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Impact of disease stage and aetiology on survival in hepatocellular carcinoma: implications for surveillance.

ABSTRACT: Variation in survival in hepatocellular carcinoma (HCC) has been attributed to different aetiologies or disease stages at presentation. While international guidelines recommend surveillance of high-risk groups to permit early diagnosis and curative treatment, the evidence that surveillance decreases disease-specific mortality is weak.We compared HCC survival figures from Japan (n=1174) and Hong Kong (n=1675) over similar time periods (Japan 2000-2013, Hong Kong, China 2003-2014). The former has an intensive national surveillance programme, while the latter has none. We also analysed changes in survival in Japan over a 50-year period including data from before and after institution of a national HCC surveillance programme.In Japan, over 75% of cases are currently detected by surveillance, whereas in Hong Kong <20% of cases are detected presymptomatically. Median survival was 52 months in Japan and 17.8 months in Hong Kong; this survival advantage persisted after allowance for lead-time bias. Sixty-two per cent of Japanese patients had early disease at diagnosis and 63% received curative treatment. The comparable figures for Hong Kong were 31.7% and 44.1%, respectively. These differences could not be accounted for by disease aetiology, and patients in Hong Kong who were detected at an early stage had a similar survival to the analogous patients in Japan.The variation in survival is largely accounted for by stage at diagnosis, which in turn relates to the intensity of surveillance programmes and the consequent variation in curative therapeutic options.

SUBMITTER: Johnson P

PROVIDER: S-EPMC5318967 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Impact of disease stage and aetiology on survival in hepatocellular carcinoma: implications for surveillance.

Johnson Philip P Berhane Sarah S Kagebayashi Chiaki C Satomura Shinji S Teng Mabel M Fox Richard R Yeo Winnie W Mo Frankie F Lai Paul P Chan Stephen L SL Tada Toshifumi T Toyoda Hidenori H Kumada Takashi T

British journal of cancer 20170112 4

<h4>Background</h4>Variation in survival in hepatocellular carcinoma (HCC) has been attributed to different aetiologies or disease stages at presentation. While international guidelines recommend surveillance of high-risk groups to permit early diagnosis and curative treatment, the evidence that surveillance decreases disease-specific mortality is weak.<h4>Methods</h4>We compared HCC survival figures from Japan (n=1174) and Hong Kong (n=1675) over similar time periods (Japan 2000-2013, Hong Kong ...[more]

PMID: 28081537

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Project description:Background & aimsIn this study we aimed to analyse the impact of the aetiology of cirrhosis on the incidence, characteristics and prognosis of hepatocellular carcinoma (HCC) diagnosed during a surveillance program.MethodsIndividual data from a randomized trial and 2 prospective cohorts of patients with compensated histologically proven cirrhosis recruited between 2000 and 2016 were pooled. The influence of cirrhosis aetiology on survival after HCC detection was assessed using multivariable regression models.ResultsAmong 3,533 patients (1,926 virus [VIR], 1,167 alcohol [ALC], 440 combined [MIX]), 431 were diagnosed with HCC after a median follow-up of 57.1 months. The 5-year HCC incidence was lowest in ALC (VIR 12.6%, ALC 9.1%, MIX 14.3%, p = 0.04). At the time of diagnosis, tumour burden and Child-Pugh score were comparable across aetiology groups, but early BCLC stages (0/A) were significantly less frequent in ALC (VIR 80%, ALC 37%, MIX 72%) as a result of worse ECOG performance status. However, similar access to first-line curative HCC treatment was reported across aetiology groups (p = 0.68). Median survival after HCC diagnosis was significantly reduced in ALC (VIR 39, ALC 21, MIX 34 months, p = 0.02). However, when adjusting for tumour size, ECOG and Child-Pugh score, the aetiology of the underlying cirrhosis no longer had a significant impact.ConclusionCompared to patients with virus-related cirrhosis, patients with alcohol-related compensated cirrhosis enrolled in a surveillance program have: i) the lowest 5-year HCC incidence; ii) worse overall prognosis, mostly driven by a poor general condition, despite similar access to first-line curative treatment.Lay summaryIt has been suggested that early detection of hepatocellular carcinoma (HCC) may be futile in patients with alcohol-related cirrhosis. By comparing outcomes in more than 3,000 patients with compensated cirrhosis included in surveillance programs, this study suggests that HCC surveillance enables early diagnosis in most patients with alcohol-related cirrhosis despite a higher competing risk of death in these patients. We also report similar access to first-line curative HCC treatment in these patients compared to those with viral cirrhosis, despite higher rates of comorbidities and impaired liver function. Following HCC detection, the later parameters were major drivers of death irrespective of the cause of cirrhosis.RegistrationCHC2000 (NCT00190385) and CIRRAL (NCT01213927) cohorts were registered at ClinicalTrials.gov and the full protocols are available at the following links (https://clinicaltrials.gov/ct2/show/NCT00190385) and https://clinicaltrials.gov/ct2/show/NCT01213927, respectively). The full CirVir protocol is available via the ANRS Web site (http://anrs.fr).

Project description:PurposeConditional survival (CS) and failure hazard estimations can provide important dynamic prognostic information for clinical decision-making and surveillance counseling. The current study aimed to investigate the CS and dynamic failure hazard in non-metastatic nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT).MethodsConditional overall survival (COS) and progression-free survival (CPFS) estimates adjusted for age and gender against each AJCC 8th stage were calculated. Multivariable Cox regression (MCR) models were fitted in the entire population at baseline and subsequently separate MCR models were fitted in patients who have maintained event-free time of 1 to 10 years to generate respective hazard ratio (HR). Annual hazard rates of death and progression over 10 years for each stage were also estimated.ResultsA total of 1993 patients were eligible for analysis. The estimated 5-year OS and PFS for entire cohort were 79.0% and 70.7% at initial diagnosis. After 5 years of event-free follow-up, additional 5-year COS and CPFS increased to 85.9% and 85.5%, respectively. Stage I/II maintained dramatically favorable CS and low hazard (< 5%) of death and progression over time. Relative to stage I/II, stage III manifested non-significantly higher failure hazard for the first 3 years of survivorship and approached to similar level of stage I/II afterwards. Stage IVA presented most impressive improvement in terms of both COS (∆=9.8%) and CPFS (∆ = 16.8%) whereas still drastically inferior to that of stage I-III across all conditional time points. After 4 years of follow-up, progression hazard of stage IVA became relatively steady of approximate 6%.ConclusionsSurvival prospect of non-metastatic NPC improves over years with distinct dynamic patterns across stages, providing important implications for personalized decision-making in terms of both clinical management and surveillance counseling. Stage-dependent and hazard-adapted clinical management and surveillance are warranted.

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Impact of disease stage and aetiology on survival in hepatocellular carcinoma: implications for surveillance.

Publications

Impact of disease stage and aetiology on survival in hepatocellular carcinoma: implications for surveillance.

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