Routes to diagnosis and the association with the prognosis in patients with cancer – A nationwide register-based cohort study in Denmark

1

Introduction

Cancer accounted for almost 1.2 million deaths in the European Union in 2016, making it the second most common cause of death [ 1 ]. Cancer is the leading cause of death in many countries, including Denmark, where cancer accounted for 29 % of all deaths in 2018 [ 2 ]. Although cancer survival is generally improving, survival rates still vary markedly across countries [ 3 ]. Denmark still lags behind other comparable countries [ 3 , 4 ].

While tumour stage, age, and comorbidities are among the principal factors affecting prognosis, research suggests that prognosis also relates to where and how cancer is identified within the healthcare system, i.e. routes to diagnosis (RtD) [ 5678910 ]. Studies from England and the United States have shown that cancer patients diagnosed through an emergency route have a worse prognosis than cancer patients diagnosed through other routes, even when patient characteristics and stage at diagnosis are taken into account [ 5 , 6 , 8 , 10 ]. In contrast, patients diagnosed through routine screening programmes have better survival compared to non-screened cancer patients [ 5 ]. However, it is unknown if the same pattern applies to other healthcare systems, such as the Danish, which is based on more outpatient care.

The process by which patients are referred to diagnostic workup (e.g. specific urgent referral routes) is also related to prognosis [ 5 , 7 , 1112131415 ]. Several programmes, including the English two-week wait from referral to first specialist assessment and the Danish cancer patient pathways (CPPs), have been established to facilitate early diagnosis and treatment within certain time frames and following specific clinical guidelines [ 16 , 17 ]. However, it remains unknown whether Danish patients referred to a CPP have a better prognosis compared to non-CPP referred patients. Previous studies were based on small cohorts, selected cancer types [ 11 ], a single-centre population [ 12 ], or concerned the CPP for non-specific symptoms and signs of cancer (NSSC-CPP) [ 18 ].

In recent years, countries like England have increasingly linked data across existing data registries to create national cohorts of cancer patients and their RtD [ 5 , 6 , 19 ]. Although Denmark is well-renowned for complete and valid national registries [ 20 ], no national data set designating RtD for individual cancer patients exists.

This study aimed to describe RtD for patients diagnosed with cancer in Denmark by using routinely collected register-based data and to investigate the association between RtD and prognosis measured by one-year all-cause mortality. We hypothesised that RtD is significantly associated with one-year all-cause mortality, that screen-detected patients display the lowest mortality followed by patients diagnosed through CPPs, and that mortality is highest among patients diagnosed through a more acute route.