NCCS guidelines for hepatocellular cancer validated in real-world study

The National Cancer Centre Singapore (NCCS) consensus guidelines for staging, prognosticating, and recommending treatment in hepatocellular carcinoma (HCC) appear to have strong applicability to the clinicians and populations for whom they are intended.

In a recent study involving 578 patients who received treatment for primary HCC at the NCCS’s Comprehensive Liver Cancer Clinic (CLCC), the guidelines were able to accurately stratify patients according to disease stage, namely early (n=129, 22.3 percent), locally advanced (n=266, 46 percent; 127 had macrovascular invasion), and metastatic (n=183, 31.7 percent). This naming system not only correlated with disease burden but also provided good prognostic applications.

Both overall (OS) and progression-free (PFS) survival worsened with increasing disease stage and/or vascular involvement. The corresponding median OS and PFS estimates were not reached and 53.4 months in the early HCC group; 25.7 and 10.3 months among patients without macrovascular invasion and 8.4 and 6.1 months among those with macrovascular invasion in the locally advanced HCC group; and 8.0 and 4.6 months in the metastatic HCC group. [Liver Cancer 2021;10:224-239]

Furthermore, treatments that did vs did not comply with the NCCS guidelines conferred superior clinical outcomes. Median OS was significantly higher among patients who received guideline-compliant treatment across the early (nonestimable vs 23.5 months; p<0.0001), locally advanced (28.1 vs 22.2 months; p=0.0216), and locally advanced with macrovascular invasion (10.3 vs 3.3 months; p=0.0013) HCC groups. This difference in OS was not observed in metastatic HCC (8.1 vs 6.8 months; p=0.6300), and PFS was similar.

“The high overall compliance rate [79.2 percent] and satisfactory clinical outcomes of patients managed according to the NCCS guidelines confirm its validity. This validation using real-world data considers patient and treating clinician preferences, thus providing a realistic analysis of the usefulness of the NCCS guidelines when applied in the clinics,” according to a team of researchers led by Dr Xin Hui Chew from the Singapore General Hospital and NCCS.

When validated against the Barcelona Clinic Liver Cancer (BCLC) guidelines in advanced HCC patients, treatment compliant with NCCS guidelines yielded better clinical outcomes compared with treatment only allowed by BCLC guidelines (median OS, 14.2 vs 7.4 months; p=0.0002; median PFS, 6.1 vs 4.0 months; p=0.0286).

However, further comparison with the Hong Kong Liver Cancer (HKLC) guidelines showed similar survival outcomes for “patients across all HKLC stages receiving NCCS-recommended treatment regardless of whether their treatment was allowed by HKLC,” according to Chew.

Chew pointed out that the NCCS guidelines cover a wider range of treatment options for each HCC stage compared to the HKLC guidelines, and the lack of difference in clinical outcomes underscores the utility of the treatments recommended in the NCCS guidelines.

Treatment flexibility based on expert consensus

At the CLCC, HCC patients are routinely assessed by a multidisciplinary tumour board that represents at least four clinical disciplines (from surgical oncology/Hepato-pancreato-biliary surgery, medical oncology, nuclear medicine, radiation oncology, interventional radiology, and diagnostic radiology).

“[P]rovisions in the guidelines specifically allow the [board] the option of consensus-based recommendation of individualized treatment regime[n] for each patient independent of the NCCS guidelines,” noted Chew.

In more advanced-stage HCC, for example, treatment recommendations become increasingly complex and are associated with less favourable risk-benefit ratios. Thus, factors like patients’ personal preference and individual physician’s recommendations become increasingly weighted in the management of this disease stage, as the expert pointed out.

Also, unlike some Western guidelines, the NCCS consensus guideline deviates from the traditional “stage hierarchy” approach. “Instead, by incorporating alternative treatment modalities or treatment stage migration, our guidelines delink disease stage and its specific treatment, providing flexibility based on expert consensus to improve patient outcomes,” Chew said. [Hepatology 2020;72:2206-2218]

“In clinical practice, some patients will receive treatment recommended for later stage patients when first-line therapy recommended for that stage is not feasible, a concept known as treatment stage migration,” he added. [JHEP Rep 2019;1:114-119]

Since its implementation in 2014, the NCCS consensus guidelines have only been validated in the present study, according to Chew. “[C]onsiderable patient and treating physician autonomy will be exercised in [real-world] treatment decisions in HCC, especially when the disease is more advanced. Multidisciplinary management, alongside treatment guidelines, is shown to enhance patient selection and optimizes treatment outcomes for individual patient.”