Introduction
It is imperative that patients with cancer are followed closely, so as to maximize treatment benefit while minimizing complications; thus monitoring the severity of symptoms and functional impairment is a critical component of patient care. Many stakeholder groups (e.g., clinicians, patients, patient advocates, those interested in quality assurance) have made a strong case for the inclusion of patient-reported outcomes (PROs) in routine oncology practice. , A PRO has been defined as “any report of the status of a patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else.” PRO assessments can detect worsening of symptoms (whether disease- or treatment-related) and decline in functioning, either before a clinic visit or between visits, when active symptom intervention is possible. Although PROs have been widely accepted in clinical research , and are endorsed by the US Food and Drug Administration (FDA) for use in drug labeling-claim trials , the introduction of PROs in perioperative patient care has not been well established. PRO use has been limited mainly to tracking pain (and, more recently, fatigue and distress).
Recognition of the potential benefits of incorporating PROs into the trajectory of surgical care has been tempered somewhat by various practical difficulties with implementing PROs. Nonetheless, significant progress has been made toward using PROs to support patient-centered care and recognizing the value of PROs in perioperative care. Studies show that PRO-based measures of symptom severity and functional impairment are sensitive to the posttreatment recovery trajectory when administered frequently and that PRO-based quality-of-life (QoL) measures can predict objective clinical outcomes, such as surgical complications. ,
Patients with cancer who undergo major surgery experience an acute systemic inflammatory, neuroendocrine, and metabolic stress response to procedure-related tissue injury and the medications used during the perioperative period. Collectively, this response often encompasses a cluster of systemic symptoms (e.g., fatigue, poor appetite, drowsiness, disturbed sleep) and organ-specific symptoms (e.g., pain, abdominal bloating). Morbidity, including high symptom burden and other complications, may cause significant postoperative functional impairment, prolong the patient’s convalescence and recovery trajectory, lead to unscheduled clinic or emergency department visits, and delay the return to intended cancer treatment.
Insufficient empirical research has combined the patient’s perspective (PROs) with clinical outcomes (risk for complications, length of hospital stay, return to planned treatment) in order to assess such issues as recovery to preoperative symptom levels or the effectiveness of Enhanced Recovery Programs (ERPs). , The knowledge gained from such research could be a clinically relevant and a critical component of routine surgical practice. Additionally, this kind of information is vital for clinicians, as it may help to determine the patient’s ability to resume additional intended cancer therapies. Thus integrating PROs into standard postoperative care has multiple advantages for monitoring and evaluating recovery from cancer surgery.
Recent advances in data-gathering methods are facilitating the use of PROs in routine clinical practice. , In the past few years, a transition from earlier methods, such as paper-and-pencil assessment at clinic visits, to electronic data capture via telephone-computer interactive voice or web-based methods on computers or smartphones has enabled frequent PRO assessments to be obtained from patients at home. These newer methods increase the feasibility of tracking patients after discharge repeatedly and with relatively little patient burden, while making these data available to clinicians in real time.
Breakthrough projects are needed to establish (1) a workable methodology for using PRO measures to characterize postoperative recovery from the patient’s perspective after complex procedures, focusing on symptom burden and functional impairment (especially once the patient is discharged from hospital), and (2) knowledge about barriers to adopting PROs in routine patient care. This chapter presents considerations for the development and use of PROs in perioperative care.
Defining PRO concepts
Ideal PRO Instruments
The ideal PRO instrument will satisfy the FDA requirements for certain development procedures that promote reliability, validity, and sensitivity (see later). Beyond such formal requirements, a good PRO instrument will also be brief, simple, and understandable by patients with diverse educational and cultural backgrounds. We find that a 0–10 numeric severity rating scale is ideal for obtaining reliable information directly from patients, because only the anchors have to be translated and adapted for different cultures, thereby minimizing possible misunderstanding. However, categorical responses (i.e., none, mild, moderate, severe) are used on many scales, including the PROMIS assessment method and the PRO-based version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Finally, the ideal PRO instrument will have been validated for repeated use and will include specific symptoms related to the site, disease stage, and treatment to be studied—in other words it will be “fit for purpose”—and will allow acquisition of real-time data during recovery, which can be viewed as a continuous process.
PRO Instrument Development
In 2009 the FDA set forth guidance on how to develop PRO instruments that are acceptable to the FDA for supporting labeling claims in medical product development. In accordance with this guidance, the development of procedure-specific PRO instruments for use in surgical settings must include both qualitative studies to establish content validity (i.e., which symptomatic outcomes might be expected) and psychometric validation studies to establish reliability, validity, and sensitivity. Besides reliability and validity, responsiveness (change in ratings when they are to be expected) also is important. To acquire comparable clinical data across various patient populations, the impact of cultural and linguistic factors on patient-reported symptoms should be reviewed and minimized to support the use of these methods in other languages and cultures.
