Understanding treatment recommendations at diagnosis of advanced cancer in pediatric oncology: the need to explore decision-making challenges globally

Pediatric oncologists strive to consider and prioritize all possible curative treatment options. Deciding not to recommend curative treatment can be difficult, particularly in the context of a new diagnosis of advanced cancer if the chance of survival is anticipated to be very low yet patients, families, and medical teams still hope for cure. Presently, the factors that influence clinicians’ upfront treatment decision-making for children diagnosed with advanced cancer with poor prognosis remain understudied.^1–3 Understanding these factors is particularly important in low- and middle- income countries (LMICs; inclusive of low-income, lower middle-income, and upper middle-income countries), where <40% of children diagnosed with cancer are estimated to survive.^4,5 When children in LMICs are diagnosed with advanced cancers that are typically treated with curative intent in higher resourced settings, recommending non-curative therapy may cause moral distress for some clinicians.⁶ This burden may be further amplified when there is limited local evidence to guide treatment decision-making and when inequities in resources and outcomes exist regionally or across bordering countries. We share here informal discussions from one setting where these challenges arise, as an example of the broader challenges that exist across many LMICs. We then present suggestions for potential future areas of research on upfront treatment decision-making for children diagnosed with advanced cancer in LMICs, topics intended as a starting place to initiate further discussions within each country’s unique context as well as more formal international research efforts.

Zimbabwe is a lower middle-income country in southern Africa, with a single pediatric oncology ward located at Parirenyatwa Hospital. As in many LMICs, children with cancer in Zimbabwe often present with advanced disease at diagnosis. Patients and families are welcome to participate in treatment decision-making, although they often prefer for the oncology team to make strong treatment recommendations. For physicians at Parirenyatwa, moral distress frequently accompanies challenging treatment decision-making when unable to provide treatment with curative intent, with concerns about whether it is ethically defensible to recommend non-curative therapies at diagnosis, focused on improving symptoms, quality of life, or prolonging life. These concerns are layered on tensions between facilitating hope for patient cure with quality of life and cost implications to families.

A partnership between pediatric oncology clinicians in Zimbabwe and the United States was developed in 2017 upon the request of the Zimbabwean team. The focus of the initial collaboration included training for pediatricians in pediatric oncology and development of clinical care guidelines adapted to the local diagnostic and therapeutic context. During the early phases of the partnership, collaborating oncologists and pediatricians caring for children diagnosed with cancer gathered in-person at Parirenyatwa Hospital to gain mutual understanding of factors influencing upfront treatment recommendations in Zimbabwe. The in-person discussions focused on prior real and challenging scenarios, with continued discussion virtually of hypothetical scenarios of children presenting with different cancer types, stages, and prognostic groups. Each clinician shared their perspective for management strategy, with advanced cancer cases eliciting robust dialogue on whether to recommend curative or non-curative therapies at the time of diagnosis.

For childhood cancers in which standard of care in high-income countries is to pursue treatment with curative intent at diagnosis, most participating clinicians recommended a curative approach for most scenarios at diagnosis, even if the anticipated potential for survival was low. They described using a “wait and see” approach, allowing lack of response to initial treatment cycles to help guide future recommendations that could include non-curative therapies. There was agreement that anticipated prognosis based on local contextual factors was critical to consider, weighing potential for survival with potential risks of toxic death or suffering. The need for transparent communication and honesty with families about limitations of care were discussed. Consensus was reached when no more than one participant answered differently than the others in initial rounds, and when all participants agreed in the final round. After sharing these values and perspectives, consensus emerged that non-curative recommendations at diagnosis could potentially be ethically defensible for certain cancer types and prognostic groups. While a formal ethical analysis is not presented here, and the summary perspectives in our discussions did not result in a standardized change in approach to upfront treatment decision-making in Zimbabwe, these discussions echo conversations happening across many institutions and countries.

Overall, clinicians agreed that nuanced contextual variables, unique to each patient and family, were important to consider when making treatment recommendations in the setting of advanced disease at diagnosis. Notably, clinicians felt that poor performance status and malnutrition should not automatically exclude children from receiving treatment with curative intent, as some children presenting with these factors may have favorable outcomes with cure-oriented therapy, particularly when treatment modifications and additional supportive care are integrated as needed. Developmental status and physicians’ corresponding perception of quality of life were considered subjective and inappropriate influencers of treatment recommendations. Financial hardship and time away from home during treatment were characterized by clinicians as potentially addressable factors or as variables that families might consider in their own decision-making.

Although there was consensus on the appropriateness of upfront non-curative treatment focused on disease stabilization, life prolongation, and symptom control for certain patients, complex discussion arose regarding the practicalities of theoretically navigating this approach. Zimbabwean team members expressed fear, guilt, and hopelessness when considering giving non-curative therapy to a child who could potentially be cured, even if the odds were extremely low. Additionally, they expressed concerns about potential second-order impacts, such as loss of community trust which might cause other families to not seek medical care for their children in the future. Throughout the conversations, a recurrent theme centered on the importance of frequently reassessing treatment protocols and outcomes data, with the goal of maintaining a commitment to improving childhood cancer survival and preventing inadvertent widening of survival disparities as local healthcare infrastructure evolves and strengthens over time. Importantly, Zimbabwean team members expressed relief in discussing the complexities of these heavy decisions with the colleagues present.

