Policies and Practices to Address Cancer’s Long-Term Adverse Consequences

Abstract

As cancer detection and treatment improve, the number of long-term survivors will continue to grow, as will the need to improve their survivorship experience and health outcomes. We need to better understand cancer and its treatment’s short- and long-term adverse consequences and to prevent, detect, and treat these consequences effectively. Delivering care through a collaborative care model; standardizing information offered to and collected from patients; standardizing approaches to documenting, treating, and reducing adverse effects; and creating a data infrastructure to make population-based information widely available are all actions that can improve survivors’ outcomes. National policies that address gaps in insurance coverage, the cost and value of treatment and survivorship care, and worker benefits such as paid sick leave can also concurrently reduce cancer burden. The National Cancer Policy Forum and the Forum on Aging, Disability, and Independence at the National Academies of Sciences, Engineering, and Medicine sponsored a virtual workshop on “Addressing the Adverse Consequences of Cancer Treatment,” November 9-10, 2020, to examine long-term adverse consequences of cancer treatment and to identify practices and policies to reduce treatment’s negative impact on survivors. This commentary discusses high-priority issues raised during the workshop and offers a path forward.

With approximately 17 million cancer survivors living in the United States, a population that is expected to grow to 20 million by 2030, more people are living with the aftermath of cancer and its treatment (1). Advancements in early detection and treatment and the resulting improvement in long-term survival for many cancers are cause for celebration. Several cancers, even some that are diagnosed at late stage, are moving toward becoming chronic. With this newfound longevity comes the need to understand the sequelae of treatment so that cancer survivors, who comprise nearly 5% of the United States population (2), have the best possible outcomes and support.

The National Cancer Policy Forum, along with the Forum on Aging, Disability, and Independence, held a 2-day virtual workshop with experts in cancer treatment and survivorship to examine critical long-term adverse consequences and to identify practices and policies to reduce the negative impact of treatment on survivors (3). These consequences span physical, social, psychological, emotional, and financial outcomes for adults and children. People with cancer require immediate actions that can be taken to prevent, mitigate, and treat adverse consequences and improve their quality of life. In addition, new strategies are needed to address emerging treatments such as oral therapies, where the home is the site of care and their unique impacts during and after treatment.

This commentary summarizes high-priority problems, potential solutions, and research needs that will improve outcomes for people with cancer, including those with metastatic disease, highlighting the many opportunities to reduce cancer’s burden. We discuss care delivery approaches and emphasize the data infrastructure requirements to better detect, track, and treat immediate and long-term adverse effects. We suggest practice and policy changes that will mitigate the challenges that survivors face, with the goal of preventing adverse consequences before they disrupt the lives of millions of survivors and their families. For this commentary, we prioritized problems and solutions that can be immediately addressed; however, the workshop proceedings contain the full set of presentations, including those that are beyond the scope of this commentary (3).

Overview of Adverse Consequences

The experience of Dr Wendy Harpham, who is a long-term cancer survivor, is briefly summarized in Figure 1. Her experiences with the immediate and long-term adverse events associated with intensive cancer treatment highlight the critical need to address adverse consequences during treatment and in the survivorship period. Her experience is not uncommon. Nonetheless, her account brings a personal context to problems survivors face and the need to systematically address these issues.

Figure 1.

Personal account of adverse consequences.

Some of the most common and immediate treatment-related adverse effects include fatigue, hair loss, appetite loss, constipation or diarrhea, sleep problems, pain, nausea or vomiting, memory problems, mouth problems, osteoporosis, infertility, gonadal dysfunction, and sexual health issues (4). Many of these conditions continue after treatment is complete. Late effects may include heart, vascular, lung, endocrine, dental, oral, and mental health consequences (5). The risk of secondary cancer may be increased due to radiation exposure and chemotherapy treatments (6,7). A heavy financial burden may result in increased debt and even bankruptcy, delayed or forgone treatment, and increased stress related to high medical charges and payments (8). Anxiety, distress, and depression are also common among cancer survivors (9). Individual risk factors for mental and emotional distress include age, sex, race and ethnicity, lack of social support, unemployment, health-care costs, and preexisting psychological problems (10). Stigma around mental health and some types of cancer, the stage of cancer at diagnosis, and prognosis can exacerbate negative psychological consequences.

In survivors of childhood cancer, adverse effects vary by diagnosis and treatments and may include radiation-induced coronary artery disease, late-onset anthracycline-related cardiomyopathy, pulmonary fibrosis, skeletal abnormalities, and endocrinopathies (11). Childhood cancer survivors are 8 times more likely to develop serious chronic conditions compared with their siblings (11). Adolescent and young adults also suffer disproportionately from anxiety, depression, and fear of cancer recurrence (12). In the older adult population, cancer survivors have increased levels of geriatric syndromes and disability and often meet vulnerability and frailty criteria that increase the risk of worse outcomes (13).

