Cancer incidence and stage at diagnosis among people with psychotic disorders: Systematic review and meta-analysis

1Background

People with psychotic disorders, including schizophrenia spectrum disorder, have elevated rates of mortality compared to the general population [12] , and it is estimated that at least half of this excess mortality is attributable to concurrent medical illnesses [3] . The cause of these disparities is thought to be the combination of biological mechanisms (e.g., ongoing antipsychotic medication use), lifestyle factors (e.g., poor diet, lack of exercise, substance use), and differential interactions within the healthcare system [14] . There has been extensive research examining concurrent medical illnesses in those with psychotic disorders, which has definitively identified elevated incidence of cardiometabolic and hepatorenal diseases compared to the general population [2] . However, the incidence of cancer in people with psychotic disorders has remained an area of contention since the Report of the Commissioners of Lunacy in 1909 567 , which first reported lower rates of cancer in patients with schizophrenia.

Subsequently, studies examining the incidence of cancer in those with psychotic disorders relative to the general population have produced contrasting results; some found a lower incidence of cancers, 8910 whereas others found the opposite [1112] . Several meta-analyses have examined the incidence of cancer at specific sites in people with schizophrenia 13141516 . These meta-analyses have identified an higher risk of breast cancer [1415] , lower risk of liver cancer [13] , and no difference in risk of lung cancer for people with schizophrenia, relative to the general population [16] .

Two prior meta-analyses have examined cancer at all sites [1718] . Catts et al. found no difference in the overall incidence of cancer between people with schizophrenia and the general population [17] . While the authors found an elevated incidence of lung and breast cancer was found, the difference was attenuated after controlling for smoking prevalence [17] . These results conflict with the results of Li et al., which found a slightly lower risk of cancer overall among people with schizophrenia, as well as lower risk of colorectal, prostate, and lung cancers in particular [18] . The findings of each review are likely impacted by which studies are included/excluded due to wide variation in direction and magnitude across cancer sites. Thus, it is important to be as inclusive as possible when summarising the evidence, as it will impact conclusions about overall cancer incidence.

There is also evidence that people with psychotic disorders are more likely to present with a more advanced stage of cancer at diagnosis. A meta-analysis of stage at cancer diagnosis and cancer-specific mortality found that people with pre-existing mental illnesses, including psychotic disorders, had 19% greater odds (OR: 1.19, 95%CI: 1.06, 1.33) of advanced stage cancer at diagnosis, whereas people with psychotic disorders had 30% greater odds (OR: 1.30, 95%CI: 1.01, 1.68), relative to those without mental illnesses [19] .

Previous meta-analyses of site-specific cancer incidence among people with psychotic disorders have focused on a limited number of cancer sites (n = 6) and restricted inclusion criteria to specific measures of incidence. In addition, several large-scale, population-based cohort studies have been conducted since the publication of the most recent review [2021] . Furthermore, best practice for systematic reviews includes risk of bias assessment [22] , which was not done in previous meta-analyses [17] or was done using reporting guidelines to assess study quality [18] . These reporting guidelines were designed for improving transparency and reporting in observational studies, not to assess study quality [2324] . The objective of this study was to perform a systematic review and meta-analysis of literature comparing the incidence and stage at diagnosis of any and all cancers among people with psychotic disorders relative to the general population.