Positron Emission Tomography in Esophageal Cancer

The use of positron emission tomography (PET) has significantly improved the staging of patients with cancer, with the greatest benefit being the avoidance of surgical resection or definitive radiotherapy in patients with otherwise unrecognized metastatic disease.^1,2 For patients with solid tumors (such as lung cancer), its use in diagnosis of the primary and staging of lymph nodes is relatively inaccurate and should not be relied upon.³

PET has been shown to be the most effective staging modality for the evaluation of distant metastatic disease for patients with esophageal cancer,^4,5 yet apparently not as effective as for patients with lung cancer. The review by Yang and colleagues in this issue of Gastrointestinal Cancer Research⁶ refers to the American College of Surgeons Oncology Group (ACOSOG) Z-0060 study, an assessment of the use of PET in the staging of patients with potentially resectable esophageal cancer (presented, but not yet published). Although not discussed in the review, this study actually failed to meet its goal; PET did not improve the staging of esophageal cancer, as it changed the management in only 4.4% of patients, less than the target of 5%.

LIMITATIONS OF PET IN ESOPHAGEAL CANCER

Why did PET fail to improve decision making and management? Some patients may not need a PET scan to complete staging; some patients may have a positive PET scan and go on to surgery anyway; and some patients may have metastatic disease that is not detectable on PET. First, patients with esophageal cancer with metastatic disease are likely to be correctly staged by other noninvasive studies, such as computed tomography (CT) and endoscopic ultrasound (EUS), with or without fine-needle aspiration (FNA). Patients with obvious liver metastases on CT do not need PET to define extent of disease. Similarly, patients with bulky celiac nodal disease (stage IVa), defined by CT or EUSFNA, are likely to be treated with chemotherapy and radiation therapy, regardless of other findings on PET. Also, the staging of patients with small pulmonary nodules detected by CT is not likely to be improved with PET. Regardless of uptake on PET, these nodules must be biopsied.

Second, ACOSOG Z-0060 demonstrated that PET may identify potential metastases without an anatomic correlate on CT, making biopsy difficult. If these patients go on to surgery, the finding on PET did not influence decision making. Finally, some patients have metastatic disease that is below the resolution of PET, yet may be easily diagnosed in other ways. For example, it is not unusual for a patient to undergo surgical exploration after induction therapy, with the finding of small deposits in the peritoneum or liver, confirming stage IVb disease and unresectability.

NCCN RECOMMENDATIONS

How should PET be used for staging patients with esophageal cancer? Treatment guidelines developed by the National Comprehensive Cancer Network (NCCN) clearly describe the appropriate use of PET for esophageal malignancy.⁵ If initial staging studies—including history, physical examination, CT of the chest and abdomen, and EUS (if necessary)—demonstrate potentially resectable disease, PET should be performed to complete the staging. For patients who are T1-2N0M0, primary surgical resection is recommended. For more advanced resectable disease, without evidence of M1 disease, the use of induction chemotherapy and radiation therapy, preferably on clinical trial, is supported.⁵

Patients with M1a disease require multidisciplinary evaluation to determine resectability, a decision that should be made prior to the initiation of therapy. PET is essential in this population to exclude distant metastatic (M1b) disease. Finally, multisite M1b disease demonstrated by PET in patients with esophageal cancer is supportive of the conclusion of stage IVb; however, histologic confirmation should be attempted in patients with a single metastatic focus on PET. Ignoring PET-positive sites that are not in the most suspicious locations (liver, lung, and bone) will unnecessarily subject patients to futile surgery.

LOOKING FORWARD

What is the future of PET in esophageal cancer? First, the future use of PET should include a better understanding of today’s evidence. Decisions that are made on the basis of PET alone, especially after induction chemotherapy and radiation therapy, are not accurate and not supported by evidence. It is not likely that further refinements of PET technology will improve outcomes in patients with esophageal cancer, as the diagnosis of occult micrometastatic disease is probably not in the scope of PET capability. However, there is information available in the current PET technology that is not being used.

For example, it is possible that serial PET scans (focusing on the uptake in the primary tumor) could identify patients who are not responding to systemic therapy, allowing a decision for alternative therapy to be made earlier, a concept not yet tested in a clinical trial. Furthermore, PET-directed biopsy in patients with suspicious sites of metastases that are not detectable on CT or EUS would improve the staging of these patients.

Ultimately, improving the outcomes of patients with esophageal cancer depends on the development of more effective systemic therapy and better strategies to achieve early diagnosis. Until then, attention and adherence to patient care guidelines⁵ and appropriate use of staging studies (such as PET) are essential to optimize outcomes today.