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Reducing Overtreatment of Cancer With Precision Medicine: Just What the Doctor Ordered.

Clinicians increasingly recognize the problem of overtreatment in medical care. Overtreatment is particularly a concern for cancer conditions that are targeted for early detection because screening results in a large population of patients with early-stage disease. Patients with early-stage disease may experience overtreatment because the cumulative morbidity and adverse consequences on quality of life of cancer therapies are often substantial, but the benefit of each single modality can be very small and uncertain in an individual patient. For example, the net 10-year survival benefit of chemotherapy for patients with node-negative, hormone-receptor positive, ERBB2-negative (formerly HER2 or HER2/neu) breast cancers smaller than 2 cm is less than 4%.1 Prior to the advent of genomic expression testing, professional consensus guidelines for treatment diverged from those of a National Institutes of Health/Centers for Disease Control and Prevention panel strongly recommending adjuvant chemotherapy in these patients, whereas an international panel was not supportive of this approach. Incontrasttothoseundergoingchronicdiseasemanagement, patients newly diagnosed with cancer have little time to learn about the disease and its management because they often have multiple treatment options directed by different specialists they generally meet for the first time. Furthermore, the clinical information that informs treatment evolves rapidly over time; and for many patients, the clinical consequences may worsen after diagnosis because the cancer is found to be more extensive after further evaluation. For patients with breast cancer, an initial diagnosis of carcinoma in situ on core biopsy may be reclassified as invasive disease after surgical excision requiring consideration of systemic therapies; findings of breast magnetic resonance imaging may suggest more extensive disease prompting more biopsies; tumor margins may be deemed insufficient after initial lumpectomy triggering discussion about reoperation; and identification of metastasis to regional lymph nodes after mastectomy may motivate a discussion about the need to add radiation therapy to the treatment course. In addition, the increasing use of multiplegene sequencing tests for patients with breast cancer exposes patients to potentially ambiguous information about future risk of a second primary cancer and new concerns regarding the risk of cancer developing in family members. This cascade of information may be emotionally difficult for patients and increase their desire to avoid future cancer recurrence at any cost. Addressing the potential for overtreatment with patients after a diagnosis of cancer is challenging. Patients fear cancer and often dread the arduous treatment course that lies ahead. Uncertainty about the disease and its management is disturbing to patients and can evoke powerful psychological reactions that frequently increase patients’ desire for more extensive treatment than may be clinically indicated. For example, anticipated regret describes patients’ fear of forgoing the most aggressive treatment now and experiencing a future disease recurrence. The possibility effect describes the strong psychological reaction to a very small potential gain that deviates from futility (eg, 0% to 3% benefit). This is a common problem in decisions about the use of systemic chemotherapy for patients with early-stage breast cancer because net benefit is often very small. Confirmation bias is the tendency to disregard potentially useful information that conflicts with existing beliefs. In clinical encounters, confirmation bias can limit a patient’s attention to useful information about net benefit of a treatment option if that information conflicts with immediate emotional reactions. While there is much research on these underlying intuitions that drive patient preferences, few strategies are available to help guide clinicians in addressing these psychological reactions with patients. Physicians’ responses to patient reactions vary markedly.2 Physicians may be concerned that resisting patient desires may decrease satisfaction. They also may be vulnerable to intuitions such as anticipated regret, triggered by recall of patients they have treated previously who have experienced disease recurrence, which may make those physicians reluctant to limit treatment. Physicians may defer to patients’ desires for more extensive treatment than may be necessary because they perceive that pursuing such treatment may reduce decision conflict or emotional burden. In addition, physicians may conflate patients’ immediate reactions to disease and prospects for treatment with long-term well-being. Taken together, the complicated dynamic of these communication and decision factors is not conducive to addressing overtreatment during brief encounters. Precision medicine most effectively reduces overtreatment because it can remove a more extensive treatment option from consideration if that treatment is deemed by clinicians to be futile. Precision medicine in cancer uses information derived from patient factors (age, comorbidity, and, increasingly, genetic predisposition) and characteristics of the diagnosed tumor to quantify the net benefit of a treatment option in an individual patient. The 3 steps to harnessing precision medicine to address overtreatment are (1) increasing the evidence base for less vs more extensive treatment in VIEWPOINT