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Poorly Differentiated Tumor Size Linked to Worse Prognosis in HCC, Study Finds


Investigators examined medical records spanning 3 decades to look at the effect of poorly differentiated tumor size on outcomes in survival in hepatocellular carcinoma (HCC).

Tumor size is a significant prognostic indicator for survival in hepatocellular carcinoma (HCC), the most common type of liver cancer, according to recent findings. The researchers said their results can help providers tailor treatment strategies for patients with HCC.

Published in the journal Liver Cancer, the study examined whether the prognostic effect of tumor differentiation on survival outcomes is modified by tumor size. Poorly differentiated HCC appears disorganized and has a tendency to spread aggressively.

To clarify the prognostic value of tumor differentiation in HCC, researchers at the Osaka City University Graduate School of Medicine in Japan probed whether different sizes of poorly differentiated tumors affect rates of early recurrence and prognosis by examining 30 years worth of data.

Researchers included 1107 patients who underwent initial and curative hepatic resection for HCC without macroscopic vascular invasion at Osaka City University Hospital between January 1991 and December 2018. Cases were grouped by tumor size: < 2 cm, 2-5 cm, and ≥ 5 cm, and were analyzed with a multivariable Cox proportional hazards regression model to understand the association between HCC and patient survival time.

Adjusted HRs for patients with poorly differentiated HCCs were as follows:

  • Reduced overall survival (OS), 1.31 (95% CI, 1.07-1.59)
  • Recurrence-free survival (RFS), 1.07 (95% CI, 0.89-1.28)
  • Early RFS, 1.31 (95% CI, 1.06-1.62)
  • Early extrahepatic RFS, 1.81 (95% CI, 1.03-3.17)

In addition, an analysis of the effect modification of tumor differentiation according to tumor size showed that poorly differentiated HCC was linked with a reduced OS (P = .033).

The HRs of poorly differentiated HCCs sharply increased in patients with tumors measuring up to 5 cm. In a statement, the researchers said a key takeaway is that ≥ 5-sized tumors have a 2.33-fold risk of early extrahepatic recurrence. For patients with tumors measuring between ≥ 2 and < 5 cm, the risk was 1.89.

The adjusted HRs of reduced OS in patients with poorly differentiated HCCs measuring < 2, ≥ 2 and < 5, and ≥ 5 cm were 1.22, 1.33, and 1.58, respectively.

The corresponding adjusted HRs of reduced early RFS were 0.85 (95% CI 0.46–1.57), 1.34 (95% CI 1.01–1.8), and 1.57 (95% CI 1.03–2.39), respectively.

Precise predictors of early recurrence and early spreading of HCC can help improve the survival rate of the disease, the authors noted.

Early recurrence is linked to worse OS, and they said the findings support close monitoring for patients with tumors measuring ≥ 5 cm. Poorly differentiated tumors up to 2 cm have better outcomes.

For patients with advanced HCC and poorly differentiated tumors, effective therapies in the adjuvant setting are not yet approved but several immune checkpoint inhibitors have recently shown durable response effects, they said. Therefore, poorly differentiated HCC measuring ≥ 5 cm could be an additional criterion for adjuvant chemotherapy after surgery.

The study had several limitations, including the long timeframe and its retrospective nature. In addition, surgical, medical, and imaging techniques likely changed over time, but that was accounted for in the regression analysis, the researchers said.


Shinkawa H, Tanaka S, Kabata D, et al. The prognostic impact of tumor differentiation on recurrence and survival after resection of hepatocellular carcinoma is dependent on tumor size. Liver Cancer. Published online August 24, 2021. doi:10.1159/000517992

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