Background
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers in the United States, with a 5-year survival rate of approximately 9%.1 Pancreatic cancer currently represents the third leading cause of cancer mortality in the United States and is expected to become the second leading cause of cancer-related death by 2030.2 Because of the often asymptomatic nature of PDAC during early stages, 80% to 90% of patients with PDAC have unresectable tumors at presentation, with therapeutic options that are noncurative and often accompanied by serious toxicities and symptoms.3,4 The high disease burden of PDAC notably affects the health-related quality of life (HRQoL) of patients, making it essential for patient preferences and goals to be adequately considered when treatment decisions are made.5
Historically, priorities in oncology emphasized clinical outcomes and the evaluation of tumor response based on physician interpretation of parameters such as laboratory values, tumor markers, and imaging. It is increasingly recognized that these clinically oriented metrics used to assess efficacy in clinical trials do not reflect the patient’s lived experience of their illness and treatments.6–8 Consequently, patient-reported outcomes (PROs) have increased in importance because of their ability to capture outcomes important to patients, such as impact of treatment adverse effects on daily functioning, emotional well-being, health perceptions, and satisfaction with care.9,10
In the 1980s, the still widely used EORTC Quality of Life Questionnaire (QLQ-C30) and the Functional Assessment of Cancer Therapy–General (FACT-G) questionnaire were developed.11,12 These questionnaires were developed without formal patient involvement and cover markedly different aspects of HRQoL, with the EORTC QLQ-C30 emphasizing physical domains more than the FACT-G questionnaire.11–13 Because multiple PRO instruments exist, the comparability of PRO data across patient care and research is suboptimal. To address these shortcomings, the NIH initiated the Patient-Reported Outcomes Measurement Information System (PROMIS) program in 2004 to standardize PRO item banks, resulting in the development of 96 PROMIS adult domains assessing aspects of patient-reported physical, mental, and social health.14,15 However, because PROMIS domains were developed for use in any disease or clinical population, the spectrum of health domains included may have varying relevance to patients with PDAC as opposed to other chronic conditions. Furthermore, studies have established that patients with cancer with shorter estimated survival times, such as those with PDAC, report greater limitations in their ability to work, poorer mental health, more fatigue, and overall greater burden than patients with other cancer types.16,17 Despite the distinct burdens of patients with PDAC, it is still poorly understood which domains of the PROMIS item banks are prioritized by these patients. After a 2016 study of patients with pancreatic cancer reported differences in the health values of patients and their healthcare providers, it became crucial to identify and address the specific inconsistencies in the health priorities of patients with PDAC and their providers.18
The purpose of this study was to establish the highest-priority PROMIS domains for patients with PDAC and compare the priorities among patients with PDAC and physician providers. By developing a focused tool for patients with PDAC using previously validated domains from the PROMIS initiative, we contrasted these patients’ reports with those of other clinical populations and hoped to increase the consistency and efficiency of PRO use in both clinical care and novel therapy development for PDAC. We also hoped to identify improvement areas for achieving more patient-centered care across this disease population.
Methods
Participants
With Cedars-Sinai Medical Center Institutional Review Board approval, we identified patients with histologically confirmed PDAC receiving care between June 2017 and June 2019 and gained their consent to participate in the survey. Only English-speaking patients aged >18 years were included.
PDAC physician specialists at sites belonging to the Pancreatic Cancer Action Network Precision Promise Clinical Trial Consortium and additional institutions across the United States and Canada were identified and recruited through electronic communication. Medical, radiation, and surgical oncologists and gastroenterologists and palliative care specialists who treated or managed patients with PDAC as part of their clinic in the past or present were included. A complete list of the 35 contacted academic and medical centers is provided in supplemental eTable 1, available with this article at JNCCN.org.
Patients with PDAC and physicians received identical questionnaires. Surveys were self-administered at a single time point. For each patient, demographic and clinical data, including age, sex, race/ethnicity, and disease status (unresectable or resectable), were recorded from the electronic health records. For physicians, a self-reported section asking for the physician’s sex and number of years of physician experience with PDAC was included. Additional information regarding the physician’s institution was separately recorded by study staff. Patients completed the survey on a tablet, whereas physicians completed it through an email link.
