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Screening

Six months or twelve? Korea's liver cancer surveillance data separate the two intervals

Among 64,674 Korean patients who developed hepatocellular carcinoma, 51.9 percent of those screened at six-month intervals received curative treatment. Among those never screened, 34.5 percent did.

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In short

In a national cohort drawn from Korea's hepatocellular carcinoma surveillance programme, 64,674 patients who developed liver cancer were grouped by how often they had been screened, and those screened at intervals of six months or less received curative therapy most often — 51.9 percent, against 48.3 percent at 7 to 12 months, 43.8 percent at 13 to 24 months, 41.3 percent at 25 to 36 months and 34.5 percent among those never screened — with all-cause mortality hazard ratios of 1.07, 1.14 and 1.37 for the two-year, three-year and never-screened groups against the six-month group.

Key takeaways

  • The study identified 3,201,852 people in the target population of Korea's national hepatocellular carcinoma surveillance programme between 2008 and 2017, of whom 64,674 developed liver cancer and were analysed.
  • Curative therapy was received by 51.9 percent of those screened at six-month intervals or less, 48.3 percent at 7 to 12 months, 43.8 percent at 13 to 24 months, 41.3 percent at 25 to 36 months, and 34.5 percent of those never screened.
  • Odds ratios for receiving curative therapy against the six-month group were 0.87 at one year, 0.76 at two years, 0.77 at three years and 0.57 for the never-screened.
  • All-cause mortality hazard ratios against the six-month group were 1.07 at two years, 1.14 at three years and 1.37 for the never-screened.
  • The annual group's hazard ratio of 0.96 was not significantly different from the six-month group, and after adjustment for lead-time bias it was 0.91.
  • Receiving curative therapy was associated with a substantial survival benefit, hazard ratio 0.26.
  • Surveillance participation among Korean people with disabilities rose from 25.7 percent in 2006 to 49.6 percent in 2015, while participation among people without disabilities rose from 24.9 to 54.5 percent.

Liver cancer surveillance is one of the few screening programmes aimed not at the general population but at a defined high-risk group — people with chronic hepatitis or cirrhosis. Korea runs one nationally, and the question its data can answer is not whether surveillance helps but how often it needs to happen.

The cohort and the gradient

Using the National Health Insurance Service database, a study in Yonsei Medical Journal identified 3,201,852 people in the surveillance programme's target population between 2008 and 2017. Of those, 64,674 went on to develop hepatocellular carcinoma, and were grouped by the interval at which they had been screened.

Receiving curative therapy for liver cancer, by surveillance interval
Surveillance intervalReceived curative therapyOdds ratio vs 6-month group
≤ 6 months51.9%—
7–12 months48.3%0.87
13–24 months43.8%0.76
25–36 months41.3%0.77
Never screened34.5%0.57

The gradient is orderly and it is the point. Curative therapy — resection, transplantation or ablation — is only possible when a liver cancer is found small enough. The more recently a patient was last screened, the more often it was.

0.26

hazard ratio for death associated with receiving curative therapy for hepatocellular carcinomaBae H et al., Yonsei Medical Journal, 2021

Where six months and twelve months differ

On mortality, the picture is more nuanced than the treatment figures suggest. All-cause mortality hazard ratios against the six-month group were 1.07 for the two-year interval, 1.14 for the three-year and 1.37 for the never-screened. The annual group came in at 0.96, which was not significantly different — and after adjustment for lead-time bias, at 0.91.

The authors' conclusion emphasises the six-month interval, on the strength of the curative-treatment gradient. The mortality data are more equivocal between six and twelve months, and the honest reading is that the case for six months rests on treatment options preserved rather than on a demonstrated difference in deaths.

Who is missing from the programme

A separate national study linked Korea's disability registration data to its cancer surveillance records. Age- and sex-adjusted liver cancer surveillance participation among people with disabilities rose from 25.7 percent in 2006 to 49.6 percent in 2015. Among people without disabilities it rose from 24.9 to 54.5 percent over the same years.

The two groups started level and finished five points apart. Participation was lowest among people with severe disabilities (adjusted odds ratio 0.71) and, most sharply, among people with renal disease (0.43), brain injuries (0.60), ostomy problems (0.60) and intellectual disabilities (0.69).

A surveillance programme's value depends entirely on being attended repeatedly, on schedule, for years. That is a demand that falls hardest on exactly the people for whom attending anything is hardest, and the widening gap is what that looks like measured over a decade.

What the design cannot rule out

Patients screened every six months differ from patients never screened in more than their screening. They are more engaged with care, more likely to have their liver disease treated, more likely to be well enough to attend. Lead-time adjustment addresses one specific artefact; it does not address that one.

What the study establishes is a consistent, ordered relationship between surveillance frequency and the chance of receiving treatment that could cure — in a cohort covering the entire national programme, with the direction of the lead-time correction arguing against the authors' own emphasis rather than for it.

Sources

  1. 1

    Bae H, Lee SA, Choi JW, Hwang SH, Park S, Park MS

    Effectiveness of hepatocellular carcinoma surveillance and an optimal surveillance interval: nationwide cohort of Korea

    Yonsei Medical Journal 2021;62(8):758-766

    doi:10.3349/ymj.2021.62.8.758 · PMID:34296554

    https://doi.org/10.3349/ymj.2021.62.8.758
  2. 2

    Seo JY, Shin DW, Yu SJ, Jung JH, Han K, Cho IY, Kim SY, Choi KS, et al.

    Disparities in liver cancer surveillance among people with disabilities: a national database study in Korea

    Journal of Clinical Gastroenterology 2021;55(5):439-448

    doi:10.1097/mcg.0000000000001405 · PMID:32889960

    https://doi.org/10.1097/mcg.0000000000001405