Incident anaemia as a marker of cancer and all-cause mortality: evidence from 380 114 adults in the population-based Stockholm Early Detection of Cancer Study (STEADY-CAN) cohort.

Objective: Anaemia is common in healthcare and may indicate undiagnosed cancer. Despite this, evidence regarding risk estimates informing clinical decision-making remains limited, particularly regarding haemoglobin dynamics and the role of mean corpuscular volume (MCV). We aimed to quantify the 18-month risks of incident cancer (IC) and all-cause mortality (ACM) following incident anaemia (IA), and to examine how MCV modifies these risks. Methods and analysis: Population-based, age- and sex-matched cohort study. The study used the Stockholm Early Detection of Cancer Study (STEADY-CAN), covering almost all adults residing in Stockholm County, Sweden, during 2011-2021. STEADY-CAN links laboratory tests with national registers, capturing healthcare use, diagnoses, cancer outcomes and prescribed medications.We included 190 057 adults with IA and 190 057 age- and sex-matched non-anaemic controls from the STEADY-CAN cohort. Eligible individuals were ≥18 years old, cancer-free, had ≥2 Hb measurements during 2011-2020 and a concurrent MCV value at the IA date. IA was defined as the first Hb value from 2012 onwards below 130 g/L in men or 120 g/L in women after prior normal values.Sex-stratified adjusted piecewise competing-risks multi-state Cox regression models were used, with separate HRs for IA during 0-3, 3-6, 6-12 and 12-18 months of follow-up. The main outcome measures were IC and ACM during the 18-month follow-up. Results: IC occurred in 6.2% of male and 2.8% of female IA cases, compared with 2.4% and 1.1% of controls. Corresponding ACM rates were 7.4% and 4.0% in IA cases versus 2.5% and 1.7% in controls. IA implied a 9.17-fold higher IC risk and 8.50-fold higher ACM risk among men during 0-3 months of follow-up, with 8.25- and 6.14-fold higher risks among women (all p<0.001). These risks decreased over time but were still significant for both sexes at 6-12 months of follow-up for IC and 12-18 months of follow-up for ACM. Microcytosis was linked to the highest IC risk, particularly for digestive and haematological cancers, whereas macrocytosis was more strongly associated with ACM. Conclusions: IA is a strong marker of both IC and ACM in routine care. Microcytic anaemia should prompt timely gastrointestinal evaluation, while macrocytic anaemia warrants broader assessments for comorbid conditions and systemic disease. Persistently elevated risks underscore the need for structured safety-netting and continued follow-up after IA, even without a cancer identification. Our findings highlight the value of using anaemia patterns and MCV in early risk stratification.