The meta-analysis showed an association between GEA and ovarian cancer patients’ overall survival. The same result was found in the subgroup analysis of EIP. Our results from the comprehensive meta-analysis coincided with most, even not all, results from recently reported studies [5, 19]. According to the COX regression analysis of included studies, the long-term prognosis of ovarian cancer patients after surgery was also related to tumor stage, whether the tumor reduction operation was complete, as showed up the outcomes part. The results of these studies are crucial in future prospective studies investigating the intriguing prospect of appropriate perioperative GEA modifying cancer recurrence.

However, the outcomes of GEA vs GA regarding TTR and EIP vs GA on TTR exhibited instability. Epidural anesthesia as an intervention shows advantages in improving overall survival (OS) in ovarian cancer patients, whereas its effect on improving TTR remains unclear, similar to the impact of combined epidural-general anesthesia on long-term survival in colorectal cancer and other kinds of cancer patients [20,21,22]. The reason for this discrepancy could be attributed to the fact that overall survival has a clearly defined time point, whereas TTR depends on the timing of patient follow-up visits, making it difficult to precisely define. Moreover, the definition of TTR is not standardized. The appearance of new lesions on imaging or an increase in CA125 levels can both be used as endpoints for defining TTR. However, the magnitude of the increase in CA125 levels is uncertain, and there is also inconsistency in imaging resolution and the diagnostic proficiency of physicians. Furthermore, all articles are retrospective ones, and most studies did not perform propensity score matching when comparing two groups. Compared to randomized controlled studies, they lack strong credibility, which is also a reason for the instability of the results. Consequently, when pooling results using TTR as an outcome, the stability of the outcome becomes uncertain.

Two articles included in this study, Lacassie 2013 and Tseng 2018, both mixed the two interventions of EIP and EP for statistical analysis, but the results were not consistent. Comparison of the two interventions (Table 4): epidural analgesic was 0.1–0.5% bupivacaine with or without opioids in Lacassie 2013, duration was “All epidural catheters remained in place for at least 48 h”. The article did not mention the respective proportions of epidural anesthesia and analgesia; the epidural analgesic in Tseng 2018 was 0.05% bupivacaine, with or without opioids, and most patients can receive oral analgesia, epidural analgesia was discontinued on medication for up to 14 days, and the rate of epidural anesthesia was more than epidural analgesia that of started postoperatively (89% vs 11%). Study populations were similar (Lacassie 2013: stage IIIC and IV, Tseng 2018: stage IIIB and IV). In conclusion, it appears that the reason Tseng 2018 obtained positive results is that there was a higher proportion of participants who received EIP compared to those who received EP, and the duration of epidural analgesia was longer. This result suggests that intraoperative epidural medication, which reduces intraoperative stress and intraoperative opioid consumption, may be beneficial to the survival prognosis of such patients, but not epidural analgesia. It is consistent with other studies [23, 24].

In general, epidural anesthesia has positively effect on the prognosis of ovarian cancer patients after cytoreductive surgery. We all know that both surgery and anesthetics may suppress the body’s immune system, causing cancer to grow and spread. The mechanisms might be explained as follows. Initially, the body’s immune function can be inhibited by opioid analgesics in a dose-dependent manner, and affect both cellular and humoral immunity when they act directly on immune cells, the hypothalamic-pituitary–gonadal axis and sympathetic activity [25], especially on NK cell activity. Morphine, alfentanil, remifentanil, fentanyl and sufentanil not only suppress NK cell activity, but change T cell differentiation. Opioids usually inhibit T-lymphocyte proliferation [26]. Furthermore, investigations have demonstrated that opioid analgesics can promote tumor angiogenesis, which can drive tumor growth and invasion [27]. Volatile anesthetics also affect immune response. Halothane decreases NK cell activity and increases expression of hypoxia-inducible factor 1α (HIF-1α) [28, 29], and sevoflurane induces T-lymphocyte apoptosis and upregulates HIF-1α expression [29, 30]. Isoflurane, sevoflurane, and desflurane have also been demonstrated to up-regulate vascular endothelial growth factor A (VEGF-A), matrix metalloproteinase 11(MMP11), transforming growth factor 1 (TGF-1) and chemotaxis in investigations. The role of chemokine receptor-2 (CXCR-2) and other cell signal transduction and protein expression related to tumor metastasis directly promotes the metastasis of ovarian cancer tumor cells [31]. However, local anesthetics play a positive role. For example, ropivacaine restrained ovarian cancer cell stemness and accelerated cell ferroptosis by inactivating PI3K/AKT signaling pathway [32]. Epidural anesthesia reduces the dosage of opioid drugs and inhalational anesthetics, thereby minimizing their negative effects while also exerting a beneficial effect in inhibiting tumor recurrence. In summary, these findings broadly support the association between epidural anesthesia and the longer survival of ovarian cancer patients.