Evidence gaps exist for people diagnosed with metastatic disease who are now living for extended periods of time and people treated with newer therapies (eg, targeted agents, immunotherapies) where treatment continues until end of life, but insufficient time has passed for population-level data collection and evaluation of long-term adverse effects. We do not yet understand the long-term toxicities of these treatments and need systematic ways to follow patients who received these agents and to rapidly understand their long-term complications. We also acknowledge there is insufficient evidence for small populations defined by residency (eg, rural and frontier areas, persistent poverty areas), racial and ethnic groups, ancestry, or exposure. The solutions we recommend are broad and aimed to make progress in filling in evidence gaps as we currently understand them.

Practice Approaches to Reduce Adverse Effects of Cancer Treatment

Collaborative Care Models

Nekhlyudov et al. (14) outline a framework of survivorship care comprising prevention and surveillance for recurrences and new cancers; surveillance and management of physical, psychosocial, and chronic medical conditions; and health promotion and disease prevention. Although there are many models of care delivery (15), the collaborative care model shows promise for implementing essential survivorship care components that require multi-disciplinary teams. In collaborative care, experts are convened to connect people with cancer to services such as rehabilitation, palliative care, primary care, psychosocial care, exercise and nutrition, cardio-oncology, dentistry, and other services that benefit the patient holistically. Collaborative care teams facilitate improved shared decision making by ensuring that people with cancer get understandable and relevant information about consequences and limitations of therapies that address their personal values.

Primary care providers (PCPs) often share in monitoring adverse events and ensure the quality of survivorship care. For example, breast cancer survivors are more likely to follow recommended treatment regimens with statin medications when a PCP is involved in managing their comorbidities (16). Likewise, blood pressure monitoring and medication adherence, which are fundamental components of care for survivors treated with cardio-toxic chemotherapies, can be improved by PCP management. When specialist care is required, the PCP coordinates the referral to oncology (or other specialty) practices within the collaborative care model. Oncology practices in England and Northern Ireland created a program where patients are triaged depending on risk and the severity of their conditions (17). Clinicians consider patients’ risk of recurrence, late effects, risk for secondary cancers, functional ability, psychological health, and social issues when making group assignments. A similar risk stratification model could be adapted, tested, and implemented in the United States if found effective.

Many health systems have services (eg, rehabilitative medicine) that could be part of a collaborative care team, but under the current fragmented system of care delivery, these services can be difficult to access. The collaborative care approach can coordinate care and potentially improve health equity by providing access to social workers, financial assistance programs, and other services (18). Ample evidence demonstrates that people with cancer who are also from racial and ethnic minority groups are less likely to receive appropriate and timely treatment and hospice care and may be more likely to have misconceptions about treatment and hospice care than their White non-Hispanic counterparts (19). A collaborative care team may overcome some of these barriers.

Standardized Treatment for Adverse Effects

Standardized approaches for detecting, tracking, and addressing treatment-related adverse effects are needed. For example, evidence-based blood pressure guidelines for cancer survivors could reduce the risk of heart disease (20-22). Clear guidelines from the United States Preventive Services Task Force are available for the general population without a cancer history, but screening strategies for those who have had a cancer diagnosis are not addressed (23). For pediatric patients with a history of cancer, the Children’s Oncology Group created long-term guidelines for adverse effect screenings related to cancer treatment (24). These guidelines are updated every few years and could serve as a model for adult cancer survivors. Standardized approaches are needed to reach oncology clinicians as well as clinical specialties outside oncology that treat cancer survivors.

Assessments Before Treatment

A cancer diagnosis can be a financial burden due to out-of-pocket treatment cost in addition to other cost-of-daily-living expenses. Loss or reduction of employment, travel expenses, childcare expenses, as well as out-of-pocket costs for medical care may create a considerable financial burden for people with cancer and their families. Screening for financial burden can normalize discussions of financial concerns and lead to ways to mitigate costs (25), especially if implemented across all patients rather than focusing on low-income or marginalized patients who may perceive financial screening as a barrier to receiving the best available care (26). Implementing routine financial screening as a quality measure for cancer care delivery could incentivize practices to incorporate these tools (27). Simultaneous with establishing routine screening for financial hardship, an infrastructure for referrals and support is needed for people who report financial burden.