Similarities and Differences Between Symptoms and QoL as Concepts
A long history of QoL research within clinical cancer research has focused on various dimensions of the patient’s perspective. Wilson and Cleary established a classic conceptual model of PROs that well defines the differences among the terms “symptom,” “functional status,” and “heath perception,” as they relate to overall QoL. They noted that “Patient-reported symptoms not only cause patients to enter the medical system, they also may affect subsequent use and the costs of medical care.” Their model indicates that how the individual evaluates his or her overall QoL depends on multiple levels of PROs; symptom status is one important determinant of functioning, whereas the physical, psychologic, social, and role functioning domains are indicative of health status. Wilson and Cleary conceived of overall QoL as “distinct from health, though related to it.”
Indeed, the similarity among these various health-related QoL domains (symptoms, functional status, health status, and overall QoL) is that all are measurable by PROs; the difference among them is that only one—symptom burden (symptoms and/or functional status)—has clinically relevant outcomes that could point to medically actionable targets for implementation in routine patient care.
Clinical Research on Pro Application in Perioperative Care
Ground Knowledge From PROs
To inform research, health care delivery, and policy, patient-centered outcomes research and comparative effectiveness research require that PRO data be captured appropriately. PRO instrument validation processes and minimum measurement standards for specific diseases or procedures are rapidly being developed to promote the proper use of PROs.
Particularly in surgical oncology practice, where debilitating radical procedures and oncoplastic reconstruction after resection are common, the advent of ERP concepts and strategies , is challenging the conventional evaluation and definition of “postoperative recovery” after major cancer surgery. Undoubtedly, following ERAS guidelines has led to fewer complications, shortened hospital stays, fewer hospital readmissions, and decreased 30-day mortality. Nonetheless, the time course and level of recovery associated with current standard care versus newer ERAS principles are still being characterized. Factors that might contribute to complications, such as advanced age, higher body mass index, the complexity and extent of resection, higher American Society of Anesthesiologists physical status classification score, and existing medical comorbidities, have been studied, but these concepts add little to our knowledge about the patient’s experience during the postdischarge recovery period.
Being free of symptoms (e.g., nausea, pain) and being independently mobile were identified by both patients and health care professionals as the most important goals of postsurgical recovery. Indeed, functional recovery after major cancer surgery dictates whether adjuvant therapy will be delayed or cancelled, either of which can negatively affect long-term clinical outcomes. Thus discussion regarding the design of PRO assessments has progressed from assessing one dimension of recovery, such as physiologic variables, to a multidimensional assessment of physical, emotive, functional, and cognitive performance. , ,
Establishing solutions that better serve key stakeholders (in particular, patients and clinicians) in tailoring and evaluating procedure-specific perioperative care after major surgery will require collaboration among investigators from surgery, symptom research, nursing, and anesthesiology. To incorporate PRO-based methods for defining major symptom burden, a research plan should include a validated PRO instrument that measures symptom burden and has been shown to be sensitive for detecting both acute and chronic treatment effects on symptoms and functioning in the patient population of interest (i.e., a fit-for-purpose measure). These methods can then be used to establish the utility of PROs as clinical outcomes in ERP practice, such as for defining functional interference and recovery during perioperative care and predicting poor recovery.
Further research is needed to investigate the challenges and barriers to adopting PROs in real-world perioperative care. Adding a measure of multisymptom and functional outcomes in care that provides the patient’s perspective on their recovery trajectory would undoubtedly improve our understanding of the impact of surgery. Other than for pain, this is yet to be studied at any depth in surgical clinical research.
Challenges and Opportunities
Recognition of the potential benefits of incorporating PROs into the trajectory of care has been tempered somewhat by awareness of problems in implementing PROs. Implementation requires not only sufficient research to provide PRO parameters that will be useful in routine patient care, but also the ability to transition from research to practice, which can take 10–20 years in a large population. A systematic review with a national focus on postacute care, which reported evidence from studies that used PROs during recovery after adult cardiac surgery, encapsulates the challenges that are similarly faced by cancer researchers. Multiple significant heterogeneity and methodological weaknesses were found, such as differing follow-up periods, lack of standardization in the frequency of measurement and the tools used to assess recovery, variations in the handling of missing data, limited domains that were assessed, and the fact that most were single-site studies without external validation. These weaknesses support concerns that the evidence base regarding postoperative patient-centered outcomes still needs to be strengthened to guide data-driven improvement in oncologic postoperative recovery.
