Measurement and impact of comorbidity in older cancer patients

Abstract

As the world population ages, oncologists are increasingly confronted with the problem of comorbidity in cancer patients. This has stemmed an increasing interest into approaching comorbidity in a systematic way, in order to integrate it in treatment decisions. So far, data on the subject have been widely scattered through the medical literature. This article is aimed at reviewing the available data on the interaction of comorbidity and prognosis. This overview should provide an accessible source of references for oncological investigators developing research in the field. Various methods have been used to sum comorbidity. However, a major effort remains to be done to analyze how various diseases combine in influencing prognosis. The main end-point explored so far is mortality, with which comorbidity globally is reliably correlated. A largely open challenge remains to correlate comorbidity with treatment tolerance, and functional and quality of life outcomes, as well as to integrate it in clinical decision-making.

Introduction

Polymorbidity is a phenomenon that increases with age. In geriatric series, people suffer on average from three different diseases [1]. Therefore, not surprisingly, older cancer patients present a high level of comorbidity, both in the general population and in oncology consultations (Fig. 1) [2], [3]. In the past, patients with comorbidities have been traditionally excluded from oncological studies. However, due to the aging of the population, this has led to a major under representation of elderly patients in cooperative studies. Whereas 60% of the cancers arise beyond the age of 65, only 20–40% of phase II and III study patients are in this age range, a large proportion of them being younger than 70 [4], [5]. Clinicians are consequently offered few data on how to adapt the results from cooperative studies to patients with comorbid diseases. Therefore, a developing approach is to integrate comorbidities in oncological studies, in the same way as functional status presently is. Functional status does not appear to correlate closely with either tumor stage or comorbidity [3]. Therefore, comorbidity should be assessed independently. However, contrary to functional status, comorbidity presents the unique challenge of being a multidimensional variable. Diseases influencing mortality may not be the same as diseases influencing function, or tolerance to treatment. Efforts to analyze the impact of comorbidity on outcome are still in their early stages but are the focus of an intense interest in oncology. In order to untangle the problem, several approaches are being used. One possible approach is to analyze disease by disease interactions. This necessitates a very large number of patients. We will briefly discuss its advantages and limits. Another approach is to attempt to summarize comorbidity in an index. Several scoring systems have been proposed to this effect. These studies are widely scattered through the literature and sometimes difficult to access. The purpose of this article is to provide the reader interested in studying comorbidity and/or integrating it in oncological studies with a convenient overview of the literature presently available on the topic. This review focuses on an extensive overview of the scoring systems available and their prognostic abilities and limits. The hope of the author is that this review will broaden and facilitate the access to background data and provide a groundwork for focusing research on pertinent issues not already addressed. The literature was screened repeatedly with Medline searches (keywords, comorbidity; comorbid diseases; the indexes discussed below by name or author name) and cross-references. No systematic attempt at contacting the authors of the indexes was made for this review, although over the years the author of this article had the opportunity to interact with several of them. The indexes discussed here were selected on the basis of two criteria: being constructed in a systematic way according to an outcome (usually death); or being used in several publications. Direct comparisons are discussed in detail, as well as studies referring to cancer patients. We refer the reader who is interested in having more details about the major indexes more specifically suitable for clinical oncological studies, including the indexes’ scoring sheets themselves, their metrological performance, and their practical implementation, to a parallel special article in the European Journal of Cancer [6].