Like financial burden, physical and emotional adverse effects may be minimized and possibly alleviated through systematic assessments before treatment. For example, geriatric assessments are important for evaluating older patients before administering cancer treatment. Older patients are underrepresented in clinical trials that lead to drug approval, suggesting caution when applying recommendations from clinical trials to older people with cancer. The same may also be true for other patient populations, including those with comorbid conditions or disabilities. Appropriate assessments include function, comorbidities, falls, depression, cognition, and nutrition (28). Such assessments could inform the selection of less toxic treatments and appropriate care plans and identify nononcologic problems that can be mitigated before cancer treatment (28,29).

Data Collection and Oversight

Data Standardization

The absence of systematic methods for detecting and tracking adverse effects in electronic health records (EHRs) and recording them as structured data that can be searched and extracted are major challenges facing survivorship research and care. Moreover, when a patient switches health insurance plans or care providers, their data are stored in different databases, making it nearly impossible to obtain the sum of the patient’s health and treatment history in a single location. Data on prescription drug use can be scattered across multiple pharmacies without any tracking in the EHR. Opportunities to improve data collection include consistent methods of collecting, reporting, and standardizing terminology across EHR systems along with the incorporation of patient-reported outcomes. With standardized data collection and centralized EHRs, structured adverse event data could inform how to improve outcomes for cancer survivors.

Standardized methods of collecting and reporting racial and ethnic data may also alleviate the confusion over how race, ethnicity, and ancestry data are recorded and interpreted in biomedical research (30). Social identity and genetic ancestry are complex, and their individual effects are difficult to disentangle. These constructs have led to misinterpretation of race, ethnicity, ancestry, and genetic risks and their relationship to cancer outcomes (31). Adding to the complexity, laboratories, biobanks, and medical records have heterogeneity in whether and how race and ethnicity are recorded. Likewise, gender identity and sexual orientation need to be more clearly specified. Additional variables such as those related to structural racism and other social exposures should also be considered. A common set of data elements has yet to be agreed on for these critical variables.

Clinical Trials and Cohort Studies

Clinical trials, critical for the development and testing of new cancer treatments as well as prevention methods, can also create knowledge gaps. Clinical trials may not track participants long term after trial completion, resulting in inadequate information about effects that occur years later. Medical claims data may partially overcome this limitation. For example, the SWOG Cancer Research Network used Medicare claims data of former trial participants and found a 25% reduction in prostate cancer among those receiving finasteride compared with the placebo 7 years later (32). Other data sources include the United States Food and Drug Administration’s (FDA) MedWatch program that tracks adverse events for FDA-regulated products (33). The Surveillance, Epidemiology, and End Results registry (34) could be expanded to include linkages with claims data such as All-Payer Claims Data (35) to capture long-term treatment outcomes and adverse events.

A recognized limitation of clinical trials is that the researchers often enroll patients who do not represent the population affected by cancer. By 2030, approximately 70% of new cancer diagnoses will be in people over the age of 65 years (36). Yet, a study that compared the median age of enrollees randomly assigned to 302 clinical trials reported the median age was 6.49 years younger than the median age of the population of those newly diagnosed (36). Similarly, only 14% of adolescent and young adult patients with cancer enrolled in clinical trials (37), which is less than 5% of all new patients in a single year (38). Focused tactics are urgently needed to increase the racial and ethnic diversity of patients enrolled in clinical trials. In 2020, the FDA reported that only 8% of trial participants in industry sponsored trials for new molecular entities and original therapeutic biologics were Black or African American, 6% were Asian, and 11% were Hispanic (39), limiting the knowledge of how emerging treatments work in the average cancer survivor (40).

Observational cohort studies are informative because they are generally more inclusive and representative of the population. These studies are often supported by the National Institutes of Health through grants or intramural research. However, some cohort studies may not be maintained beyond initial development and have only limited access to outside researchers, creating inefficiencies for funders, researchers, and the administrators who construct the initial cohort. Sustained financial support is needed to build a larger, coordinated data infrastructure, but to achieve this goal, extensive collaboration is required. Partnerships such as those established by the Medicaid Outcomes Distributed Research Network can serve as a model for establishing a common data model and a process for data sharing across states (41). Similar networks exist for comparative effectiveness research, biomedical research, medical product safety, and public health surveillance (42) that could serve as models for cancer research. Data generated from publicly funded cohorts should be standardized and publicly available. The process used by the Agency for Healthcare Research and Quality Healthcare Utilization and Cost Project may serve as a model for variable standardization, data deidentification, and distribution. A federally led initiative to create a more comprehensive cancer data infrastructure, using the many existing cohorts as a starting point, is a worthwhile pursuit.

