Hepatocellular Carcinoma Extrahepatic Metastasis in Relation to Tumor Size and Alkaline Phosphatase Levels

Abstract

Background: Hepatocellular carcinoma (HCC) is known to metastasize. However, there are few reports on patients with metastasis at the time of HCC diagnosis. Aims: To evaluate the incidence and characteristics of extrahepatic metastasis patients presenting at baseline with noncurable, advanced HCC. Results: The total HCC cohort was initially dichotomized into 2 subcohorts, with (n = 214) and without (n = 719) extrahepatic metastasis (‘metastasis'), and patient baseline characteristics were compared. The main findings for patients with metastasis (22.9% of total cohort) compared with other, nonmetastatic patients were: more advanced tumors, as judged by larger tumor diameters, more tumor multifocality and percent with portal vein thrombosis, higher blood α-fetoprotein and des γ-carboxy prothrombin levels and alkaline phosphatase (ALKP), but not bilirubin levels, and a lower incidence of cirrhosis. There was a strong correlation between increases in tumor size and percent of patients with metastasis. A subset of patients with larger tumors was identified with low blood ALKP levels and better survival. Survival in the total metastasis cohort was lower than in the non-metastasis cohort, as expected, but only in patients with smaller tumors. In patients with larger tumors, survival with or without metastasis was similar and poor. Conclusions: There was a lower incidence of cirrhosis in HCC patients with metastasis, and they had larger and more aggressive primary tumors. Patients with smaller, but not larger, tumors and metastasis had worse prognosis than patients without metastasis. A distinct subset of metastatic patients was identified that had better prognosis and low ALKP levels.

Nomogram predicting extrahepatic metastasis of hepatocellular carcinoma based on commonly available clinical data

“…Carr et al . reported a relationship between increasing HCC size and the percentage of patients with EHM . In the current study, tumor size was an independent predictor of EHM ( P = 0.004).…”

“…41 Carr et al reported a relationship between increasing HCC size and the percentage of patients with EHM. 42 In the current study, tumor size was an independent predictor of EHM (P = 0.004). We used a tumor size of ≥3 cm in the current study because a tumor size cut-off value of 3 cm or 5 cm has a similar HR for EHM.…”

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“…There is something interesting about the 5-cm size limit, beyond which the incidence of both portal vein thrombosis and extrahepatic metastasis increases. 10,11 We hypothesize that increasing lesion size is associated with a change in biology or aggressiveness, and this has indeed been recently demonstrated. 12 However, other possible contributors to HCC recurrence after OLTx include immune suppression with increased tumor growth, 13,14 circulating tumor cells, [15][16][17][18] enhanced carcinogenesis in the presence of recurrent hepatitis, and patients living longer after transplant, thus having more time for preexisting micrometastases to grow.…”

“…Almost 50% of recurrences occur outside the liver, 10,[19][20][21] suggesting the presence of micrometastases at the time of OLTx. However, immune suppression may also alter the biology of HCC.…”

Albumin-to-alkaline phosphatase ratio serves as a prognostic indicator in unresectable pancreatic ductal adenocarcinoma: a propensity score matching analysis

“…Accordingly, oxidative stress plays a vital role in the tumorigenesis of PDAC [42]. Elevated ALP levels may serve as a potential predictor of oxidative stress [43], thereby contributing to cancer progression and poor disease outcomes [44] [45]. Because of this, patients with low AAPR might have a poor prognosis.…”