Survey Development
Each of the 96 adult PRO domains from the PROMIS initiative were considered in the study’s “PancPROMIS” survey, informed by the literature and previously established core outcome sets for pancreatic cancer and a consensus-based approach.19,20 Using a consensus-based approach, 2 medical oncologists (A.S. and A.E.H.) specializing in the care of patients with PDAC independently screened the 96 PROMIS domains for adults to evaluate relevancy to PDAC (Figure 1).21 Overlapping domains were grouped and summarized as displayed in supplemental eTable 2. PRO domains identified as infrequent or overly specific, including substance abuse (alcohol, smoking) and itching, were excluded. Any discrepancies in selection of PROMIS domains were resolved through discussion at weekly meetings, and additional discrepancies were resolved by a third investigator (V.R.P.H.). The final PancPROMIS survey included 31 domains across 4 categories: global health (1 domain), mental health (11 domains), physical health (12 domains), and social health (7 domains) (supplemental eFigure 1). Maximum Difference Scaling (MaxDiff) software (Lighthouse Studio, Sawtooth Software) was used to create the final survey. The 31 PRO domains were displayed in a series of 20 questions generated by the MaxDiff software, with each domain appearing 3 or 4 times as determined by the software algorithm. For each question, participants were given a list of 5 PROMIS domains and asked, “Please choose the most important aspect/domain and the least important aspect/domain of HRQoL when assessing someone with pancreatic cancer” (supplemental eFigure 2).
Flowchart of study procedures.
Abbreviations: MaxDiff, Maximum Difference Scaling; PanCAN, Pancreatic Cancer Action Network; PDAC, pancreatic ductal adenocarcinoma; PRO, patient-reported outcome; PROMIS, Patient-Reported Outcomes Measurement Information System.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 18, 8; 10.6004/jnccn.2020.7548
Statistical Analysis
Descriptive analyses were reported to characterize the patient and physician populations. Demographic and clinical factors were expressed appropriately as continuous (means and standard errors [SEs]) or categorical variables (frequencies and percentages). Preference scores for each of the 31 PRO items were generated and ranked separately for physicians and patients using the MaxDiff software.
Preference scores were analyzed using MaxDiff, a type of conjoint analysis, via Lighthouse Studio software.18 MaxDiff analysis is a standard method used to rank patient preferences based on an individual’s responses to a series of questions that involve selecting a single preference from among a list of options. The survey consisted of 31 items and 5 items per set, with a total of 20 sets.
Logit modeling was used to generate individual-level preference scores for each of the 31 PRO domains for patients and physicians, based on their cumulative responses. MaxDiff analysis was run for patients grouped based on age, sex, disease status, and race/ethnicity. Physicians were grouped together based on sex, specialty, years of experience treating patients with PDAC, institution type, and institution region. Preferences were reported separately for patients and physicians and by each of the previously listed variables. Rescaled scores using 0 to 100 scoring were computed to allow comparison of preferences. For example, an item with a score of 10 is twice as important/preferred as an item with a score of 5. Raw scores and SEs were also exported from the Lighthouse Studio software, and differences in means were calculated using t tests for 2 independent samples and simple linear regression.
Results
Of 328 patients screened, a total of 135 eligible patients with PDAC who were treated at Cedars-Sinai Medical Center completed this research survey between June 2017 and April 2019 (Figure 1). Participant characteristics of patients and physicians are shown in Table 1. Participants included 71 male (52.6%) and 64 female (47.4%) patients (mean and median, 68 years; range, 37–95 years). Of the 98 physicians contacted, 54 (55.1%) completed the online survey, including 41 male and 13 female physicians from 25 institutions (Table 1 and supplemental eTable 1).
