Cancer incidence and competing mortality risk following 15 presenting symptoms in primary care: a population-based cohort study using electronic healthcare records

Abstract

Objectives: Comprehensive assessment of risk of cancer diagnosis and non-cancer mortality following primary care consultation for 15 new-onset symptoms. Design: Cohort study. Setting: UK primary care (CPRD Gold), 2007 - 2017. Participants: Patients aged 18-99, comprising a randomly-selected reference group and a symptomatic cohort of patients presenting with one of 15 new onset symptoms (abdominal pain, abdominal bloating, rectal bleed, change in bowel habit, dyspepsia, dysphagia, dyspnoea, haemoptysis, haematuria, fatigue, night sweats, weight loss, jaundice, breast lump, post-menopausal bleed). Main outcome measures: Risk of cancer diagnosis and risk of death in the 12 months following index consultation. Time-to-event models were used to estimate outcome-specific hazards for site-specific cancer diagnosis and non-cancer mortality; results were combined using the latent failure time approach to estimate cumulative incidence. Results: Data were analysed on 1,622,419 patients, of whom 36,802 had a cancer diagnosis and 28,857 died without a cancer diagnosis within 12 months of first consultation. Absolute non-cancer mortality risk exceeded cancer diagnosis risk in the reference group and in symptomatic patients with dyspnoea, dysphagia, weight loss, fatigue, or jaundice; absolute cancer risk exceeded mortality risk for patients with breast lump or post-menopausal bleed; for other symptoms the risk of a cancer diagnosis and non-cancer mortality were similar. Ever-smoking was associated with raised cause-specific hazard for lung cancer (e.g., in women HR 4.8, 95%CI 4.2 to 5.6), and slightly raised hazards for upper GI and urological cancers. For patients with red-flag symptoms, the risk of specific cancers exceeded the UK urgent referral risk threshold of 3% from a relatively young age (e.g., for male smokers with haemoptysis the risk of lung cancer exceeded 3% from age 55). For non-organ-specific symptoms (such as loss of weight, or fatigue), while the risk of any cancer often exceeded 3%, the risk of any individual cancer type either did not reach this threshold at any age, or reached it only in older patients. Conclusions: In patients with new-onset symptoms in primary care the risk of cancer diagnosis and of non-cancer mortality are often comparable. Smoking-status is highly informative for cancer risk in patients with respiratory or non-organ-specific symptoms. A holistic approach to risk assessment that includes the risk of multiple different cancer types alongside the risk of mortality due to consequential illnesses other than cancer, especially among older patients, is needed to inform management of symptomatic patients in primary care, particularly for patients with non-organ-specific symptoms.