Cancer Pain and Frailty: A Scoping Review of How Cancer Pain Is Evaluated and Treated in the Frail and Elderly : Rehabilitation Oncology

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Cancer Pain and Frailty: A Scoping Review of How Cancer Pain Is Evaluated and Treated in the Frail and Elderly

McLarney, Mitra MD1; Johnson, Taylor MD2; Bajaj, Gurtej MD3; Lee, David MD4; Zheng, Jasmine MD5

Author Information
Rehabilitation Oncology 41(2):p 69-77, April 2023. | DOI: 10.1097/01.REO.0000000000000338


With improved diagnosis and treatment of cancers, patients are living longer and requiring rehabilitation in survivorship.1,2 Successful rehabilitation of the individual with cancer requires understanding of the complex components to cancer-associated pain and the effective management of pain.3 Pain is experienced by the majority of cancer patients during their illness course, with the prevalence further increasing in those with metastatic, advanced, or terminal disease.3,4 Various analgesic options are available for cancer-related pain, including anti-inflammatories, acetaminophen, and opioids, in addition to adjuvant medications such as antidepressants, antiepileptics, and sedatives.5 Many of these medications have side effects such as sedation, respiratory depression, delirium, and gastrointestinal upset that can be of greater risk in the elderly,6 who make up approximately 50% of all individuals with cancer.7 Given these limitations, many individuals with cancer are unable to reach optimal pain control with greater than 40% reporting untreated pain.8

Frailty is both an age-related phenomenon and multidimensional process that makes it more difficult for individuals to respond to stressors, with notable increase in vulnerability, and risk for worsened health outcomes.9 Currently, there is no standard definition of frailty and in the literature there exists both operational and conceptual definitions to identify and measure frailty.10 Although frailty is correlated with age, disability, and comorbidities, it is a unique geriatric syndrome that has been linked to higher rates of mortality, nursing home admissions, and falls.11 For these reasons, the frail oncologic patient is at unique risk. More than half of older individuals with cancer are prefrail or frail, which has been shown to limit cancer treatment options, negatively impact oncologic treatment outcomes, and worsen functional outcomes in rehabilitation.12–15

Further, both individuals with cancer and frail individuals are at risk of polypharmacy, which is defined by the World Health Organization (WHO) as the concurrent use of multiple medications, often 5 or more.16,17 In addition to the increased pill burden and complex medication regimens, polypharmacy increases risk of cognitive impairment, delirium, falls, adverse drug events, and hospitalizations.18,19 Polypharmacy can include both appropriate and inappropriate use of multiple medications.18 Potentially inappropriate medications (PIMs) include medications that serve duplicate purposes, result in drug-drug interactions, are medically unnecessary, and/or have a higher risk relative to potential benefit.20,21 Studies have estimated that older Americans are at risk of polypharmacy and PIM, with recent studies estimating over 30% prevalence.22 All of these factors suggest that frail and elderly individuals with cancer would benefit from a more targeted approach to pain control during their rehabilitation course; however, it is currently unclear how treatment of pain is addressed in this unique population.

The purpose of this scoping review was to understand the current state of pain treatment in the frail, elderly individual with cancer, as well as clinical considerations by medical professionals when considering treatment in this population.


We used the scoping review methodology as outlined by Arksey and O'Malley23 and advanced by Levac et al.24 This framework includes 6 steps: (1) identifying the research question; (2) identifying the relevant studies; (3) study selection; (4) charting the data; (5) collating, summarizing, and reporting the results; and (6) consultation with consumers.23 Reporting was performed as defined in the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist.25 There was no published review protocol for this study.

Research Questions

The purpose of this review was to understand the current literature on how cancer pain is treated in the frail elderly individual. This assessment was completed by pursuing the following research questions:

  1. What is the prevalence of pain in the frail, elderly individual with cancer?
  2. What is the relationship between pain and frailty in the elderly individual with cancer?
  3. What treatment options (pharmacologic and nonpharmacologic) are used in the frail, elderly individual with cancer?
  4. What are providers' perceptions of how to treat cancer pain in the elderly and frail?