Therefore, we boldly predict that whether the use of intrathecal (IT) infusion of local anesthetic, like bupivacaine, to treat patients with chronic refractory pain has fewer adverse reactions and prolongs the survival time compared with opioid drugs such as morphine alone. Dose escalation with chronic IT opiates has been a cause for concern [33]. Research has demonstrated that local anesthetics, such as bupivacaine, exhibit a synergistic interaction with opiates [34]. From a logical standpoint, it is believed that effective pain management positively contributes to extending the survival time of patients. However, at present, there is a lack of research evidence to support this claim. Further research is needed in this area.

Of course, there are different meta-analysis conclusions. Epidural anesthesia combined with general anesthesia reduces tumor recurrence and metastasis in patients with prostate cancer but not with colorectal cancer [35]. The above findings may be attributed to epidural anesthesia having different effects on different tumors, which may be related to different pathologies and metastases. Another factor that we discussed for this effect was the duration of surgery. Ovarian cancer cytoreductive surgery often requires joint operation of several departments, the operation scope is large and time-consuming. There may be a difference between patients undergoing epidural anesthesia for colorectal cancer and prostate cancer due to the longer operative time for the latter [36, 37]. Therefore, we believe that epidural anesthesia’s effect is statistically significant only for time-consuming and traumatic operations. However, large-scale clinical studies involving different cancer types are needed to investigate the potential influence of the anesthetic technique used during surgery on cancer-related outcomes.

The tumor stage in ovarian cancer patients has a significant impact on prognosis [38]. Higher stages of ovarian cancer (such as stage III and IV) are associated with a worse prognosis compared to lower stages (stage I and II). Higher stages indicate more extensive spread of the tumor beyond the ovaries, which makes treatment more challenging and increases the risk of recurrence.

Regarding the impact of residual nodules during cytoreductive surgery for ovarian cancer cells, it has been observed that smaller residual nodules are associated with longer recurrence-free intervals and improved overall survival rates [39]. This suggests that achieving complete tumor removal during surgery is crucial for better outcomes.

However, our conclusions should also be interpreted carefully, as more randomized controlled trials are needed to verify them.

All the cited articles omitted any mention of total opioid use, thereby rendering it arduous to quantify the impact of opioids, which hold a significant role in general anesthesia. The effect of inhalation anesthetics on the prognosis of ovarian cancer is not discussed in detail in this study.

The studies incorporated in this analysis were all retrospective and not randomized controlled trials. Although we employed the Newcastle–Ottawa Scale (NOS) to assess the potential bias within these cohort studies, yielding outcomes of high quality, there still exist uncontrollable variables, such as substantial discrepancies in the number of research participants between groups. Anesthesiologists exhibited a preference for epidural anesthesia in patients suitable for complete debulking, which inevitably influenced the outcomes. Furthermore, the FIGO stage of patients in each study exhibited inconsistency, consequently impacting the survival time.

Despite the absence of RCTs among the articles encompassed in this meta-analysis, the intervention of epidural anesthesia and analgesia, after accounting for numerous confounding factors, still merits recommendation and support. We eagerly await large-scale randomized controlled trials that will furnish further elucidation.