Comorbidities and advanced stage diagnosis (ASD) are both associated with poorer cancer outcomes, but the association between comorbidities and ASD is poorly understood. We summarized epidemiological evidence on the association between comorbidities and ASD of selected cancers in a systematic review and meta-analysis. We searched PubMed and Web of Science databases up to June 3rd, 2021 for studies assessing the association between comorbidities and ASD of lung, breast, colorectal, or prostate cancer. Summary odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated using random-effects models. Also, potential variations in the associations between comorbidities and ASD by cancer type were investigated using random-effects meta-regression. Thirty-seven studies were included in this review, including 8,069,397 lung, breast, colorectal, and prostate cancer patients overall. The Charlson comorbidity index score was positively associated with ASD (stages III–IV) of breast cancer but was inversely associated with ASD of lung cancer ( p interaction = 0.004). Regarding specific comorbidities, diabetes was positively associated with ASD (OR = 1.17, 95%CI = 1.09–1.26), whereas myocardial infarction was inversely associated with ASD (OR = 0.84, 95%CI = 0.75–0.95). The association between renal disease and ASD differed by cancer type ( p interaction < 0.001). A positive association was found with prostate cancer (OR = 2.02, 95%CI = 1.58–2.59) and an inverse association with colorectal cancer (OR = 0.84, 95%CI = 0.70–1.00). In summary , certain comorbidities (e.g., diabetes) may be positively associated with ASD of several cancer types. It needs to be clarified whether closer monitoring for early cancer signs or screening in these patients is reasonable, considering the problem of over-diagnosis particularly relevant in patients with short remaining life expectancy such as those with comorbidities. Also, evaluation of the cost-benefit relationship of cancer screening according to the type and severity of comorbidity (rather than summary scores) may be beneficial for personalized cancer screening in populations with chronic diseases.
- • The association between comorbidity and advanced stage diagnosis (ASD) depends on the type of cancer and comorbidity.
- • Certain comorbidities (e.g., diabetes) are positively associated with ASD.
- • It needs to be clarified whether closer monitoring for early signs or screening in these patients is reasonable.
- • Evaluation of the benefit of screening according to the type of comorbidity may be beneficial for personalized screening.
Cancer is the second leading cause of death globally . In 2018, there were about 18.1 million new cancer cases and about 9.6 million deaths were attributed to cancer . Alongside improved treatment strategies, early detection has contributed to the improved cancer survival observed in many countries .
The incidence of advanced stage diagnosis (ASD, defined as stages III-IV), the main negative prognostic factor regarding cancer survival, of several cancers including breast and prostate cancer is declining in many countries. However, it is still high for some cancers such as lung and colorectal cancer . In the US Surveillance, Epidemiology, and End Results (SEER) data (2008–2017), for example, ASD (regional and distant stages) represented about 70%, 55%, and 36% of all lung, colorectal, and breast cancer cases, respectively . Besides demographic (e.g., ethnicity) and health system-related factors (e.g., insurance and access to screening services) , patient factors such as comorbidities may also affect ASD. For instance, comorbidities may mask early cancer signs, leading to delayed help-seeking for symptoms and referrals for further investigations . Also, hyperinsulinemia and hyperglycemia in diabetic patients may promote tumor growth, leading to ASD . By contrast, frequent healthcare visits due to comorbidities may increase the chances for opportunistic screening , leading to early detection .
It is well documented that cancer patients with comorbidities have poorer prognosis . Besides directly causing non-cancer death and the fact that comorbid patients utilize cancer treatments less often , one of the possible mechanisms by which comorbidities may affect cancer survival is through ASD. In recent decades, several epidemiological studies have investigated the associations between comorbidities and stage at diagnosis, but no study has summarized results in a systematic review or meta-analysis. Assessment of this association is important for understanding the mechanisms underlying the apparent poorer prognosis in cancer patients with comorbidities and for enhanced identification of persons at increased risk of ASD.
Our aim was to systematically review the available literature and perform a meta-analysis on the associations between comorbidities and ASD of the four most common cancer types in the world in terms of incidence (lung, female breast, colorectal, and prostate cancer).