Cancer Prevention for Survivors: Incidence of Second Primary Cancers and Sex Differences-A Population-Based Study from an Italian Cancer Registry

Abstract

Background: The number of cancer survivors continues to increase, thanks to advances in cancer diagnosis and treatment. Unfortunately, the incidence of a second primary cancer (SPC) is also increasing, but limited studies reporting incidence data are available regarding multiple cancers. This study presents our observations on multiple primary malignant cancers, the associations between sites, and the inherent sex differences.

Patients and methods: We report the data, disaggregated by sex, concerning the SPCs that were recorded in the "Registro Tumori Integrato" (RTI) a population-based cancer registry in Sicily, Italy, as observed in the period from 2003 to 2017, in a total population of approximately 2,300,000. SPCs were divided into synchronous and metachronous cancers. The International Classification of Diseases for Oncology, third edition (ICD-O-3), was used for topographical and morphological classifications. Multiple primary cancers with multi-organ primitiveness were selected from the database of the RTI by extracting patients with more than one diagnosis. SPCs had different histology or morphology from the particular cancer that was considered to be the index cancer case. Multicenter or multifocal cancers, or metastases, were excluded. The percentages of cancer by sex and topography, the average age of incidence, and a breakdown by age were computed.

Results: Differences were observed between sexes in terms of incidence and site for SPCs. The most frequent SPC was skin cancer (20% of the SPCs observed). The associations among sites of multiple cancers are reported.

Conclusion: There are many gaps in our knowledge of sex differences in cancer. The study of multiple primary cancers could bring more likely opportunities for evaluation of the cancer burden and trends that can be used to identify new research areas by population health programs, as well as for clinical researchers.

Keywords: cancer prevention; cancer registry; cancer survivors; multiple primary cancer; second primary cancer; sex differences.

Figure 1

Second primary cancer sites, according to the site of the first primary cancer. FPCs are listed in white font and shown in decreasing order (the data can be found in Table S4 of the Supplementary Materials); percentages are shown of all SPCs, with the five most frequent sites listed in colored fonts, displayed in decreasing order from top to bottom (data in Table S5 of the Supplementary Materials).

Figure 3

The raw incidence rate data in patients from RTI 2003–2017, by age class, at diagnosis of the FPC. M, males, F, females; <50 = aged 0–49; 50–69 = aged 50 to 69 years old; 70+ = aged 70 and above.

Figure 2

Sites of second primary cancers, shown by decreasing frequency of occurrence. The most frequent SPC sites are detailed, in decreasing order from bottom to top; other cancers, combined, represented 30.0% in males and 38.8% in females (data in Table S5 of the Supplementary Materials).

Figure 4

Percentage incidence of a second primary cancer in patients, 2003–2007. Panel A: M, males; Panel B: F, females. Age ranges at the diagnosis of an FPC: 0–49 years old; 50–69 years old; 70+ = age 70 and above. Second diagnosis was within a time frame of 6 months (synchronous), between 7 and 60 months, or after 60 months (five years) during follow-up. Note: * significantly different, p < 0.05, chi-squared tests; error bars: 95% confidence intervals.