Extracutaneous second primary cancer risk in nonmelanoma skin cancer patients: A systematic review and meta-analysis

Survivors of nonmelanoma skin cancer (NMSC) may be at an elevated risk of developing second primary cancers (SPCs), but high-risk sites and specific population characteristics remain unclear.

PubMed, Embase, Medline, Web of Science, and the Cochrane Library were systematically searched to identify population-based studies reporting standardized incidence ratios (SIRs) of SPCs in NMSC patients. Meta-analyses were performed for non-skin cancer risk and 34 site-specific SPCs. Subgroup analyses were stratified by gender, NMSC category, age, time since NMSC diagnosis, and geographic region. Heterogeneity was assessed using Q-test and I² statistic.

Nineteen studies involving 560371 NMSC survivors and 77507 SPC cases were included. NMSC patients exhibited elevated risks for non-skin SPCs (SIR = 1.20, 95 % CI = 1.13-1.29). The risks were elevated for 20/34 site-specific SPCs. The highest extracutaneous cancer risks were observed in salivary glands (SIR = 4.75), lip (SIR = 2.90), and nose (SIR = 1.96). Subgroup analyses showed that basal cell carcinoma patients had increased risks for more SPC types than squamous cell carcinoma patients (15/30 vs. 9/28 sites analyzed). Patients diagnosed before age 60 showed elevated cancer risks of breast and liver/gallbladder. The SPC risks increased beyond 5 years post-diagnosis.

Our findings identified high-risk NMSC survivors who would benefit most from enhanced SPC surveillance. Instead of universal screening, we recommend risk-based surveillance for patients diagnosed before age 60, with basal cell carcinoma, or with longer post-diagnosis intervals. This targeted strategy balances early SPC detection with resource use.