For clinicians and nurses involved in perioperative care after cancer surgery, the feasibility of using PROs in this setting is influenced by difficulties with integrating PROs into clinical workflows and concerns that PRO assessment is a time-consuming effort that adds little in terms of clinical benefit. The length of time needed for patients to complete a multi-item PRO instrument has been an issue for both patients and clinicians. Further, although validated PRO instruments are available, their utility and meaning within a defined clinical setting remain relatively unexplored. These challenges to PRO adoption might be met by providing empirically established methods for interpreting PRO measurements.
One result of time-related concerns related to multiitem PRO assessments is low temporal granularity in measurement. However, today’s digital platforms may allow for high-frequency PRO measurements, as frequent as on a daily basis. Leveraging such technology provides novel opportunities to obtain granular insights into the recovery process. The methods could enhance perioperative care, not only during hospitalization after surgery, when patients are highly symptomatic, but also after discharge during the functional recovery period.
The expansion of electronic data-capture systems to be deployable on home phones or computers, smartphones, and tablet computers makes it much more feasible to collect patient reports outside the clinic in real time. , This allows patient status to be followed frequently throughout active treatment and even after treatment has been discontinued. As the feasibility of adopting electronic PRO capture increases, the relationship between the patient’s perspective and postoperative clinical outcomes as associated with different diseases and procedures should be further examined. Questions to be answered include: What symptom score presents a clinically meaningful trigger point that needs an intervention? What functional interference score should trigger action, so as to prevent further delay of adjuvant cancer therapy?
Clinical Research Outcomes
Despite the challenges inherent in PRO implementation, incorporating PROs as clinical research outcomes in perioperative care has numerous potential benefits. When collected longitudinally, PROs can be used to quantify perioperative symptom severity and functional status trajectories , which should be interpretable for both clinical research and practice. The definition of symptom recovery and functioning recovery can be established either by using preoperative symptom and functional impairment levels in comparison with postsurgical and postdischarge levels, or by using mild-level symptom and interference severity cutoff points, below which patients can perform their daily activities without medical assistance. Time to recovery , which is the time needed to return to preoperative or no/mild symptom and interference levels, can inform comparisons between surgical techniques or between perioperative care strategies, for example, ERP versus standard care. It is worth mentioning that, because patients may report a PRO score below a predefined severity threshold at one time and above it at the next assessment, two consecutive below-threshold scores might better signify a recovery event; in this scenario, the time of the first assessment is considered as the time of recovery.
Methodologies for Applying Pro Measures in Perioperative Care
How can PROs inform and change real-world practice? We already have a widely used, acceptable PRO-based method for assessing pain in routine patient care: verbally asking patients to rate their pain on a 0–10 scale. This method is standard care across most health care systems and offers an excellent example of how PROs can be feasible and useful in real-world applications. Nonetheless, the transition from academic knowledge to good clinical utility for other PROs in perioperative practice is hindered by multiple factors, as represented by Rogers’ classic Diffusion of Innovation Theory. This theory provides an appropriate framework for understanding the challenges inherent in bringing a new process, characterized by Rogers as “hardware” and “software,” to acceptance by users and, ultimately, successful adoption. Hardware is “the tool that embodies the technology in the form of a material or physical object”; in PRO implementation, it is the instrument itself, its method of delivery, and the real world clinical needs by cohort. Software is “the information base for the tool”; in PRO implementation, it is a set of clear and simple methods for how to use the instrument, its compatibility for patient-care clinicians implementing it as a new outcome measure (awareness, advice, concern), and its acceptability to patients (complexity of delivery). We are hopeful that the decision by various electronic medical record builders to include fit-for-purpose PROs in their foundational system for nationwide use will meet the software needs for most patient-care clinicians in a perioperative setting, as a part of an ERP.
The methods and procedures for using PROs in patient care include assessment tool selection, data collection and display, and data interpretation with clinically meaningful trigger points, algorithms, or pathway-of-action points, all of which must be carefully studied and supported by clinical research.
Considerations in Selecting Assessment Tools
Currently, PROs are used mainly in clinical research and are endorsed by the FDA for use in drug labeling-claim trials. The PRO-CTCAE is mostly used in clinical trials. Symptom tools are far more relevant to the disease and treatment process for everyday clinical care than are QoL measures, as symptom alleviation is the first critical step toward improving a patient’s overall QoL, the final endpoint in Wilson’s model. Understanding this theoretical difference between symptom and functional interference measures versus more conceptually broad health-related QoL measures is challenging for most clinicians and is a major barrier to the adoption of PROs in practice, as is the historical use of health-related and overall QoL measures, rather than symptom-specific measures, in clinical trials and research (e.g., the 36-item Short Form Health Survey [SF-36], Functional Assessment of Cancer Therapy [FACT], and European Organization for Research and Treatment of Cancer core QoL questionnaire [EORTC-QLQ-C30]). In contrast, only pain and distress are typically assessed quantitatively in routine patient care.
