Targeted therapy: based upon the primary tumor or on its metastases?

Most of the primary tumors at various stages are resected or destroied by radiotherapy. Meanwhile, contemporary target therapies are administered in advanced stages, but the required molecular pathologic analysis is performed on the primary tumor supposing stable genetic profi ls durings at different stages of cancer progression. Advanced molecular technologies provided high resolution images on the clonal heterogeneity of the primary tumors and its role in cancer progression. Data indicate that in early and locoregional stages/recurrences the chance for genetic discordance is low while, in late visceral metastases this risk is increasingly higher. The clinical relevance of the genetically discordant metastatic tumors is proven by several retrospective studies. This is the basis of the recommendations that in case of progressing cancer molecular pathologic tests must be performed on metastatic tumors, especially when the primary tumor is resected. On the other hand, it is an unresolved issue what to do in case of discordance between the primary and the metastasis.