stratification solely based on preoperative imaging and laboratory factors was not inferior to that based on postoperative histopathologic risk factors in predicting early recurrence after curative resection in within Milan criteria single HCC patients.

Keyword

Prediction model; Laboratory factors; Imaging factors; Pathologic factors

MeSH Terms

Area Under Curve
Aspartic Acid
Carcinoma, Hepatocellular*
Humans
Magnetic Resonance Imaging
Methods
Recurrence*
Retrospective Studies
Risk Factors
ROC Curve
Aspartic Acid

Figure

• 

  Fig. 1 Flow diagram of patient selection for study. HCC = hepatocellular carcinoma, MRI = magnetic resonance imaging, RFA = radiofrequency ablation, TACE = transarterial chemoembolization

• 

  Fig. 2 MRI of 54-year-old male with HCC. Arterial phase tumor rim enhancement, peritumoral parenchymal enhancement, and high APRI were noted. APRI level was 0.456. In S8 dome, 3-cm sized lobulated mass showing strong enhancement on arterial phase (A) with subsequent washout on portal phase (B) is present. Of note, arterial phase enhancement is not homogeneous; enhancement is seen mostly in outer or peripheral portion of tumor while inner portion shows poor enhancement. Peritumoral parenchymal enhancement on arterial phase (arrow) (C) was noted beyond tumor margins that can be defined on hepatobiliary phase (D). E, F. Segmentectomy was performed for HCC. Seven months after surgery, subtraction of pre-contrast from arterial phase images demonstrated multiple recurrent HCCs in liver (arrows). APRI = AST/platelet ratio index, AST = aspartate aminotransferase

• 

  Fig. 3 MRI of 54-year-old female with 1.6-cm sized HCC in S7 of liver (not shown). A. Preoperative MRI revealed 1-cm sized NHHN at S4 on HBP. Enhancement of this lesion was not perceivable on arterial phase (not shown). B. Gadoxetic acid-enhanced MRI with diffusion-weighted images performed 18 months after right hemihepatectomy showed that NHHN on HBP had increased in size, measuring 1.9 cm. C. On arterial phase, nodular enhancement within lesion had developed (arrow). D. On diffusion-weighted images, enhancing focus showed high signal intensity (arrow) indicating nodule-in-nodule type HCC. HBP = hepatobiliary phase, NHHN = nonhypervascular hepatobiliary hypointense nodules

• 

  Fig. 4 ROC curve analysis of two prediction models using preoperative laboratory and imaging factors of gadoxetic acid-enhanced MRI only (gray curve) and using both preoperative and postoperative pathologic factors (black curve). Comparison of area under ROC curves of two models showed that performance of prediction model built on preoperative factors only was not inferior to that of one using both pre-/postoperative factors (preoperative factors only; 0.673 [95% CI: 0.623–0.723] vs. after adding postoperative factors; 0.691 [95% CI: 0.639–0.744]; p = 0.0013). AUC = area under curve, CI = confidence interval, ROC = receiver operating characteristic

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