Nonetheless, several validated multi-symptom assessment tools are available for focusing directly on symptom burden and its impact on functional status (e.g., the Edmonton Symptom Assessment System [ESAS], MD Anderson Symptom Inventory [MDASI], and the short form of Patient-Reported Outcomes Measurement Information System [PROMIS]). Few symptom PRO measures have been adopted in perioperative care, even though they are already accepted in other areas of oncology research, academia, and patient care, nor has the concept of PRO outcomes been broadly included in existing ERP-style programs or censuses.
Using PROs to assess symptom severity and its impact on daily functioning has proven to be a valid and sensitive approach to quantifying the patterns of change in perioperative symptoms and functioning over the course of recovery. When used to longitudinally measure physical functioning status, PRO-measured interference with walking ability significantly correlated with an objective performance-measured outcome, the 6-min walk test. In a population with decreased physical functioning, the PRO measure generated less missing data than the 6-min walk test.
The 2009 FDA guidance suggests that it is preferable for patients to report their current or recent symptom and functional status with a short recall period. In the perioperative setting, especially in the first few days after surgery, symptoms and functional status change every day. Thus a recall period of 7 days may not capture the daily changes in a patient’s status. Tools with a shorter recall periods (e.g., in the past 24 h, or currently) would be more suitable for this situation.
To successfully integrate PROs into patient care, an evidence-based subset of clinically meaningful symptoms that can be used to identify, triage, and treat patients at high risk for postoperative complications is needed. However, no symptom-specific PRO questionnaire has yet been adopted for evaluating relevant patient-reported symptom burden after patients are discharged from the hospital during postoperative recovery; this is a vital need, because an objective measure of functioning would not be feasible after discharge, when patients are at home. A recently published study demonstrated that critical PROs (such as the walking and general activity interference items on the MDASI) could quantify a patient’s physical functioning that was verified by the Get up and Go test after gynecologic surgery.
Assessment Schedules
PRO assessment schedules must match perioperative care needs and more importantly, align with expected changes in patient status. Further, the schedule should minimize the assessment burden for both patients and professionals. For example, PROs should be assessed more frequently during hospitalization (probably daily), but only weekly or twice weekly after discharge. Such a measurement schedule ensures timely capture of changes in symptoms and functional status, which should accurately describe the recovery trajectory and identify high-risk individuals in need of symptomatic intervention.
Cutoff Points as Thresholds to Trigger Intervention
A PRO measure should be easily understood and its scores must be interpretable, if it is to be of any clinical use. Although the use of continuous variables is statistically preferable to the use of categorical variables, in practice, changing a PRO variable from continuous to categorical form by using empirically derived cutoff points may better inform treatment decision making for clinicians. The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Adult Cancer Pain defined “mild,” “moderate,” and “severe” as clinically meaningful severity categories. These guidelines define a rating of 1–3 on a 0–10 numeric scale as mild, 4–5 as moderate, and 7–10 as severe, for the purposes of establishing alerts to inform clinical consequences or actions according to treatment algorithms and for defining high-risk complications. The NCCN used a similar approach to establish guidelines for fatigue and distress management. ,
Although mild, moderate, and severe categories are discrete, a specific cutoff point for triggering clinical action still needs to be established for different symptom items. Cutoff points should be based on an anchor that is clinically interpretable (e.g., change in performance status or postdischarge complications to define the cutoff points for PRO-assessed physical functioning) and should be well correlated with the PRO measure.
Examples of Using PROs to Define Recovery After Thoracic Surgery
As an integral part of the development of the PRO outcomes for recovery from thoracic surgery in patients with early-stage non-small cell lung cancer (NSCLC), treatment-naive patients undergoing either standard open thoracotomy (n = 31) or video-assisted thoracoscopic surgery (VATS; n = 29) , used the MDASI, an extensively validated PRO measure of cancer-related symptom burden, to rate symptoms and their impact on daily functioning in the past 24 h. The MDASI asks patients to rate the severity of each symptom and functional interference item at its worst on a 0–10 numeric rating scale: for the symptom items, 0 represents “not present” (no symptom) and 10 represents “as bad as you can imagine”; for the interference items, 0 represents “did not interfere” and 10 represents “interfered completely.” Fig. 55.1 shows MDASI trajectories for fatigue, shortness of breath, disturbed sleep, drowsiness, and pain, the most severe symptoms after thoracic surgery. The MDASI was sensitive enough to detect differences in symptom and functional recovery between open surgery versus VATS.
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