Ultrasonographic findings can identify 'pseudoprogression' under nivolumab therapy

'Pseudoprogression' is often seen in patients with melanomas who are treated with immune checkpoint inhibitors such as nivolumab or ipilimumab. We sometimes evaluate metastatic lesions by imaging tests such as computed tomography (CT) or positron emission tomography-CT. 'Pseudoprogression' usually occurs upon the initial administration, which may make it difficult for the physician to determine the disease condition. In our two cases of metastatic melanoma treated with nivolumab (antiprogrammed cell death-1 antibody), we examined the ultrasonography (US) of target lesions that could be accessed from the body surface, such as those of the regional lymph node or subcutaneous metastasis. In both cases, the US revealed a lesion approximately 10% greater in size after 40-50 days of nivolumab administration, even though the blood flow inside the tumour was reduced by about 20% within 50 days. From about 100 days after blood flow reduction was detected by US, the tumours began to decrease in size. However, contrast CT was unable to detect the association between tumour size and tumour blood flow. The present cases suggest that US could be a powerful tool for differentiating between 'pseudoprogression' and real progressive disease in patients treated with cancer immunotherapies such as those involving immune checkpoint inhibitors. The misdiagnosis of progressive disease can lead to unnecessary alterations to the current treatment. Therefore, the US findings in our study could be clinically useful and educational for physicians.