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Review

Anesthesia Options and the Recurrence of Cancer: What We Know so Far?

ORCID Icon, ORCID Icon, &
Pages 57-72 | Published online: 07 Jul 2020

Abstract

Surgery is a critical period in the survival of patients with cancer. While resective surgery of primary tumors has shown to prolong the life of these patients, it can also promote mechanisms associated with metastatic progression. During surgery, patients require general and sometimes local anesthetics that also modulate mechanisms that can favor or reduce metastasis. In this narrative review, we summarized the evidence about the impact of local, regional and general anesthesia on metastatic mechanisms and the survival of patients. The available evidence suggests that cancer recurrence is not significantly impacted by neither regional anesthesia nor volatile or total intravenous anesthesia.

Introduction

Cancer is a major cause of mortality worldwide with an estimated 9.6 million deaths per year.Citation1 Lung, colorectal, stomach and liver are the most common types of cancer and account for nearly half of cancer-related deaths. By 2040, it is estimated that there will be approximately 30 million new cases of cancer.Citation1 It is projected that a large proportion of patients will need surgery for tumor resection despite rapid and substantial advances in treatments, including chemotherapy, targeted therapy, radiotherapy, and immunotherapy.

Surgery causes the local and systemic release of inflammatory mediators and promotes high levels of angiogenesis. Also, surgery is associated with high concentrations of circulating catecholamines and immunosuppression that can last for days or weeks postoperatively, making this a period of high vulnerability for complications and tumor progression.Citation2,Citation3 Some evidence suggests that certain anesthetics or anesthesia techniques may also affect the growth of the so-called minimal residual disease.Citation4,Citation5 Total intravenous anesthesia (TIVA) with propofol was associated with prolonged overall survival in patients with metastatic and non-metastatic cancers.Citation6 Local anesthetics and regional anesthesia can also modify cancer progression by limiting inflammation, immunosuppression, and angiogenesis.Citation4,Citation7,Citation8 However, a recently published randomized controlled trial concluded that compared to sevoflurane-based general anesthesia, regional anesthesia did not improve the survival nor reduced recurrences after breast cancer surgery.Citation9

Investigators have hypothesized that the technique of general anesthesia (total intravenous vs volatile-based or regional anesthesia) has a significant impact on caner progression. In this narrative review, we will discuss the evidence of the impact of different anesthetics and anesthesia techniques on metastatic progression after surgery. Our work will include current basic, translational and clinical studies addressing the effects and association between different anesthetics and cancer progression.

Perioperative Metastasis Formation

The growth of metastatic colonies outside the primary tumor is a multi-step process. Colonization of distant sites by circulating tumor cells (CTCs) is a rate-limiting step during the metastatic process. In general, it is well accepted that metastasis may be part of a dominant clonal subpopulation that originated within the primary tumor.Citation10 By virtue of tumor-secreted factors and tumor-secreted exosomes, the microenvironment of distant organ sites is modified into prometastatic niches that contain recruited stem cells and stromal cells.Citation11

A critical event in the metastasis process is the epithelial-mesenchymal transition (EMT) that CTCs undergo to increase mobility and invasiveness (). The EMT process is orchestrated by transcription factors (ie, Snail, Slug, Twist, and Zeb1) that, in turn, respond to extracellular molecular signals occurring in the nearby tumor stroma such as inflammation.Citation12 Once in the bloodstream, CTCs interact with other cells, including platelets and lymphocytes. Platelets can provide shelter to CTCs and hide them from lymphocytes such as natural killer (NK) cells. Also, activated platelets can release soluble mediators such as transforming-growth factor beta (TGF-β), platelet-derived growth factor (PDGF), and adenosine triphosphate (ATP). These factors are known to suppress the killing activity of NK cells and enhance vascular permeability.Citation12 Once CTCs extravasate via transendothelial migration (TEM), they find the extracellular tissue stroma where they may reside and proliferate. Some of those cells in the new forming metastatic colony retain features of cancer stem cells (CSC), which have tumor-initiating ability and can drive colony expansion.Citation12

Figure 1 Perioperative events that influence tumor metastasis and cancer recurrence. Surgery for tumor resection triggers the release of catecholamines, immunosuppression, and angiogenesis. It has been speculated that these factors facilitate epithelial-mesenchymal transition (EMT) and promote a conducive microenvironment (tumor niche) for cells to migrate, invade and proliferate.

