Patterns of presentation and diagnostic delays in biliary tract cancers: a real-world European study

Biliary tract cancers (BTCs) often present late due to nonspecific symptoms and a lack of effective population screening. We characterised diagnostic routes, symptom-to-diagnosis intervals, and their relationship with stage and outcomes across three European centres.

We conducted a retrospective observational study of consecutive patients diagnosed with BTC assessed by medical oncology from 1 June 2022 to 31 January 2024 in Spain, Slovenia, and Italy. Demographics, presenting symptoms, route of diagnosis, investigations, treatments, and outcomes were extracted from electronic medical records. Survival was assessed using Kaplan-Meier analysis and Cox regression. The study was approved by local ethics committees.

Eighty-six patients were included [Spain 59 (68.6%), Slovenia 16 (18.6%), and Italy 11 (12.8%)]; the median age was 71 years (range 40-96); and 65.1% were male. Tumour types included intrahepatic cholangiocarcinoma (41.9%), distal cholangiocarcinoma (23.3%), gallbladder (12.8%), ampullary (11.6%), and perihilar cholangiocarcinoma (9.3%). Presentation routes included: primary care (46.5%), the emergency department (45.3%), and incidental (8.1%). The median time from symptom onset to diagnosis was 2.56 months [95% confidence interval (CI) 1.78-3.09], which was longer with primary care (versus emergency department) (4.13 months versus 1.37 months, P = 0.14). According to symptoms, delays were longest for weight loss (3.47 months) and asthenia/anorexia (3.28 months), and shortest for jaundice (1.36 months). Country-level differences in symptom patterns were observed, along with differences in presentation routes. At diagnosis, 55.8% had metastatic disease and 16.3% were diagnosed based on cytology only. Diagnostic work-up varied by country (first imaging ultrasound (Slovenia) versus magnetic resonance imaging (Italy), P < 0.001). Multidisciplinary tumour board discussion occurred in 77.9% of patients. Treatment included surgery with curative intent in 43% of patients (of whom 56.8% received adjuvant chemotherapy) and first-line palliative chemotherapy in 61.6% (of whom 67.6% received subsequent lines). No active anticancer therapy was administered in 12.8% of patients. After a median follow-up of 13.47 months, the estimated median overall survival (OS) was 22.28 months (95% CI 17.42-34.51). In multivariable analysis, curative surgery [hazard ratio (HR) 0.19, 95% CI 0.04-0.86, P = 0.032] and first-line palliative systemic therapy (HR 0.15, 95% CI 0.05-0.44, P < 0.001) were associated with longer OS, whereas male sex (HR 3.69, 95% CI 1.17-11.67, P = 0.026) and jaundice at diagnosis (HR 2.48, 95% CI 1.11-5.54, P = 0.027) were associated with shorter OS. Neither route of diagnosis nor diagnostic delay was associated with OS, although this analysis may have been underpowered.

BTC continues to be diagnosed at advanced stages and is frequently associated with diagnostic delays, often presenting with nonspecific symptoms. Strengthening referral pathways and improving early recognition of warning signs, particularly in primary care, may help optimise diagnostic processes and should be further evaluated in future studies.