As medical imaging technology has advanced, clinical conditions not previously detectable by symptoms, physical examination, or older technologies have been increasingly diagnosed. Medical evidence has accumulated, albeit more slowly, establishing that observation can be a reasonable, even preferable, clinical approach to monitor diagnoses with favorable prognoses. Yet, the uncertainty and anxiety that comes with such conservative approaches can make adherence to this pathway difficult for patients and physicians.

Multiple malignant cancers are considered appropriate for clinical observation without active medical or invasive surgical treatment unless changes in surveillance tests require further evaluation, biopsy, or treatment. These include localized prostate cancer, papillary thyroid cancer, lobular breast cancer in situ, and indolent hematologic malignant neoplasms. The proportion of patients with clinically localized prostate cancer undergoing observation with disease progression triggering treatment has been reported to be 59.7% (median follow-up, 12.7 years), while 15.9% of papillary thyroid microcarcinomas demonstrated enlargement (10-year follow-up).^1,2 However, no difference in all-cause or disease-specific mortality was detected in a randomized clinical trial of prostatectomy compared with active surveillance for early prostate cancer.¹ In a thyroid cancer observational study, all patients who underwent rescue surgery for disease progression were successfully treated without further recurrence, and none of them died of papillary thyroid cancer.²

Yet, despite the favorable prognoses of these conditions, cancer often remains a feared illness. Thus, as observational regimens become established as acceptable clinical practice, efforts have been made to change the language used to describe low-risk cancers and their management. Per the National Cancer Institute, low-risk cancers can be defined as those that tend to grow slowly and for which delayed or no treatment does not negatively impact outcomes. Recommendations have relabeled neoplastic conditions from cancers or carcinomas to tumors or nodules in the setting of low-risk neoplasms. Similarly, the terminology to describe conservative management of low-risk cancers has shifted to active surveillance due to concerns that watchful waiting implies an overly passive approach.

The trade-offs between clinical benefit and harm made in the decision to observe are important to communicate to the patient from psychological and ethical perspectives. The choice to wait typically confers benefit by avoiding the risks of unnecessary interventions, while the harms may involve a greater likelihood of cancer recurrence and (rarely) foregone therapeutic gains.

What makes even low-risk cancers an aversive condition for patients is uncertainty about whether they will be one of the many who enjoy a favorable outcome or one of the unfortunate few who will not. People managing uncertainty can only wait to see what happens and often experience high levels of emotional distress and anxiety while waiting. For example, a study of the period preceding a breast cancer diagnosis (ie, waiting for biopsy results) documented high anxiety levels in otherwise asymptomatic women.³ This example highlights 1 dimension of waiting that deserves attention: whether the waiting is short term (the return of test results with a definitive answer) or long term (surveillance approaches for indolent cancers). For many slowly progressing cancers, long-term active surveillance can include periodic laboratory tests or imaging with waiting periods in between, resulting in what has been called scanxiety.⁴

There is no definitive cure for uncertainty. No amount of scientific information—whether about the diagnosis, prognosis, or treatment of low-risk cancer—can completely eliminate uncertainty. For any individual, the possibility of a bad outcome always remains, thus making uncertainty a psychologically aversive experience. For many individuals, uncertainty produces a variety of primarily negative cognitive, emotional, and behavioral responses, including perceptions of vulnerability, feelings of fear, and a propensity to avoid decision-making—a syndrome of responses known as uncertainty aversion. For patients with low-risk cancer in active surveillance, uncertainty is a condition that requires therapeutic attention in addition to the cancer itself. While these patients wait for the future to declare itself, the many negative effects of uncertainty should be addressed.

The challenge of uncertainty may seem like an existential problem, but there are several potential, accessible interventions that can be applied to help people wait. To the extent that deleterious effects of uncertainty result in anxiety, multiple interventions appear to be promising.

Psychological interventions that have been developed for patients with anxiety disorders and also used among patients with more advanced cancer could be adapted for those undergoing active surveillance. Acceptance and commitment therapy has been tested among patients with metastatic breast cancer to improve symptom interference with function.⁵ Cognitive behavioral therapy and supportive expressive therapy have also been tested in multiple randomized clinical trials to improve psychological outcomes.⁶ Other potential approaches to managing uncertainty and anxiety include mindfulness meditation programs, which have been associated with small to moderate reductions in multiple negative dimensions of psychological stress.⁷ A trial established the feasibility and acceptability of 8 weeks of mindfulness meditation training among men diagnosed with prostate cancer receiving active surveillance.⁸ These approaches may help patients tolerate waiting for what are likely to be benign clinical findings.

Information-focused interventions like patient decision aids provide balanced information to increase knowledge of clinical options as well as clarify and express patient values. Decision aids may be valuable in helping patients manage the uncertainty created by pseudodisease, or diagnoses that will never cause the patient any clinical issues. Furthermore, clinical decision support tools may educate physicians who do not have a full understanding of their patients’ prognoses or surveillance options.

Health care delivery and the health care workforce should be patient centered and account for distress among patients caused by diagnostic experiences whether they are receiving active treatment or not. Primary care is the foundation of longitudinal health care and optimally integrates with mental health services to manage uncertainty over time. Oncologists may consider low-cost practitioners and practices to support less intensive, more holistic care when appropriate.

Important directions for future research include elucidating the underlying mechanisms linking uncertainty and anxiety and evaluating interventions focused on different mechanisms—for example, emotional (acceptance and commitment therapy, cognitive behavioral therapy) and informational (decision aids).⁹ More research is needed to understand how patients’ responses to the uncertainty of waiting vary over time and how tailored approaches can be adapted to respond to changing patient needs given the long lifespans of many patients under observation. Cognitive behavioral therapy was shown to have a positive effect on the symptoms of generalized anxiety disorder a decade after an initial trial exposure.¹⁰

Implementation science research will also be needed to determine how to adopt uncertainty management interventions in routine clinical care. One key question is whether to implement such interventions among physicians in primary care, where patients are most often seen in follow-up; in specialty care, where physicians have cancer expertise; or among mental health care physicians, who have expertise in managing anxiety. Further questions will include how to disseminate these interventions, what role health information technology plays, and how to reach vulnerable populations.

Clinical observation for low-risk cancers is typically suggested as an option only when therapeutic gains are unlikely, but it can be associated with significant patient distress. For patients, the waiting may be the hardest part. For physicians, it is important to increase awareness of patient concerns, monitor for anxiety during active surveillance, and implement effective, low-risk strategies to manage the associated anxiety. While these low-risk diagnoses continue to be made by physicians, proactive strategies for managing uncertainty should not be something for which patients need to wait any longer.

Corresponding Author: David A. Haggstrom, MD, MAS, Indiana University School of Medicine, 1101 W 10th St, Indianapolis, IN 46202 (dahaggst@iu.edu).

Published Online: August 15, 2024. doi:10.1001/jamaoncol.2024.2667

Conflict of Interest Disclosures: None reported.