Dear Editor,

In the February 2020 issue of Journal of Immunotherapy and Precision Oncology, Dr. Alshehri et al propose comprehensive guidelines for assessment and management of oligometastatic disease.[1] In particular, they discuss stereotactic body radiation therapy (SBRT) and surgical metastatectomy for metastatic disease in the brain, spine, lung, head and neck, abdomen including liver, and adrenal glands and bones. The authors are members of the Saudi Lung Cancer Guidelines Committee, but their recommendations are specific neither to lung cancer nor to Saudi Arabia and can be broadly applicable to a wide range of disease sites and settings.

The concept of oligometastatic disease was first proposed by Hellman and Weichselbaum[2] as a distinct state of cancer between localized and widespread metastatic disease. It has been hypothesized that these patients may benefit from integration of ablative local therapy into their treatment framework. Thus far, five randomized phase II studies have assessed this question and have shown an improved progression-free survival or overall survival with the addition of metastasis-directed local therapy to standard of care.[37] There are ongoing phase III trials seeking to define appropriate patient populations for whom aggressive metastasis-directed therapy has the highest likelihood of prolonging and improving quality of life; however, until these trials are reported, consensus guidelines, such as the current one proposed by Alshehri et al, are important for standardizing care such that outcomes can be prospectively studied.

There are several points from the guidelines that merit further discussion. First, the authors are to be commended for their emphasis on the importance of multidisciplinary care for patients with oligometastatic disease. Indeed, optimal integration of local with systemic therapy requires discussion between multiple specialties including surgery, medical oncology, radiation oncology, radiology, and pathology. This will become even more necessary as the modalities for ablative therapy increase. Second, choosing appropriate endpoints for assessment of response to local therapy is critical. In particular, prior studies on local therapy for oligometastatic disease have largely used progression-free survival as a primary endpoint. This surrogate endpoint includes radiographic progression as an event of interest, which is usually measured by RECIST criteria. Unsurprisingly, when metastatic sites are ablated with SBRT, follow-up scans will likely show response in the treated sites. In contrast, patient-relevant endpoints of interest include quality of life and length of life (overall survival); thus I would recommend that the authors also incorporate these measurements in their response assessment. Third, ongoing and future studies seek to define oligometastatic disease based upon tumor biology, using molecular subtypes to predict potentially curable oligometastatic disease. Circulating tumor DNA is also being explored as a means to identify differentiate patients with truly limited sites of disease. As these studies come to fruition, validated biomarkers should also be used for patient selection criteria.

It was a pleasure to read these insightful guidelines on management of oligometastatic disease by Alshehri and colleagues. As I write this letter, we are currently in the midst of the global COVID-19 pandemic, which, among other realities, has demonstrated how interconnected we are as citizens of the world. This also includes care of our cancer patients. I look forward to learning more about oncology care in Saudi Arabia and congratulate the authors for their efforts in guiding management of oligometastatic cancer.

References

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Competing Interests

Source of Support: None. Conflict of Interest: None.