PET and PET/CT have revealed a good diagnostic accuracy in visualizing both primary cancer and metastatic lesions, and many clinical studies demonstrate that they can compete with the morphological conventional diagnostic modalities mainly in staging, detecting tumor relapses, evaluating tumor response to therapy and giving useful prognostic indications. Data about the usefulness of PET to stage axillary nodes in breast cancer patients are controversial, also considering that another nuclear medicine technique, the sentinel lymph nodes biopsy (SLNB) after localization with lymphoscintigraphy, is very reliable for this indication. It is well known that SLNB today is considered the standard nuclear medicine method for staging axilla. This chapter is focused on the diagnostic potential of PET in studying lymph node axillary metastases that are one the most important prognostic factors affecting the therapeutic strategies. The diagnostic results of the most important clinical trials carried out with FDG-PET in axillary staging of breast cancer patients have been examined and reported. However, the position of FDG-PET in studying the loco-regional lymph nodal involvement still has to be completely evaluated, since the main problem is the absence of long-term prospective studies able to evaluate the outcome of the patients after FDG-PET staging and treated or not with ALND according to FDG negative or positive uptake. The main reason for the discussions in the field is the limitation of FDG-PET in depicting the small metastases spread to axillary lymph nodes. This lack in sensitivity has become particularly evident since the introduction of very aggressive pathologic techniques with SLNB, such as multi-slice sectioning and immunocytochemistry staining. These approaches have significantly increased the rate of detection of micrometastases shown in the biopsies from the studies on the clinical validation of SLNB and ALND. On the contrary, the detection of micrometastases with FDGPET is very critical, being limited by the spatial resolution of the PET scanner. Any discussions about this indication for PET in clinical oncology should take into consideration the fact that at present the standard method for staging axilla remains the ALND, which does not entail any intrinsic risk of downstaging the axillary status. The SLNB plays an important role in selecting patients that should undergo ALND due to its high sensitivity, also for micrometastases, even if the SLNB also has a non-negligible false-negative rate in almost all studies. The combined used of SNLB and FDG-PET is a new strategy that has been recently proposed. According to the conclusions of some recent studies, this means that FDG-PET does not have to be considered as an alternative diagnostic tool instead of SLNB, but in those patients with clinically negative axillary lymph nodes, PET could discriminate patients eligible for ALND from the patients who should undergo SLNB. This is based on the FDG axillary uptake and on the high positive predictive value of PET. Therefore, breast cancer patients with FDG-positive uptake should directly undergo ALND rather than SLNB for axillary staging. On the contrary, those cases without FDG uptake in the axilla should be examined with SLNB in order to select candidates for ALND. This approach of course has to be validated through adequate large prospective studies with a follow-up evaluation, but it is important to stress the fact that in this way it is possible to take advantage of the strength of the two methods. Probably the role of PET, even in this new clinical perspective, should be reconsidered due to the improvements of the scanner technology, such as with the hybrid system PET/CT or other more sophisticated advances in the detectors and/or dedicated software.
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