Resection and pathological response after neoadjuvant nivolumab plus chemotherapy for lung cancer in a Turkish Oncology Group (TOG) real-world study
This Turkish Oncology Group real-world study confirms that neoadjuvant nivolumab plus chemotherapy yields pathological response rates comparable to the CheckMate 816 trial in resectable non-small cell lung cancer, though over one-third of patients ultimately did not undergo surgery due to factors like T4 tumor status.
Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer
Lung cancer remains the leading cause of cancer death worldwide, a relentless disease that often strikes before it can be caught. For decades, the standard approach for patients whose tumors were still contained within the chest was to remove them surgically, sometimes followed by chemotherapy to clean up any remaining microscopic cells. However, this sequence often left behind a stubborn problem: the cancer would return in roughly one-third of patients who had undergone a complete removal. The medical community realized that waiting until after surgery to attack the cancer with modern drugs might be too late. The immune system, the body's natural defense force, needs to recognize the enemy to fight it effectively. If the tumor is removed first, the immune system loses the training ground where it learns to identify the cancer's unique markers. This insight led to a shift in strategy: giving powerful immune-boosting drugs before the operation, while the tumor is still in place, to wake up the immune system and let it attack the cancer from the inside out.
A large team of researchers across Turkey recently put this new strategy to the test in the real world, moving beyond the controlled environment of clinical trials to see how it works in everyday hospitals. They followed 211 patients with locally advanced lung cancer who were treated at 28 different medical centers. These patients received a combination of standard chemotherapy and a drug called nivolumab, which helps the immune system recognize and destroy cancer cells, before any surgery was attempted. The goal was to see if this approach could shrink the tumors enough to make them easier to remove and, more importantly, to see if it could eliminate the cancer entirely in the tissue that was eventually taken out. The researchers were particularly interested in a group of patients often left out of such studies: those who started the treatment but, for various reasons, never made it to the operating room.
The results showed that the treatment was highly effective at shrinking tumors. In fact, the vast majority of patients saw their tumors respond to the therapy, with many showing significant reduction in size. When the researchers looked at the patients who did undergo surgery, they found that the treatment had done its job remarkably well. In nearly 40 percent of those operations, the surgeons found no living cancer cells left in the removed tissue or the nearby lymph nodes, a result known as a pathological complete response. When they included the patients who never had surgery in their calculation—counting them as if the treatment had not worked for them—the overall rate of complete cancer elimination was still a strong 24.6 percent. This figure aligns closely with the best results seen in major international trials, suggesting that the powerful effect of this treatment holds up even in a diverse, real-world population where patients are often older and have more health complications than those in strict clinical studies.
However, the study also highlighted a significant hurdle in the path to a cure. While the treatment worked well for many, more than one-third of the patients who started the therapy never reached the operating room. The researchers found that the main reason these patients did not proceed to surgery was not necessarily a failure of the drug, but rather the nature of their disease at the start. Those who did not get surgery were more likely to have tumors that had grown into nearby structures, making them technically difficult or impossible to remove safely. For these patients, the treatment did not disappear, but the path forward changed. Instead of surgery, the majority of those who could not be operated on received radiation therapy, often combined with chemotherapy, to try to control the disease locally.
The study also examined what happened to the patients after their treatment. Those who successfully underwent surgery lived longer and had a lower chance of the cancer returning compared to those who did not. The researchers found that the amount of cancer left behind in the body after treatment was a strong predictor of the future. Patients whose surgery showed no remaining cancer had the best outlook, with a very high chance of remaining disease-free two years later. Interestingly, the level of a specific protein on the cancer cells, known as PD-L1, helped predict how well the tumor would respond to the drug. Patients with higher levels of this protein were more likely to have a major reduction in their cancer. Yet, the study also noted that even patients without this protein marker could still benefit, meaning the treatment is not limited to just one specific type of tumor.
Safety was another key focus, as powerful drugs can sometimes cause the immune system to attack healthy parts of the body. The researchers found that serious side effects were relatively rare, occurring in a small fraction of patients. The most common issues were manageable problems like an underactive thyroid or inflammation in the lungs or colon. These side effects did not appear to be the main reason patients were unable to undergo surgery, suggesting that the treatment is generally safe enough to be used widely.
Ultimately, this research confirms that giving immune therapy before surgery is a powerful tool for treating lung cancer, capable of wiping out the disease in a significant number of patients. It also brings a necessary dose of realism to the field. While the treatment is effective, it is not a magic bullet that works for everyone, and a substantial portion of patients will still face the challenge of having tumors that cannot be surgically removed. For these individuals, the treatment still offers a chance to control the disease with radiation and other therapies, but the path to a cure remains more difficult. The study concludes that the next step for doctors and researchers is not just to confirm that the drug works, but to understand why some patients cannot reach the operating room and how to help them get there, or to find equally effective alternatives for those who cannot.
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