Cancer rarity and mortality: Evidence from a nationwide cohort study

Patients with rare cancers have consistently been reported to have poorer survival than patients with common cancers. We hypothesized that the excess mortality could be attributable to differences in tumor histology and stage at diagnosis and, explored whether it reflected a broader relationship between cancer incidence and mortality.

In a nationwide, population-based cohort study, we included adults diagnosed with a first primary solid malignant tumor in Denmark between 2004 and 2023. Cancers were classified according to Tier 2 of the RARECAREnet classification (rare cancer: incidence <6/100.000). Hazard ratios (HRs) of all-cause mortality according to rarity were estimated using Cox regression adjusted for age, sex and calendar period. Additional analyses further adjusted for tumor histology and stage at diagnosis. Tumor entities were also grouped into six incidence categories to examine survival across the incidence continuum.

20.6% of cancer patients were diagnosed with a rare cancer. Patients with rare cancers had a 74% higher mortality than those with common cancers (HR: 1.74, 95% CI: 1.72 to 1.76), but mortality did not generally increase with increasing rarity. After adjustment for tumor histology and stage at diagnosis, the HR was close to unity (HR: 0.96, 95% CI: 0.95 to 0.98).

Patients with rare cancers experienced higher mortality than those with common cancers. The excess mortality was attenuated after adjustment for tumor histology and stage at diagnosis, indicating that these factors largely explain the survival disadvantage in rare cancers. Improving outcomes for patients with rare cancers should focus on earlier diagnosis and tumor-specific management.