Risk of second primary malignancies in older long-term survivors of breast, prostate, colon, and rectal cancer

BACKGROUND: Cancer survivors face an increased risk of second primary malignancies (SPMs). Understanding SPM incidence and risk factors is crucial for long-term survivorship care. METHODS: This was a SEER-Medicare retrospective cohort study of breast, prostate, colon, or rectal cancer survivors diagnosed between 2003-2011 at age 66+ years who survived ≥5 years post-diagnosis. The primary outcome was a 'late' SPM, defined as invasive cancer occurring ≥5 years after initial diagnosis. Restricted mean survival time (RMST) regression was used to assess demographic, clinical, and treatment related factors associated with late SPMs. SPMs were categorized as hematologic, screen-detectable (breast, prostate, lung, colon, or rectal), or non-screen detectable solid tumors. RESULTS: Of 90,261 long-term survivors, 11.2% (10,116) developed at least one late SPM. The cumulative incidence of late SPMs over 8 years was highest in prostate cancer survivors. Non-screen detectable cancers composed the largest proportion (47.8%) of 10,220 total late SPMs. The most common late SPM site was lung in colon (14.9%), and rectal (16.1%) cancer survivors, urinary bladder in prostate (17.0%), and new-primary breast cancers in breast cancer survivors (36.5%). In RMST regression, significant associations with demographic, index cancer, treatment, and clinical characteristics and late SPMs ranged from 3.6 months shorter to 4.4 months longer time without late SPM during the 8 years assessed. CONCLUSIONS: Between 10-14% of older long-term cancer survivors developed a late SPM during 5-13 years after index cancer diagnosis. Over 40% of late SPMs were screen-detectable, highlighting the need for surveillance strategies beyond 5 years from index cancer diagnosis.