Temporal trends in the risk of developing multiple primary cancers: a systematic review

Yuanzi Ye, Amanda L. Neil, Karen E. Wills, Alison J. Venn

Cancer survivors are at risk of developing second and subsequent primary cancers, referred to as multiple primary cancers (MPCs). It is not clear whether the risk of MPCs has increased over recent decades, but increasing use of radiological imaging and potentially harmful effects of certain cancer treatments raise this possibility. A systematic review was undertaken to assess whether there has been a temporal change in the risk of developing MPCs. A systematic search to identify population-based studies of MPCs was performed in Medline/PubMed and Embase databases from inception to August 2016. Included studies were those reporting risk of MPCs for all sites combined following a first cancer at any site or a specific site, using standard incidence ratios (SIRs) or equivalent, and with analysis stratified by calendar years. We identified 28 articles eligible for inclusion, comprising 26 population-based studies and two monographs. MPC incidence was reported in nearly 6.5 million cancer survivors. For all first cancer sites combined, a higher rate of MPCs was reported in more recent than earlier calendar periods in four of the six relevant studies. The SIRs ranged from 1.14 for a first cancer diagnosis in the early 1980s to 1.21-1.46 in the late 1990s in the USA and Australia. Two studies from Italy and France showed no significant difference in SIRs across time periods 1978-2010 and 1989-2004. The remaining 22 studies reported various temporal trends in the risk of developing MPCs after a first cancer at a specific site, but most showed little change. Overall, the risk of developing MPCs appears to have increased since the 1980s when considering studies of all primary cancer sites combined from the USA and Australia but not from Europe. With the introduction of more routine nuclear medical imaging over the last 15 years, more studies are needed to confirm recent trends of MPC risk in adult cancer survivors.