Policies to Reduce Adverse Consequences

Insurance Coverage

New cancer drugs can cost $120 000 or more per year (43), creating financial barriers to treatment (44). High treatment costs can lead to delayed or forgone treatment, increased stress and worry about cost, and difficulty paying medical bills (8). High-deductible health plans, as well as increased cost sharing, are becoming more common, shifting the financial burden to patients (27). Adequate insurance coverage reduces some barriers to treatment and decreases the risk of long-term adverse financial consequences.

The Patient Protection and Affordable Care Act provided new health insurance options such as expanded Medicaid coverage for individuals with lower income, tax credits, cost-sharing subsidies, and coverage for patients with preexisting conditions (45). In states that expanded Medicaid, the percent of uninsured persons was reduced relative to the period before expansion (46). Early detection of most cancers also improved in expansion states, along with reductions in the numbers of patients who reported care unaffordability (46). Access to health insurance is positively correlated with patients receiving effective treatment and improved survival after cancer diagnosis (46). Additional state Medicaid expansions could lead to greater access to health insurance.

Paid Sick Leave

Increasing the availability of paid sick leave across all employers, large and small, can enable people with cancer and their caregivers to maintain employment throughout treatment. Without paid sick leave, patients and caregivers are at an increased risk of losing employment and experiencing financial hardship (25). Paid sick leave is also correlated with increased cancer screenings, whereas workers without paid sick leave are less likely to have recommended screening, including mammography, Pap tests, or endoscopy (47).

Disincentives for Low-Value Care

Physicians and health systems are often reluctant to abandon ineffective care as new evidence evolves and practice guidelines change. This may be partially spurred by the reluctance to tell patients that further treatment is futile and patients’ requests for aggressive treatments that offer little hope for extended survival. New treatment guidelines are also unevenly disseminated, leaving ineffective treatments in use (48). As an example, studies suggest that 80% or more of women aged 70 years and older with Hormone Receptor (HR+) breast cancer receive sentinel lymph node biopsy despite evidence that the procedure offers little benefit (49). Similarly, the addition of cetuximab or bevacizumab to chemotherapy treatment offers no additional benefits to colorectal cancer survivors while increasing overall costs (50). Even when a new technology or treatment is found superior, the treatment may be added on to standard practice instead of used as a replacement (48). For example, nuclear medicine brain scans have not been completely replaced by computed tomography scans and are sometimes used in conjunction with computed tomography scans (51) despite Choosing Wisely cancer-related recommendations that focus on reducing unnecessary imaging, testing, and overtreatment that may cause harm (52).

Payment methods have been used to reduce the use of low-value care. The Oncology Care Model (OCM), for example, aligned financial incentives with guideline-based care, care coordination, and access to care for Medicare beneficiaries receiving cancer treatment (53). To disincentivize low-value care, the OCM implemented quality metrics and predetermined payments for an episode of cancer treatment and performance-based payment (53). Quality measures included emergency room visits, hospice enrollment, pain and depression screening along with follow-up plans, and the patient-reported experience of care. Moreover, OCM required providers to use certified EHRs to monitor quality improvement, 24/7 access to care, patient navigation, and care consistent with national guidelines. Although the OCM reduced monthly spending (54), disappointingly, many cancer care episodes exceeded target costs (55) and resulted in net losses for Medicare (56).

Other options to reduce low-value care include adequate insurance coverage for clinicians' time devoted to shared decision making with patients before treatment, during the cancer continuum, and as part of advanced care planning (57). Shared decisions facilitate effective patient-clinician understanding about benefits, limitations, consequences, and costs of testing and treatments. In addition, incorporating preference and values into the treatment decision improves adherence to recommended treatment and self-management (58).

Randomized controlled trials (RCTs) of treatments of uncertain value may persuade clinicians to stop using low-value, high-cost treatments (59). Three RCTs found that high dose chemotherapy followed by autologous hematopoietic stem cell transplantation was not more effective than traditional chemotherapy for women with breast cancer and led to a reduction of this treatment (60). When an RCT reported that axillary lymph node dissection after a positive sentinel node biopsy did not produce improved outcomes (61), the use of this practice declined.

Conclusions

Reducing the burden of treatment-related adverse consequences is daunting, but changes in cancer care delivery, data collection, payment incentives, and national policy could make important, positive changes in the survivorship experience to benefit all survivors. As summarized in Box 1, many improvements can be made to track and address adverse consequences of cancer treatment that may inform changes in treatment. Policy solutions are also available to minimize these consequences and improve the quality of life for cancer survivors.

