Lung Cancer: Advances in Diagnosis and Management

Percy Lee, MD

Jonathan Goldman, MD

Jessica S. Donington, MD, MSCR

In this issue of Seminars in Respiratory and Critical Care Medicine, leading researchers from around the world provide state-of-the-art review on impactful topics related to the clinical management of lung cancer. As lung cancer has been a devastatingly challenging disease to treat that requires multidisciplinary management to achieve optimal outcomes, this issue focuses broadly on advances in diagnosis and treatment from the thoracic surgery, radiation oncology, and medical oncology perspectives.

From the thoracic surgery perspective, the landscape of care for early stage nonsmall cell lung cancer (NSCLC) is rapidly evolving, even though progress is less dramatic than what has occurred for advanced disease in recent years, There are continuous improvements in our ability to diagnose disease earlier, stage it more accurately, and improve the tolerability of treatment. The 2011 publication from the National Lung Screening Trial led to Center for Medicare & Medicaid Services (CMS) reimbursement for low-dose computer tomography (LDCT) screening for lung cancer in high risk cohorts in 2015. Recent results from European screening trials have furthered the excitement regarding the immense potential of LDCT screening to decrease lung cancer mortality. Efforts now focus on heavily implementation strategies, as only a fraction of eligible individuals undergoing screening. Resections for early stage NSCLC continue to become safer and more tolerable. The majority of stage-I cancer resections are currently performed via minimally invasive techniques, robotic, or video-assisted. The ability to perform anatomic lung resection with small incisions and without rib-spreading significantly decreases perioperative pain, complications, length of stay, and time to recovery without negatively impacting long-term oncologic outcome. Minimally invasive surgery is finally becoming the standard of care for stage-I NSCLC treatment. Efforts to improve tolerability of lung cancer resections extend throughout the perioperative period. Enhanced recovery pathways are revolutionizing surgical care, focusing on smoking cessation, minimally invasive approaches, decreased fasting, opioid-sparing analgesia, early mobilization, and increased patient education. These programs not only decrease opioid use, length of stay, and cardiopulmonary complications but also help to facilitate additional oncologic therapies. In locally advanced disease, there is continued evidence for the value of resection as part of a multimodality approach in selected populations and incredible excitement generated by induction strategies which now include immunotherapies.

From the radiation oncology perspective, there has been tremendous excitement in the synergy between novel immunotherapeutics and radiation therapy. As radiation therapy remains an important modality for the treatment of medically inoperable early stage, local regionally advanced, and metastatic lung cancer, understanding the potential synergistic effects between novel biologics and immunotherapy with radiation therapy is critical. There is encouraging early preclinical and clinical data from combining immunotherapy and radiotherapy that will require further explorations to understand its underlying mechanisms and implications for this novel dual therapy. Several early clinical studies and post hoc analyses are supporting a growing body of evidence in combining radiation and immunotherapy for the treatment of lung cancer from early stage to metastatic disease. A second topic of interest is the emerging role of local therapies such as radiation and surgery for patients with oligometastatic or oligoprogressive disease status in lung cancer. The oligometastatic paradigm, which was proposed in the early 90's, hypothesized in some patients that metastatic disease is confined to a small number of sites. It is further postulated that gaining control of these oligometastatic sites may lead to potential cures for this subset of lung cancer patients. Several recent randomized phase-II studies support the use of ablative therapies for oligometastatic lung cancer. They suggest an improvement in progression free and overall survival when oligometastatic disease sites are consolidated with local therapies. Larger phase-III validation studies are currently ongoing, as well as smaller trials, exploring ablative therapies for polymetastatic lung cancer. Finally, yet importantly, there has been an increase in use of patient-reported outcome (PRO) measures in lung cancer clinical trials. Studies have shown that PROs may be better prognostic factors for survival compared with traditional factors such as performance status. PROs in recent large immunotherapy trials in lung cancer find that PROs are improved with immunotherapy compared with chemotherapy, showing an improvement in quality of life, as well as extension of life, with immunotherapy. This review will also underscore the current state of the science in PRO research including challenges of applying appropriate PROs in future clinical trials.

From the medical oncology perspective, the last 5 years have seen dramatic improvements in immunologic and targeted approaches to systemic lung cancer care, leading to both improved survival and enhanced quality of life. They have transformed the treatment landscape for non-small cell lung cancer and made the first steps in improving small cell lung cancer outcomes that we have had in more than 3 decades. Several immune checkpoint inhibitors have been FDA-approved for NSCLC, as monotherapy or in combination with chemotherapy. Not only does immunotherapy improve short-term parameters such as response rate, it also leads to a very durable response in as many as a quarter of patients, with survival extending beyond 5 years in some sizable subgroups. Modern targeted therapies, usually orally-available tyrosine kinase inhibitors, have been applied to oncogene driven subsets of NSCLC, frequently with response rates over 65% and progression-free survivals between 18 and 36 months. Along with chemotherapy, which continues to play an important role in the treatment of many patients, immunotherapy and targeted therapy now allow nearly all lung cancer patients to benefit from at least the initial lines of therapies, with a preserved quality of life and functionality. These advances have occurred due to the recent explosion of clinical research in lung cancer, an effort that continues to expand.

We would very much like to thank each of the contributing authors for this special issue of Seminars in Respiratory and Critical Care Medicine dedicated to important and timely topics on the multidisciplinary management of lung cancer. The management of lung cancer has had significant and meaningful advancements in the last few years. We believe that the current state-of-the-art reviews presented here by internationally recognized patient experts in the diagnosis and management of lung cancer will provide a useful resource for clinicians and researchers.