Abstract: We identified 35 trials evaluating surgery plus adjuvant chemotherapy versus surgery alone. IPD were available for 26 of these trials and our analyses are based on 8447 participants (3323 deaths) in 34 trial comparisons. There was clear evidence of a benefit of adding chemotherapy after surgery (hazard ratio (HR)= 0.86, 95% confidence interval (CI)= 0.81 to 0.92, p< 0.0001), with an absolute increase in survival of 4% at five years. We identified 15 trials evaluating surgery plus radiotherapy plus chemotherapy versus surgery plus radiotherapy alone. IPD were available for 12 of these trials and our analyses are based on 2660 participants (1909 deaths) in 13 trial comparisons. There was also evidence of a benefit of adding chemotherapy to surgery plus radiotherapy (HR= 0.88, 95% CI= 0.81 to 0.97, p= 0.009). This represents an absolute improvement in survival of 4% at five years. For both meta-analyses, we found similar benefits for recurrence outcomes and there was little variation in effect according to the type of chemotherapy, other trial characteristics or patient subgroup. We did not undertake analysis of the effects of adjuvant chemotherapy on quality of life and adverse events. Quality of life information was not routinely collected during the trials, but where toxicity was assessed and mentioned in the publications, it was thought to be manageable. We considered the risk of bias in the included trials to be low. Results from 47 trial comparisons and 11,107 patients demonstrate the clear benefit of adjuvant chemotherapy for these patients, irrespective of whether chemotherapy was given in addition to surgery or surgery plus radiotherapy. This is the most up-to-date and complete systematic review and individual participant data (IPD) meta-analysis that has been carried out.

Plain-language summary: We searched for relevant trials up to December 2013. The studies brought together trial data from all over the world with 26 trials (34 trial comparisons) and 8447 patients in the first meta-analysis (surgery versus surgery plus adjuvant chemotherapy); and 12 trials (13 trial comparisons) and 2660 patients in the second meta-analysis (surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapy). Trials were carried out between 1979 and 2003. Results found that people with non-small cell lung cancer that had surgery followed by chemotherapy (with or without radiotherapy), lived longer than those who had surgery without chemotherapy (with or without radiotherapy).  After five years, 64 out of every 100 patients who were given chemotherapy after surgery were alive compared to 60 patients out of every 100 who just had surgery. For those who also received radiotherapy, after five years, 33 out of every 100 patients who received chemotherapy, surgery and radiotherapy were alive compared to 29 out of every 100 patients who received surgery and radiotherapy. Quality of life information was not routinely collected during the trials, but where toxicity was assessed and mentioned in the publications, it was thought to be manageable.  In both studies, there was little variation in the effect of chemotherapy according to the type of chemotherapy given, other trial characteristics, or by the type of patient included in the trial. These systematic reviews and meta-analyses use individual participant data, which is considered the gold standard of this type of review. We included all eligible trials if possible, no matter what language they were published in or whether they were published or not.  The first meta-analysis (surgery versus surgery plus adjuvant chemotherapy) included 92% of all patients in eligible trials and the second meta-analysis (surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapy) included 86% of all patients in eligible trials. We are confident that further research is unlikely to change the findings. The studies were well designed and conducted, address the review question, and the effects are consistent across trials. The impact of any data we have not been able to include in our analyses is small.