This study is the first to determine the optimal cutpoint for total number of symptoms in patients with advanced cancer. This finding suggests that the concept of a clinically meaningful cutpoint for symptom severity scores is transferable to total number of symptoms. In this sample, the cutpoint of 12 symptoms successfully differentiated between patients with advanced cancer based on a significant jump in both MQOL-CA2 subscale and total scores.
Validation of 12 symptoms as the optimal cutpoint was supported by significant between-group differences in depression and anxiety scores and in a generic measure of QOL. As shown in , between-group differences in these scores equate with medium to large effect sizes.40
Previous research suggests that an effect size of 0.2 to 0.5 is considered a minimally important difference and a clinically meaningful difference in QOL measures.41–43
Cinical significance goes beyond statistical significance to identify whether a change is large enough to be noticed by the patient.44–47
Our findings suggest that when a patient crosses the threshold from 12 to 13 symptoms he or she may notice a decrease in various aspects of QOL.
Effects Sizes for Between-Group Differences (High-Low) in Subscale and Total Scores for the Validation Scales for Depression, Anxiety, and Quality of Life
MQOLS-CA2 total scores in this study were similar to those reported in previous studies of oncology patients.48,49
Overall, patients with advanced cancer appear to have moderate decrements in QOL. However, further research is needed to determine the generalizability of these findings and whether response shifts occur in evaluations of QOL in these patients.50,51
The cutpoint that differentiated between low and high number of symptoms was validated by between-group differences in the rank order of the psychological symptoms on the MSAS. All four psychological symptoms (worrying, feeling sad, feeling nervous, feeling irritable) were among the top 12 symptoms in the high symptom group. In contrast, in the low symptom group, each psychological symptom had a lower overall rank and occurrence rate, and only worrying and feeling sad were in the top 12 symptoms.
CES-D scores for the low and high symptom groups in this study were similar to scores reported by patients with advanced head and neck cancer.52,53
In contrast, higher total CES-D scores were reported by patients with advanced stages of ovarian54
cancer. These inconsistent findings may be attributed to heterogeneity in cancer diagnoses, treatment regimens, and timing of assessments.
Mean state and trait anxiety scores in this study are similar to previous reports of patients with advanced cancer.56–58
State anxiety increases in response to physical danger and psychological stress, whereas higher trait anxiety is associated with diagnoses of psycho-neuroticism and/or depression.31,59
The consistent levels of anxiety across studies suggest that patients with advanced cancer may experience acute anxiety from a variety of physical and emotional stressors as well as chronic anxiety associated with depressive symptoms.
In this study, mean MOS-SF36 subscale and component scores for the total sample ranged from 32.1 (±8.8) for the physical component score to 64.8 (±19.8) for the mental health subscale. These scores are similar to those reported in one study,60
lower than scores reported in three studies of patients with advanced cancer,61–63
and higher than scores reported in another study64
of patients with advanced cancer. Reasons for these inconsistencies may include differences in studies' definition of advanced cancer, their inclusion and exclusion criteria, and timing of the assessments.
Differences in patients' reports of symptom occurrence and the rank order of the most common symptoms support the between-group differences found for the depression, anxiety, and psychological/mental health domains of the MOS-SF36. The largest effect sizes were found for the mental component and subscale scores related to psychological status (social functioning, vitality, role limitations–emotional, mental health). Emerging evidence suggests that psychological symptoms contribute to decrements in QOL in patients with advanced cancer.65–68
For example, higher depression scores were associated with higher symptom severity scores.69
In addition, in a study of cancer patients in their last year of life,68
higher levels of depressive symptoms at enrollment were associated with a worse symptom experience over time. It is not clear if psychological symptoms result in more symptoms or if length of time since diagnosis produces psychological “wear and tear” that results in more psychological and physical symptoms. Furthermore, it is not known if psychological and existential distress increase in patients with advanced cancer as they approach the end of life.70
Several study limitations need to be acknowledged. In this relatively small sample, only one optimal cutpoint for total number of symptoms was found. However, studies with larger samples may identify additional cutpoints. The fairly homogeneous sample of white and well-educated adults, all of whom had pain, limits the generalizability of the findings. However, given that pain was a highly prevalent symptom in both symptom groups, it is unlikely that the results of this study could be attributed only to pain. Finally, it is not possible to separate the effects of cancer and its treatment (e.g., side effects of medications) and the effects of chronic medical conditions on the patients' symptom experience.
Study findings suggest that a threshold exists between low and high number of symptoms in patients with advanced cancer. Additional research is needed to confirm these results and determine if additional cutpoints can be identified. In addition, studies need to determine if the use of cutpoints for total number of symptoms leads to improvements in clinical assessments and more tailored interventions for this vulnerable population. With the movement in health care toward systematizing best practices in an efficient manner, a need exists to develop screening criteria which, even if automated, would assure that the maximum number of patients who are at greatest risk for worse symptom outcomes are recognized with the minimum amount of effort. In the meantime, clinicians can administer a symptom checklist like the MSAS on a routine basis. Patients who report the occurrence of ≥13 symptoms warrant more detailed evaluation and more aggressive symptom management.