A new ASCO guideline provides key recommendations for the evaluation and management of stage III non–small cell lung cancer (NSCLC). Recommendations made by the ASCO expert panel cover evaluation and staging of NSCLC, neoadjuvant and adjuvant therapies, and the management of unresectable disease.1
The Need for Expert Guidance
Stage III NSCLC is a heterogeneous subgroup of lung cancer. “Consequently, it is also the subgroup in which choice and sequence of multimodality treatment vary significantly among clinicians, with variations being observed across institutes as well as within an institute,” said Navneet Singh, MD, DM, of the Postgraduate Institute of Medical Education & Research in Chandigarh, India, and Guideline Co-Chair.
Navneet Singh, MD, DM
Megan E. Daly, MD
The disease also features a wide range of treatment options, underscoring the need for a standardized, consensus-driven approach to managing carefully selected patients with appropriate therapies. Megan E. Daly, MD, of UC Davis Health, and Guideline Co-Chair, explained that the new ASCO guideline represents an important factor in guiding clinicians in each step of the decision-making process. “We hope that this guidance will allow patients with stage III NSCLC to receive optimized workup and treatment based on the latest data,” she said.
Although previous ASCO guidelines provide recommendations on adjuvant chemotherapy and adjuvant radiation therapy for stages I to IIIA NSCLC, the new guideline updates clinicians on the integration of immunotherapy and targeted therapies as well as radiation dose and fractionation for stage III disease specifically, given the advancements made in this field in recent years.
Guideline Development and Recommendations
The ASCO expert panel that developed the new NSCLC guideline comprised specialists across several disciplines, all of whom reviewed 127 relevant studies published between 1990 through 2021 to inform the recommendations. Disease-free or recurrence-free survival and quality of life were the main outcomes of interest for the guideline.
In the guideline, the writing committee emphasized the need for all patients with suspected stage III NSCLC “to be thoroughly evaluated clinically as well as by means of appropriate imaging modalities to exclude metastatic disease and as far as possible to confirm any suspected metastatic site pathologically,” Dr. Singh said. At a minimum, the guideline recommends conducting a history and physical exam and computed tomography (CT) scan of the chest and upper abdomen.
Additionally, clinicians are encouraged to confirm mediastinal lymph node status in patients with stage III NSCLC who plan for curative-intent treatment. Confirmation should be made using pathologic assessment with endoscopic techniques. In patients with resected stage III NSCLC who are to undergo multimodality treatment (surgical resection and systemic neoadjuvant therapy), the guideline recommends offering adjuvant platinum-based chemotherapy in those who did not initially receive neoadjuvant systemic therapy.
Concurrent chemotherapy and radiation therapy is recommended as the “treatment of choice” for patients with stage III NSCLC who are medically or surgically inoperable and have a good performance status, whereas those who are deemed not suitable for the concurrent regimen should be offered sequential chemotherapy and radiation therapy.
Recommendations were also made on dose/technique of radiation delivery. For instance, the guideline recommends that patients receiving concurrent chemoradiation should be treated to 60 Gy. Although doses higher than 60 Gy and at a maximum of 70 Gy may be an option for some patients, the guideline committee suggests that clinicians should monitor the heart, lungs, and esophagus to mitigate the risk of excessive morbidity and mortality associated with therapy.
One of the key recommendations in the guideline, according to Dr. Daly, is the support for consolidation durvalumab for up to 12 months following concurrent chemoradiation. This is based on a marked survival benefit with the durvalumab-based approach observed in the randomized phase III PACIFIC trial.2
Additionally, recent data from the ADAURA trial informed a recommendation on the use of adjuvant osimertinib after platinum-based chemotherapy, particularly in patients with EGFR exon 19 deletion or exon 21 L858R.3 “Thus, this new guideline incorporates targeted therapy and immunotherapy—the two latest pillars of treatment—apart from the conventional treatment modalities, such as surgery, chemotherapy, and radiation,” Dr. Singh said.
The guideline committee also emphasized the importance of multidisciplinary decision-making in the care process. “Treatment of stage III NSCLC includes many specialists, including medical and radiation oncologists, thoracic surgeons, pulmonologists, radiologists, and pathologists,” Dr. Daly said. “As such, the inclusion of a multidisciplinary team is critical.”
Additional Questions Remain
Dr. Daly noted that additional well-designed studies with modern radiation, systemic therapy, and surgical techniques are needed to further define which patients with stage III NSCLC may benefit from the inclusion of surgery in their management. “Ongoing studies should also help address any role for immunotherapy concurrent with chemoradiation and/or with resectable disease,” she said.
Further research is also needed to clarify patient selection for immunotherapy. The guideline authors also stated that patient selection for consolidative immunotherapy is not clearly defined, suggesting future studies may help inform future recommendations on this approach in the context of stage III NSCLC.
1. Daly ME, Singh N, Ismaila N, et al: Management of stage III NSCLC: ASCO guideline. J Clin Oncol. December 22, 2021 (early release online).
2. Faivre-Finn C, Vicente D, Kurata T, et al: Four-year survival with durvalumab after chemoradiotherapy in stage III NSCLC: An update from the PACIFIC trial. J Thorac Oncol 16:860-867, 2021.
3. Wu YL, Tsuboi M, He J, et al: Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med 383:1711-1723, 2020.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, December 23, 2021. All rights reserved.