Intrahepatic cholangiocarcinoma (iCCA) hidden amongst the unknown: A retrospective analysis of cancer of unknown primary (CUP) cases from a tertiary cancer centre

Abstract

Background: Many patients (pts) with CUP present with presumed metastatic disease to the liver. Due to lack of definitive histological markers, iCCA may be an overlooked diagnosis. With the emergence of efficacious molecularly targeted therapies in iCCA, this study assessed the potential frequency of iCCA (previously not identified) within a CUP cohort. Methods: A single-centre retrospective study of sequential pts referred to a regional CUP multi-disciplinary team (MDT) (Jan 2017 - Apr 2020) was performed. Demographic data, histopathology, MDT history, treatment/survival outcomes were collected. For pts presenting with liver involvement, baseline diagnostic imaging was reviewed independently by a hepatobiliary radiologist and/or oncologist. Pts with radiological features of iCCA (dominant liver lesion, capsular retraction) were identified. For a subset of pts molecular characterisation of tumour tissue was performed. Results: Of 233 pts referred to the CUP MDT, 74 pts had malignancy involving the liver. For 13 of these pts, a primary tumour diagnosis (different primaries) was subsequently established. Of the remaining liver-involved CUP cohort (n�61), 56 pts had evaluable radiology reviewed and 25 (43%) had radiological features consistent with iCCA. These 25 pts were predominantly female (n�19; 77%) with a median age of 65 years (range 31-79). 64% had an ECOG PS ?2 and 50% received first line platinum-based chemotherapy. Molecular alterations (IDH mutations/FGFR fusions) supporting an iCCA diagnosis were detected in a subset of pts where testing was performed. Median overall survival (OS) of the potential iCCA group (n�25) and remaining liver involved CUP group (not iCCA) were similar (OS 3.8 vs 3.9 months, logrank p-value � 0.805); comparatively, patients with subsequent primary diagnosis (and liver involvement, n�13) had significantly better OS (10.2 months, logrank p-value � 0.0227). Conclusions: In this study 41% of patients referred with liver-involved CUP, matched the radiological criteria for an iCCA diagnosis, highlighting the importance of identifying these pts within CUP cohorts, ensuring correct diagnosis, molecular characterisation and treatment. Annals of Oncology abstracts