Different rules for registering multiple primary (MP) cancers are used by cancer registries throughout the world, making international data comparisons difficult. This study evaluates the effect of Surveillance, Epidemiology, and End Results (SEER) and International Association of Cancer Registries (IACR) MP rules on population-based cancer survival estimates.

Data from five US states and six metropolitan area cancer registries participating in the SEER Program were used to estimate age-standardized relative survival (RS%) for first cancers-only and all first cancers matching the selection criteria according to SEER and IACR MP rules for all cancer sites combined and for the top 25 cancer site groups among men and women.

During 1995–2008, the percentage of MP cancers (all sites, both sexes) increased 25.4 % by using SEER rules (from 14.6 to 18.4 %) and 20.1 % by using IACR rules (from 13.2 to 15.8 %). More MP cancers were registered among females than among males, and SEER rules registered more MP cancers than IACR rules (15.8 vs. 14.4 % among males; 17.2 vs. 14.5 % among females). The top 3 cancer sites with the largest differences were melanoma (5.8 %), urinary bladder (3.5 %), and kidney and renal pelvis (2.9 %) among males, and breast (5.9 %), melanoma (3.9 %), and urinary bladder (3.4 %) among females. Five-year survival estimates (all sites combined) restricted to first primary cancers-only were higher than estimates by using first site-specific primaries (SEER or IACR rules), and for 11 of 21 sites among males and 11 of 23 sites among females. SEER estimates are comparable to IACR estimates for all site-specific cancers and marginally higher for all sites combined among females (RS 62.28 vs. 61.96 %).

Survival after diagnosis has improved for many leading cancers. However, cancer patients remain at risk of subsequent cancers. Survival estimates based on first cancers-only exclude a large and increasing number of MP cancers. To produce clinically and epidemiologically relevant and less biased cancer survival estimates, data on all cancers should be included in the analysis. The multiple primary rules (SEER or IACR) used to identify primary cancers do not affect survival estimates if all first cancers matching the selection criteria are used to produce site-specific survival estimates.