Literature Search

A systematic search of the following databases was completed: Ovid (MEDLINE, PsycINFO, Cochrane Reviews, and Ovid Nursing Database), PubMed, and EMBASE. Database searches were performed between September 23, 2022, and October 29, 2022. Relevant keywords based on the research question of interest were compiled by all authors. The keywords were classified as terms that addressed the 3 areas of cancer, pain, and frailty. The final list of terms included: (1) “oncology,” “cancer,” “malignancy,” and “tumor,” (2) “pain,” “chronic pain,” “analgesia,” “pain management,” “opioids,” and “pharmacy,” and (3) “sarcopenia,” “elders,” “frailty,” “aged,” “old,” “geriatric,” “frail elderly,” “geriatric assessment,” and “aged.” Please see Supplemental Digital Content Appendix A (available at: for a complete description of the search strategy that was employed for each database.

The selection process is shown in the Figure. Inclusion criteria for articles in this scoping review were: (1) articles published from database inception to September 23, 2022; (2) articles written in English; (3) original research articles or review articles; and (4) articles that discussed pain in cancer patients who were frail and elderly. Exclusion criteria were: (1) articles not written in English; (2) articles that did not report on pain in the frail and elderly cancer patient; and (3) book, book chapters, or expert consensus.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram of the search and study selection procedure.

A total of 2007 articles resulted from the database search. After narrowing for our inclusion criteria, 541 articles remained. An initial screening of titles and abstracts was performed on these 541 articles, which yielded 39 articles for a full text evaluation. Of these identified articles, 6 were found to be relevant and included in the scoping review. Excluded articles at this stage did not look at the relationship between cancer pain and frailty. All authors (D.L., G.B., J.Z., M.M., and T.J.) contributed to the review process independently. Any disagreements during the screening stages were resolved by study authors J.Z. and M.M. after further discussion.

Data Extraction

Data were extracted by each reviewer through a standardized form that was created and approved by the research team. The results were combined in an Excel document on an electronic shared folder. The extracted data included: (1) the study citation; (2) study design; (3) study setting; (4) study population and if applicable patient characteristics (eg, gender, age, primary tumor type, and stage of disease); (5) study objective; (6) frailty definition; (7) inclusion/exclusion criteria; and (8) relevant findings to the objective of the review. A descriptive analysis of the data was completed for each study, with the same questions asked of each study to limit bias. Information from each article was captured on how frailty was defined and the type of frailty measurement used, and the specific characteristics of the population examined. Data were further analyzed by whether studies assessed pain medication prevalence, whether studies discussed polypharmacy, whether clinician characteristics in prescribing were evaluated, and whether specific classes of pain medication were analyzed. The study results were identified and synthesized after review of the extracted data by authors J.Z. and M.M.


Our investigation revealed 6 studies that were relevant to our goal of determining the current management of cancer pain in frail elderly individuals and the relationship between frailty and cancer pain. A summary of these studies is provided in the Table. Of the 6 studies that were ultimately included in this review, 5 were observational prospective studies that assessed individuals and individual-associated characteristics.26–30 All 6 studies were published between 2010 and 2022. Two studies took place in Italy, 1 was in the United States, while the remaining 3 studies were conducted in Australia.

TABLE - Summary of Included Studies
Study Design Healthcare Setting Population Terms and Definitions Relevant Findings
Saarelainen et al26
Prospective observational Outpatient oncology clinic within a large acute care hospital
  • Patients (n = 385)

  • Aged ≥70 y with cancer

  • Female: 41%

Modified Freid frailty phenotype: weight loss (>5% in previous 6 mo), KPS score (<70%), IADL score (dependence in ≥1 IADL), exhaustion score ≥3, physical function score (dependence in ≥1 SF-36 physical function domain)
Robust if 0 criteria met, prefrail if 1-3 criteria met, frail if 4-5 criteria met
PIM use: defined by Beers criteria
  • 26.5% of older cancer patients used 1 PIM

  • PIM use associated with age 75-79 y, polypharmacy, frailty

Jamsen et al27
Prospective observational Outpatient oncology clinic within a large acute care hospital
  • Patients (n = 385)

  • Aged ≥70 y with cancer

  • Female: 35%

  • Robust, 46% prefrail, 38% frail

Modified Freid frailty phenotype: weight loss (>5% in previous 6 mo), KPS score (<70%), IADL score (dependence in ≥1 IADL), exhaustion score ≥3, physical function score (dependence in ≥1 SF-36 physical function domain)
Robust if 0 criteria met, prefrail if 1-2 criteria met, frail if 3-5 criteria met
  • Frail cancer patients had higher pain scores, higher prevalence of analgesic use, and more likely to use polypharmacy

  • Analgesic use increased linearly with pain in frail patients

  • Frail cancer patients were more likely to receive opioids and less likely to receive NSAIDs

Crosignani et al29
Prospective observational Inpatient oncologic rehabilitation unit
  • Patients (n = 45)

