A Systematic Review of Comorbidity Indices used in the Nonmelanoma Skin Cancer Population

Nonmelanoma skin cancer (NMSC) is more common than all other cancers combined in the United States, and despite low mortality, their management is associated with significant cost. Questions have been raised regarding appropriate treatment in patients with limited life expectancy, as well as the best way to determine which patients fall in this category.¹ Prioritizing comorbidity rather than age may be preferred for informing treatment decisions in the very elderly.

A systematic review of the literature was conducted to identify comorbidity instruments used in the NMSC population. SCC and BCC were included, while Merkel cell carcinoma or adnexal tumors were excluded, given the inherently different natural history of these lesions. A total of 2608 titles and 1407 abstracts were identified, of which 22 studies used a comorbidity assessment tool.

Three comorbidity assessment tools in the localized nonmelanoma skin cancer population were identified: the Charlson Comorbidity Index (CCI), the American Society of Anesthesiologists risk classification system (ASA), and the Adult Comorbidity Evaluation-27 (ACE-27) (Table 1). The CCI, was the most commonly utilized in 18 studies involving the NMSC population, and offers the advantages of extensive use and validation in additional cancer populations. (Supplemental table 1) The CCI was shown to predict life expectancy in nonagenarians who had NMSC treated by MMS.² An additional study in a VA population showed an association between increased CCI score and death.³ Dhiwakar and colleagues showed a significantly higher CCI score in a group of patients greater than age 80 with head and neck skin tumors, compared with patients less than age 80.⁴ However, a separate study of patients aged 90 years and older undergoing MMS did not show a correlation between CCI score and life expectancy after Mohs surgery.⁵

Table 1.

Characteristics of Comorbidity Indices

	Charlson Comorbidity Index	Adult Comorbidity Evaluation-27	American Society of Anesthesiologists
Categories	19 conditions	27 conditions	6 categories of operative risk
Conditions and organ systems included	Myocardial infarct, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, connective tissue disease, peptic ulcer disease, liver disease, diabetes, hemiplegia, renal disease, any tumor, leukemia, lymphoma, AIDS.	Myocardial infarct, angina, coronary artery disease, congestive heart failure, arrhythmias, hypertension, venous disease, peripheral artery disease, respiratory disease, hepatic disease, stomach/intestinal disease pancreatic disease, end-stage renal disease, diabetes, stroke, dementia, paralysis, neuromuscular disease, psychiatric disease, rheumatologic disease, immunologic system disease (AIDS), solid tumor, leukemia/myeloma, lymphoma, alcohol abuse, illicit drug use, obesity.	No specific condition. Categories include: A normal healthy patient. A patient with mild systemic disease. A patient with severe systemic disease. A patient with severe systemic disease that is a constant threat to life. A moribund patient who is not expected to survive without the operation. A declared braindead patient whose organs are being removed for donor purposes.
Weighted conditions	Yes	Yes	No
Formal Comorbidity Index	Yes	Yes	No
Advantages	Most extensively used in the localized skin cancer population.	More inclusive of conditions. Designed specifically for a cancer population.	Widespread availability in medical records of surgical patients.
Disadvantages	Assumes “additive impact” of all conditions	Limited use in skin cancer population.	Not formally developed as comorbidity index. Data available only for surgical patients. Limited use in skin cancer population
Prior use(s) in the skin cancer population	Evaluation of surgical and nonsurgical skin cancer population	Evaluation of surgical and nonsurgical skin cancer population	Preoperative screening for patients undergoing surgery for skin cancer

The ASA risk classification was developed in an attempt to define operative risk, and has been used preoperatively in 3 NMSC studies. (Supplemental table 1) The ASA, while not formally developed as a comorbidity index, has been used for decades pre-operatively to predict risk in patients undergoing general anesthesia, and has performed comparably to formal indices as a comorbidity measure.⁶ An advantage of the ASA is its widespread use in patients who have undergone general anesthesia, many of whom may have this information documented in pre-surgical paperwork.

The ACE-27, is a modification of the Kaplan-Feinstein Index and was used in two studies in the localized skin cancer population, showing superior performance to a standard medical interview in identifying comorbidity, as well as a correlation between more severe comorbidity and lower survival.^7,8 (Supplemental table 1) The ACE-27 includes more comorbid conditions than the CCI and was designed specifically for a cancer population. Both the CCI and the ACE-27 allow investigators to calculate scores retrospectively through medical chart review. They have also been adapted into the form of patient reported questionnaires for ease of data collection.

While three comorbidity measures were identified for the NMSC population, studies are small and limited by significant heterogeneity. The ACE-27 captures more conditions and allows for comorbidity grading which is not possible with the CCI. Perhaps the ACE-27 will be more accurate in comorbidity assessment however larger studies are needed. As demographics shift to an older population over the next two decades, an evidence-based approach to management will depend on better understanding the impact of comorbidity and age on patient outcomes. Comorbidity tools may facilitate the decision-making process for physicians and patients, however, further studies are needed to better define their role.

Abbreviations

NMSC

Nonmelanoma Skin Cancer

CCI

Charlson Comorbidity Index

ASA

American Society of Anesthesiologists risk classification system

ACE-27

Adult Comorbidity Evaluation-27