Treatment for early-stage lung cancer: what next?

Lung cancer is the leading cause of cancer-related mortality worldwide, accounting for 19% of cancerrelated deaths. This devastating toll is the consequence of a high incidence (1·8 million new diagnoses in 2012) and a low rate of cure. Most patients continue to be diagnosed at advanced disease stages. Moreover, the outcome of patients who present with resectable and operable lung cancer (about 25% of cases) is substantially worse than that noted in many other earlystage solid tumours, with most patients eventually developing systemic relapse. Based on the ability of systemic chemotherapy to improve outcome in advanced non-small-cell lung cancer (NSCLC), treatment strategies complementary to radical surgery, including adjuvant and neoadjuvant cytotoxic treatment, have been extensively studied. Indeed, postoperative chemotherapy has been consistently shown to prevent recurrences and increase survival in many clinical trials. The most recent publication of the NSCLC Meta-analysis Collaborative Group, based on 34 trials and 8447 patients, showed an absolute survival improvement at 5 years of 4% (hazard ratio [HR] 0·86, 0·81–0·92). Another meta-analysis that comprised fi ve recent large trials (4584 patients), assessing cisplatin-based chemotherapy, estimated a 5 year survival benefi t of 5·4% for patients receiving adjuvant therapy compared with those that underwent surgery alone (0·89, 0·82–0·96). Consequently, adjuvant cisplatin-based chemotherapy has been widely adopted as the standard of care for patients with resected lung cancer. Evidence to support the use of adjuvant tegafur-uracil is mostly restricted to patients of east Asian origin with early-stage adenocarcinoma. In The Lancet, Sarah Burdett and colleagues report a systematic review and individual patient data meta-analysis on the eff ect of preoperative chemotherapy with subsequent surgery compared with surgery alone. The meta-analysis has been well conducted, included most randomised controlled trials (15) and patients (2385) treated in this context, and the results are scientifi cally sound and relevant for routine clinical practice. This analysis formally confi rms that neoadjuvant chemotherapy improves overall survival to a similar extent as adjuvant treatment (HR 0·87, 95% CI 0·78–0·96; or an increment in 5 year survival rate from 40% to 45%). This eff ect was essentially due to a reduction in distant recurrence rate (0·69, 0·58–0·82), since no clear eff ect on locoregional failure was evident (0·88, 0·73–1·07). Subgroup analysis suggested no diff erential eff ect on the basis of chemotherapy regimen used (number of drugs or treatment courses, platinum analogue employed), adjuvant radiotherapy received, or other patient and tumour characteristics. However, the robustness of these subanalyses is limited because some subsets of patients were scarcely represented (eg, stage IA or III). This meta-analysis more defi nitively substantiates the value of preoperative chemotherapy than individual trials or literature-based meta-analyses. Indirect comparisons with adjuvant studies suggest a similar eff ect on survival (4–5% absolute gain at 5 years), although populations of patients might not be comparable because patients included in neoadjuvant trials probably had a higher risk of recurrence. Concordant with these data, three small studies that compared neoadjuvant with perioperative or postoperative chemotherapy in early-stage NSCLC showed similar outcomes for these diff erent treatment strategies. Similarly, the sequence of local and systemic treatment does not seem to aff ect cure rates in other disease settings such as osteosarcoma, or breast or 6 Zablocki RW, Edland SD, Myers MG, Strong DR, Hofstetter CR, Al-Delaimy WK. Smoking ban policies and their infl uence on smoking behaviors among current California smokers: a population-based study. Prev Med 2014; 59: 73–78. 7 Gilpin EA, Messer K, Pierce JP. Population eff ectiveness of pharmaceutical aids for smoking cessation: what is associated with increased success? Nicotine Tob Res 2006; 8: 661–69. 8 Jin Y, Seiber EE, Ferketich AK. Secondhand smoke and asthma: what are the eff ects on healthcare utilization among children? Prev Med 2013; 57: 125–28. 9 Howrylak JA, Spanier AJ, Huang B, et al. Cotinine in children admitted for asthma and readmission. Pediatrics 2014; 133: e355–62. 10 Nurmagambetov TA, Barnett SB, Jacob V, et al. Economic value of home-based, multi-trigger, multicomponent interventions with an environmental focus for reducing asthma morbidity a community guide systematic review. Am J Prev Med 2011; 41: S33–47. 11 Centers for Disease Control and Prevention. Vital Signs: asthma in the US. Atlanta: United States Centers for Disease Control and Prevention, 2011. http://www.cdc.gov/vitalsigns/pdf/2011-05-vitalsigns.pdf (accessed Jan 27, 2014). 12 Braman SS. The global burden of asthma. Chest 2006; 130: 4S–12S. 13 Lightwood J, Glantz SA. The eff ect of the California tobacco control program on smoking prevalence, cigarette consumption, and healthcare costs: 1989–2008. PLoS One 2013; 8: e47145.