In light of his presentation at the ESMO 2023 Annual Meeting, Medicom Medical Publishers spoke with Prof. Witold Rzyman, Chief Surgeon at the Department of Thoracic Surgery, Medical University of Gdańsk, Poland. Prof. Rzyman spoke of screening-detected non-small cell lung cancer (NSCLC) in the session Is stereotactic radiotherapy a valid alternative to surgery for patients with stage I NSCLC? [1].
Early detection of NSCLC is of paramount importance due to the significant impact it has on patient outcomes and overall survival. NSCLC is often diagnosed at advanced stages, leading to a poorer prognosis and limited treatment options. Early detection facilitates the identification of tumours at a localised or regional stage when they are more amenable to curative interventions such as surgery, stereotactic body radiotherapy (SBRT), or other potentially less invasive approaches. Timely diagnosis 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 personalised treatment strategies and inclusion in clinical trials, advancing our understanding of the disease and contributing to the development of more effective therapies. Screening programmes, particularly those utilising imaging techniques like low-dose computed tomography (LDCT), play a crucial role in identifying NSCLC at an early, more treatable stage, underscoring the significance of early detection in improving patient outcomes and reducing the overall burden of this challenging malignancy.
Adjuvant immunotherapy for early NSCLC includes 2 approved agents: atezolizumab and pembrolizumab [2,3]. Atezolizumab's endorsement originated from the randomised IMpower010 study, which involved 1,280 participants with stage IB to IIIA NSCLC [2]. The study compared 1 year of atezolizumab with best supportive care following adjuvant chemotherapy. Notably, individuals with PD-L1 expression ≥1% 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 ≥50%.
Also at ESMO 2023, an exploratory analysis of IMpower010 showed that disease-free survival could be predicted by a high expression of TGFβ CAF in participants in the atezolizumab arm but not 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, Medicom asked Prof. Rzyman for more information.
Why is early detection of lung cancer so crucial?
“Lung cancer screening is becoming a crucial tool for early diagnosis due to its 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 essential [5–7]. The United States implemented screening in 2016, and 6 countries currently have population-based screening financed from the budget. Several European countries are in the process of implementing screening, which will lead to earlier detection of lung cancer.”
What about the treatment outcomes of early lung cancer?
“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. The 5-year survival rates are promising, and mortality and morbidity after surgery are generally low, with some series reporting zero mortality post-surgery. SBRT has potential, although randomised-controlled trials comparing surgery and SBRT are lacking. Observational studies including data prospectively, like the ongoing IELCART study, may provide valuable insights for future treatment options [8].”
What is the role of perioperative or peri-SBRT immunotherapy?
“Data on perioperative or peri-SBRT immunotherapy is insufficient at the moment. Ongoing randomised-controlled trials show promising results, but most trials focus on more advanced stages (i.e. IIIa). Stage I data is limited, making it challenging to determine the role of additional treatment. Biomarkers predicting the benefit of immunotherapy in stage I are crucial, but, currently, there's a lack of reliable markers. Promising ones include circulating tumour DNA showing benefits in only 50% of cases.”
If you had unlimited funds, would your priority go to screening?
“I would allocate all the funds into well-structured lung cancer screening, considering it the most challenging of all cancers. Organising it effectively is crucial, and integrating artificial intelligence (AI) tools to support radiologists is essential. AI has emerged as a promising tool in the screening for early lung cancer. AI algorithms, particularly in conjunction with medical imaging techniques like low-dose CT scans, have shown the potential to enhance the accuracy and efficiency of early cancer detection. These algorithms can analyse 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 randomised-controlled trials in early-stage NSCLC. Screening organisation and implementation, especially with the aid of AI, should take precedence over other aspects.”
- Rzyman, W. Characteristics and treatment outcomes of screening-detected early NSCLC. Session 22, ESMO Congress 2023, 22–24 October, Madrid, Spain.
- Felip E, et al. 2021;398(10308):1344–1357.
- O'Brien M, et al. Lancet Oncol. 2022;23(10):1274–1286.
- Altorki NK, et al. Abstract 1264MO, ESMO Congress 2023, 22–24 October, Madrid, Spain.
- Aberle DR, et al. N Engl J Med. 2011;365(5):395–409.
- National Lung Screening Trial Research Team, Aberle DR, Adams AM, et al. J Natl Cancer Inst. 2010;102(23):1771–1779.
- Henschke CI, et al. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med. 2006;355(17):1763–1771.
- Henschke CI, et al. J Thorac Oncol. 2023 Oct 6:S1556-0864(23)02265-7.
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