Incidence and relative risk of metachronous second primary cancers for 16 cancer sites, Osaka, Japan, 2000-2015: Population-based analysis

Abstract

Background: An increasing number of cancer survivors have developed multiple primaries. This study aims to describe the incidence and risk patterns of metachronous second primary cancers (SPCs) in Osaka, Japan.

Methods: Data were obtained from the Osaka Cancer Registry, a population-based database of all cancers diagnosed in Osaka. The study subjects were individuals who were first diagnosed with invasive cancers in 16 major cancer sites during 2000-2014, aged 15-79 years, survived at least 3 months, and were followed up for 10 years. We measured incidence rates, cumulative risks, and standardized incidence ratios (SIRs: with the Osaka general population as the referent) of developing SPCs during 3 months to 10 years after the first diagnosis.

Results: During 2000-2015, among 418,791 cancer survivors, 24,368 (5.8%) developed SPCs within 10 years of first diagnosis. Males had higher incidence rates than females except among young-onset survivors (aged 15-39 years). 10-year cumulative risks among survivors aged 70-79 years (the most dominant age group) were 24.0% (male) and 11.8% (female). 10-year SIRs were 1.38 (95% CI, 1.36-1.40; male) and 1.44 (95% CI, 1.41-1.48; female) with higher estimates among younger survivors in both sexes. Strong bidirectional associations were observed between oral/pharyngeal, esophageal, and laryngeal cancers. Survivors of any smoking-related cancers had elevated SIRs of developing smoking-related SPCs. Similar results were observed for alcohol-related cancers.

Conclusions: Cancer survivors are at excess risk of developing SPCs compared to the general population. Continued surveillance is warranted to inform survivorship care through risk-based long-term care planning and lifestyle-changing efforts to prevent new cancers.

Keywords: alcohol-related cancer; cumulative risk; epidemiology; incidence rate; multiple primary cancers; smoking-related cancer; standardized incidence ratio.

FIGURE 1

Age‐specific incidence rates of metachronous second primary cancers per 100,000 person‐years by sex and calendar year of diagnosis of the first primary cancer, Osaka Cancer Registry, Japan, 2000–2015. Note: A metachronous second primary cancer was defined as a subsequent primary cancer that occurred during 3 months to 10 years after diagnosis of the first primary cancer. Person‐years at risk were calculated as the time from 3 months after diagnosis of the first primary cancer until whichever of the following came first: (i) December 31st, 2015, (ii) diagnosis of an SPC, (iii) death, or (iv) 10 years after the FPC diagnosis

FIGURE 2

Standardized incidence ratios of developing smoking‐/alcohol‐related metachronous second primary cancers among survivors of smoking‐/alcohol‐related cancers, Osaka Cancer Registry, Japan, 2000–2015. FPC, first primary cancer; SPC, second primary cancer; SIR, standardized incidence ratio; CI, confidence interval. Note: A metachronous second primary cancer was defined as a subsequent primary cancer that occurred during 3 months to 10 years after diagnosis of the first primary cancer. SIRs were calculated as the ratio of the observed number to the expected number of second primary cancers to compare the risk of developing an SPC to the general population