Elsevier

Lung Cancer

Volume 66, Issue 2, November 2009, Pages 198-204
Lung Cancer

Comparison of EUS-guided fine needle aspiration and integrated PET-CT in restaging after treatment for locally advanced non-small cell lung cancer

https://doi.org/10.1016/j.lungcan.2009.01.013Get rights and content

Abstract

Background

After induction treatment restaging of mediastinal disease in patients with stage III non-small cell lung cancer (NSCLC) may lead to selection of candidates for further surgical treatment. Nodal down-staging is the best predictive characteristic for proceeding with surgery.

We report our experience in restaging with endoscopic ultrasound-guided fine needle aspirations (EUS-FNA) and with repeated integrated positron emission tomography and computed tomography (PET–CT).

Methods

Twenty-eight patients with stage III NSCLC were staged with integrated PET–CT, cerebral magnetic resonance imaging (MRI) and pathologically proven nodal disease.

Restaging was performed with PET–CT and EUS-FNA on the same nodes that showed initially metastatic disease provided these nodal sites determined the tumor stage. Cerebral MRI was not repeated.

When restaging EUS-FNA revealed no malignant cells anymore, patients were operated. The postoperative pathologic results were compared with the preoperative restaging EUS-FNA results. Also, patterns of decreased fluoro-2-deoxyglucose (FDG) uptake were compared with the postoperative pathologic results.

Results

Restaging EUS-FNA was well tolerated in all patients even in those with clinical signs of radiation esophagitis.

Of the 28 patients 15 were down-staged based on cytologic findings with restaging EUS-FNA and in one patient the cytology was not conclusive. Of these 15 patients, down-staging was histologically confirmed after mediastinal exploration in 11 patients and 1 patient had persistent nodal disease at resection. In 3 patients no mediastinal tissue verification was performed. Two subjects were not fit for operation, and in the other patient intraoperative nodal staging was omitted. The negative predictive value for restaging EUS-FNA was 91.6%. The accuracy of EUS-FNA was 92.3%.

Concordance between findings of restaging EUS-FNA and metabolic response of lymph node metastases occurred in 17 out of 27 patients.

Conclusion

Restaging with EUS-FNA after induction chemo(-radiotherapy) is well tolerated and predicts the absence of nodal metastasis reliably. Although changes in mediastinal FDG-PET uptake show a high concordance with EUS-FNA, pathological confirmation is still superior and therefore necessary. EUS-FNA is the procedure of first choice for mediastinal restaging.

Introduction

Several studies demonstrated that down-staging mediastinal node metastases predicted prolonged survival after induction therapy with chemotherapy and chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC) [1], [2], [3], [4], [5], [6]. Concurrent chemo-radiotherapy seems the most effective way to clear tumor cells from nodal stations in stage III disease [6]. Diagnostic procedures for restaging vary in performance and the way they come to conclusions. It is important to determine down-staging of mediastinal nodes and subsequently for selecting patients for surgery. Restaging is difficult especially when mediastinoscopy has been performed previously. Remediastinoscopy gives inadequate information caused by incomplete procedures in 40% of patients due to fibrosis [7]. PET–CT is by far superior to remediastinoscopy [8]. Restaging mediastinal metastases with PET as described in four studies show sensitivities of 50–71% after various induction therapies reflecting the need for pathologic confirmation [9]. A study in 93 patients, restaged after chemo-radiotherapy with repeated PET–CT and various biopsy techniques (including EUS) demonstrated a false negative rate of 20% and a false-positive rate of 25%. Repeated PET–CT was more accurate than repeated CT for all stages [10].

Endoscopic techniques are of interest because they can be performed repeatedly and deliver material for cytopathologic analysis through transbronchial fine needle aspirations (TBNA). Recently a study was published on restaging with TBNA after induction chemo-radiotherapy [11]. A correct diagnosis was obtained in 71% of patients. Nowadays this technique can be performed under guidance of linear ultrasound bronchoscopes (EBUS-TBNA). This technique is very useful in staging the mediastinum in patients without a prior treatment [12], [13]. A recent study described the experience with EBUS-TBNA in restaging the mediastinum after induction chemotherapy in patients with stage IIIA NSCLC [14]. A sensitivity, specificity, positive and negative predictive value and diagnostic accuracy of 76%, 100%, 100%, 20% and 77% respectively were found.

Also endoscopic ultrasound (EUS) is feasible in mediastinal restaging after induction chemotherapy as demonstrated in a study of 19 patients with a reported sensitivity of 75% and accuracy of 83% [15]. This sensitivity is lower than sensitivities reported in the pre-treatment analysis [16]. EUS-FNA for restaging after chemo-radiotherapy has been described in two studies [10], [17]. One study described restaging results in 93 patients but did not report data on the accuracy of EUS in this setting [10]. One study in 14 patients reported a diagnostic accuracy of 86% [17].

The paucity of articles describing the use of EUS for restaging might be caused by a reluctance to perform this procedure on patients with a radiation esophagitis.

In this prospective study, both PET–CT and EUS-FNA were used for restaging patients with stage III NSCLC after induction therapy (chemotherapy or concurrent chemo-radiotherapy).

The performance of both tests was compared with those of surgical dissection of the mediastinum.

Section snippets

Entry criterion

Between February 2006 and May 2008 patients with stage III NSCLC were included after a written informed consent was obtained.

All patients were initially staged with MRI or CT of the brain and integrated PET–CT. Subsequently the mediastinal nodal status was verified with EUS-FNA in 26 patients, cervical mediastinoscopy in 1 patient and transbronchial needle aspiration in 1 patient. Patients were eligible if the pathologically proven metastatic site determined the disease stage and could be

Patient characteristics

Table 1 shows the characteristics of the 28 patients included.The median number of nodal sites biopsied during initial staging procedures was 3 (range 1–6).

Six patients received chemotherapy and 22 patients concurrent chemo-radiotherapy as induction treatment. In 13 of the patients who received concurrent chemo-radiotherapy, two courses of full dose chemotherapy preceded chemo-radiotherapy.

Restaging EUS-FNA and PET–CT was performed within 2 weeks from last treatment date (median 10 respectively

Discussion

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a mediastinal staging modality that has been developed in the last decade. High sensitivities and specificities have been reported in a large number of studies and in a recently reported meta-analysis [16]. Since resolution of ultrasound techniques is high and fine needle aspirations are performed in real-time, EUS and EBUS or combinations of both with FNA have higher diagnostic accuracies than blind TBNA and PET–CT. Therefore

Conflict of interest

The authors declare no conflict of interest.

Acknowledgement

Remco Boksem is acknowledged by the authors for the statistical analysis of survival data.

Reference (22)

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