In daily oncology practice, clinicians constantly weigh the expected benefit of treatment against exposure to possible treatment-related adverse events (AEs).1 Especially in patients with advanced disease, for whom the survival benefit of (systemic) treatments may be limited, the number and extent of AEs and their impact on patient quality of life (QoL) are important.2 Providing a representative overview of treatment-related AEs is essential for patients to make an informed decision to undergo treatment.3,4
Currently, the main source of information on toxicity in randomized controlled trials (RCTs) is a clinician-based assessment of AEs during clinic visits using the NCI Common Terminology Criteria for Adverse Events (CTCAE).5,6 However, this may be suboptimal, because the reporting of AEs in RCTs is primarily focused on high-grade AEs (grades 3–4), whereas the lower-grade AEs are not always incorporated.7 Although a description of high-grade toxicities is important and relevant to determine drug safety, patient QoL is also likely to be influenced by the often daily (re)occurring, longer-lasting grade 1 or 2 AEs throughout therapy, because these determine drug tolerability. We recently studied the burden of cumulative toxicity in patients with colorectal cancer (CRC) and found that cumulative toxicity scores comprising all-grade AEs were associated with patients' physical QoL, whereas the total score of high-grade AEs was not.8 The cumulative toxicity scores reported in our study were based on clinician-reported AEs, whereas the accuracy of assessment and reporting of AEs by clinicians has been recently questioned.8 Symptomatic AEs associated with anticancer treatments seem to be underreported by clinicians and when data are prospectively collected within RCTs.9,10 Patient-reported outcomes to assess AEs may provide an alternative measure for patients' treatment experiences.11
The purpose of this prospective study in patients with metastatic castration-naïve prostate cancer (mCNPC) was to determine whether cumulative toxicity comprising all-grade AEs (grades 1–4) is more associated with QoL than cumulative toxicity comprising high-grade AEs only (grades 3–4), and whether cumulative toxicity reported by patients is more associated with QoL than cumulative toxicity reported by clinicians.
Dr. Verheul has disclosed that he has received grant/research support from Roche, Vitromics Healthcare System, Novartis, Immunovo B.V., and Amgen; nonfinancial support from Pfizer; and honoraria from Boehringer Ingelheim. Dr. Joly has disclosed that she has received grant/research support from Sanofi, and that she has served on the advisory board for Sanofi and Janssen. The remaining authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.
Drs. Dekker and Verheul received a grant from Alpe d'Huzes/Dutch Cancer Society (VU 2011-5279) during the conduct of the study.
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. Basch E Pugh SL Dueck AC Feasibility of patient reporting of symptomatic adverse events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a chemoradiotherapy cooperative group multicenter clinical trial. Int J Radiat Oncol Biol Phys 2017; 98: 409– 418.
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. Jensen K Bonde Jensen A Grau C The relationship between observer-based toxicity scoring and patient assessed symptom severity after treatment for head and neck cancer. A correlative cross sectional study of the DAHANCA toxicity scoring system and the EORTC quality of life questionnaires. Radiother Oncol 2006; 78: 298– 305.