An effort to establish a standard approach for the use of definitive radiotherapy in patients with oligometastatic non-small cell lung cancer (NSCLC) recently brought together a diverse, multidisciplinary group of experts from the American Society for Radiation Oncology (ASTRO) and the European Society for Therapeutic Radiology and Oncology (ESTRO). After reviewing the available evidence, the task force published a new guideline in 2023.
ILCN had an opportunity to interview the chairs of the taskforce, Puneeth Iyengar, MD, PhD, Director of Metastatic Service in the Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center, New York, and Matthias Guckenberger, MD, Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, to discuss the development of the guideline. The interview has been edited for length and clarity.
ILCN: What was the reason to establish these guidelines now?
Dr. Guckenberger: The motivation for this guideline was the observation that many centers worldwide have implemented the use of definitive radiotherapy or surgery for oligometastatic NSCLC patients, despite a lack of data from randomized phase III trials proving benefit for multimodality treatments. This joint ASTRO and ESTRO guideline aims to provide guidance on how to select oligometastatic NSCLC patients for multimodality treatment, and how to best combine systemic therapy and definitive local therapies.
Dr. Iyengar: This idea of using local treatment in the setting of metastatic cancer, and in this case metastatic lung cancer, has been evolving very rapidly during the past 15 to 20 years. More physicians and radiation oncologists are using local therapy in the management of metastatic patients than ever before. Before it was for palliation. Now we are trying to use it as a curative or definitive approach for select patients. We have done this largely before evidence has demonstrated at the highest levels that it is appropriate to do so. So I think this was the right time to establish a standardized approach based on science that is appropriate for our patient population… Generally, when guidelines are made, the work is to collate data that has been generated to establish standard practice. In our guideline, it was a little bit of that and a lot of extrapolation. Knowing when to stop with the extrapolation, knowing our limits, was key.
ILCN: You assembled a diverse taskforce for this project—geographically and in terms of discipline. Why was international collaboration important for this project?
Dr. Guckenberger: Oligometastatic disease is heterogeneous and evidence from randomized phase III trials is lacking. In this guideline, we therefore aimed for a project team integrating broad and complementary experiences and competences. The composition of the guideline was multidisciplinary including radiation oncologists, medical physicists, medical oncologists, and thoracic surgeons, and it was international with ASTRO and ESTRO providing experts.
ILCN: Additionally, a patient representative was involved from the start and co-authored the guideline. Has this been done before? How do you think the experience of having a patient perspective on the taskforce will impact the development of future clinical practice guidelines?
Dr. Iyengar: I think working with our patient advocate Jill Feldman was one of the most enjoyable and impactful experiences that I’ve been part of. She herself is a lung cancer survivor. She has multiple generations of family members who have perished because of lung cancer. She is the epitome of what we need in patient involvement in the process. I think the guidelines were heavily enriched by her point of view. I’ll give you an example. We always say we are incorporating the patient’s perspective in decision-making. However, one of the key points she made was that not every patient is going to have the same tolerance or desire to have therapy. Not everyone’s goal is to live as long as possible. For many people the goal is to have the best quality of life as possible for however long they live. This means not viewing and treating all patients the same way. To listening to them. In the future, I would imagine that most guidelines will incorporate a patient advocate or survivor because it really fulfills an obligation that we have as a community to optimize these therapies on behalf of the patient.
Dr. Guckenberger: Oligometastatic disease is considered an intermediate cancer stage between localized and metastatic disease. Despite multimodality treatment including definitive local therapy for oligometastatic NSCLC patients aims for cure. However, this is not achieved in most patients today, and there is a lack of level 1 evidence proving the curative potential of a multimodality treatment strategy. Based on these uncertainties, we felt it was especially important to integrate the patient perspective into the discussions and writing of the guideline. Retrospectively, this proved as highly valuable.
ILCN: Tell me about the challenges with accruing definitive phase III trials in this space when current data have led many treating physicians to offer treatment outside of a trial.
Dr. Guckenberger: The enthusiasm in the oncological community about the value of a multimodality treatment strategy is based on several randomized phase II trials, which all reported a clinically significant and consistent benefit for the experimental treatment arms. The magnitude of benefit, the consistency of trial results and the hope for a curative potential has spurred the implementation into routine practice, which makes randomized clinical trials more difficult to conduct. The current guideline is cautious in its recommendations, aiming to find a balance between opportunities for our patients and evidence-based practice approach, with special consideration of the patient perspective.
ILCN: Given the lack of phase III evidence, the guideline stresses the importance of multidisciplinary teams in making treatment decisions. Can you explain why this was important to underscore in the guideline.
Dr. Iyengar: Multidisciplinary decision-making is important for all cancer in general, but I think it is especially important when you are talking about multimodal therapy. We are at a point in cancer care, and especially lung cancer care, where every stage of disease can potentially be treated with every treatment modality. When you are dealing with multiple types of therapy, it really improves the decision-making to be driven by the multidisciplinary approach. Some would say this is obvious, but it needs to be established and reiterated: a multidisciplinary approach and patient involvement in the decision-making are key. The multidisciplinary approach should not be taken for granted.
Dr. Guckenberger: The heterogeneity of oligometastatic lung cancer patients and available evidence often make strong recommendations impossible. Optimal treatments depend on appropriate balance and integration of local treatment and systemic treatment components. For the local treatment strategies, additional guidance was needed to choose between surgery and radiotherapy. This guideline was successful in bringing all involved therapeutic disciplines to one table to integrate their competencies into balanced recommendations.
ILCN: With this guideline, patients may now be treated at centers where ablative treatment of oligometastases is routinely considered. Is this a real problem now? How would these guidelines help patient-clinician dialogue regarding this treatment option, especially when high-level evidence from randomized trials is lacking?
Dr. Guckenberger: This guideline emphasized the need for an interdisciplinary decision-making process for finding the optimal patient-specific treatment recommendation. This requires that all required competencies and all disciplines are available. Patients should be aware that the choice of a treatment site capable of integrating multidisciplinary competencies into centralized and coordinated structures may influence treatment recommendations and the treatment itself.
Dr. Iyengar: I think the guideline will expose more physicians and patients to the possibilities of getting local therapy in the advanced setting. What we tried to do in the guideline was to temper our enthusiasm by saying that we do not have level 1 data based on phase 3 trials. We also do not have high level data from studies that incorporated the most modern systemic therapies with local therapy. So we cannot know for sure whether the toxicities are going to increase, stay the same, or decrease in the most modern settings. By highlighting those points and tempering our enthusiasm by saying that the data is only conditional, I think we were able to convey to physicians and patients the need to show caution when approaching these treatment-decision mechanisms. Because remember, one difficult treatment may delay patients from receiving systemic therapy down the line. And systemic therapy is a lifeline for many patients.
ILCN: Any additional thoughts?
Dr. Iyengar: This is a living document. This document should be altered and modified and updated frequently to keep up with the emerging data. I think for this oligometastatic space, we need to keep updating as things evolve and not be concerned about lowering suggestions or lowering the value that we give to a certain treatment approach if the data ends up not supporting it.
