Perioperative Therapy in Resectable NSCLC: The Drive for a Cure

Dr. Joshua K. Sabari is the editor-in-chief of CURE.

Over the past 20 years, there have been dramatic advances in treatment options for people diagnosed with lung cancer. Small molecules that target specific alterations in lung cancer, referred to as targeted therapies and immunotherapies, which activate our immune system to better recognize cancer as foreign, have revolutionized how we think about and treat lung cancer. These therapies were initially studied in people with stage 4 metastatic or incurable lung cancer and have dramatically improved outcomes and quality of life for our patients and family members.

Historically, people diagnosed with early-stage lung cancer (stage 1B to 3A) who underwent curative intent surgical resection had unacceptably high rates of recurrence of their disease. Staging systems using the TNM classification — (T) tumor size, (N) lymph nodes and (M) metastases — help us better prognosticate risk of recurrence and potential benefit for therapy before resection (neoadjuvant) or after resection (adjuvant). The recognition that micrometastatic disease, cancer cells outside the primary tumor and beyond the surgeon’s grasp, can contribute to recurrence of disease has driven the field to take a more holistic approach to reduce the recurrence risks and increase the rate of cure. Systemic therapies are critical in reducing the risk of recurrence and increasing the rates of cure. Unfortunately, chemotherapy only minimally improved the rates of survival in resectable early-stage lung cancer.

Due to tremendous advances in our understanding of the biology of cancer, novel systemic therapies such as immunotherapy and targeted therapy are now being utilized in early-stage lung cancer with dramatic improvements in outcomes. As a practicing thoracic medical oncologist, I now recommend perioperative therapy: systemic treatment both before and after resection. I often discuss this approach as having “two shots on goal.” The surgery is a window into how well the treatments worked, and we can now understand the degree or depth of response to treatment based on the resected surgical specimen.

Ms. D., a kindergarten teacher and grandmother with a history of smoking and high blood pressure, was diagnosed with stage 3 lung cancer. The tumor measured 5 centimeters and was in her right upper lung. Based on initial imaging and testing, she was found to have involvement of one lymph node with lung cancer adjacent to the primary tumor. Given the size of her tumor and lymph node involvement, it was determined to be stage 3 lung cancer. After consulting with thoracic surgery, radiation oncology and medical oncology, she was deemed to have resectable disease. I explained to her that with resection alone, there was approximately a 75% chance that her cancer would recur over the ensuing five years and that by utilizing a perioperative approach of chemotherapy and immunotherapy, we could reduce the risk of recurrence dramatically. She opted to receive three months of chemotherapy and immunotherapy before surgery and tolerated treatment well overall.

Our first interval imaging revealed a significant reduction in the tumor size, and the previously enlarged lymph node was no longer visible.

Given her encouraging response to neoadjuvant therapy, she proceeded to the operating room, where she underwent a robotic resection of her right upper lobe and sampling of her lymph nodes in the chest. We were very encouraged when the final pathology results showed that she had no evidence of any cancer present, known as a complete pathologic response. Clinical trials utilizing perioperative approaches with chemotherapy and immunotherapy have shown improvement in overall survival and have now become a standard of care in clinical practice.

Perioperative therapy represents a real step forward in patient care. This approach not only boosts survival rates but may also facilitate less extensive surgeries by reducing tumor size and burden, potentially improving surgical outcomes and recovery time for our patients.

Chemotherapy and immunotherapy are not without side effects; these approaches should be discussed with your medical team. It is also important to note that some people diagnosed with lung cancer may not have deep responses to immunotherapy, such as people with a specific driver mutation (for example, EGFR). These patients may benefit more from targeted therapies. Therefore, it is critical to discuss these options with your health care team to craft the best personalized approach.

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