# Cancer-related symptom burden

Cancer-related symptom burden refers to the cumulative impact of physical, psychological, and emotional symptoms—such as pain, fatigue, nausea, and emotional distress (e.g., anxiety, depression)—experienced by individuals with cancer due to the disease and its treatment. This burden encompasses both the severity of these symptoms and the patient's perception of their impact on daily life and overall well-being.

## Definition

Conceptually, the term cancer-related symptom burden, does not appear to fall under any particular theoretical framework. Decades of oncology research, including multiple efforts to include patient-reported outcomes (PROs) within cancer clinical trials, have informed the current conceptualization of the term.
In 2013, the Eastern Cooperative Oncology Group (ECOG), informed by recommendations from an expert panel from the Center for Medical Technology Policy and comprehensive systematic reviews, established core symptoms that represent commonly reported cancer-related (including treatment-related) symptoms for the purposes of clinical research and assessment of quality of care. Individuals with breast, prostate, colorectal, and lung cancers—of all disease stages and phases of care—were represented in their large multi-center study. These symptoms include, but are not limited to:
* Fatigue/tiredness
* Disturbed sleep
* Pain
* Dry mouth
* Distress
* Numbness/tingling
* Shortness of breath
* Lack of appetite
* Sadness
* Constipation
* Diarrhea
* Nausea
* Vomiting
Other patient-reported outcomes such health-related quality of life (HRQoL), a broader construct which subjectively assesses life as a whole, may be confused with cancer-related symptom burden. Both constructs are considered when effectively defining endpoints in cancer clinical trials that share a common goal of symptom reduction. Contrary to HRQoL, cancer-related symptom burden focuses more on the impact of nonspecific, often co-occurring symptoms, and symptom clustering which are not are not monitored as closely as other toxicities within clinical settings, to ultimately inform symptom management.
Measures that assess for cancer-related symptom burden recognize that patients can experience multiple symptoms as a result of disease and/or treatment. Collectively, they can be thought of as an indicators of symptom severity and the perception of the extent to which these symptoms affect daily functioning.

## Screening and assessment

A variety of PROs are utilized to assess symptom burden among cancer patients participating in cancer clinical research. Common measures recommended due to their psychometric properties and utility in cancer clinical research include:
* Edmonton Symptom Assessment System
* Functional Assessment of Cancer Therapy - General
* Linear Analog Self-Assessment
* MD Anderson Symptom Inventory
* Memorial Symptom Assessment Scale
* Patient Care Monitor
* Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events
* Patient-Reported Outcomes Measurement Information System
* European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire
* Rotterdam Symptom Checklist
* Symptom Distress Scale
Many of these measures also have adapted versions according to specific cancer and/or illness type. In addition to clinical trials, many PROs are increasingly being collected within ambulatory care settings to inform symptom management and intervention as well as through electronic methods such as electronic patient-reported outcomes.

## Diagnosis

There is no formal diagnosis for cancer-related symptom burden as it is conceptualized as a constellation of concerns commonly reported by individuals with cancer, any of which, may be endorsed at any time before, during, or after treatment and throughout the cancer control continuum.
Accurate assessment of cancer-related symptom burden requires repeatedly measuring the types, severity, and effects symptoms that patients experience throughout their cancer journey. Scientific review studies have advocated for standardization among PROs to capture this information in a consistent manner. Existing measures allow clinicians to measure the severity of symptoms and follow their progression over time to ensure timely interventions can be made to minimize any negative patient impacts.
Further, scientific reviews have identified common clusters of symptoms in cancer patients such as fatigue, pain, and depression. Identification of such clusters is important since they can contribute to increased symptom burden and negatively impact quality of life. Holistic diagnostic methods that recognize the interactions between several symptoms are important to appropriately diagnosing and treating these symptoms. Standardized PROs along with identification of common symptom clusters can help provide clinicians with the necessary information to manage symptom burden in a timely manner, thereby improving patient care and outcomes.

## Current interventions

Recent research on ePROs have provided general support for the implementation of ePRO-based interventions to improve symptom burden, quality of life, and survival among individuals with cancer. Additionally, among patients receiving specific treatments, these interventions were found to be effective in reducing symptom burden and promoting better quality of life.
A scientific review also highlighted potential non-pharmacological interventions for individuals with cancer experiencing pain concerns and facing social disparities such as identifying as an ethnic minority, having low income, and vulnerable women. This study revealed a high risk of bias across studies evaluating education, coaching, and online support group interventions and underscored the need to further investigate supportive care interventions that are responsive to the needs of individuals facial social disparities.
Another review of randomized controlled trials evaluating nursing interventions aimed at reducing symptom burden in adult cancer patients highlighted some clinically meaningful reductions in symptom burden but cautioned against making any definitive conclusions and potential generalizations regarding key components, circumstances, and target population of the interventions and called for further research.
There is also some support for the potential utility of mindfulness based interventions (MBIs) in reducing symptom burden among individuals with cancer.

## Prognosis

Comprehensive review studies demonstrate that symptom burden can often persist beyond completion of primary treatment. A meta-analysis that included breast, gynecological, prostate, and colorectal cancer survivors showed that fatigue, pain, and psychological distress persisted well beyond treatment completion, ultimately impacting quality of life negatively. This in turn, highlights the need for continued symptom monitoring, management, and supportive care that is responsive to the long-term needs of cancer survivors.
Additionally, studies suggest that cancer patients with advanced disease often have several different co-occurring symptoms, which translates into a high overall burden. One scientific review revealed that pain, fatigue, and depression symptoms overlapped in a way that negatively impacted daily functioning and quality of life in these patients. Understanding and treating these symptom clusters from a holistic palliative care perspective is critical to patients' outcomes and quality of life.
The general increase observed in both symptom burden and HRQoL in late stage vs. early stage disease across 10 cancer types studied in a recent scientific review, also underscores the need for earlier detection and intervention to promote survival as well as minimize the adverse effects on symptom burden and HRQoL.
These findings underscore the need for comprehensive, ongoing symptom assessment and treatment across the cancer control continuum to improve cancer patient outcomes and reduce symptom burden.

## Socio-cultural considerations

Recent research has revealed that cancer-related symptom burden varies widely by race and ethnicity. For example, a retrospective analysis of symptom burden by race and ethnicity in a large cohort of cancer patients revealed that racial and ethnic minority patients experienced greater symptom burden than non-Hispanic White patients.
Additionally, studies on social determinants of health and symptom burden in cancer treatment suggest that marginalized cancer survivors might experience significantly greater symptom burden including higher frequency and severity, and higher levels of depression and anxiety. Supporting this notion, findings from a review that examined quality of life among U.S. Latino cancer survivors revealed that compared to other racial/ethnic communities, Hispanic/Latinos reported higher symptom burden across several HRQoL domains. Further, there is some evidence to suggest a disparity in the reporting of symptom burden within routine cancer care among individuals who identify as Black.
Overall research on potential symptom burden disparities among individuals with cancer from historically-marginalized populations is currently limited. Another recent review that examined cognitive impairment among Black, Hispanic, and Asian breast cancer survivors from the U.S. revealed that Black and Hispanic patients were more likely to report cognitive impairment concerns relative to White patients, pre and post chemotherapy. Additionally, Black cancer survivors reported greater cognitive concerns when compared to their White counterparts.