  • Mean age 72 y with cancer

  • Female: 44%

  • Primary cancer: solid tumor: 77%, hematologic: 23%

  • Advanced disease: 86%

Frailty Index: computed from CGA data that included 35 deficits assigned a score
  • Frailty was associated with persistent pain and pain intensity

Brunello et al28
Prospective observational Outpatient oncology clinic within a comprehensive cancer center
  • Patients (n = 745)

  • Aged ≥70 y with cancer

  • Female: 49%

  • Primary cancer type: 49.4% GI, 18.5% breast, 13.4% urological, 18.7% other

  • Metastatic: 37.2%

Based on CGA results, patients defined as frail if dependence in ≥1 ADL item, and/or aged ≥85 y, and/or if have a geriatric syndrome, and/or if presented with several moderate-grade associated diseases or ≥1 severe associated disease beyond cancer; vulnerable if presented with dependence in ≥1 IADL, comorbidities present but manageable, absence of geriatric syndromes, mild depression or mild cognitive impairment; fit if no functional dependence in ADL and IADL, no relevant comorbidities, no geriatric syndromes
  • 37% of older cancer patients reported pain

  • Frail patients reported significantly less pain than fit and vulnerable patients

  • One-third of patients reporting pain were not managed with pain medication

  • Pain prevalence and severity were underestimated by oncologists

Turner et al30
Prospective observational Outpatient oncology clinic within a large acute care hospital
  • Patients (n = 385)

  • Aged ≥70 y with cancer

  • Female: 41%

  • Primary cancer: 26.2% GI, 23.6% lung, 10.6% breast, 6.0% prostate, 4.4% hematologic

Modified Freid frailty phenotype: weight loss (>5% in previous 6 mo), KPS score (<70%), IADL score (dependence in ≥1 IADL), exhaustion score ≥3, physical function score (dependence in ≥1 SF-36 physical function domain)
Robust if 0 criteria met, prefrail if 1-3 criteria met, frail if 4-5 criteria met
  • Polypharmacy associated with 57% of older cancer patients

  • Frailty, prefrailty, and impaired physical functioning associated with polypharmacy

  • Polypharmacy associated with 4 times higher odds of being frail

  • Analgesics were the fifth most prevalent medication type, used in 32.2% of patients

Shugarman et al31
United States
Survey study 19 hospital and community-based primary care, oncology, and cardiology clinics at 8 geographically dispersed sites in 2 large VA hospital systems
  • Practitioners (n = 189) in primary care, oncology, and cardiology clinics

  • Greater intent to prescribe opioids or antidepressants was associated with female gender and greater confidence in pain management skills

  • Greater intent to prescribe an antidepressant was associated with greater trust in validity of pain ratings

Abbreviations: CGA, comprehensive geriatric assessment; GI, gastrointestinal; IADL, instrumental activities of daily living; KPS, Karnofsky Performance Status; NSAID, nonsteroidal anti-inflammatory drug; PIM, potentially inappropriate medication; SF-36, 36-Item Short Form Health Survey; VA, Veterans Affairs.

One study was a survey study that sought to better understand clinician-associated factors affecting pain management,31 while the remaining 5 focused on the patient perspective. Of these 5 studies, 4 evaluated individuals in outpatient oncology clinics26–28,30 while 1 looked at individuals with cancer in an inpatient rehabilitation unit.29 Included individuals with cancer were 70 years or older, mostly male with solid tumors and at varying stages of disease.26–30 Specific details of the population are included in the Table.

Frailty Assessments

Frailty assessments varied depending on the study. Crosignani et al29 used the Frailty Index which was computed from data obtained from the comprehensive geriatric assessment (CGA).12 Similarly, Brunello et al28 used CGA results to classify subjects as frail or nonfrail. Saarelainen et al,26 Turner et al,30 and Jamsen et al27 identified frailty using a modified version of Fried's frailty phenotype, by exhaustion score (≥3), weight loss (>5% in the previous 6 months), Karnofsky Performance Scale (<70%), instrumental activities of daily living (IADL) (dependence in at least 1 IADL), and physical function score (dependence in at least 1 36-Item Short Form Health Survey physical function domain). They further divided groups into robust, prefrail, and frail depending on how many of the above criteria were met. The Table provides a comparison of these different measures.

