FDG-PET in the clinical management of carcinoma of unknown primary with metastatic cervical lymphadenopathy: shifting gears from detecting the primary to planning therapeutic strategies

Dear Sir, With the introduction of FDG-PET in clinical oncology, one of several unresolved areas that are being investigated is detection of the primary tumor in patients with nodal metastases from an unknown site. The results, however, have indicated varying degrees of success, with the rate of detection of putative primary tumors ranging from 10% to 60%. This wide variation can be attributed to the criteria adopted to define the “unknown primary” in different clinical settings. According to the strict definition, the term “unknown primary” should be used when clinical examination, CT/MRI and panendoscopy fail to reveal a primary tumor. Unfortunately, only a few studies have adhered to such a strict definition. A careful analysis of the studies which employed these uniform criteria reveals only a modest increase in the detection rate when using FDGPET. Systematic reviews [1–4] published at various stages of evolution of PET have continued to contradict each other on this issue; the two most recent reports [1, 2] estimated the benefit to be modest at best (27% and 25% respectively) after all other modalities had failed. A head-to-head comparison of the performance of CT, PET, PET and CT side-by-side, and co-registered PET-CT documented a success rate of 25%, 25%, 29%, and 33% respectively, with no statistically significant difference among the modalities [5]. There are reports from prospective studies [6] that FDG-PET does not add significantly in finding the occult primary in a carefully worked-up CUP, especially if conventional imaging modalities are negative. In practice, it is not uncommon to find that a primary detected by FDGPET was actually a “missed primary” rather than an unknown primary in the true sense. While the results of FDG-PET in detecting an occult primary in the setting of CUP are not encouraging, an important observation which has gradually become obvious as an offshoot in several studies (including those in which FDG-PET was found to be non-contributory in detecting the primary after conventional work-up) has been the serendipitous discovery of multiple sites of disease, which has implications for the treatment strategy. By virtue of its exquisite sensitivity, FDG-PET whole-body survey can be extremely useful in guiding the therapeutic strategy by identifying or ruling out additional sites of disease in patients who present with a single metastatic site. The study by Fogarty et al. [6], which found a limited role for FDGPET in diagnosing occult primaries, concluded that the modality is of substantial benefit in the detection of unsuspected distant disease in patients with undifferentiated nodal disease and in the delineation of regional disease in patients with N2 disease. In a cohort study reported by Johansen et al. [7], whole-body F-FDG PET had treatment-related implications in 24% of patients. Finally, a systematic review [2] of 16 studies on 302 patients found that FDG-PET detected previously unrecognized metastases in 27% of patients, of which 11% were distant metastases, and resulted in changes in treatment in 24.7% of cases. This is an important consideration while planning treatment for patients with CUP with cervical node metastasis. While locoregional treatment is planned for those with one site, it is rarely considered for those with distant metastatic sites. Also, the detection of distant metastases can lead to a change in the treatment intent, from cure to palliation. Eur J Nucl Med Mol Imaging (2007) 34:427–428 DOI 10.1007/s00259-006-0313-1