Defining Oligometastatic Disease Vital to Support Interpretation of Breast Cancer Trial Results

The definition of oligometastatic disease has continued to be shrouded in uncertainty due to the varying assessment criteria that exist at present during trial analyses, according to session moderator Filipa Lynce, MD, of the Dana-Farber Cancer Institute, in a session at the 2021 American Society of Clinical Oncology Annual Meeting.

To address this challenge, there is a need to establish a consensus in the field around an exact definition for the disease state in order to avoid problems and confusion in relation to the analysis of trial data on the subject.

“This uncertainty is reflected in the different eligibility criteria for trials focused on oligometastatic disease, which sometimes can make the interpretation of the results more challenging,” Lynce said during the session.

The trials that have recently developed in the field and the criteria these trials used have also contributed to some of the confusion around a consistent definition of oligometastatic disease, according to session panelist Jennifer De Los Santos, MD, of the NRG Oncology and Grandview Cancer Center.

“I know as a radiation oncologist, we often use 1 to 5 metastatic lesions that can be safely treated as a target,” De Los Santos said during the session. “I think that many of us, if we had a patient who had 2 metastatic lesions—for instance one in the liver and one in the bone—would consider ablating it if there was a reasonable timeframe between their initial presentation and the primary that’s controlled.”

The bulk of the data that are prospective and reasonably reliable are in the same group regarding the use of 1 to 5 metastatic lesions as a definition for oligometastatic disease, according to Seema Ahsan Khan, MD, FACS, MPH, of the Lurie Cancer Center of Northwestern University. However, she noted that the issue of the organ site of the metastatic lesions is also important to consider as well.

“I think it’s reasonable to debate whether metastatic lesions in different organ sites, such as 3 in different organ sites, are the same as 3 in 1 organ site,” Khan said during the session. “To me it makes more sense that it would also be a solitary organ site involved, but that hasn’t been included in the definition formally.”

For this reason, Khan noted that using the definition set at 1 to 5 metastatic lesions for oligometastatic disease is the most commonly used definition during clinical trials, which makes it the most reasonable definition for use in discussions of the parameters for assessment purposes.

Additionally, most in the field would agree upon under 5 metastatic lesions being a definition of oligometastatic disease, according to Constantinos Sofocleous, MD, PhD, of the Memorial Sloan Kettering Cancer Center. However, if the tumors are very big, they may also involve a very large volume of disease, complicating things further.

“On the other hand, if there are more than 5 metastatic lesions with very low tumor burden, and you have some tests of time showing that this is not rapidly developing and there is some stability, then you can customize local approaches provided there is a rationale, with the overall treatment of the patient and the desire of the patient to take any additional risk that any of those local therapies may provide,” Sofocleous said during the session.

In this way, timing and overall volume of the metastatic lesions also play into deciding whether to offer any local therapies in addition to systemic therapy, regardless of whether they are confined to the strict definition of oligometastatic disease, Sofocleous explained.

Lynce noted that a recent consensus document on the definition of the disease state released in 2020 from the European Society for Radiotherapy and Oncology and American Society for Radiation Oncology defined oligometastatic disease from a radiation oncology perspective as 1 to 5 metastatic lesions that can be safely treated with control of the primary tumor being optional.

The 5th international consensus guidelines for advanced breast cancer from the European School of Oncology and the European Society for Medical Oncology also released a definition of oligometastatic disease. The variation from the prior consensus was the emphasis on low volume metastatic disease with limited number and size of metastatic lesions. In addition, the definition established that the metastatic lesions could potentially be amenable for local treatment aimed at achieving a complete remission status.

With these consensus guidelines, the establishment of a definition of oligometastatic disease remains an important discussion in the field.

REFERENCE

Lynce F, Khan SA, Sofocleous CT, De Los Santos JF. A Multidisciplinary Approach to the Treatment of Oligometastatic Breast Cancer. Presented at: ASCO 2021 Annual Meeting. June 4, 2021. Accessed June 7, 2021.

Update June 9, 2021 at 12:20 PM ET