Dr Postow on Distinguishing Between Late-Onset irAEs and Underlying Comorbidities in Melanoma

“[For a multidisciplinary care team], talking to each other as much as possible is the best way to try to get [the answers] to these diagnostic uncertainties and the best care for those patients.”

Michael A. Postow, MD, chief of the Melanoma Service at Memorial Sloan Kettering Cancer Center, discussed the importance of distinguishing between late-onset immune-related adverse effects (irAEs) and underlying comorbidities unrelated to treatment in melanoma care.

Trying to determine whether a clinical manifestation is treatment related or not remains one of the more nuanced diagnostic challenges in oncology today, Postow explained. As patients receiving immune checkpoint inhibitors grow older and carry increasingly complex medical histories into treatment, clinicians must carefully parse whether a new or worsening condition reflects a treatment-related toxicity, disease progression, or a pre-existing comorbidity that has evolved independently over time.

The diagnostic difficulty is compounded by the fact that cancer itself can produce symptoms that closely mimic irAEs, further blurring the clinical picture. A patient who presents with a cardiac condition several years after completing immunotherapy, for example, may have underlying coronary artery disease that predates treatment entirely, or may be experiencing a delayed immune-mediated effect that only became apparent long after therapy concluded, Postow described. Determining which of these explanations is driving a patient's presentation requires careful longitudinal thinking and input from multiple specialists.

Close, consistent communication across a multidisciplinary care team is essential to navigating these uncertainties, Postow underscored. When that team operates within a single institution, coordination is relatively straightforward. The greater challenge arises when patients receive care across multiple institutions with fragmented records and limited cross-system communication. Gaps in electronic health record integration and the absence of shared communication platforms represent real logistical barriers that can delay diagnosis and compromise the quality of care that patients receive.

Better integration of health record systems and communication infrastructure will be critical to closing these gaps going forward. In the meantime, providers are encouraged to engage in as much direct dialogue as possible across care settings, Postow noted. Proactive outreach between oncologists, cardiologists, rheumatologists, and other relevant specialists remains the most practical tool available for resolving diagnostic uncertainty and ensuring that patients with potential late-onset irAEs receive timely, accurate, and coordinated care.