PancPROMIS Survey Patient and Physician Demographics and Clinical Data
Preference scores for patients and physicians for each domain are presented in Table 2 and Figure 2. The top-ranked domain for patients was “ability to be physically functional” (physical functioning [PF] domain), with a mean preference score of 0.48 (SE, 0.12) and rescaled value of 7.49, whereas the lowest-ranked domain was “anger,” with a mean preference score −2.81 (SE, 0.13) and rescaled value of 0.57. PF was thus ranked 15 times as important as anger among patients. Among physicians, “pain and its effect on life” was ranked highest (mean, 0.70; SE, 0.20) with a rescaled value of 8.32, and “sexual satisfaction and functioning” was ranked lowest (mean, −3.58; SE, 0.22) with a rescale score of 0.32 (Table 2).
Preference Scores and Rankings by Patients With PDAC and Physicians
Preference rankings of PRO items among (A) patients with PDAC (n=135), and (B) PDAC physicians (n=54).
Abbreviations: PDAC, pancreatic ductal adenocarcinoma; PRO, patient-reported outcome.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 18, 8; 10.6004/jnccn.2020.7548
Pain (P<.001), anxiety/fear (P=.001), and depression/sadness (P<.001) were ranked significantly higher in importance by physicians than by patients. PF (P<.05); ability to do things for yourself, family, and friends (P<.049); ability to interact with others to obtain help (P=.006); and sleep quality (P<.001) were among some of the domains ranked significantly higher by patients than by physicians. Among the domains ranked similarly by physicians and patients are fatigue and its impact on functioning (P=.442), ability to manage recommended medications and treatments (P=.412), and diarrhea (P=.279), which are domains important for patients in their HRQoL through day-to-day activities and for providers as a means of assessing clinical improvement or response to various interventions. Additional comparisons in mean priority scores between patients and physicians are displayed in Figure 3.
Differences in mean preference scores between patients with pancreatic ductal adenocarcinoma and physicians, grouped by domain. SMD=0, no difference in preferences between physicians and patients; SMD>0, physicians scored higher than patients; SMD<0, patients scored higher than physicians. The dotted red line indicates overall SMDs in priority scores between patients and physicians.
Abbreviations: PROMIS, Patient-Reported Outcomes Measurement Information System; SMD, standardized mean difference.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 18, 8; 10.6004/jnccn.2020.7548
Overall, PF was ranked highest by patients across most subgroups, including sex and age and among non-Hispanic white patients (supplemental eTable 3). The social and mental aspects of health, including the ability to perform daily activities, participate in work and social activities, do things for oneself, and ability to manage symptoms, were among the top 5 ranked preferences of all patients (n=135) and in adults aged <65 years, women, men, and white patients. General well-being was among the top 5 ranked items by men, Hispanic patients, and Asian patients, whereas sleep quality appeared in the top 5 ranked items only for Asian patients. Physicians rated pain and its effect on life to be most important, followed by the ability to perform daily activities (mental), ability to manage symptoms (mental), ability to be physically functional (physical), and general well-being (general) (supplemental eTable 3).
Discussion
To our knowledge, this is the first study reporting PDAC-specific patient and physician rankings of the priorities of the NIH’s PRO domains as determined for 135 patients with PDAC and 54 PDAC physician specialists. This study compares the variations in the health priorities of patients with PDAC and their providers, specifically the importance patients placed on PF and autonomy to perform daily and social activities, as opposed to PDAC physicians’ current emphasis on pain. These findings can inform PDAC providers regarding ways to achieve more patient-centered care, and facilitate the design of PDAC trials that address outcomes identified as important by patients.
In the past few decades, there has been increased emphasis on the use of PROs to improve shared decision-making between patients and physicians. However, there is limited research on the relevancies of the numerous available PROs to patients with PDAC and whether these align with what their physicians believe are patient priorities. In a 2016 study that observed patients with pancreatic cancer during their care, contradictions were revealed between medical staff preconceptions of patient experiences and what patients reported, including assumptions that long-term survival outcomes are most important for these patients.18 This study illustrated that discrepancies in health values between patients with PDAC and their providers exist, which we further examined through individual-level guidance from patients and physicians.
