Quality of life versus length of life considerations in cancer patients: A systematic literature review

Abstract Objective Patients with cancer face difficult decisions regarding treatment and the possibility of trading quality of life (QoL) for length of life (LoL). Little information is available regarding patients' preferences and attitudes toward their cancer treatment and the personal costs they are prepared to exchange to extend their life. The aim of this review is to determine the complex trade‐offs and underpinning factors that make patients with cancer choose quality over quantity of life. Methods A systematic review of the literature was conducted using MeSH terms: cancer, longevity or LoL, QoL, decision making, trade‐off, and health utility. Articles retrieved were published between 1942 and October 2018. Results Out of 4393 articles, 30 were included in this review. Older age, which may be linked to declining physical status, was associated with a preference for QoL over LoL. Younger patients were more likely to undergo aggressive treatment to increase survival years. Preference for QoL and LoL was not influenced by gender, education, religion, having children, marital status, or type of cancer. Patients with better health valued LoL and inversely those with poorer physical status preferred QoL. Conclusion Baseline QoL and future expectations of life seem to be key determinants of preference for QoL versus LoL in cancer patients. In‐depth studies are required to understand these trade‐offs and the compromises patients are willing to make regarding QoL or LoL, especially in older patients with naturally limited life expectancy.

harms. 1 The primary focus of cancer treatment has always been to increase overall and disease free survival; however, quality of life (QoL) has been increasingly recognized as an important end point. 2 Although there is an instinctive understanding of the term "quality of life," there are multiple definitions, which gives testimony to the fact that it is a complex concept with many diverse facets and components. The standard dimensions used in QoL questionnaires measure the presence or absence of specific symptoms or overall general health. They do not measure patients' beliefs or attitudes toward treatment and intervention outcomes. 3 Decision making in a cancer setting can be a difficult process due to its multifaceted nature. The patients' outlook and beliefs are paramount, but this is heavily influenced by their own experiences and those of friends and family. 4 In addition, current QoL and physical status can affect subsequent decisions.
Most cancer trials primarily focus on the standard oncology end points relating to survival, but it is possible to derive composite measures, which assess the impact of QoL on the final outcome of different therapies. These are called quality adjusted survival metrics or health utility metrics, and a wide range of them have been developed over the past 30 years. Utility measures allow patients a chance to value a different perspective on treatment and outcomes. Two methods of utility measurement that may be used to calculate quality adjusted life years (QALY) or quality adjusted survival are standard gamble and time trade-off (TTO). 5 In standard gamble, patients are asked to choose between staying in a state of ill health for a specified time period or choosing a treatment that may either cause their death or restore perfect health. In the case of TTO, the individual expresses a preference between two choices, usually between LoL or a better health status. 4 These methods have been increasingly adapted in cost-utility analyses of pharmaceuticals and various health-care interventions. In reality, scenarios are often more complex with disease and treatment effects impacting variably on QoL over a prolonged time course. There may be a significant drop in QoL after an intervention but an overall better long-term QoL and increased life expectancy. QoL measurement should not just focus on a single time point when assessing an intervention.
In cancer treatment, patients are often required to make trade-offs between QoL and length of life (LoL). 6 Tumor-specific therapy can potentially prolong life; however, this may reduce QoL significantly. Some patients are willing to endure toxicities associated with treatment in order to increase their LoL, while others value QoL more and are reluctant to spend their remaining years in a compromised state. 7 This involves weighing the risks and benefits of treatment and managing the patients' concerns and expectations. There may be personal reasons associated with their health, the effect on their family and friends, and the consequences of the treatment itself. A tradeoff for potential gain in life expectancy may involve short-term debility from treatment (postsurgical pain, chemotherapy-induced nausea and alopecia, and etc) or permanent side effects (stoma, disfigurement, physical dependency, and etc). Moreover, the compromise is not always related to health but instead may be about financial burdens and increased dependency on friends and family.
To understand cancer treatment choices concerning trade-off, various questionnaires and methodologies have been devised to understand patient preferences and priorities toward cancer treatment.
Quality-adjusted time without symptoms or toxicity (Q-Twist) allows the combination of both quality and quantity of survival time. 8,9 The principle hypothesis of this method is that patients without disease symptoms or treatment toxicity have a better health-related quality of life (HrQoL) than those who have disease-specific symptoms and toxicity. Q-TWiST was initially used to assess adjuvant therapy for breast cancer and has now been adapted in other cancers. [10][11][12] The Quality/Quantity Questionnaire designed by Stiggelbout and colleagues was created to assess patients' preferences toward either QoL or LoL when deciding about cancer treatments. 7 Other methods include discrete choice experiments and various bespoke questionnaires tailored to a specific study. [13][14][15] The aim of this review was to determine the factors influencing patient preferences for either QoL or LoL and how these impacts on cancer treatment choices. Study selection was by a two-step process by two independent reviewers (A.S. and C.M.), at titles and abstract stage with arbitration for articles with uncertainty. In the second stage, full-text articles were independently reviewed ( Figure 1). Reference lists of all selected articles were reviewed to identify any additional relevant articles, identifying five further articles. When an article referred to additional publications for more details concerning study methods and design, those publications were also acquired.

