THE NEED FOR SYSTEMIC THERAPIES IN HEPATOCELLULAR CARCINOMA

Recent years have seen major advances in local control of hepatocellular carcinoma (HCC), and the relevant approaches are described in detail elsewhere in this volume. Thus, although surgical resection (and orthotopic liver transplantation) has long been seen as the only approach to offer cure, or at least long-term survival, other locoregional therapies including percutaneous ethanol injection and thermal ablation now appear to be rivaling surgical resection by many criteria of efficacy. However, it is clear that all these approaches (including surgical resection) are less effective as the tumor increases in size, and conventionally, most are confined to lesions smaller than 5 cm in diameter. This probably reflects the fact that as tumors increase in size, the frequency of vascular invasion increases and with it, the likelihood of metastasis. Thus, if local treatments are applied to larger lesions then the rate of recurrence increases dramatically.

Similarly, trans-catheter approaches are recognized to cause extensive tumor necrosis, but evidence of survival improvement has been more difficult to demonstrate because disease progression and tumor re-vascularization are still the rule. Thus to complement these local measures, systemic treatment is urgently required to expand the indications for local therapies and to decrease the recurrence rate (i.e., in the adjuvant setting).

At the outset, it should be noted that, largely because of the progress in local treatment, systemic agents have moved “down the scale” so that new chemotherapeutic agents have been tried mainly in patients with advanced or even terminal disease and this necessarily limits the scope for observing effective treatments.