ASTRO, ESTRO Release First Guideline for Definitive Local Therapy in Oligometastatic NSCLC

The American Society for Radiation Oncology (ASTRO) and European Society for Radiotherapy and Oncology (ESTRO) jointly released a clinical guideline on the use of definitive local therapy for the treatment of oligometastatic non–small cell lung cancer (NSCLC).

The guideline, which was published in Practical Radiation Oncology, is the first to address definitive local therapy, such as radiation, surgery, or other ablative methods, for oligometastatic NSCLC—a disease state with a small number of extracranial metastases in addition to a primary tumor. Standard treatment for this disease stage typically involves systemic therapy, with local therapy options only used for symptom relief or palliative treatment.

The guideline addressed 5 key questions surrounding the use of local therapy for oligometastatic NSCLC:

• What are the optimal patient/disease characteristics to select patients with oligometastatic NSCLC for definitive treatment combining systemic and local therapies?
• What are the selection criteria for choice of local treatment modality in the management of patients with oligometastatic NSCLC?
• What are the appropriate sequencing and timing of systemic therapy and definitive local therapies for patients with oligometastatic NSCLC?
• What are the optimal dose-fractionation regimens, planning, and delivery technique of radiotherapy (RT) for patients with oligometastatic NSCLC?
• After a definitive local therapy approach for oligometastatic NSCLC, what are the indications for additional local therapy upon disease progression?

“Despite the widespread enthusiasm in the field of oligometastatic disease, the quality of evidence supporting the integration of definitive local therapy into a multimodality treatment strategy is still lower as compared to indications such as locally advanced NSCLC,” Matthias Guckenberger, MD, cochair of the guideline task force and a professor and chairman of radiation oncology at the University Hospital Zurich in Switzerland, said in a statement. “To compensate for this lack of highest-quality evidence, recommendations of this guideline were established by a broad consensus involving experts from ASTRO and ESTRO, colleagues from the fields of thoracic surgery and medical oncology and a patient representative.”

Overall, the guideline emphasizes the need for a patient-centered, multidisciplinary approach to treatment decision-making for cases of oligometastatic NSCLC, especially considering the lack of significant randomized phase 3 trials in this setting.

Regarding patient selection, the guideline only recommends integrating definitive local therapy for those with 5 or fewer distant, extracranial metastases in cases where it is technically feasible and clinically safe to treat all sites where metastases are present. The guideline conditionally recommends definitive local therapy in addition to standard-of-care systemic therapy for patients who have synchronous oligometastatic, metachronous oligorecurrent, induced oligopersistent, or induced oligoprogressive conditions for extracranial disease.

The only recommended local therapy modalities were radiation and surgery, with radiation recommended in cases where multiple organ systems are involved or when minimizing breaks from systemic therapy is ideal; surgery was recommended when molecular testing of large tissue samples would help guide systemic therapy decision making. The guidelines also recommend up-front definitive local treatment for symptomatic metastases but recommend at least 3 months of systemic therapy before definitive local treatment of metastases in cases of asymptomatic synchronous disease.

The guideline also provides recommendations for dose-fractionation regimens, planning, and RT delivery technique. Additionally, they stress the importance of appropriate imaging to guide treatment.

“To optimally manage oligometastatic NSCLC, careful staging can identify the location, volume, number, and if serial imaging is available, growth rates of metastases to assure that all sites of metastatic disease are addressed,” the authors wrote. They also recommend pathological confirmation of metastases.

Recommendations for patients with oligometastatic NSCLC whose disease progresses after definitive local treatment, which is a common occurrence, were also discussed.

In cases when disease progresses at a limited number of sites, whether previously treated or new, repeat local definitive therapy may be beneficial to prolong progression-free survival or delay a change in systemic treatment. These patients should be discussed at a multidisciplinary tumor board that considers a range of factors. These include the time from previous definitive therapy, the feasibility and safety of administering local therapies, and the availability of new systemic treatments for the patient’s specific subtype of lung cancer.

“Oligometastatic NSCLC is a phase in lung cancer development that may offer us new opportunities to improve patient outcomes, because it typically is more treatable than widely metastatic cancer,” Puneeth Iyengar, MD, PhD, cochair of the guideline task force and an associate professor of radiation oncology at UT Southwestern Medical Center in Dallas, said in a statement. “The research on local therapy for oligometastatic cancer is still at a relatively early stage, but we already see indicators of potential benefits for patients. Adding local therapy to systemic therapy may lead to more durable cancer control, potentially improving progression-free survival, overall survival and quality of life.”

References

1. Iyengar P, All S, Berry MF, et al. Treatment of oligometastatic non-small cell lung cancer: an ASTRO/ESTRO clinical practice guideline. Pract Radiat Oncol. Published online April 25, 2023. doi:10.1016/j.prro.2023.04.004

2. ASTRO and ESTRO issue clinical guideline on local therapy for oligometastatic lung cancer. News release. ASTRO. April 25, 2023. Accessed April 26, 2023. https://www.astro.org/News-and-Publications/News-and-Media-Center/News-Releases/2023/ASTRO-and-ESTRO-issue-clinical-guideline-on-local