Following his presentation at the European Society of Medical Oncology (ESMO) 2023 Annual Meeting, held in Madrid, Spain, Physician’s Weekly spoke with Witold Rzyman, MD, PhD. Dr. Rzyman presented in a session titled, “Is Stereotactic Radiotherapy a Valid Alternative to Surgery for Patients with Stage I Non-Small Cell Lung Cancer (NSCLC)?”1
Early detection of NSCLC significantly impacts patient outcomes and overall survival; however, NSCLC is often diagnosed at advanced stages, leading to a poorer prognosis and limited treatment options. Timely diagnosis facilitates tumor identification at a localized or regional stage when they are more amenable to curative interventions such as surgery, stereotactic body radiotherapy (SBRT), or other potentially less invasive approaches. Early detection also increases the likelihood of successful treatment, reduces the need for aggressive interventions, and improves the chances of long-term survival. Additionally, early detection allows for the implementation of personalized treatment strategies and inclusion in clinical trials, advancing our understanding of the disease and contributing to the development of more effective therapies. Screening programs, particularly imaging techniques like low-dose computed tomography (LDCT), play a crucial role in identifying NSCLC at an early, more treatable stage, which underscores the significance of early detection in improving patient outcomes and reducing the overall burden of this malignancy.
Adjuvant immunotherapy for early NSCLC include includes two approved agents: atezolizumab or pembrolizumab.2,3 The IMpower010 study2, a randomized trial involving 1,280 patients with stage IB to IIIA NSCLC, endorsed atezolizumab. The study compared 1 year of atezolizumab with best supportive care following adjuvant chemotherapy. Notably, individuals with PD-L1 expression 1% or higher experienced a significant enhancement in disease-free survival with atezolizumab. The FDA subsequently approved adjuvant atezolizumab for stage II to IIIA resected NSCLC post-surgical resection and adjuvant chemotherapy, with preliminary data indicating a modest but noteworthy improvement in overall survival, particularly for those with PD-L1 at least 50%.
At ESMO 2023, researchers presented an exploratory analyses of IMpower010 that showed disease-free survival could be predicted by high expression of TGFβ CAF in patients in the atezolizumab arm, but not in the control arm, regardless of histology or PD-L1 expression level.4 Given recent advances and the potential curative nature of detecting and treating NSCLC at an early stage, Physician’s Weekly asked Dr. Rzyman for additional insight.
PW: Why is early detection of lung cancer so crucial?
Dr Rzyman: Screening is a crucial tool for early diagnosis due to lung cancer’s poor prognosis, primarily resulting from late detection and often no symptoms. Primary prevention through smoking cessation is vital, but effective secondary prevention via screening is also essential.5-7 The United States implemented screening in 2016, and currently, six countries have population-based screening financed from the budget. Several European countries are in the process of implementing screening, which will lead to the early detection of lung cancer.
PW: What about the treatment outcomes of early lung cancer?
Dr Rzyman: Available data on outcomes is limited due to the low proportion of lung cancer cases in the general population. However, long-term survival rates are high, with 80-90% of cases being in stage I or II. Five-year survival rates are promising, and mortality and morbidity after surgery are generally low, with some series reporting zero mortality post-surgery. SBRT shows potential, although randomized control trials comparing surgery and SBRT are lacking. Observational studies including data prospectively, like the ongoing IELCART study8, may provide valuable insights for future treatment options.
PW: What is the role of perioperative or peri-SBRT immunotherapy?
Dr Rzyman: Data on perioperative or peri-SBRT immunotherapy is insufficient at the moment. Ongoing randomized control trials show promising results, but most trials focus on more advanced stages (IIIa). Stage I data is limited, making it challenging to determine the role of additional treatment. Discovering biomarkers that predict the benefit of immunotherapy in stage I is crucial, but currently, there’s a lack of reliable markers. Promising ones, like circulating tumor DNA, show benefits in only 50% of cases.
PW: If you had unlimited funds, would you prioritize screening?
Dr Rzyman: I would allocate all the funds into well-structured lung cancer screening, considering it the most challenging of all cancers. Organizing it effectively is crucial, and integrating AI tools to support radiologists is essential. Artificial Intelligence (AI) has emerged as a promising tool in the screening for early lung cancer. AI algorithms, particularly in conjunction with medical imaging techniques like LDCT, have shown the potential to enhance the accuracy and efficiency of early cancer detection. These algorithms can analyze vast amounts of medical data, identifying subtle patterns or anomalies that may be indicative of early-stage lung cancer. The integration of AI in screening processes holds the promise of improving diagnostic precision, reducing false positives and negatives, and ultimately contributing to more timely interventions and improved patient outcomes in the battle against this challenging disease. What is important in lung cancer screening is to implement as many AI tools as possible to support radiologists because, for them, lung cancer screening is a burden. Likewise, I would concentrate on these randomized control trials in early-stage NSCLC. Screening organization and implementation, especially with the aid of AI, should take precedence over other aspects.
