Illustration of lung cancer cells with PD-L1 markers.

Lung Cancer Breakthrough: Personalized Treatment Paths with PD-L1 Testing

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Jordan Keane in Health & Wellness November 2026 • 4 min read.

"New research highlights the importance of PD-L1 testing in tailoring lung cancer treatments, offering hope for more effective and personalized care."


Lung cancer remains a leading cause of cancer-related deaths worldwide, but advancements in understanding its complex biology are paving the way for more personalized and effective treatments. Among these advancements, the identification and targeting of specific molecular markers, such as Programmed Death-Ligand 1 (PD-L1), have emerged as critical strategies.

PD-L1 is a protein that helps cancer cells evade the immune system. By binding to the PD-1 receptor on immune cells, PD-L1 inhibits their ability to attack and destroy cancer cells. Immunotherapies that block this interaction have shown remarkable success in treating various cancers, including non-small cell lung cancer (NSCLC). However, not all patients respond to these therapies, making it essential to identify those who are most likely to benefit.

Recent research underscores the significance of assessing PD-L1 expression in lung cancer cells to guide treatment decisions. These studies delve into the reliability and validity of PD-L1 testing methods, compare results across different types of tissue samples, and explore innovative approaches to evaluate surgical margins. The findings aim to refine patient selection criteria and improve outcomes in lung cancer therapy.

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Real-World PD-L1 Treatment Patterns

Contemporary real-world data on advanced non-small cell lung cancer (aNSCLC) treatment patterns across PD-L1 expression levels and testing status remain limited. A retrospective cohort examined adults newly diagnosed with aNSCLC between January 1, 2018, and July 31, 2021, who initiated first-line treatment. The College of American Pathologists provides evidence-based recommendations for PD-L1 and tumor mutation burden testing in patients with lung cancer, while the American Lung Association describes PD-L1 testing as immunohistochemical staining of tumor tissue that measures the percentage of cells expressing PD-L1.

From Biology to Treatment Decisions

PD-L1 testing has become part of treatment decision-making in non-small cell lung cancer, but expert commentary emphasizes both its significance and its limitations. The 2026 review, “The Role of PD-L1 in Lung Cancer: From Biology to Clinical Application,” examines PD-L1 biology, expression patterns, regulatory mechanisms, assessment methods, and clinical relevance for immunotherapy strategies. Lung Cancer Foundation of America show notes explain how PD-L1 scores and Tumor Proportion Scores guide immunotherapy discussions while also highlighting the need to understand what the test means for treatment choices.

Why PD-L1 Testing Matters in Lung Cancer Treatment

Illustration of lung cancer cells with PD-L1 markers.

PD-L1 testing is revolutionizing lung cancer treatment by enabling doctors to tailor therapies to individual patients. These tests measure the amount of PD-L1 protein on cancer cells, helping predict how likely a patient is to respond to immunotherapy. The higher the PD-L1 expression, the more likely immunotherapy will be effective.

Traditionally, PD-L1 testing has been performed on tissue samples obtained through biopsies or surgical resections. However, recent studies have explored the use of cytology specimens, which are collected through less invasive methods like fine needle aspirations or pleural effusions. Cytology offers a convenient alternative, particularly for patients who may not be able to undergo more invasive procedures.

  • Accuracy and Reliability: Research indicates that PD-L1 testing on cytology samples provides reliable results, comparable to those obtained from tissue samples. This is crucial for ensuring that treatment decisions are based on accurate information.
  • Comprehensive Assessment: Studies have assessed the performance of different PD-L1 immunohistochemistry (IHC) kits, such as 28-8 and SP263, to determine their agreement in evaluating cytology specimens. Good agreement between kits ensures consistency in PD-L1 assessment.
  • Interobserver Agreement: The evaluation of PD-L1 expression in cytology specimens has shown good to excellent interobserver agreement, meaning that different pathologists interpreting the same samples arrive at similar conclusions. This is vital for the reproducibility of PD-L1 testing in clinical practice.
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Improving PD-L1 Assessment

The advent of PD-1 and PD-L1 inhibitors has transformed lung cancer treatment and increased the need for accurate PD-L1 immunohistochemical assessment. The PubMed search results specifically identify research on PD-L1 testing in cytology specimens and the validation of related assessment methods. These findings point to an ongoing research focus on determining whether cytology-based testing can provide reliable information for treatment decisions.

