A RECENT study has revealed significant discrepancies between clinician- and patient-reported symptom severity in individuals with locally advanced or metastatic urothelial carcinoma (la/mUC) treated with pembrolizumab. Pembrolizumab, an immune checkpoint inhibitor, is a standard second-line therapy for this cancer type, but its side effects, often immune-related, can escalate quickly and impact patient wellbeing.
Traditionally, adverse events (AEs) have been assessed by clinicians using the Common Terminology Criteria for Adverse Events (CTCAE). However, CTCAE lacks the nuance of capturing patient experiences, particularly for subjective symptoms such as fatigue or dry mouth. To bridge this gap, the Patient-Reported Outcome-CTCAE (PRO-CTCAE) was used in this study to collect patients’ perspectives alongside clinician assessments.
The analysis included patient-reported symptoms from treatment initiation to cycle 12 of pembrolizumab. Researchers found that patients consistently reported symptoms earlier and more frequently than their healthcare providers. The PRO-CTCAE completion rate remained stable, starting at 77.5% and ending at 69.2%, reinforcing its feasibility in longitudinal monitoring.
Comparison with previous clinical trial data (KEYNOTE-045) showed clinicians under real-world conditions reported fewer grade ≥3 symptoms. The discrepancy was further highlighted using the toxicity index, a method for summarising cumulative and longitudinal symptom burden. Agreement between patient and clinician assessments was statistically poor, confirming earlier findings from studies in other cancers.
The study emphasises the potential underestimation of pembrolizumab-related toxicity by clinicians, possibly due to a focus on measurable lab results rather than patient-experienced symptoms. It also suggests that patients may underreport side effects for fear of treatment discontinuation.
These findings support the integration of PRO-CTCAE into both routine care and clinical research. Electronic symptom monitoring has already shown to improve quality of life and patient adherence. In clinical trials, PRO-CTCAE can enhance toxicity evaluation, even aiding dose decisions in early-phase studies.
Despite some limitations, such as a pre-specified symptom list and limited CTCAE grading, the study provides strong evidence that incorporating patient-reported data is essential for comprehensive cancer care.
Reference
Annakib S et al. Patient versus clinician reported symptoms agreement in advanced metastatic bladder cancer patients. Cancer Med. 2025;14(8):e70896.