| Data abstraction
Data extraction was performed by two independent reviewers (A.S. and C.M.). The information collected included study design, aim of study, location of study, sample size and response rate, age of the sample, type of cancer, any research tools used in the form of questionnaires and the findings of the study relating to QoL versus LoL preferences.

| Quality assessment
The Mixed Methods Appraisal Tool (MMAT) was used to quality assess the articles that were included in the study. The 2011 MMAT tool encompasses five types of mixed methods study components or primary studies: qualitative, quantitative randomized controlled trials, quantitative nonrandomized, quantitative descriptive, and mixed methods, each with its own set of methodological quality criteria.
For each item the response categories were "yes," "no," or "can't tell" followed by comments. 16 Higher quality is denoted by the number of stars (*) in the tables. Quality assessment was independently scored by two reviewers (A.S. and C.M.). No study was excluded based on quality assessment, as all were of acceptable quality.

| RESULTS
The literature search revealed 4388 articles. A total of 843 abstracts were excluded because of duplication, and 3494 articles were declined as they were either reviews, expert opinions/editorials, or not suitable for the topic under review. A total of 56 articles were reviewed fully, and only 30 deemed suitable for inclusion. The 26 rejected papers were not suitable as they were either reviews or not relevant ( Figure 1). Included studies are summarized in Tables 1 (quantitative), 2 (mixed methods), and 3 (purely qualitative) (Tables 2 and 3).
The majority of studies identified in this review were quantitative.
Generic questionnaires (EORTC-QLQ-C30 and FACT-G) and disease specific questionnaires (EORTC-QLQ-H&N) were used to assess QoL. The studies were mainly conducted to understand the decision-making process in the advanced cancer setting. The studies had wide focus that included understanding the role of the doctor and the attitude the patient has toward their treatment, among other themes. Understanding QoL and LoL trade-offs as part of the decision-making process, usually formed a limited part of many of these studies.

| QoL versus LoL
Meropol and colleagues (2008) suggested that QoL and LoL are both equally important; however, the majority of patients with advanced cancer in this study prioritized QoL over LoL. 41 This was also reflected  by the study of Jenkins and associates. 36 Silvestri and associates noted although there were some patients who would endure treatment and associated toxicities just to live a single day longer, there were also patients who would decline all treatments. These latter patients would rather maintain their QoL and having to withstand the adverse effects of treatment would not be a worthwhile trade-off. 20 The authors postulated that patients may opt for enhanced QoL only if the chance of survival was less than 50% relative to baseline survival (without treatment). 42 Many patients in the study by Brom and colleagues felt that they ought to have some sort of intervention for their cancer and found it difficult to accept the concept of LoL and QoL. Although some patients opted for treatment initially, they expressed the view that if it was affecting their QoL, they would cease treatment. 39 Marta and colleagues noted that the majority of patients in their study wanted to undergo a treatment that would prolong life but not compromise their QoL. 43 In a qualitative study by Gerber and colleagues, patients stated that they were keen to maintain their activities and not be a burden on family, and therefore not undergo chemotherapy if those factors were compromised, indicating the importance of QoL. 38

| Survival and baseline QoL
Survival seemed to be a key feature in the decision-making process and patients were found to opt for treatment if they felt that their prognosis was likely to improve. 15,19,28,40 Their current health status also affected their choice. Perez and associates found that those who wanted to trade time, scored lower in many of the domains of the baseline HRQoL questionnaires. 3 Patients in better health were found to rate LoL more highly, whereas those who were in poorer health strived to maintain their QoL. 7 Unemployed patients prioritized QoL. 6 Wong and colleagues concluded that those who were able to pay for their treatment chose to have treatment to prolong their life. 45 These latter findings are only relevant in self paying health care systems.
Many of the studies carried out have not been age specific; therefore, it has been difficult to make inferences about the influence of  QoL was important, compared with 87.5% and 90.3%, respectively, in the greater than 65-year-old age group. 33 Stiggelbout and associates noted that when age was adjusted for in their statistical calculations, those in relationships and with children preferred longevity. 7 Derks and colleagues found that older patients were less likely to receive standard treatment, an effect that was more evident in those above the age of 80 years old. Reasons behind this included lack of social support and being widowed. Patients who did not receive standard treatment also prioritized QoL more strongly. 27

| Symptom trade-off
When looking at symptom tradeoffs against longevity, patients were prepared to tolerate certain treatment side effects to live longer.
Patients were willing to prioritize survival over intact sexual function in prostate cancer for instance. 18

| Study limitations
This study is the first to use a rigorous and systematic approach to Many of these studies have mainly focused on advanced cancers of all types. For patients who are facing mortality imminently, the decision to prioritize QoL and LoL is pertinent. In the case of slow growing cancers such as prostate and breast cancers, where conservative management is widely accepted, the choice between QoL and LoL can be more complicated. Patients often die from other causes rather than the cancer itself. 54 As the majority of the articles identified in this search did not involve early stage cancer, it is difficult to know what patients envisage from their treatment and what trade-offs they were willing to make as well as how these factors may change with the course of the natural disease process. This is where patients' age and comorbidities may play a larger role in whether the patient opts for QoL or LoL.

| Clinical implications
This review has several important clinical and research implications. This may go a long way in elucidating what aspects of their life they are willing to trade to maintain their QoL or increase LoL. Older age specific issues and cancer specific decision-making processes also need exploring.