Elsevier

The Lancet Oncology

Volume 14, Issue 7, June 2013, Pages e270-e274
The Lancet Oncology

Review
Treatment of early-stage lung cancer detected by screening: surgery or stereotactic ablative radiotherapy?

https://doi.org/10.1016/S1470-2045(12)70592-2Get rights and content

Summary

A randomised trial of screening for lung cancer using CT showed a survival benefit with screening, but issues surrounding risks arising from screening remain. The appropriate treatment of early-stage lung cancer detected in this way is receiving increasing attention. This Review discusses treatment-related issues for such tumours and explores the merits of surgery versus stereotactic ablative radiotherapy (SABR), both of which are effective treatments but have different risks for acute toxicity. Although surgery is widely deemed to be the preferred treatment for patients who are fit, growing evidence suggests that SABR achieves similar local control rates, but without the risks associated with surgery. Choice of local treatment should also be made with consideration of the high rates of disease recurrence and second primary lung tumours in patients after curative therapy for early-stage lung cancer. Careful collaborative evaluation by pulmonologists, interventional radiologists, thoracic surgeons, and radiation oncologists should guide decision making for each patient with a screen-detected early-stage lung cancer.

Introduction

The randomised controlled National Lung Screening Trial (NLST) reported a reduction in lung-cancer-related mortality of 20·0% (95% CI 6·8–26·7; p=0·004) and in overall mortality of 6·7% (95% CI 1·2–13·6; p=0·02) when using low-dose CT instead of chest radiography.1 Although CT scans can detect pulmonary nodules a few mm in size, almost all of these are benign.2 In the NLST trial, screen positivity was defined by a greatest nodule diameter of 4 mm or larger, and 24% of all CT screens were positive using this definition.1 Consequently, screened patients with benign lesions could have invasive diagnostic procedures such as a trans-thoracic needle biopsy or surgery, with a risk of complications.

Approaches such as the nodule volume doubling time (VDT) and 18F-fluorodeoxyglucose (18F-FDG) PET scans can minimise the risk of false-positive findings. Some CT screening studies have used a nodule VDT of fewer than 400 days to reduce unnecessary excisions.3, 4 Although results of a meta-analysis showed 18F-FDG PET to have a high sensitivity (>95%) and specificity (77·8%) for malignant pulmonary nodules, few data are available for nodules less than 10 mm in size.5 However, if 18F-FDG-PET uptake and VDT are in accordance, the probability of a false diagnosis of malignancy is small (5%), compared with the likelihood of benign disease when PET and VDT differ (43%).4 New CT screening studies and current practice guidelines have incorporated similar nodule management protocols,6, 7 and the likelihood of identification of benign lesions will be lower than noted in the NLST screening study.

The diagnostic evaluation and treatment for patients enrolled in the NLST were mostly done at expert centres (82% of which were large academic medical centres), which must be kept in mind.1 The potential for harm when CT screening is done in the community setting is significantly higher, as shown by higher complications rates of CT-guided biopsy of pulmonary nodules in population-based data.8 Similarly, surgical mortality and morbidity for lung cancer in population settings are inferior to those reported in clinical trials or specialised surgical databases.9

An anatomical surgical resection is the current standard of care for patients with early-stage non-small-cell lung cancer (NSCLC), but many patients do not have surgery because of age-related and tobacco-related comorbidity. In the past decade there has been a significant increase in use of stereotactic ablative radiotherapy (SABR), which is also called stereotactic body radiotherapy, for treatment of early-stage lung cancer in patients unfit for surgery.10 SABR is a high-precision radiotherapy technique for tumour ablation given in an outpatient setting, with few side-effects and high local control rates.11 Data from population-based studies reveal that use of SABR has led to better survival than conventionally fractionated radiotherapy.12 SABR has also been shown to achieve high cure rates in potentially operable patients.13, 14 The growing evidence on SABR outcomes has led to discussions about optimum treatment of screen-detected tumours. The number of patients presenting for a resection has been estimated to potentially increase by ten times if CT screening becomes widespread, with significant potential for morbidity and even mortality.2 In this Review we address the pros and cons of both modalities in the treatment of screen-detected stage I NSCLC.

Section snippets

Surgery as the preferred treatment for screen-detected tumours

Despite the use of elaborate algorithms and VDT measurements, imaging techniques provide only a likelihood of malignancy and never a certain diagnosis, even for large nodules. False-positive PET scans could arise in cases of focal pneumonia, aspergilloma, granulomas, inflammation, and tuberculosis.15, 16 Consequently, an exact diagnosis before treatment can only be established by tissue sampling, and this process is often attempted by CT-guided fine-needle biopsy. Although the sensitivity and

Role of SABR in the treatment of stage I NSCLC

SABR is now an established curative treatment for patients with a stage I NSCLC who are unfit for surgery, with results of population-based studies providing the strongest supporting evidence.10, 30 In particular, data for 4605 patients from the Netherlands Cancer Registry revealed an improvement in median survival of 9·3 months in patients aged 75 years and older who had radiotherapy between 2001 and 2009.10 Techniques for SABR delivery have evolved in the past decade, with current delivery

Surgery or SABR: weighing the arguments

Less toxic treatments for screen-detected early-stage NSCLC are clearly needed. In Dutch patients aged 75 years or older, a population-based study showed 30-day and 90-day mortality rates after surgery for stage I NSCLC of 5·4% and 9·3% respectively.10 A systematic review of treatment outcomes in patients with severe chronic obstructive pulmonary disease and stage I NSCLC reported no 30-day mortality after SABR, but the 30-day mortality ranged from 7% to 25% after surgery, with a weighted mean

Surgery or SABR: role of the patient in decision making

Patients increasingly wish to participate in making decisions that take into account their personal preferences,52 and the so-called shared decision-making process is relevant for the treatment of screen-detected early-stage lung cancer. Guidelines for the implementation of CT screening recommend that patients receive detailed information about risks of detection of abnormalities, the probability of additional invasive procedures, and risk of a final benign diagnosis.7 Surgery and SABR are two

Conclusions

For peripheral screen-detected early-stage lung cancer detected in fit patients, a guideline-specified surgical resection seems to be the preferred treatment because it provides a definitive diagnosis and accurate staging. Such patients could benefit from tailored therapy if occult nodal metastases or adverse prognostic factors are found at histological examination. Patients who are at high risk of surgical complications should be informed of the merits of SABR, since surgery could be

Search strategy and selection criteria

SS and MAP independently undertook electronic literature searches with PubMed (Medline). The search strategy applied was as follows: (lung cancer [title/abstract] OR CT screening [title/abstract] OR benign nodules [title/abstract]) AND “early-stage lung cancer” (MeSH). Only studies published in English, in peer-reviewed journals, between Jan 1, 2000, and Aug 31, 2012, were included. We then selected relevant articles from titles and abstracts. We used the related articles function to

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