In our study, we found that patients placed significantly higher value than physicians on their ability to engage in social interactions and independently do things for themselves and for others. The top 5 patient health priorities included statements beginning with “ability to,” emphasizing patient desires for preserving autonomy and minimizing disease-related disruptions in their lives. Unfortunately, these social health and role function domains are currently understudied and underused in PDAC.22 In 2013, one of the first pancreatic cancer PRO tools was developed: the Pancreatic Cancer Disease Impact score, which is calculated from 8 health domains of pain, fatigue, anxiety, bowel problems, loss of appetite, dry mouth, itchiness, and nausea.23 Notably, these items are predominantly disease-related physical symptoms, which have been shown to be lower-priority concerns for patients with PDAC in our study and more recent PRO studies.24 Similarly, the PROMIS questionnaire contains a larger percentage of questions relating to physical health than those concerning mental or social health (supplemental eFigure 1). Furthermore, the 26-question EORTC QLQ-PAN26 assessment tool that was designed to be used in conjunction with the 30-question EORTC QLQ-C30 contains an overwhelming number of questions with emphasis on highly specific physical symptoms that are not of top-priority interest to patients with PDAC.24
Our study also noted that physicians ranked pain, anxiety, and depression of greater importance than patients did, which is consistent with the results of the 2017 Core Set of Patient-Reported Outcomes in Pancreatic Cancer study, which used a Likert scale design to survey patients with pancreatic cancer and providers.20 In our study, pain and its impact on life was ranked highest by physicians, whereas patients ranked it as the sixth most important. Interestingly, pain, anxiety, and depression represent some of the most commonly cited symptoms reported in advanced cancers.25 The benefits of palliative care integration into oncology care, as recommended in the 2016 ASCO clinical practice guideline update, are also becoming more recognized and may also contribute to this increased focus on symptoms such as pain.26 To demonstrate this point, palliative care programs in American hospitals have tripled since 2000.27
Although palliative care often focuses on addressing immediate physical, psychologic, and social distress concerns related to HRQoL, the solutions offered are frequently short term and centered on the management of complex or refractory symptoms.28 Conversely, rehabilitation services focus more on long-term solutions for restoration and optimal function at home, at work, and in the community through interventions addressing the physical, psychologic, and vocation-related impairments that patients with cancer may encounter.29,30 Our study showed that PF was ranked as the top priority for patients and a top 5 priority for physicians, revealing a consensus understanding of patients’ desires to resume daily activities and self-sufficient lifestyles. Unfortunately, cancer rehabilitation services are still underused, despite numerous studies documenting improvements in general well-being, symptom severity, physical performance status, and HRQoL in patients with advanced cancer with the incorporation of a rehabilitation program.18,30–33
Routine multidisciplinary consultation with services such as supportive care, nutrition, genetic counseling, and social services should also be used to understand each patient’s unique perspectives, questions, and concerns. Support and patient advocacy groups can also aid patient understanding of potential treatment-related ramifications and how they may impact domains of importance to patients. A multidisciplinary focus, in addition to services tailored to improving PF and other disease-related processes affecting PF, is necessary to minimize discord between patients and providers and move toward a more patient-centered, shared–decision-making approach to care.
It should be noted that this study is limited by its single-institution design, cross-sectional nature, imbalances in provider characteristics, and heterogeneity in patients’ treatment and disease courses. Expanding this study into a multicenter longitudinal study over multiple time points to capture potential changes in priorities across patients’ disease courses and compare across predefined patient characteristics would enhance the generalizability of our findings and further validate these domains. Currently, however, this study has identified opportunities for patient care HRQoL intervention, especially among patients with unresectable PDAC.
Conclusions
Identifying patients priorities is the first step toward encouraging the medical community to recommend these desired multidisciplinary services to colleagues, patients, and families earlier in the continuum of care. Through integration of additional interdisciplinary services in earlier phases of PDAC care, the severity of treatment-related impairments that later develop may be reduced, which is especially relevant to a high–symptom burden disease such as PDAC. Further research on the feasibility of incorporating PROs in pancreatic cancer care is needed so that awareness of unmet patient needs can increase and advances in patient health, function, HRQoL, and satisfaction in care can occur.
Acknowledgments
We wish to thank all the patients in our clinic who took the time to complete our survey and the physicians across the country who responded to our survey invitations. We also acknowledge the Pancreatic Cancer Action Network’s Precision Promise Clinical Trial Consortium.
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