Diabetes mellitus and prognosis of non‐small‐cell lung cancer patients after surgery: What do we know?

Dear Editor, The prognosis of non‐small‐cell lung cancer (NSCLC) remains dismal, accounting for 19.4% of the cancer‐related deaths worldwide. Apart from the characteristics of the tumor, comorbidities have an unignorable effect on NSCLC patients’ survival after surgery, of which diabetes mellitus (DM) was one of the most prevalent. Recently, Kaseda et al. has published a retrospective study exploring the prognostic factors of operable NSCLC patients with DM in the Journal of Surgical Oncology. Excluding patients who underwent preoperative chemoradiotherapy, they divided 1231 NSCLC patients treated with surgery into the DM group (139 patients) and non‐DM group (1092 patients). They found that the DM group had a significantly higher incidence of postoperative complications than the non‐DM group (28.1% vs. 20.7%; p= .047), especially the incidence of wound infection (4.3% vs. 0.9%; p= .001) and acute interstitial pneumonia (5.0% vs. 0.8%; p= .004). But the difference was not significant when 30‐day and 90‐day mortality were compared between the two groups. Furthermore, the DM group had worse overall survival (OS) than the non‐DM group (p= .024), while the recurrence‐free survival (RFS) and cancer‐specific survival were not significantly different. Moreover, the number of deaths from non‐cancer causes was much more in the DM group than in the non‐DM group (50.0% vs. 34.9%; p= .048). Multivariate analyses of the prognostic factors of OS revealed that the hazard ratio of poorly controlled DM (HR=1.88) was much higher than well‐controlled DM (HR=1.43). Actually, many other studies have also discussed the controversial topic of DM's impact on the survival of lung cancer patients after surgery. However, different from Kaseda's study, some studies showed no relevance between DM and survival of NSCLC patients. Previously, we did a systematic review and meta‐analysis focusing on DM and survival of NSCLC patients after surgery and got similar results as Kaseda. In our study, 13 retrospective cohort studies with a total of 4343 patients were included, and we found that patients with DM had shorter OS than patients without (HR =1.30; p = .016), while there was no significant difference in RFS (HR= 1.06; p = .78). Taken together, we believe that DM does have an unfavorable effect on the overall survival of NSCLC patients after surgery, while it had no significant impact on tumor recurrence. Therefore, it is speculated that the negative effect of DM on the survival of NSCLC patients was largely dependent on other pathophysiological processes caused by the DM disease itself rather than the impact of DM on tumor progression. For example, diabetes regarded as a complex systematic disease can accompany fatal complications such as renal diseases, peripheral neuropathy, and arterial disease. But the exact causes of death other than the tumor in surgically treated NSCLC patients is unknown and rarely studied. Therefore, for diabetic patients with resectable NSCLC, we should emphasize the importance of blood glucose control more than the disease of DM. However, there is no suggested ideal fasting glycemic control or HbA1c level for surgically treated NSCLC patients with DM to achieve better OS. Further investigation digging into the interactive mechanisms between diabetes and NSCLC is needed, which should raise the level of awareness of thoracic surgeons.