Treatment Choice and Testing Variation

For advanced NSCLC, first-line treatment selection depends in part on oncogene-driven alterations such as EGFR mutations and ALK translocations. Evidence comparing chemoimmunotherapy with immunotherapy alone in patients with high PD-L1 expression, defined in one review as at least 50% or very high expression of at least 90%, remains limited. A 2026 meta-analysis is evaluating whether PD-L1 expression differs between biopsy and surgical specimens, while the Ring Study examined international differences in PD-L1 diagnostic assays and interpretation.

The ability to reliably assess PD-L1 expression in cytology specimens expands the accessibility of personalized lung cancer treatment. It allows more patients to be considered for immunotherapy, potentially improving their outcomes and quality of life. As research continues to validate these findings, PD-L1 testing is poised to become an even more integral part of lung cancer management.

The Future of Lung Cancer Treatment: Personalized and Precise

As our understanding of lung cancer biology deepens, personalized approaches like PD-L1 testing are becoming increasingly important. By tailoring treatments to individual patients, we can improve outcomes, reduce side effects, and enhance the quality of life for those affected by this disease. The ongoing research and development in this field promise a future where lung cancer is managed with precision and care.

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Guideline-Based Biomarker Testing

The College of American Pathologists published a guideline on PD-L1 testing for patients with lung cancer. Dr. Sholl is identified as a co-chair of the evidence-based guideline covering immunotherapy biomarkers, including PD-L1 and tumor mutation burden, in patients with non-small cell lung carcinoma. The guideline therefore places PD-L1 testing within a broader biomarker-testing framework rather than treating it as an isolated measurement.

Biology and Clinical Complexity

The review “The Role of PD-L1 in Lung Cancer: From Biology to Clinical Application” examines the biological features of PD-L1 and its expression patterns in lung tumors. Its stated purpose is to connect those biological characteristics with clinical application. This framing reflects the challenge of translating variable tumor biology and PD-L1 expression into clinically useful treatment decisions.

Outcomes Beyond the Test Result

A 2025 real-world Canadian study reported that the PACIFIC regimen's treatment benefit and safety were validated in routine practice. Among patients who received chemoradiotherapy followed by durvalumab, increasing PD-L1 status correlated with improved overall survival, while patients who discontinued durvalumab early because of adverse events had shorter overall survival. Other real-world studies examined treatment patterns in advanced NSCLC, including whether adding chemotherapy to an immune checkpoint inhibitor provides an outcomes advantage for patients with metastatic disease and high PD-L1 expression who are not eligible for targeted therapy.

What cytology agreement figures mean in context

  • 0.84 sensitivity; 0.88 specificityAt the ≥1% cutoff, cytology compared with paired histology had pooled sensitivity of 0.84 and specificity of 0.88. These measure how often cytology matched histology for identifying positive and negative results, respectively.[1]

What cytology can show-and what it cannot settle

Cell-block testing makes qualitative assessment feasible across many cytology sample types, yet limited tumor and immune cells, missing tissue context, and possible false negatives constrain exact measurement.[2]

Taken together, these findings support cytology as a potentially useful source of test material, not as an exact substitute for the tissue context that can be missing from small samples.[2] [3]

How specimen comparisons and scoring results differ

The cited trial result describes longer progression-free survival with nivolumab plus ipilimumab than with chemotherapy among patients with high tumor mutational burden, regardless of PD-L1 expression. It shows that this result was not restricted by PD-L1 status, but does not establish how cytology testing performs in treatment selection.[4]

What evidence could clarify PD-L1 testing by cytology

  • How closely would cytology results track histology at cutoffs beyond the ones assessed in a small-sample report?[2]
  • How much can a cell block represent the tumor when a small biopsy captures only limited tissue?[3]
  • How reproducible are PD-L1 scores when observers assess the same staining, given reported variability and reproducibility concerns?[5]

Questions about the testing context

What role does PD-L1 IHC have in NSCLC biomarker testing?