Prevalence of Pain in the Frail and Elderly Individual with Cancer

In Brunello et al, 37% of subjections reported pain.28 Pain was cancer-related in 21.4% of cases, cancer treatment or medical procedure-related in 27.8% of cases, with the remaining claissifed as non-cancer-related pain. One-third of individuals with cancer on pain medications were on nonsteroidal anti-inflammatory drugs (NSAIDs), one-third were on weak opioids, and one-third were on strong opioids 80.4% reported pain relief of 50% or more.28

Characteristics of Pain Management in the Frail and Elderly Individual with Cancer

Brunello et al28 and Jamsen et al27 assessed the association between analgesic use and frailty. In Brunello et al,28 one-third of individuals reported that pain was not managed with pain medications. Female gender, metastatic disease, fitness at CGA, and single or divorced status of individuals with cancer were significantly associated with higher pain. Frail individuals at CGA reported significantly less pain compared with fit and vulnerable individuals.

Jamsen et al27 found individuals with cancer who were frail had higher pain scores, higher prevalence of analgesic use, and were also more likely to use polypharmacy.27 Analgesic use, which included opioids, acetaminophen, and anti-inflammatories, increased linearly with pain in frail individuals. Frail individuals with cancer were more likely to receive opioids and less likely to receive NSAIDs.27

Three studies included analysis of polypharmacy and association with frailty.26,27,30 Saarelainen et al26 looked at PIM use as defined by Beers criteria.32 Of their sample, the mean number of medications used was 5.7 with 26.5% of individuals with cancer using one or more PIM. The 5 most prevalent classes of PIMs used included benzodiazepines, tricyclic antidepressants, and NSAIDs, all of which are classes of medications that can be used for pain management. PIM users were associated with frailty, polypharmacy, and age 75 to 79 years.26 However, this study did not associate PIM use with age greater than 80 years.26 In a separate study30 also looking at an outpatient oncology population, 57% of individuals met the criteria for polypharmacy which was associated with frailty, prefrailty, and impaired physical function. Analgesics, the fifth most prevalent medication type, were used in 32.2% of the total cohort.30 In the only study29 that examined individuals with cancer in an inpatient rehabilitation unit, frailty was associated with persistent pain and pain intensity. There was no association between persistent pain and the number of prescribed analgesic medications.29

Provider Factors Affecting Pain Management

There was one study that assessed clinician factors affecting pain management.31 This was a survey study in which clinicians were given a hypothetical case of a frail and elderly individual with cancer and were asked about their intentions for treatment. Greater intent to prescribe an opioid or an antidepressant was positively associated with female gender and greater confidence in pain management skills. Greater intent to prescribe an antidepressant was also associated with greater trust in the validity of pain ratings. Those clinicians who had personally experienced a painful condition or trusted the clinical implications of pain screening tools were associated with higher intent to examine an individual's existential well-being.31


Both cancer and frailty are common diagnoses seen in the rehabilitation patient population, especially as cancer treatments and survival improve.33,34 Addressing pain is a key component of rehabilitation care, and an important part of improving health-related quality of life measures.35 Treating pain in the frail and elderly patient with cancer is a complex issue requiring patients and providers to balance a number of competing concerns. One of the difficulties in addressing cancer pain results from the multifactorial etiology of this pain with pain generators arising directly from the tumor, related treatments, as well as associated conditions.36 Despite the recent updates to the WHO pain ladder for addressing cancer pain with evidence supporting the use of interventional procedures and alternative therapies, pharmacologic therapy remains a mainstay of treatment.37 Unfortunately, many of these medications referenced in the ladder place individuals at increased risk of sedation, cognitive changes, and subsequently falls or injuries.38 This requires providers to employ a cautious and thoughtful approach to addressing pain in the frail, elderly individual with cancer. However, this task is complicated by the relative dearth in research and guidelines on how to provide pain management in this population.39

Our review highlights several key principles when it comes to addressing cancer pain in the frail, elderly cancer patient. First, cancer patients who are elderly and frail are at risk of pain; however, the severity and prevalence of this pain in comparison to their robust peers is unclear. Two studies found frail individuals with higher reported levels of pain27,29 while 1 study found frail individuals to have a lower level of pain.28 The mixed conclusions may suggest that cancer pain in the frail and elderly is not accurately reported or measured, as the elderly may underreport pain, may experience pain differently from their younger peers, or may have higher thresholds for pain. Interestingly, the studies by Crosignani et al29 and Brunello et al28 were both conducted in Italy, so cultural differences in expression of pain may not explain the differences found. However, Crosignani et al's study looked at individuals with cancer in an inpatient rehabilitation unit, whereas Jamsen et al27 and Brunello et al28 looked at individuals with cancer in the outpatient setting, and it is possible this impacted the findings. Pain may also be inaccurately assessed by medical professionals. This assertion is further supported by the study by Brunello et al,28 which reported “minimal” agreement between an individual's reported pain level and the provider's score with only 42% of scores correlating.28 As was highlighted in the article by Shugarman et al,31 this can be problematic as a discrepancy between provider perception and individual's perceived pain can result in an underprescribing of pain-relieving medications and inadequate treatment of pain.

