Optimizing Clinical Screening for Chemotherapy-Induced Peripheral Neuropathy

Context: Efficient and accurate clinical screening for treatment-related toxicities is a critical component of optimal patient management. A number of alternate screening tools for chemotherapy-induced peripheral neuropathy (CIPN) have been proposed in response to demonstrated limitations with standard clinical screening, although their relative diagnostic value is unclear.

Objectives: The aim of this study is to evaluate the relative construct validity and discriminant properties of available CIPN screening tools.

Methods: Patients treated with known potentially neurotoxic therapies underwent CIPN evaluation at one or multiple timepoints (N = 316 patients; age = 56 ± 13 years). At each testing session (N = 644 testing sessions), patients were evaluated using screening tools and comprehensive CIPN assessments. Comprehensive assessments were clinician-rated (Total Neuropathy Score, reduced) or patient-reported outcome (PRO; Functional Assessment of Cancer Therapy-Gynecologic Oncology Group/Neurotoxicity questionnaire). Similarly, screening tools were clinician-rated (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE]) or PRO (Patient Neurotoxicity Questionnaire, PRO-CTCAE).

Results: Analyses revealed moderate-to-high correlations between screening tools and comprehensive assessments (0.55 ≤ rho ≤ 0.75; P < 0.001) and similar discriminant properties across screening tools (P > 0.01). Screening tool grading corresponding to clinically significant (grade 2/3) vs. low-grade (grade 0/1) CIPN would correspond to greater ratings of CIPN severity by more comprehensive assessments in a predicted 77%-91% of cases (c-statistic = 0.77-0.91; P < 0.01).

Conclusions: PRO screening tools provide adequate CIPN screening while avoiding potential biases demonstrated to limit currently used clinician-rated screening tools. Addition of a brief objective test did not add value to PRO screening. Up to 23% of patients would be misidentified through screening, providing quantitative evidence of the limitations of available screening tools. More extensive CIPN evaluations are critical in patients at risk of serious neurotoxicity.