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Background: Esophageal cancer is notorious for its rapid dissemination, both locally and to distant sites. Accurate staging at the time of diagnosis is of crucial importance to identify patients eligible for curative treatment. For the vast majority of these patients the preferred strategy consists of neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy. Given the aggressive nature of esophageal tumours, it is conceivable that in a significant portion of patients treated with nCRT, dissemination becomes manifest during this preoperative course (interval metastasis). Since metastatic disease is an absolute contraindication for esophagectomy, we added a post-neoadjuvant therapy PET-CT (restaging PET-CT) to the standard work-up of patients with potentially resectable esophageal carcinoma at initial presentation.
Aim: Determine the value and diagnostic accuracy of PET-CT after neoadjuvant chemoradiotherapy in identifying patients with interval metastases preoperatively.
Methods: From January 2011 until September 2012 all consecutive esophageal cancer patients deemed eligible for a curative approach with nCRT and surgical resection underwent a PET-CT after completion of nCRT (median interval 18 days). Staging at initial presentation consisted of endoscopy with biopsy, endoscopic ultrasonography, external ultrasonography of the neck and a thoracoabdominal CT scan. A PET scan was not part of the initial staging. Neoadjuvant therapy consisted of 5 cycles of carboplatin AUC 2, paclitaxel 50 mg/m2 and concurrent radiotherapy (41.4 Gy). If abnormalities on restaging PET-CT were suspect of metastases, histologic proof was acquired. This study was approved by the local ethics committee.
Results: During the study period a total number of 280 new esophageal cancer patients were analysed at the outpatient clinic. Of these patients 148 underwent a restaging PET-CT. The remaining 132 patients were considered ineligible for curative esophagectomy at initial presentation due to comorbidity, unresectable tumours or distant metastases (94 cases), refused to undergo surgery (12), were operated without nCRT (13) or did not complete nCRT in our centre (13). In 29 patients (19.6%) restaging PET-CT showed abnormalities suspicious for dissemination requiring additional imaging and/or biopsy, resulting in 16 cases of proven interval metastasis (10.8%) and a false-positive rate of 8.8% for restaging PET-CT. Of the patients without proven metastatic disease 116 patients have been operated at this time. In 4 of these 116 cases distant metastases were detected intraoperatively, leading to a false-negative rate of 3.4%.
Conclusion: 10.8 percent of esophageal cancer patients develop detectable distant metastases during neoadjuvant chemoradiotherapy. To avoid non-curative resections we advocate restaging PET-CT as part of the standard work-up of candidates for surgery.