In addition, this review identified that frail individuals with cancer are at an increased risk of polypharmacy from various classes of medications used for pain relief such as opioids and sedatives.26,27,30 Previous studies of polypharmacy in the elderly individual have found similar results and suggest that there may be a causal relationship between polypharmacy and frailty.40 In addition to the relationship between frailty and polypharmacy, other risks of polypharmacy in the elderly include death, hospitalization, falls, and physical impairment.40 Efforts need to be taken by providers to focus on a more multimodal treatment plan for these individuals. Especially in the rehabilitation setting, providers frequently incorporate nonpharmacologic interventions into care, such as manual therapy and physical modalities such as heat/cold, ultrasound, and transcutaneous electrical nerve stimulation.41 These interventions, along with interventional pain procedures, do not have the systemic side effects of oral pharmacologic agents nor contribute to polypharmacy. Further exploration of these treatment options for frail elderly patients is recommended.

Two included studies addressed the question of what agents are used to manage pain in the elderly individuals with cancer. Both studies reflected a treatment regimen consistent with the WHO pain ladder with a progression from nonopioids to low-dose opioids to high-dose opioids.27,28 No included studies discussed use of oral antidepressants as adjuvants, incorporating interventional procedures to address pain such as intrathecal drug delivery, neurolytic blocks, neuromodulation, or steroid injections.42 Previous studies have highlighted the benefit these modalities can have for individuals with intractable cancer pain that is unable to be managed by oral or transdermal opioid analgesics42,43 and may be an additional area to further explore for the frail elderly individual.

Only one article identified in this review looked at clinician factors in pain prescription31 and found certain clinician characteristics were associated with likelihood of prescribing pain medications for the elderly individual with cancer. Interestingly, clinician confidence in pain management skills and validity of pain ratings were associated with increased likelihood of prescription of opioids and antidepressants, suggesting potential opportunities for intervention at the provider level to improve pain management in the elderly.31 As van den Beuken-van Everdingen et al44 discussed, individuals with cancer may be uncomfortable in bringing up even the most bothersome symptoms with their clinicians and may have misconceptions regarding pain medications and their efficacy. On the other hand, physicians are not consistently measuring pain levels in patients nor assessing undertreatment of cancer pain.44 Rehabilitation providers are trained to assess and understand the biopsychosocial effects of pain in their patients45 and may be especially equipped to provide the right environment for productive provider-patient conversations on cancer pain management.

To our knowledge, these 6 studies represent the most comprehensive data to accurately evaluate our objective; they assessed polypharmacy and PIM use, trends in analgesic use in our target population, the relationship between frailty and cancer pain, and provider attitudes toward frailty and cancer pain. The scarcity of literature on our topic may reflect the lack of established guidelines in managing cancer pain in frail, elderly individuals and provider uncertainty in addressing pain in our target population. By reviewing the results of these 6 studies, we have identified a vulnerable, yet growing, population that would benefit from a more targeted approach to pain management.


This scoping review was conducted following the scoping review methodology. One limitation of our search methodology is that we only looked at articles written in the English language, possibly omitting relevant articles in other languages. There were also only 6 total studies included in our final review. Three major electronic biomedical databases were included in our search strategy, and it is possible that the inclusion of more databases could have led to additional relevant studies. We did notice duplicate studies included in our search of the 3 databases, however, suggesting that additional databases may not have led to more unique and relevant articles. We also did not include rehabilitation as a term in our search strategy but made this decision purposefully, as we felt that information about pain management in nonrehabilitation settings can be translated into rehabilitation care.


The frail and elderly individual with cancer is at risk of pain and polypharmacy and may be at higher risk than their peers. Care must be taken as medical providers to appropriately assess pain in the frail individual with cancer and identify appropriate treatment options, while minimizing additional agents that provide limited benefit. Further study is needed on how to assess cancer pain in the frail, elderly individual, and recommendations for how to risk stratify these individuals when considering different treatment options.


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aged; cancer pain in older adults; pain management; pain treatment

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