Shifting from clinician-ordered to pathologist-initiated reflex testing for NSCLC biomarkers combines diagnosis and molecular analysis into one workflow. This operational change minimizes delays, increases testing rates, and optimizes the use of small biopsy samples, getting actionable results to oncologists faster.

The four TCGA molecular profiles (e.g., POLE-mutated, p53-abnormal) have evolved beyond predicting outcomes to actively guiding treatment, such as de-escalating therapy for low-risk groups and escalating for high-risk ones.

To reduce treatment delays, pathologists should initiate biomarker testing reflexively. Waiting for a medical oncologist to order tests at a first visit is a system failure, wasting critical time and risking the need to retrieve archived samples.

Clinicians should consider re-biopsying tumors at recurrence, not upfront. Endometrial cancer can evolve, and a metastatic site may develop new targetable markers, like HER2, that were not present in the primary tumor, opening up new treatment avenues.

Establishing a multi-disciplinary molecular tumour board helps operationalize biomarker strategies. This collaborative body, including oncologists and surgeons, not only interprets complex molecular data for trial matching but also collectively advocates for health insurance reimbursement for necessary tests, addressing a key practical barrier.

For certain therapies like Enhertu, eligibility is based on immunohistochemistry (IHC), not NGS. Labs must run HER2 IHC in parallel because NGS, as a population-based test, can miss intratumoral heterogeneity (small clusters of positive cells) that IHC can detect, thus identifying more eligible patients for targeted therapy.

Clinicians ordering "NGS for lung" often misunderstand that Next-Generation Sequencing alone does not cover all actionable biomarkers, such as PD-L1 or HER2. This requires pathologists to interpret the clinician's intent and order a more comprehensive and appropriate test panel.

Inconsistent methods for assessing biomarkers like PD-L1 (CPS vs. TAP scoring), p53 (IHC vs. sequencing), and HRR (different panels) across major clinical trials make it difficult to compare results and identify a reliable predictive marker for endometrial cancer.

While most MMR-deficient patients don't have Lynch syndrome, the biomarker is a crucial screening tool for this hereditary cancer condition. This finding has significant implications for both the patient and their family's health through cascade genetic testing.