There are major discrepancies between patient and physician reports of toxicity related to breast cancer treatment, a new study suggests. The results are troublesome because accuracy in assessing toxicity can impact not only the supportive care patients receive but also patients’ ability to complete a planned course of therapy and benefit from it. In addition, clinical studies rely on physicians’ assessments of toxicity in making judgments about the risk-benefit ratio for new treatments.

The current study was conducted by Reshma Jagsi, MD, DPhil, of the University of Michigan, Ann Arbor, and colleagues from the Michigan Radiation Oncology Quality Consortium (MROQC). Dr. Jagsi presented the study’s results at the 2020 San Antonio Breast Cancer Symposium (Abstract GS3-07). The study enrolled 13,725 breast cancer patients who received breast-conserving radiotherapy over an 8-year time span. The investigators asked patients to report their symptoms during radiation via patient-reported outcome (PRO) questionnaires. Physicians were asked to complete standard toxicity assessments, according to the Common Terminology Criteria for Adverse Events, within 3 days of a patient’s office visit. A total of 9,941 patients completed at least one questionnaire, and the investigators compared 37,593 independent paired observations from patients and their physicians.

Dr. Reshma Jagsi

The investigators were specifically interested in how the physician-patient pairs reported four symptoms: pain, pruritus, edema, and fatigue. Physicians were deemed to have underrecognized pain when patients reported moderate pain (score, 4-6) that the physician recorded as grade 0, or when patients reported severe pain (score, 7-10) that the physician recorded as grade 1 or less.

Physicians were deemed to have underrecognized pruritus, edema, or fatigue when they recorded those adverse events as grade 0 for a patient who reported being bothered often or all the time from pruritus, edema, and fatigue. In all, 53.2% of patients had at least one moderate to severe symptom. About one-third of patients had substantial breast pain (35.4%) or pruritus (30.6%). About a quarter of patients noted moderate to severe edema (23.9%) or fatigue (24.9%). In the analysis of paired reports from patients and their physicians, the physicians underrecognized pain in 30.9% of cases, pruritus in 36.7% of cases, edema in 51.4% of cases, and fatigue in 18.8% of cases. Of the patients reporting at least one substantial symptom, 53.2% did not have their physician report the severity of that symptom accurately. Higher risk of underrecognition To evaluate predictors of symptom downgrading, the investigators performed multivariate logistic regression analyses. They found that race, age, and radiotherapy regimen were significantly associated with symptom underrecognition. For example, patients aged younger than 60 years (hazard ratio, 1.2; P = .006) and especially younger than 50 (HR, 1.4; P < .001) had increased odds of symptom underrecognition. Compared with White patients, Black patients (HR, 1.92; P < .001), and patients of races other than Black or Asian (HR, 1.82; P = .0021) had increased odds of symptom underrecognition. With lower statistical significance, patients who did not have a supraclavicular field (HR, 1.2), those who received conventional fraction radiation (HR, 1.15), or those who received treatment at an academic facility (HR, 1.13) had more symptom underrecognition. What is causing this? Although it is treacherous to assess causation in an observational study, caregivers may have unconscious biases that influence their interpretation of what they hear from their patients. Alternatively, patients from certain demographics may be less forthcoming to their physicians – to their own potential detriment. Top image credit: Dr_Microbe/Getty Images Image credit: DR P. MARAZZI / Science Source

Why this is important In an era in which office visits are increasingly conducted through telemedicine and interpersonal interactions are truncated by other pressures, oncologists need to be especially proactive about addressing any deficiencies in communication with patients and patients’ willingness to confide in them. The challenges will likely be augmented in the telemedicine era. As Dr. Jagsi suggested, better recognition of and acting upon treatment-related toxicity is one way in which physicians can improve health equity. It is “targetable” and within our control as providers. Unfortunately, it may also be more widespread than the specific example that was studied by these investigators. Underrecognition of acute adverse events has been observed in patients receiving pelvic radiation (J Clin Oncol. 2018 Aug 20;36[24]:2538-44) and those receiving chemotherapy for advanced cancer (JAMA. 2017;318[2]:197-8.). It is easy to imagine that accurate assessment of late toxicities is even more fraught with obstacles.

Benefits beyond symptom control There is at least one evidence-based path forward: collection of PROs in clinical practice and clinical trials. After implementing routine collection of PROs, one group of investigators identified significant benefits in quality of life and 1-year quality-adjusted survival, duration of chemotherapy, and emergency department use (J Clin Oncol. 2016;34[6]:557-65). At a median follow-up of 7 years, PRO processes were associated with a median overall survival duration of 31.2 months (95% confidence interval, 24.5-39.6) in the PRO group and 26.0 months (95% CI, 22.1-30.9) in the usual care group (P = .03). In a multivariable model, results remained statistically significant (HR, 0.83; 95% CI, 0.70-0.99; P = .04). Moving beyond ‘usual care’ Many clinical trials are incorporating PROs as a tool for measuring the impact of new therapies on participating patients. The Centers for Medicare & Medicaid Services Innovation Center has proposed and requested public comment about including PROs in an alternative payment model for medical oncology care (JAMA. 2020;323[3]:213-4). From every conceivable perspective, it is important for patients and their caregivers to be more attentive to the bidirectional flow of information regarding acute toxicity from cancer treatment. Our shared goals of treatment, our mission to provide equitable cancer care, and our interest in the accuracy of risk-benefit calculations in trials of new therapies all depend on our ability to communicate more openly and precisely with the people who entrust their care to us. Dr. Jagsi’s study and MROQC were sponsored by Blue Cross Blue Shield of Michigan (BCBSM) and the Blue Care Network as part of the BCBSM Value Partnership program. Dr. Jagsi disclosed financial relationships with Amgen, Equity Quotient, Genentech, Vizient, law firms, various foundations, the National Institutes of Health, and BCBSM for the MROQC. Image credit: FatCamera/Getty Images

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.