While these discussions unfolded in one cancer center in one country, participating team members recognized resonance and overlapping content from subsequent discussions with other pediatric oncologists and pediatricians caring for children diagnosed with cancer in LMICs. Treatment decision-making for children diagnosed with advanced or incurable cancer in LMICs remains largely unsupported on a practical level by existing treatment guidelines that are structured by general capacity levels, within which individual institutions may not fit neatly.^6–15 There are nuanced variables to consider in decision-making specific to diverse cultures and contexts, and patient and family preferences that may be at odds with local capacity.⁶

These discussions have led us to believe that local, community-based research efforts that encompass all impacted voices are needed to better support the challenges of goal setting during upfront treatment decision-making for children diagnosed with advanced cancer with poor prognosis in LMICs. This includes understanding patient and caregiver experiences and preferences for level of involvement in decision-making, and formal ethical analyses specific to context on optimal approaches to upfront treatment recommendations. To begin to address these needs, the authors iteratively reviewed and summarized the content of discussions to propose domains for future inquiry related to decision-making, communication, ethics, and palliative care. Table 1 presents suggestions for research areas related to upfront treatment decision-making for children diagnosed with advanced cancer in LMICs. Importantly, this list is neither comprehensive nor generalizable; rather, it offers a starting point to spark further discussions, advance the literature, and ultimately improve outcomes for children with cancer and better support all those involved in decision-making. Each pediatric oncology center, patient, and family may identify different patterns of needs, preferences, and priorities influencing upfront treatment decision-making.

Table 1:

Research areas to support upfront treatment decision-making for children diagnosed with advanced cancer with poor prognosis in low- and middle-income countries.

Decision-Making Processes
Identify and characterize variables impacting clinician, patient, and caregiver approaches to upfront treatment decision-making
Evaluate understanding and perceptions of curative and non-curative treatment recommendations among involved parties*
Explore patient and caregiver preferences for level of involvement in decision-making and the interplay with cultural norms and historical approaches
Integrate non-curative treatment approaches focused on comfort and life prolongation where appropriate, considering available local resources and involved party views
Communication
Explore patient and caregiver preferences for bidirectional communication about prognosis and treatment intent (e.g., curative or non-curative)
Explore facilitators to trusting communication between involved parties, such as open discussion and support of non-harmful traditional therapies
Describe preferences for shared language surrounding non-curative approaches to care (e.g., use of quality of life, palliative, non-curative, or care-directed terms; what qualifies as suffering or a poor prognosis; etc.)
Develop and pilot interventions, including educational resources and training, to support clinicians in communicating prognosis and treatment recommendations with patients and caregivers
Ethics
Understand and assess the prevalence of moral distress around upfront treatment decision-making, comprising both curative and non-curative regimens
Examine the feasibility and ethical purview of regional or international referral networks when access to curative treatment does not exist within a country, and how best to ensure equitable access to these systems
Explore diverse ethical theories and frameworks and perform formal ethical analyses in consideration of the spectrum of ethically defensible and culturally appropriate approaches to upfront treatment recommendations
Evaluate where involved party biases may impact upfront treatment options recommended and develop strategies to aid minimizing the impact of these biases
Palliative Care
Assess the potential for palliative care integration at the time of diagnosis and, if implemented, the impact on patient and caregiver outcomes, clinician resilience, and healthcare resource utilization
Develop strategies to mitigate moral distress experienced by all involved parties in the care of children diagnosed with advanced or incurable cancer
Characterize variables in upfront treatment decision-making that impact involved party grief and bereavement outcomes and develop support strategies targeting these variables

^*Involved parties: including, but not limited to, patients, caregivers, multidisciplinary clinicians, and members of the community.

We hope for, and work towards, a day when all children with cancer will have equitable access to cure, regardless of where they live in the world. The pediatric oncology field is collectively working to improve survival globally, and these efforts take time.¹⁶ In the interim, physicians must continue to make treatment recommendations for patients with advanced cancer who have a low probability of achieving cure. These decisions are challenging in all countries, but particularly in LMICs, where the greatest burden exists and lack of resources and practical support represent barriers to care. Alongside efforts to achieve equity in the survival of children with cancer globally, interventions that improve access to high quality palliative care and optimize quality of life are needed.^4,17,18 The WHO Global Initiative for Childhood Cancer highlights this imperative, aiming not only to increase survival for childhood cancer, but also to holistically address suffering.¹⁶ As the global community continues to address these needs, understanding the factors that influence upfront treatment decision-making from the perspectives of all involved parties will be crucial for the development of resources that respect local contextual factors and support equitable and ethically defensible approaches to the care of all children diagnosed with cancer globally.

Abbreviations key:

LMICs

low- and middle-income countries

HICs

high-income countries