Symptoms reported at initial diagnosis of (metastatic) pancreatic adenocarcinoma ([m]PAC) in routine clinical practice and variation in frequencies across Europe
Authors: D. Melisi, B. Westphalen, None àMellbring, A. Carrato, J. Taieb, G. Prager, T. Macarulla Mercadé, N D´ Esquermes, A. Ferreras, F. de Jong
Journal: Annals of Oncology (2018)

Introduction: PAC is projected to become the second leading cause of cancer death by 2030. It is typically diagnosed late in the course of the disease, amongst other reasons due to lack of screening tests, limited understanding of risk factors, and any clear symptoms typically only appearing late. Systemic treatment options applied in advanced disease vary and recent data on choices and outcomes outside clinical trials are scarce. The goal of this pan-European project was to generate data on diagnosis, treatment patterns and outcomes from the records of patients who completed first-line metastatic PAC treatment across Europe. Methods: In this observational chart review, physicians completed a retrospective electronic record from initial diagnosis onwards for patients with the following minimal inclusion criteria: completed first-line (m)PAC treatment between 07/2014-01/2016 and ≥18 years. In each country, respondents were recruited across different regions and settings (university and general hospitals, cancer and reference centers, office-based specialists) to ensure a balanced selection. Physicians were encouraged to enter as many second-line metastatic patients as possible. Study endpoints included initial/subsequent treatments, dose modifications, and treatment outcomes. We report here on selected patient and tumor characteristics and incidences of reported symptoms (including variation across countries) at initial PAC diagnosis. Data are descriptive. Results: A total of 2,565 online patient records were completed by 225 physicians (9 countries; n = 500-504 for France/Germany/Italy/Spain/UK). At diagnosis, 89.5% of patients had advanced disease, median age was 64 years, and 57.7% was male. Primary tumor location was head/head+body/body/body+tail/tail in 40.2%/16.3%/23.2%/9.6%/10.1%. Tumor grade was 1/2/3/unknown in 5.3%/39.5%/38.1%/17.2%. Median CA19-9/albumin/bilirubin levels were 387U×mL-1/34.0g×L-1/1.8mg×dL-1. WHO performance status was 0/1/2/3/unknown in 20.4%/55.8%/21.9%/1.6%/0.4%. At initial diagnosis, on average 3.14 symptoms were reported per patient from 15 pre-listed symptoms. Averages for France/Germany/Italy/Spain/UK varied with -6.3%/+18.9%/-18.4%/+12.3%/-6.7%. Symptoms in decreasing order were: abdominal pain_65.0%; weight loss_61.5%; jaundice:31.1%; nausea_28.3%; mid-back pain_26.8%; bloating_19.0%; vomiting_18.1%; dark urine_12.7%; itching_12.3%; cachexia_8.6%; deep vein thrombosis (DVT)_8.1%; steatorrhea_7.0%; depression_5.9%; diarrhea_5.9%; and recent unexpected diabetes_3.4%. Variation was highest for more frequently reported symptoms (mid-back pain, nausea, weight loss, and bloating). Absolute differences of ≥∣10%∣ versus the mean were identified for nausea (+14.6%_Germany), mid-back pain (+12.5%_Germany), and weight loss (-11.1%_Italy). Absolute differences between countries (highest versus lowest) were greatest for nausea (Δ22.1%: Germany_42.9% versus France:20.8%), mid-back pain (Δ18.7%: Germany_39.3% versus UK_20.6%), and weight loss (Δ18.3%: Germany_68.7% versus Italy_50.4%). Relative differences of ≥∣50%∣ versus the mean were reported for depression (+142.4%_Spain; -72.9%_UK), steatorrhea (+90.0%_Spain; -57.1%_France), cachexia (+59.3%_Spain), DVT (+56.8%_Germany), diabetes (+52.9%_France), and nausea (+51.6%_Germany). Relative differences (highest versus lowest) were greatest for depression (8.9×: Spain_14.3% versus UK_1.6%), steatorrhea (4.4×: Spain_13.3% versus France:3.0%), and DVT (2.8×: Germany_12.7% versus UK_4.6%). Conclusion: In this European retrospective chart-review, the average number of symptoms at initial diagnosis of (m)PAC reported by treating physicians varied between countries. Most frequently symptoms reported were abdominal pain, weight loss, jaundice, nausea, and mid-back pain. Substantial variation was seen for individual symptoms. Appropriate awareness of and attention to symptoms in the general public and by health care providers may help improve (m)PAC diagnosis, care and outcomes.