Our study found no correlation between intraoperatively administration of dexamethasone and survival in NSCLC patients after lung cancer resection. While patients given dexamethasone had better disease-free survival in the subgroup of anesthetic time less than 2 hours. Intraoperative administration of dexamethasone may improve overall survival in the subgroup of VATS. Our results indicate that intraoperative dexamethasone, commonly used for prevention of postoperative nausea and vomiting (PONV), do not augment cancer recurrence and affect overall survival in non-small cell lung cancer patients having lung cancer resection. However, intraoperative administration of systemic dexamethasone is probably favorable in the aforementioned populations.
Glucocorticoids (GCs), such as dexamethasone, can arrest growth or induce apoptosis in lymphocytes. In leukemia and lymphoma, dexamethasone is the cornerstone of treatment for all lymphatic cancers and hematopoietic malignancies. Moreover, dexamethasone performs a variety of functions, including preventing postoperative nausea and vomiting, reducing postoperative pain, anti-inflammation, antianaphylaxis, immunosuppression and so on[12, 24, 25]. The administration of dexamethasone during treatment of nonhematologic malignancy is at issue. The effect of dexamethasone on oncological outcomes has been investigated by another researchers. Obradovic MMS et al. reported that glucocorticoids increased the risk of breast cancer metastasis by activating glucocorticoid receptor. Similarly, immunosuppressive dose of dexamethasone might enhance prostate cancer progression. In rectal cancer patients with curative resection, there was an association between low-dose perioperative dexamethasone and poorer survival. On the contrary, glucocorticoids perform a beneficial effect in certain solid tumors. Perioperatively administration of dexamethasone may improve survival in pancreatic adenocarcinoma patients. A retrospective study noted that perioperatively dexamethasone had no effect on ovarian cancer recurrence. The aforementioned studies implied that dosage, timing and frequency of dexamethasone played a decisive role in different oncological outcomes. Histopathological type of tumor and primary site of tumor were equally important. As a consequence, further researches are wanted to verify the effect of dexamethasone on other cancer.
A few studies suggested the correlation between administration of dexamethasone and survival in non-small lung cancer patients with lung cancer resection. One study noted that NSCLC patients treated with lung cancer resection may get survival benefit from perioperatively administration of dexamethasone. A systematic analysis reported that glucocorticoids might have a deleterious effect in NSCLC patients. Another study indicated that dexamethasone was not associated with recurrence-free survival and overall survival after lung cancer resection for NSCLC patients. These results are inconsistent and inadequate, and more studies are necessary. Our study provides more evidence to verify the association between intraoperatively administration of dexamethasone and survival in NSCLC patients as well as in some certain subgroup populations.
Lack of correlation between intraoperatively administration of dexamethasone and survival may be associated with the following several factors. On one hand, two factors may facilitate favorable effect of dexamethasone on survival for NSCLC patients. Dexamethasone reduces stress response which has a detrimental influence on host immune function. In addition, dexamethasone can suppress proliferation of non-small cell lung cancer by inactivating estrogen. On the other hand, intraoperatively administration of dexamethasone augments the risks of cancer recurrence and metastasis through several possible ways. Dexamethasone depresses host immune defense system by inhibiting the function of natural killer cell (NK), which takes part in tumor cytotoxicity. Besides, low concentrations of dexamethasone not only induce proliferation of normal cells, but also induces proliferation of cancer cell in vitro, including glioma and astrocytoma. Meanwhile, dexamethasone, as a long half-life glucocorticoid, may remain stable for 36–72 hours in humans. Thus, the detrimental effects of dexamethasone might persist for a relatively long period of time in non-small cell lung cancer patients. As a consequence, these deleterious effects may be just right to counteract the favorable effects of dexamethasone to generate an overall neutral effect.
This study has some limitations. Firstly, sample size was relatively small. Our study consisted of 148 patients receiving intraoperative dexamethasone and 675 patients who were not given dexamethasone. After propensity score matching, there were only 206 patients in the non-DEX group and 103 patients in the DEX group. Secondly, we performed a propensity score matching analysis to decrease the potential confounding effect of each variable. But we failed to take into consideration those unknown confounding factors. Thirdly, the date of cancer recurrence could be inaccuracy and we may overestimate the date of cancer recurrence. Because relapse may occur before relapse was detected by imaging or histopathological examination. Moreover, our study couldn’t collect the details of intraoperative and postoperative opioids administration, so we couldn’t assess the effect of opioids on survival. Finally, we couldn’t avoid selection bias on account of retrospective analysis. This could be an important reason that we found no association between intraoperative dexamethasone and survival.
Our results show that there was no correlation between intraoperatively administration of dexamethasone and survival in NSCLC patients after lung cancer resection. However, we still don’t know whether the correlation between intraoperatively dexamethasone and survival is coincidental. The exact effects of intraoperative dexamethasone on non-small cell lung cancer patients with lung cancer resection should be verified in further researches. An adequately powered randomized control trial (RCT) that has strict inclusion criteria and exclusion criteria will verify the effect of intraoperative dexamethasone on disease-free survival and overall survival for non-small cell lung cancer patients.