Figure 1 Perioperative events that influence tumor metastasis and cancer recurrence. Surgery for tumor resection triggers the release of catecholamines, immunosuppression, and angiogenesis. It has been speculated that these factors facilitate epithelial-mesenchymal transition (EMT) and promote a conducive microenvironment (tumor niche) for cells to migrate, invade and proliferate.

It is speculated that micrometastasis or dormant colonies are contained by immune surveillance or by the lack of supporting factors that can sustain cell proliferation.Citation13 Thus, the transition from single cell or colony of cells to micrometastasis to clinically relevant metastasis can take months to years.Citation12,Citation14 Remarkably, surgery can facilitate the homing of CTCs and growth of micrometastasis by releasing cytokines, angiogenic factors, and catecholamines. In mice, surgery-induced inflammation promoted the outgrowth of T cell restricted distant tumors by mobilizing myeloid cells and recruiting tumor-associated macrophages.Citation15

Neutrophil extracellular traps (NETs) has been recognized as a mechanism that facilitates colonies formation. NETs are web-like structures formed by DNA fragments and proteins that can sequester CTCs.Citation16,Citation17 In mice, surgery promoted NETs and micrometastasis. When mice were treated daily with DNAase after surgery, it reduced tumor growth.Citation16 Circulating neutrophils entrapped in clumps formed by platelets or in the extracellular matrix can also provide a conducive environment for CTCs to survive by further suppressing the activity of NK cells.Citation12

Several studies have shown a decrease in the number and function of circulating NK cells after surgery.Citation3 Subsequently, investigations revealed that surgery-induced reduction in circulating NK killing activity could promote metastasis ().Citation18 Interestingly, it has been demonstrated that the transcriptome profile of circulating NK cells is significantly different from NK cells located in metastasis suggesting that the role of NK cells in the micrometastatic niche during surgery might be different from those circulating.Citation19

It is worth considering that the metastatic process is also affected by factors including the use, timing, and completion of adjuvant therapies (ie, chemotherapy, radiation, and immunotherapies). For instance, it is now well understood that for some malignancies, delaying the return to oncological therapies after surgery has a significant impact on patients’ survival.Citation20 Another important factor associated with cancer progression is the occurrence of complications in the postoperative period and perioperative blood transfusions.Citation21,Citation22 Therefore, it has been suggested that patients undergoing cancer surgery should be evaluated and treated by a multidisciplinary team dedicated to assess modifiable risks and propose a coordinated plan of measures (ie, anemia treatment) tailored to reduce postoperative complications and accelerate recovery.Citation23

In the following sections, we will discuss how anesthetics may or may not interfere with the process involved in the metastatic process and metastatic cancer progression.

Local Anesthetics

Local anesthetics can act on several steps of the metastatic process (). The administration of intravenous lidocaine (1.5 mg/kg followed by infusion of 2 mg/kg) under sevoflurane anesthesia reduced postoperative lung metastasis by decreasing serum concentrations of the metalloproteinase (MMP)-2 in a murine surgical breast cancer model.Citation24,Citation25 It was speculated that changes in MMP-2 resulted in a reduced ability of CTCs to form metastasis.Citation24 Local anesthetics also impair the movement of malignant cells in vitro.Citation26,Citation27 As an example, ropivacaine inhibited migration and invasion of esophageal and colorectal cancer cells.Citation26 Although, the anti-metastatic effects of ropivacaine in esophageal cancer cells were independent of voltage-gated sodium channel (VGSCs) blockade and mediated by inhibition of RhoA, Rac1 and Ras, they were dependent on Nav1.5 blockade in colorectal cancer cells.Citation26,Citation28

Figure 2 Several mechanisms have been associated with the anti-metastatic effects of local anesthetics. Intracellular they inhibit signaling events linked to angiogenesis, migration, and invasion.

Abbreviation: VEGF, vascular endothelial growth factor.
Figure 2 Several mechanisms have been associated with the anti-metastatic effects of local anesthetics. Intracellular they inhibit signaling events linked to angiogenesis, migration, and invasion.

