For pIIB-pIIIB NSCLC patients, the incidence of non-cancer specific death of POCT subsequent to pneumonectomy was low among carefully selected patients. The recurrence rate slightly reduced by POCT, but it did not reach statistical significance. POCT did not prolong cancer-specific survival in those who underwent R0 resection with pneumonectomy, particularly in stage pIIIA/pIIIB-N2 patients.
The safety of chemotherapy after pneumonectomy is an important issue in clinical practice. It is generally known that, in addition to the intraoperative risks, pneumonectomy has a high postoperative morbidity and mortality. Removal of an entire lung leads to a dramatic reduction in pulmonary volume, an increase in pulmonary vascular resistance and an increased right ventricle workload, rendering patients vulnerable10. Moreover, drugs used for NSCLC chemotherapy have toxic effects and can cause deaths in 0.8% of treated patients11. Whether a combination of pneumonectomy and POCT will increase the postoperative mortality is unclear. It has been reported that pulmonary and cardiac complications are the factors that negatively influence overall survival after pneumonectomy12, and patients with these complications are more likely to die from the severe toxicity of POCT than those without these complications. Actually, in clinical practice, not all individuals after pneumonectomy indicated for POCT receives it. Even for those who start POCT, the completion rate is significantly lower after pneumonectomy than after lobectomy13.
In this study, all patients included were in stage pIIB to pIIIB, and they should receive POCT theoretically, but only 68.53% (98/143) of them did and only 54.90% of them completed the four cycles of chemotherapy. Some patients in the study complained of frequent shortness of breath in their daily life and they had to rest in bed most of the time, even several months postoperatively. Thus, they did not receive POCT and their five-year non-cancer specific death rate was 11.1%.
On the other hand, we carefully selected patients to receive POCT based on performance status, age, cardio-pulmonary function and subjective willingness, that was also adopted in a previous study1. The patients who received POCT all tolerated it well, and the five-year non-cancer specific death was only 5.5%. Thus, our results indicate that POCT after pneumonectomy is a safe process in carefully selected patients.
As for the site-specific recurrence pattern, we found that distant recurrence (46.6%) was the main reason for treatment failure after pneumonectomy, followed by local recurrence (19.4%). This was consistent with the recurrence patterns of a previous study that recruited stage pIII-N2 NSCLC patients for chemoradiotherapy subsequent to pneumonectomy, that the distant recurrence (the rate was 48.7%) was the main cause of treatment failure, and the local-regional recurrence rate accounted for 32.8%14.
In this study, POCT slightly reduced the rate of recurrence, and the effect was insignificant, while pathologic TNM stage and pleural invasion played a crucial role in predicting recurrence. Our study did not find a significant difference, but it was likely underpowered to detect any such differences, particularly considering that with the strong impact of TNM stage and pleural invasion on recurrence, the effect of POCT could not be revealed in a retrospective cohort design. A specific analysis of the risk for developing local and distant recurrence after pneumonectomy may be useful to identify the best candidates for adjuvant therapies15.
A series of studies have proven that patients with resected stage IIB to IIIB NSCLC could earn survival benefits from receiving chemotherapy3,4,11. However, most patients in these studies recruited cases of lobectomy. Pignon et al. conducted a pooled analysis in which the benefit of POCT on overall survival was not significant in a subgroup analysis of pneumonectomy8. Asad et al. found that adjuvant therapy predicted improved survival in pneumonectomy of stage IIIA NSCLC, but he also proposed that it was uncertain that the result was due to the oncologic effect of POCT or selection bias because patients selected to receive POCT were in a good performance status. Ramnath et al. suggested that POCT should only be prescribed for those who were unable to achieve R0 resection in pneumonectomy and were in good physical condition16. In this study, we found that survival was not prolonged by POCT after R0 resection in pneumonectomy, after excluding patients who died of non-cancer causes. The trend is more obvious in the analysis of the N2(+) group. This is a retrospective analysis, so there is inevitable bias and no robust conclusion could be drawn. A large-scale, prospective study focusing on pneumonectomy is urgently needed to verify these results and to confirm the best candidates to receive POCT.
There are a few limitations of the present study. First, the results probably could not be generalized as it is a retrospective study extending over a period of 8 years. However, the study was performed in a single institution with a regular follow-up schedule. Second, cases were not randomized to POCT, suggesting that selection bias may have existed. Third, the number of patients recruited was relatively small, because of the strict indications for pneumonectomy over the past decade. On the other hand, cases in this study could represent the current features of pneumonectomy well, as the included patients were all treated in the last 15 years.