Early and Often: The Need for Comprehensive Discussion of Treatment-Induced Cancer Late Effects

Imagine your worst fear realized as an oncologist confirms that your child has cancer. During the initial clinic visit, you will be informed of your child’s diagnosis and his or her prognosis¹  contingent on the best available treatment protocol, usually based on years of comprehensive clinical research. In the uncommon case that no best-practice protocol is available for your child, treatment options will be presented for you to help choose a course of action. Ideally, that discussion will include the pros and cons of each choice, including prognostic estimates, acute toxicities, and potential long-term effects on your child’s health and psychosocial well-being as they may evolve over the life course.

From knowledge gained through clinical research and observational follow-up studies of cancer cohorts,²  the unambiguous association between therapeutic exposures and specific acute and long-term effects in childhood cancer has led to a focus in treatment protocols on maintaining high survival probability while minimizing serious late effects and optimizing quality of life. For example, efforts to reduce late effects have included omission or reduction of cranial radiotherapy for children <3 years of age, given the profound neurologic and endocrine toxicities,³  and avoidance of chest irradiation in patients with Hodgkin and non-Hodgkin lymphoma to minimize risk of subsequent breast cancer and cardiotoxicities.^4,5  Limited attention, however, has been directed toward understanding how parents and physicians consider the long-term consequences of cure when making initial treatment decisions. This is important because by 45 years of age, 4 in 5 childhood-cancer survivors will have developed a severe or life-threatening health condition associated with their treatment exposures.⁶  The study by Greenzang et al⁷  in this issue of Pediatrics provides new information derived from parental and physician responses to hypothetical scenarios that address the issue of treatment decisions in relation to cure and long-term toxicities. Results of the study suggest that both parents and physicians might prioritize avoidance of specific late effects for a small reduction in the probability of cure, with severe neurocognitive impairment identified as the most concerning late effect. Importantly, this study also revealed that parents and physicians may differentially prioritize avoidance of specific late effects (eg, infertility) when making treatment decisions.

Despite the novelty of this study, given limitations in study design, the results may have narrow clinical application. For example, the current study focused on 5 individual late effects, but it is well established that survivors are at risk for developing a plethora of sequelae across multiple organ systems and that these often co-occur.^6,8  Data suggest that by 50 years of age, a childhood-cancer survivor has experienced, on average, 4.7 severe or life-threatening chronic health conditions, with much of this morbidity being driven by second malignancies, endocrinopathies, and cardiac and pulmonary disease.⁹  Psychological, academic, occupational, and other social problems are also common in survivors of childhood cancer.^10,11  An understanding of the possible role of long-term toxicities derived from hypothetical scenarios that do not depict the full burden of late effects may not reflect a realistic understanding of the complexity of decisions to be made in a real-life diagnostic setting. Also important to consider is the temporal incongruency of parental responses in these scenarios with the course of treatment. Parents enrolled in the current study were within one year of their children being diagnosed with cancer rather than when treatment decisions were made. This time frame may not be an accurate reflection of what a parent would decide at the point of diagnosis, when they are emotionally overwhelmed and distressed.¹² 

Nevertheless, one piece of valuable information that the study revealed is the large proportion of parents who did not perceive the actual risk of late effects for their children (Table 1). Only 11% of parents perceived their children to be at risk for developing neurocognitive late effects; in fact, other than infertility (20%), no specific late effect under inquiry was perceived by the parents to be very likely to occur (≤8% likelihood). Thus, there appears to be significant parental underestimation of perceived threat from long-term consequences of cancer and its treatment,^13–17  which highlights the need for better education about late effects early in the diagnostic and treatment process.¹⁸  We believe these discussions would best occur beginning at diagnosis and during the informed consent process and should continue throughout the course of treatment and long into the maintenance and surveillance period after the declaration of cure.¹⁹ 

As the number of childhood-cancer survivors continues to grow,²⁰  there is a clear need for research on physician–parent communication around potential late effects and the impact of these discussions on parental awareness and treatment decision-making. The current article by Greenzang et al⁷  provides us with a good starting point for that conversation.