The association between unexpected weight loss and cancer diagnosis in primary care: a matched cohort analysis of 65,000 presentations

Abstract

Background: We aimed to understand the time period of cancer diagnosis and the cancer types detected in primary care patients with unexpected weight loss (UWL) to inform cancer guidelines.

Methods: This retrospective matched cohort study used cancer registry linked electronic health records from the UK's Clinical Practice Research Datalink from between 2000 and 2014. Univariable and multivariable time-to-event analyses examined the association between UWL, and all cancers combined, cancer site and stage.

Results: In all, 63,973 patients had UWL recorded, of whom 1375 (2.2%) were diagnosed with cancer within 2 years (days-to-diagnosis: mean 181; median 80). Men with UWL (HR 3.28 (2.88-3.73)) and women (1.87 (1.68-2.08)) were more likely than comparators to be diagnosed with cancer within 3 months. The association was greatest in men aged ≥50 years and women ≥70 years. The commonest cancers were pancreas, cancer of unknown primary, gastro-oesophageal, lymphoma, hepatobiliary, lung, bowel and renal-tract. The majority were late-stage, but there was some evidence of association with stage II and stage III cancers. In the 3-24 months after presenting with UWL, cancer diagnosis was less likely than in comparators.

Conclusion: UWL recorded in primary care is associated with a broad range of cancer sites of early and late-stage.

Fig. 1. Study population flow diagram.

This flow diagram details the source population, cohort entry criteria, exclusion criteria, the frequency of the eligible population with and without unexpected weight loss, and the study exit criteria.

Fig. 2. Risk of cancer diagnosis over time.

Univariate smoothed hazard rate and cumulative hazard of cancer diagnosis by unexpected weight loss status.

Fig. 3. Risk of cancer over time by gender.

Univariate smoothed hazard rate and cumulative hazard of cancer diagnosis by gender in patients with and without unexpected weight loss. In men, 441 cancers (1.7%) were diagnosed in 25,551 men with unexpected weight loss in the first 3 months rising to 548 (2.1%) cases over the first 6 months compared with 575 (0.5%) in 10,7706 men without unexpected weight loss in the first 3 months rising to 1215 (1.1%) by 6 months. In women, 282 cancers (0.8%) were diagnosed in 36,057 women with unexpected weight loss in the first 3 months rising to 360 (1.0%) over 6 months compared with 630 (0.4%) in 145,203 women without unexpected weight loss over 3 months rising to 1305 (0.9%) over 6 months.

Fig. 4. Predicted hazard ratios by age and gender.

Population level predictions of the hazard ratio for cancer in the next three months for people with unexpected weight loss by age and gender using marginal effects at representative values.

Fig. 5. Risk of cancer by site and stage.

Adjusted hazard ratios for cancer in people with unexpected weight loss in men (5a) and women (5b) in the 6 months following presentation derived using cox regression adjusted for all covariates.

Fig. 6. Risk of cancer over time by cancer stage.

Univariate smoothed hazard rate and cumulative hazard by cancer stage in patients with and without unexpected weight loss. In men, 54 cancers (0.2%) were diagnosed with late-stage cancer in 25,551 men with unexpected weight loss in the first 3 months rising to 66 (0.3%) cases over the first 6 months compared with 46 (0.04%) of 10,7706 men without unexpected weight loss in the first 3 months rising to 88 (0.08%) by 6 months. In women, 37 late-stage cancers (0.1%) were diagnosed in 36,057 women with unexpected weight loss in the first 3 months rising to 52 (0.1%) over 6 months compared with 38 (0.02%) in 145,203 women without unexpected weight loss over 3 months rising to 75 (0.05%) over 6 months.