Surgery for limited-stage small-cell lung cancer

Background

There are different types of lung cancer. One type is called small-cell lung cancer. Small-cell lung cancer is considered limited-stage if it is still within the chest or extensive-stage if it has spread outside the chest. Currently, chemotherapy and radiation therapy is recommended for treatment of limited-stage small-cell lung cancer if it is localised and has not spread outside one side of the chest.

Review question

We wanted to know if people with small-cell lung cancer that has not spread outside the chest live longer with an operation to remove the tumour, whether accompanied by chemotherapy, radiotherapy, or both or neither, compared to chemotherapy, with or without radiotherapy.

Study characteristics

We searched for clinical trials up to 11 January 2017, and we included three studies with 330 people who had been diagnosed with small-cell lung cancer which had not spread outside the chest. Some were given surgery only, and some were not. Also, some were given chemotherapy and radiotherapy along with their surgery, and some were given chemotherapy and radiotherapy without surgery. We looked for a difference in how long people lived, and if their treatment caused any side effects.

Key findings

The data were all of very low quality. All three studies were quite different so could not be combined. One study reported that people lived longer without surgery (but with radiotherapy) than with surgery. One study reported 4% of people surviving at two years with surgery compared to 10% of people surviving with radiotherapy. One study reported 52% of people surviving with surgery compared to 18% of people surviving with radiotherapy. Our evidence does not support the use of surgery for people with small-cell lung cancer, but the quality of data is low and from more than 20 years ago. Better trials are needed to properly compare surgery with no surgery in people with small-cell lung cancer.

Quality of the evidence

We rated the quality of the evidence using one of the following grades: very low, low, moderate, or high. Very low quality evidence means we are uncertain about the results. High-quality evidence means we are very certain about the results. For this Cochrane Review, we found that the evidence was of very low quality for all the outcomes studies. We could not combine the trials as they were all very different, and the trials were very old. Some trials did not give enough information about their quality.

Authors' conclusions: 

Evidence from currently available RCTs does not support a role for surgical resection in the management of limited-stage small-cell lung cancer; however our conclusions are limited by the quality of the available evidence and the lack of contemporary data. The results of the trials included in this review may not be generalisable to patients with clinical stage 1 small-cell lung cancer carefully staged using contemporary staging methods. Although some guidelines currently recommend surgical resection in clinical stage 1 small-cell lung cancer, prospective randomised controlled trials are needed to determine if there is any benefit in terms of short- and long-term mortality and quality of life compared with chemo-radiotherapy alone.

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Background: 

Current treatment guidelines for limited-stage small-cell lung cancer (SCLC) recommend concomitant platinum-based chemo-radiotherapy plus prophylactic cranial irradiation, based on the premise that SCLC disseminates early, and is chemosensitive. However, although there is usually a favourable initial response, relapse is common and the cure rate for limited-stage SCLC remains relatively poor. Some recent clinical practice guidelines have recommended surgery for stage 1 (limited) SCLC followed by adjuvant chemotherapy, but this recommendation is largely based on the findings of observational studies.

Objectives: 

To determine whether, in patients with limited-stage SCLC, surgical resection of cancer improves overall survival and treatment-related deaths compared with radiotherapy or chemotherapy, or a combination of radiotherapy and chemotherapy, or best supportive care.

Search strategy: 

We performed searches on CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science up to 11 January 2017. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles.

Selection criteria: 

We included randomised controlled trials (RCTs) with adults diagnosed with limited-stage SCLC, confirmed by cytology or histology, and radiological assessment, considered medically suitable for resection and radical radiotherapy, which randomised participants to surgery versus any other intervention.

Data collection and analysis: 

We imported studies identified by the search into a reference manager database. We retrieved the full-text version of relevant studies, and two review authors independently extracted data. The primary outcome measures were overall survival and treatment-related deaths; and secondary outcome measures included loco-regional progression, quality of life, and adverse events.

Main results: 

We included three trials with 330 participants. We judged the quality of the evidence as very low for all the outcomes. The quality of the data was limited by the lack of complete outcome reporting, unclear risk of bias in the methods in which the studies were conducted, and the age of the studies (> 20 years). The methods of cancer staging and types of surgical procedures, which do not reflect current practice, reduced our confidence in the estimation of the effect.

Two studies compared surgery to radiation therapy, and in one study chemotherapy was administered to both arms. One study administered initial chemotherapy, then responders were randomised to surgery versus control; following, both groups underwent chest and whole brain irradiation.

Due to the clinical heterogeneity of the trials, we were unable to pool results for meta-analysis.

All three studies reported overall survival. One study reported a mean overall survival of 199 days in the surgical arm, compared to 300 days in the radiotherapy arm (P = 0.04). One study reported overall survival as 4% in the surgical arm, compared to 10% in the radiotherapy arm at two years. Conversely, one study reported overall survival at two years as 52% in the surgical arm, compared to 18% in the radiotherapy arm. However this difference was not statistically significant (P = 0.12).

One study reported early postoperative mortality as 7% for the surgical arm, compared to 0% mortality in the radiotherapy arm. One study reported the difference in mean degree of dyspnoea as −1.2 comparing surgical intervention to radiotherapy, indicating that participants undergoing radiotherapy are likely to experience more dyspnoea. This was measured using a non-validated scale.

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