Dissociated Response in Metastatic Cancer: An Atypical Pattern Brought Into the Spotlight With Immunotherapy

When evaluating metastatic tumor response to systemic therapies, dissociated response is defined as the coexistence of responding and non-responding lesions within the same patient. Although commonly observed on interim whole-body imaging, the current response criteria in solid cancer do not consider this evolutive pattern, which is, by default, assimilated to progression. With targeted therapies and chemotherapies, dissociated response is observed with different frequencies, depending on the primary cancer type, treatment, and imaging modality. Because FDG PET/CT can easily assess response on a lesion-by-lesion basis, thus quickly revealing response heterogeneity, a PET/CT dissociated response has been described in up to 48% of women treated for a metastatic breast cancer. Although some studies have underlined a specific prognostic of dissociated response, it has always ended up being described as an unfavorable prognostic pattern and therefore assimilated to the "Progressive Disease" category of RECIST/PERCIST. This dichotomous imaging report (response vs. progression) provides a simple information for clinical decision-support, which probably explains the relatively low consideration for the dissociated response pattern to chemotherapies and targeted therapies until now. With immune checkpoint inhibitors, this paradigm is quickly changing. Dissociated response is observed in around 10% of advanced lung cancer patients and appears to be associated to treatment efficiency. Indeed, for this subset of patients, a clinical benefit of immunotherapy and favorable prognosis are usually observed. This specific pattern should therefore be considered in the future immunotherapy-adapted criteria for response evaluation using CT and PET/CT, and specific clinical managements should be evaluated for this response pattern.