The cited source describes PD-L1 immunohistochemistry as the only available biomarker that can guide treatment with immune checkpoint inhibitors in non-small cell lung cancer.[6]

Sources

  1. Accuracy of Cytologic vs Histologic Specimens for Assessment of Programmed Cell Death Ligand-1 Expression in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis. (pubmed.ncbi.nlm.nih.gov)
  2. A noninterventional, multinational study to assess PD‐L1 expression in cytological and histological lung cancer specimens (pmc.ncbi.nlm.nih.gov)
  3. Cell Block as a Surrogate for Programmed Death-Ligand 1 Staining Testing in Patients of Non-Small Cell Lung Cancer (pmc.ncbi.nlm.nih.gov)
  4. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of non-small cell lung cancer (NSCLC) (pmc.ncbi.nlm.nih.gov)
  5. PD-L1 assessment in lung cancer biopsies-pitfalls and limitations. (journals.sagepub.com)
  6. PD-L1 Testing in Non-small Cell Lung Cancer: Past, Present, and Future (pmc.ncbi.nlm.nih.gov)

About this Article -

Written with AI assistance from published research, and reviewed by the Mystum team. See our About page for more information.

Everything You Need To Know

1

What is PD-L1, and why is it important in lung cancer?

PD-L1, or Programmed Death-Ligand 1, is a protein that cancer cells use to avoid being detected and destroyed by the immune system. Specifically, PD-L1 binds to the PD-1 receptor on immune cells, which inhibits the immune cells' ability to attack the cancer. This interaction is significant because blocking it with immunotherapies can allow the immune system to target and eliminate cancer cells. However, not all lung cancer patients respond to these immunotherapies, making PD-L1 testing essential to determine which patients are most likely to benefit. The implications of understanding PD-L1 are far-reaching, enabling tailored treatment plans and improved patient outcomes.

2

How does PD-L1 testing help in treating lung cancer?

PD-L1 testing measures the amount of PD-L1 protein present on lung cancer cells. This is important because the level of PD-L1 expression can help predict how likely a patient is to respond to immunotherapy. Higher PD-L1 expression often indicates a greater chance of success with immunotherapy treatments. The implication is that doctors can use PD-L1 testing results to determine the most effective treatment strategy for each patient, potentially improving outcomes and reducing unnecessary exposure to treatments that are unlikely to work. This guides treatment decisions to individual patients.

3

What are cytology specimens, and why are they relevant for PD-L1 testing?

Cytology specimens are samples collected through less invasive methods, such as fine needle aspirations or pleural effusions, instead of traditional biopsies or surgical resections. Using cytology specimens for PD-L1 testing matters because it offers a more convenient and accessible way to assess PD-L1 expression, especially for patients who may not be able to undergo more invasive procedures. It ensures that a broader range of patients can be considered for personalized lung cancer treatment. The implications include expanded access to immunotherapy and potentially improved outcomes for a larger population of lung cancer patients. These samples are more accessible for patients.

4

Why is it important that PD-L1 testing is accurate and reliable?

The accuracy and reliability of PD-L1 testing are vital because treatment decisions are based on the test results. If PD-L1 testing provides reliable results, doctors can confidently tailor therapies to individual patients. Good agreement between different PD-L1 immunohistochemistry (IHC) kits, such as 28-8 and SP263, ensures consistency in PD-L1 assessment. Excellent interobserver agreement among pathologists is crucial for the reproducibility of PD-L1 testing in clinical practice. The implication is that consistent and accurate PD-L1 testing leads to more effective and personalized lung cancer treatment.

5

What does personalized lung cancer treatment mean, and why is it important?

Personalized lung cancer treatment involves tailoring therapies to individual patients based on specific characteristics of their cancer, such as the expression of Programmed Death-Ligand 1 (PD-L1). It's important because it allows doctors to select the treatments most likely to be effective for each patient, improving outcomes and reducing unnecessary side effects. The implications of personalized medicine are significant, as it represents a shift towards more precise and effective cancer care, ultimately enhancing the quality of life for those affected by lung cancer. The goal is to ensure that treatments are matched to the unique characteristics of each patient's cancer.

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