Risk Of Developing Liver Cancer After HCV Treatment

Thursday, July 26, 2012

Potentially Curative Treatment in Patients With Hepatocellular Cancer


From Alimentary Pharmacology & Therapeutics

Potentially Curative Treatment in Patients With Hepatocellular Cancer

Results From the Liver Cancer Research Network

F. Kanwal; A. Befeler; R. S. Chari; J. Marrero; J. Kahn; N. Afdhal; T. Morgan; L. Roberts; S. R. Mohanty; J. Schwartz; D. VanThiel; J. Li; A. Zeringue; A. Di'Bisceglie

Discussion Only

Full Text @ Medscape

In this large multicenter observational study, less than one-third of patients with HCC were diagnosed at an early stage. Consistent with other studies, patients with early HCC who underwent potentially curative treatment had excellent survival.[4, 7, 9–11, 13, 14] However, only 70% of patients with early disease received potentially curative treatment. Although we could not ascertain whether and to what extent patients in our study received surveillance for HCC prior to their diagnosis, given that the data represent patients seen in centers with specialized expertise in management of HCC patients, these estimates likely represent the maximum benefit that can be expected from the current practice of HCC surveillance and treatment. Indeed, an analysis of Surveillance, Epidemiology, and End Results registry showed that 21% of patients with small, non-metastatic HCC received liver transplantation.[17]

Another study limited to 65 years and older Medicare population found that 34% of patients with early HCC (defined as patients with single lesions or those with lesions <3 cm) received any potentially curative treatment.[18] Our data show that, in the best case scenario, these rates can be twice as high as reported in these population based studies, and thus provide the upper boundary of the potential effect of HCC surveillance and treatment—data that are relevant in counseling patients regarding chances of treatment receipt and outcomes, in conducting cost-effectiveness analyses, and in guiding policies regarding HCC surveillance in the vulnerable cohort of patients at risk for HCC.
We also found that 36% of patients who were not candidates for curative treatment based in the staging system received curative treatment and that these patients had significantly improved survival compared to patients without such treatment. Although there is no one universally accepted HCC staging system, many have adopted the BCLC system, and we used this system to stratify our patients for this study. The goal of BCLC (and other staging systems) is to predict patients' outcomes and to tailor therapy in order to maximize overall effectiveness of treatment. In our study, stage of HCC was the strongest driver of treatment decisions—and hence the prognosis of patients. Nonetheless, we found that physicians frequently crossed these stage-specific boundaries to extend curative treatment to patients with more advanced HCC.

Our results suggest that this decision, at least in part, is guided by the general health of the patient. Specifically, we found that patients with advanced HCC but with well-preserved performance status were 4-fold more likely to receive curative treatment compared to those with compromised performance status. These patients with non-early HCC, when treated, had modest improvement in their survival. Collectively these data suggest that physicians might be using the correct heuristic in identifying candidates for curative treatment and that this heuristic might tap into aspects of underlying risk or disease severity that are not fully captured by staging alone. We found that performance status provides important prognostic information in patients with HCC that goes beyond the information furnished by clinical and tumour burden variables used in routine practice. Our data, therefore, provide a compelling rationale for incorporating formal evaluation of patients' performance status into clinical decision-making in patients with HCC.

We also found that individual centers might vary in how they manage patients with early HCC. Patients with early HCC who were seen in high volume centers were significantly more likely to receive a potentially curative treatment than those seen in low-medium volume centers after controlling for patient-related variables. However, due to the limited sample size in this sub-group, our estimates may not be optimally reliable and thus should be interpreted with caution. Despite this, our data provide preliminary insight into the likely importance of center effect in explaining the variation in treatment rates among patients with early HCC.

There are several other possible explanations for lack of curative treatment in the 30% of patients with early HCC who did not receive such treatment. It is plausible that despite being in the 'early' HCC group, patients without curative treatment had higher tumour burden (i.e. larger lesions, etc.) compared to those who received curative treatment, and our results support this possibility (Appendix S4). Another explanation may be presence of more advanced liver disease and higher comorbidity—factors that are important drivers of HCC treatment decisions. Indeed, we found that early HCC patients who did not receive curative treatment were older, were more likely to have medical comorbidity, and more severe liver disease than those who received curative treatment, although these estimates were not statistically significant, perhaps because of power limitations. Other possible explanations may include patient preference and insurance related barriers. We lacked reliable variables to determine the role of these factors as part of this study. Larger studies with longer follow up are needed to confirm our observations and to evaluate the impact of center effect as well as other variables.

Our analysis has several strengths. First, we used data from a prospectively enrolled cohort of patients with HCC instead of using administrative databases. The study relied on standardized criteria for HCC diagnosis that in turn were directly derived from the available clinical practice guidelines in HCC. As a result, we minimized any ascertainment bias in classifying patients with HCC. Second, our analysis used data from a demographically diverse group of patients with HCC seen in different regions of the U.S. Third, the Liver Cancer Network database included a broad array of data, allowing us to capture and adjust for the full range of patient-level variables that might affect the receipt and outcomes of treatment among treatment-eligible patients. These included socio-demographic characteristics, tumour-related characteristics, stage of liver disease, and medical comorbidity, among others.

Our analysis also has potential weaknesses. The sample population constituted primarily of patients with access to healthcare system that were seen at tertiary care centers. Thus, as stated earlier, our results are likely biased upwards. However, our data provide the upper limit of potential effect of current process of care in HCC. Second, the observational nature of the study makes it hard to draw firm causal inferences regarding impact of curative treatment on patient survival. However, randomized controlled trials designed to determine the effect of potentially curative treatments are not possible because of cost, feasibility, and ethical considerations. Within the limitations of the study design, the longitudinal nature of the data, finding of a strong association, and the temporality of the cause and effect suggest that the receipt of potentially curative treatment is causally linked to better outcomes in this geographically diverse sample of patients with HCC. Third, due to power limitations, estimates from the sub-group (i.e. sensitivity) analyses may not be optimally reliable. Future research will aim to confirm these findings and to determine the role of patient related factors using larger sample sizes and longer duration of follow-up.

In conclusion, our results suggest that survival in HCC can be improved if it is diagnosed at an early stage and potentially curative therapy is applied in a timely manner. However, only 28% of patients have early stage disease at the time of HCC diagnosis, suggesting that the most important step to make inroads into the problem of suboptimal outcomes in HCC may be to focus on implementation of routine surveillance in patients who are at risk for HCC so that more patients are diagnosed earlier in the course of their disease. We also found that approximately one-third of patients with non-early stage disease received potentially curative treatment, and that these patients had improved outcomes. Evidence based modifications in HCC staging algorithms and routine incorporation of performance status into clinical decision-making may help achieve the goal of making treatment more effective and cost-effective in patients with HCC.

Full Text @ Medscape

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