Surgery for limited-stage small-cell lung cancer

Abstract

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. 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. 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. 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. 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. 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. 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. La chirurgie pour le cancer bronchique à petites cellules en phase limitée Les directives de traitement actuelles pour le stade local du cancer bronchique à petites cellules (CBPC) recommandent une chimio-radiothérapie concomitante à base de platine associée à l'irradiation crânienne prophylactique, en se basant sur le postulat que le CBPC se propage de manière précoce et est chimiosensible. Cependant, bien qu'il existe généralement une réponse initiale favorable, la récidive est courante et le taux de guérison pour les CBPC en phase limitée reste relativement faible. Certaines directives récentes pour la pratique clinique ont recommandé la chirurgie pour les CBPC de stade 1 (localisé) suivie d'une chimiothérapie adjuvante, mais cette recommandation est largement basée sur les résultats d'études observationnelles. Déterminer si, chez des personnes ayant un CBPC en phase limitée, la résection chirurgicale du cancer améliore la survie globale et les décès liés au traitement par rapport à une radiothérapie ou une chimiothérapie, ou une combinaison de la radiothérapie et de la chimiothérapie, ou à de meilleurs soins palliatifs. Nous avons effectué des recherches dans CENTRAL, MEDLINE, Embase, CINAHL et Web of Science jusqu'au 11 janvier 2017. Nous avons effectué une recherche manuelle dans des articles de revue, des registres d'essais cliniques et dans les références bibliographiques des articles identifiés. Nous avons inclus les essais...