VGSCs regulate the metastatic activity of cancer cells. These channels are located in the cell membrane, in particular in cellular structures called invadopodia, which are essential for degrading the extracellular matrix.Citation29 In the invadopodia, VSGCs promote polymerization of actin filaments via Src signaling.Citation29 In vitro studies demonstrate that downregulation of VSGCs via shRNA inhibits tumor invasion by blocking the invadopodia.Citation30

Local anesthetics have shown anti-angiogenic effects. Lidocaine (30 mg/kg) inhibited tumor growth in mice bearing melanoma tumors by inducing apoptosis in endothelial cells.Citation31 In these cells, lidocaine suppressed VEGF-increased phosphorylation of VEGF receptor 2.Citation31 Similarly ropivacaine induced apoptosis on tumor-associated endothelial cells by inducing mitochondrial dysfunction.Citation32 Local anesthetics also modulate inflammation (). Notably, lidocaine reduced pro-inflammatory cytokines [ie, tumor necrosis factor (TNFα) and interleukin-6 (IL-)] in a mice model having breast cancer surgery.Citation33 Furthermore, lidocaine and ropivacaine inhibited migration and invasion of lung cancer cells by inhibiting TNFα- induced phosphorylation of Src and reducing the expression of ICAM-1 (glycoprotein essential for cellular adhesion).Citation34,Citation35 A reduction in the concentrations of pro-inflammatory concentrations is observed in humans receiving intravenous lidocaine during surgery.Citation36

Figure 3 Effect of local anesthetics on immune and inflammatory cells. Local anesthetics modulate the activity of different immune cells. They potentiate natural killer cells cytotoxicity, facilitate antigen presentation, and have shown to modulate the function of neutrophils, macrophages, and dendritic cells.

Abbreviations: LA, local anesthetics; TNF, tumor necrosis factor.
Figure 3 Effect of local anesthetics on immune and inflammatory cells. Local anesthetics modulate the activity of different immune cells. They potentiate natural killer cells cytotoxicity, facilitate antigen presentation, and have shown to modulate the function of neutrophils, macrophages, and dendritic cells.

Increased vascular permeability, as it occurs during periods of exaggerated inflammation, facilitates TEM and can promote the implant of metastatic cells. The intravenous administration of lidocaine (1 and 3 mg/kg) to mice inoculated with LPS significantly reduced lung permeability. The postulated mechanisms included a reduction of inflammatory cytokines (TNFα, IL-6, and MCP-1) and impairment of antigen presentation, a process done by dendritic cells (DC) ().Citation37,Citation38 As an example, lidocaine inhibited the expression of proinflammatory cytokines in bone marrow-derived DC that were stimulated with LPS.Citation38

Inflammation also induces DNA methylation, a mechanism linked with metastasis.Citation39,Citation40 Local anesthetics such as lidocaine and ropivacaine induce, in vitro, DNA demethylation in breast cancer cells which correlates with the overexpression of the tumor suppressor genes (RARB2 and RASSF-1A).Citation41Citation43 Lidocaine also induces modulation of microRNAs.Citation44Citation47 Treatment of lung cancer cells with 8 mM of lidocaine significantly increased the expression of miR-539, which then induced the downregulation of the epidermal growth factor receptor (EGFR) and suppressed migration and invasion.Citation45 The intravenous injection of lidocaine (1.5 mg/kg) to mice bearing retinoblastoma caused significant tumor reduction by inducing the expression of miR520a-3p and inhibiting EGFR.Citation46 MicroRNAs are also involved in chemo-resistance. Lidocaine, in vitro, inhibited the expression of miR-21 and sensitized chemo-resistant lung cancer cells to cisplatin.Citation48 On the other hand, lidocaine by inducing the expression of miR-493 downregulated the transcription factor Sox-4, which ultimately sensitized melanoma cells to the effect of 5-fluorouracil.Citation49

