This prospective cohort study of middle-aged and older individuals with cancer shows that comorbidities are common in individuals with cancer; with nearly a third of middle-aged individuals and nearly half of older adults with cancer reporting comorbidities. Those with 3 comorbidities or more were at higher risk of mortality, and comorbidity was associated with functional impairment in older but not middle-aged individuals.
The prevalence and types of comorbidities reported in this study was similar to that reported in other studies of individuals with cancer from UK, Europe and New Zealand [17–19] reflecting high prevalence of comorbidities in the general population that is not confined to just older individuals. In fact, the prevalence of comorbid disease in the older cohort in the present study reflects those reported in cancer studies but is lower than what is reported in the general population study for the similar age group which shows prevalence or more than one chronic condition of 64.9% in those 65–84. This finding may suggest that older patients with cancer may be preselected for cancer treatment and those with many comorbidities may not be treated or followed up for cancer.
The unique contribution of the present study is the analysis of the impact of comorbidities on mortality and functional status. Our data suggests that the impact of comorbidity on mortality is greater in middle age than in older individuals. We are unable to determine the reason for this finding. It may reflect a selection bias with older individuals who have survived with comorbidities possibly being fitter and better adapted to life with comorbidities or underreporting their comorbidities. Similarly, polypharmacy which could serve as a surrogate for comorbidities was a stronger predictor of mortality in middle-aged, more than in older individuals. Given that data on medications was more likely to be accurately extracted from the hospital records, it is less likely that this finding reflects the selection bias or under-reporting but rather than in older individuals, the impact of comorbidity on mortality is likely to diluted by the expected age related mortality much more so than in younger individuals.
Polypharmacy but not comorbidity predicted functional impairment perhaps suggesting that polypharmacy is a more sensitive indicator of severe disease. This observation highlights the importance of selecting the optimal tool to assess comorbidity – simply counting comorbid conditions may not be the most sensitive way of identifying those with the highest disease burden. Surrogate markers like assessment of polypharmacy may be more useful. Research into optimal comorbidity assessment tools including function assessment and biomarkers is needed. 
In our cohort the pattern of change of functional impairment showed that some individuals recovered but the recovery was more likely in the middle-aged individuals than older individuals. Further research is needed as to why this is so. The faster recovery may reflect the different biology of functional impairment in different age groups or the health system issues where older patients who have functional decline are not offered care to assist them in recovery.
Our findings suggesting that comorbidity and its surrogate, polypharmacy, may be more important than age alone in identifying individuals with cancer at risk of poor outcomes. These findings have important implication for practice of oncology underscoring the importance of assessment of comorbidity and function in older and younger individuals with cancer, similarly to what is increasingly recommended in the general population. Special attention should be paid to those individuals who have more than one comorbid condition and coinciding functional impairment. While the emergence of geriatric oncology as a discipline, facilitates care delivery for the older individuals with cancer and comorbid conditions, there are currently no provisions for similar approaches for younger individuals. As research suggests that cancer and its treatment are associated with premature ageing, there is also a need for a more fundamental research into the understanding of multimorbidity in cancer and its aetiology especially in younger individuals.
The strength of this study lies in its large size, prospective nature and long follow-up. Its limitations relate to missing data and using hospital records for data sources which may be incomplete. Some subgriyos included only small numbers of individuals (for example there were only few individuals with comorbidities who had no functional impairment) leading to wide confidence intervals for some of the analyses.
In conclusion, this study of middle aged and older adults with cancer shows that comorbid disease is common in younger and older individuals with cancer and is associated with higher risk of mortality and functional impairment. There is a need for research into comorbidities in younger individuals with cancer and for the development of tools to assess and manage comorbid conditions in all individuals with cancer, not just those who are older.