As we celebrate achievements in detection and treatment that lead to extended cancer survivorship, the fragmentation of care delivery and the information systems that track cancer care and increasing treatment costs stand in the way of minimizing the adverse consequences for survivors. Therefore, we must improve coordinated care delivery and the collection of outcomes data on survivors who are largely underrepresented in research. As described in the 2017 National Cancer Policy Forum workshop on delivery of long-term survivorship care after cancer treatment (62), there remains a need to address the multiple challenges cancer survivors face from the time of diagnosis through end of life, including a focus on palliation of symptoms, prevention of late effects, and health promotion. Reducing the burden of chronic illness and second malignancies in survivors will require a greater focus on standardized approaches for tracking and treating adverse consequences of treatment and to improve the design of risk-adapted therapies. Addressing the long-term financial burden of cancer care will require policies such as expanded health insurance coverage so that survivorship care and surveillance for adverse consequences are accessible and affordable. Increasing our understanding of treatment’s long-term consequences is a critical part of improving health outcomes of cancer survivors, especially as new treatments are rapidly approved and becoming available to patients.

Funding

None.

Notes

Role of the funder: Not applicable.

Disclosures: The authors have no conflicts of interest to report.

Author contributions: Conceptualization: CB, SK; Supervision: CB; Writing—original draft: CB, SK; Writing—review and editing: CB, SK, SB, JB, GD, JL, RO, LS, LKS.

Acknowledgements: The activities of the National Cancer Policy Forum are supported by the Centers for Disease Control and Prevention, the National Cancer Institute/National Institutes of Health, the American Association for Cancer Research, the American Cancer Society, the American College of Radiology, the American Society of Clinical Oncology, the Association of American Cancer Institutes, the Association of Community Cancer Centers, Bristol-Myers Squibb, the Cancer Support Community, the CEO Roundtable on Cancer, Flatiron Health, Merck, the National Comprehensive Cancer Network, the National Patient Advocate Foundation, Novartis Oncology, the Oncology Nursing Society, Pfizer, Inc, Sanofi, and the Society for Immunotherapy of Cancer. We thank the workshop planning committee members and speakers for their contributions to the National Cancer Policy Forum’s workshop on Addressing the Adverse Consequences of Cancer Treatment. We are grateful for the support of the National Cancer Policy Forum staff team: Francis Amankwah, Rachel Austin, Lori Benjamin Brenig, Erin Balogh, and Sharyl Nass.

Disclaimer: The authors are responsible for the content of this commentary, which does not necessarily represent the views of the National Academies of Sciences, Engineering, and Medicine.

Data Availability

There was no new data associated with this commentary.

Box 1. Summary of policies and practices to reduce adverse effects of cancer treatment

Practice approaches

Collaborative care Include primary care to reduce adverse effects and improve quality of life Include specialists outside oncology, such as social workers, nutritional services, and mental health support, to provide holistic care Provide access to programs that assist people with cancer based on their needs, preferences, and goals to improve health equity Standardize how providers communicate with each other Standardized screening and treatment for adverse effects after treatment Develop blood pressure and cardiac guidelines for cancer survivors to identify and address cardiovascular complications Develop cancer and noncancer screenings guidelines for cancer survivors Financial screening and other assessments before treatment Standardize and normalize financial screenings to address patients’ financial needs and reduce stress related to financial burden Geriatric assessments to identify potential age-related issues that can be mitigated or require treatment modifications to prevent poor outcomes Cardiovascular screening before treatment to identify those at increased risk of developing cardiovascular consequences from treatment

Data collection and oversight

Standardization Standard terminology, methods of reporting, and patient reported outcomes to reduce inconsistency and improve interoperability in electronic health records (EHRs) Structured data within EHRs that assess patient-reported outcomes, toxicity assessments, and overall quality of life Standard collection of race, ethnicity, and ancestry data in EHRs and clinical trials Clinical trials Link to current and future insurance claims data Increase diversity in clinical trials to have an accurate picture of how the real-world population will respond to and tolerate interventions

Policies to reduce adverse consequences

Insurance coverage Adequate and equitable insurance coverage to protect patients from financial hardship and improve timely diagnosis and treatment Paid sick leave Paid sick leave to maintain employment and insurance coverage throughout treatment Reducing use of low-value care Implement alternative payment methods, such as the Oncology Care Model, to provide financial incentives that improve effectiveness of care and health outcomes Shared decision making between patients and clinicians to foster education and knowledge of treatment options, reducing low-value care and activating self-care Randomized controlled trials to reduce low-value care when the trial proves the treatment ineffective or less effective than previously believed