Elsevier

The Lancet

Volume 359, Issue 9315, 20 April 2002, Pages 1388-1392
The Lancet

Articles
Effectiveness of positron emission tomography in the preoperative assessment of patients with suspected non-small-cell lung cancer: the PLUS multicentre randomised trial

https://doi.org/10.1016/S0140-6736(02)08352-6Get rights and content

Summary

Background

Up to 50% of curative surgery for suspected non-small-cell lung cancer is unsuccessful. Accuracy of positron emission tomography (PET) with 18-fluorodeoxyglucose (18FDG) is thought to be better than conventional staging for diagnosis of this malignancy. Up to now however, there has been no evidence that PET leads to improved management of patients in routine clinical practice. We did a randomised controlled trial in patients with suspected non-small-cell lung cancer, who were scheduled for surgery after conventional workup, to test whether PET with 18FDG reduces number of futile thoracotomies.

Methods

Before surgery (mediastinoscopy or thoracotomy), 188 patients from nine hospitals were randomly assigned to either conventional workup (CWU) or conventional workup and PET (CWU+PET). Patients were followed up for 1 year. Thoracotomy was regarded as futile if the patient had benign disease, explorative thoracotomy, pathological stage IIIA–N2/IIIB, or postoperative relapse or death within 12 months of randomisation. The primary outcome measure was futile thoracotomy. Analysis was by intention to treat.

Findings

96 patients were randomly assigned CWU and 92 CWU+PET. Two patients in the CWU+PET group did not undergo PET. 18 patients in the CWU group and 32 in the CWU+PET group did not have thoracotomy. In the CWU group, 39 (41%) patients had a futile thoracotomy, compared with 19 (21%) in the CWU+PET group (relative reduction 51%, 95% Cl 32–80%; p=0·003).

Interpretation

Addition of PET to conventional workup prevented unnecessary surgery in one out of five patients with suspected non-small-cell lung cancer.

Introduction

Accurate staging of patients with a pulmonary lesion suspected of being non-small-cell lung cancer is needed to restrict surgical or multimodality treatment to those who will potentially benefit from these treatments. Several imaging techniques and invasive tests are available to the clinician to detect mediastinal lymph-node involvement, distant metastases, or both. International guidelines to make the most of this process1, 2, 3, 4 have been formulated, but routine clinical practice remains variable.5, 6, 7, 8 Despite current diagnostic workup, early local and distant relapses are frequent, and surgery is done for preoperatively suspicious lesions that can prove to be benign. Therefore, surgery can be regarded as futile in up to 50% of patients with presumably resectable non-small-cell lung cancer.8, 9, 10

Positron emission tomography (PET) with the tracer 18-fluorodeoxyglucose (18FDG) has emerged in the past decade as a promising oncological imaging tool. Results of several accuracy studies have suggested that 18FDG-PET is better at assessment of suspicious lung lesions and nodal or extra-thoracic tumour status in non-small-cell lung cancer than conventional workup.11, 12, 13, 14 Accuracy studies are, however, not designed to show added value of diagnostic tests. Like phase II studies for development of treatments, they are subject to bias, which make generalisation of results to predict an effect in routine practice difficult.15 In general, these drawbacks lead to overestimation of worth.16 As a result, whether and to what extent patients will benefit from use of PET in a routine clinical setting cannot be directly inferred from existing published work.17, 18

As in assessment of new treatments, new diagnostic technologies need to be compared with current strategies with respect to relevant clinical outcomes.19, 20, 21 Workers on major health-technology assessment reports20, 22 concluded that improvement of diagnostic accuracy by PET was difficult to quantify because of variable quality of studies, and that direct evidence on the effect of PET in improvement of patients' outcomes was still lacking.

The PLUS (PET in LUng cancer Staging) study was designed to work with routine clinical workup of patients with suspected non-small-cell lung cancer. We compared the current strategy of conventional diagnostic methods with a strategy in which PET was added to non-invasive diagnostic techniques. The primary outcome measure was number of futile thoracotomies.

Section snippets

Patients

We invited patients with suspected or proven non-small-cell lung cancer that was judged to be medically operable and potentially resectable by the referring clinician on the basis of clinical staging—but not surgical staging—to participate in the study. Eligible patients had to be older than age 18 years. All patients gave written informed consent in accordance with requirements set by local medical ethics committees. Eight community and one university hospital recruited patients for the study.

Procedures

Baseline characteristics

Between January, 1998, and January, 1999, we enrolled 188 patients from nine hospitals (between five and 50 patients per hospital)—96 in the CWU group and 92 in the CWU+PET group (figure). 70% of patients in each group had clinical stage I/II disease (table 1). Pre-randomisation workup was closely similar for both groups, and included at least a chest CT scan, which usually included the liver and adrenals (89%). All CT scans were done with at least third-generation scanners: spiral modality in

Discussion

Our study showed that addition of PET to conventional workup can strikingly reduce the number of futile thoracotomies in patients with suspected potentially resectable non-small-cell lung cancer. The main effect of PET was to upstage patients (12% in the CWU group compared with 27% in the combined group). Obviating surgery in such patients improves patients' management.

Our findings are directly applicable to clinical practice. Data from the Netherlands Cancer Registry28 suggest that our study

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    Members of the PLUS study group are listed at the end of the report

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