Additionally, cytological specimens have been shown to be useful for ancillary testing in patients when surgical resection specimens or biopsies are not available. Using morphological evaluation, CTCs in body fluids could be used for primary diagnosis in the setting of cancer of unknown primary (CUP) or in initial or early diagnostic scenarios. However, these have limitations, of which most of them do not have the ability to perform morphological evaluation. Current methodologies are based on quantifying CTCs and include technologies based on physical, immunological, and molecular techniques. Although the current clinical utility has been focused on the prognostic significance, other clinical applications are being explored, such as determining if a patient is a candidate for treatment, determining the efficacy of treatment, evaluation for resistance to therapy, prediction of metastatic site, or as an early predictor of metastases.

Circulating tumor cells (CTCs) are the precursors to metastases and increased numbers of CTCs in the peripheral circulation have been shown to correlate with decreased progression-free and overall survival.

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