Another described mechanism that can contribute to the anti-metastatic effects of local anesthetics include the induction of oxidative stress, and a reduced formation of MMP-9.Citation30,Citation34,Citation35,Citation50,Citation51 Local anesthetics act on different components of the innate and adaptive immune system has been investigated experimentally and in humans. We demonstrated that lidocaine in clinically relevant concentrations increased the in vitro cytotoxic activity of NK cells by stimulating the release of perforins ().Citation52,Citation53 In humans with abdominal pain, an intravenous injection of 1 mg/kg of lidocaine preserves the count and function of circulating NK cells.Citation54 Few studies have investigated the impact of intravenous lidocaine on lymphocytes counts or function during and after oncologic surgery.Citation54,Citation55 Wang et al conducted a randomized controlled trial (RCT) in women having a radical hysterectomy and compared the effects of lidocaine versus placebo on peripheral blood lymphocytes. The postoperative proliferative rate of lymphocytes was higher in patients treated with lidocaine.Citation55 The authors speculated that lidocaine protected lymphocytes by preserving the IFN-g/IL-4 ratio and by decreasing inflammation, as demonstrated by lower circulating concentrations of the high mobility group box-1 protein.Citation55 Similarly, patients with abdominal pain had a preserved CD4/CD8 ratio, and normal T and B cell counts after injection of 1.5 mg/kg of lidocaine.Citation54

Local (Infiltration or Intravenous) vs General Anesthesia: Human Studies

To date, there is no strong evidence from human studies indicating that local anesthesia modifies oncologic outcomes after cancer surgery (). Schalengenhauff et al included 4329 patients with melanoma and showed that the use of general anesthesia was associated with a decreased survival rate.Citation56 A more recent retrospective study suggests that tumescent local anesthesia, in comparison to general anesthesia, is associated with longer metastasis-free survival also after melanoma surgery. However, overall and disease-free survival were not affected.Citation57

Table 1 Summary of Clinical Studies, Systematic Reviews and Meta-Analysis on the Impact of Regional Anesthesia/Analgesia in Cancer Outcomes

Zhang et al recently assessed the impact of intravenous lidocaine on cancer progression. The authors reported that the intraoperative use of lidocaine was associated with longer overall survival in patients undergoing pancreatic cancer surgery.Citation58 Several randomized controlled trials are being conducted in patients with breast (NCT01204242; NCT01916317), pancreatic (NCT0408278), lung (NCT04074460) and colorectal (NCT04074460) cancers.

Regional vs Opioid-Based Analgesia: Humans Studies

Since 2008 there has been an increase in human studies testing the impact of regional anesthesia on cancer recurrence or recurrence-free survival after surgery.Citation9,Citation56,Citation59Citation89 The findings are controversial.Citation8,Citation59,Citation90 However, a recent RCT could not confirm the anti-cancer effects of regional anesthesia in women undergoing breast cancer surgery.Citation9 Patients were randomized to either regional anesthesia (preferentially paravertebral block) with propofol sedation or sevoflurane/opioid-based general anesthesia.Citation9 It can be speculated that regional anesthesia probably did not produce a robust immunomodulatory or anti-inflammatory effect and/or, the concentrations of local anesthetics in micrometastatic niches may not have been high enough to produce significant effects.Citation91Citation93 In line with this notion, Kim et al concluded that continuous local wound infiltration did not impact one-year recurrence rate after colorectal cancer surgery despite a statistically significant improvement in NK cell function postoperatively.Citation65 Another factor was the short-term exposure to the intervention. Perioperative immune suppression and inflammation can last beyond the “protective” effects of regional anesthesia. Our group demonstrated in patients having major oncologic surgery, the serum IL-6 levels do not return to preoperative concentrations even two weeks after surgery.Citation94 Furthermore, the immune “protective” effects attributed to regional anesthesia in sub-studies of Sessler’s trial indicate that such benefits were not clinically relevant.Citation95,Citation96 Other studies have been designed to test whether regional anesthesia can improve survival or reduce recurrence after bladder (NCT:03597087), non-small cell lung cancer (NCT02840227), colorectal (NCT02786329), and pancreas (NCT03245346).

In summary, the available evidence indicates that the impact of regional anesthesia on cancer recurrence might be negligible or not existent. It remains unknown whether perioperative intravenous lidocaine infusion has any impact on cancer progression.

General Anesthetics and Cancer Progression

Volatile Anesthetics

General anesthetics modify intracellular signaling mechanisms involved in metastasis. Isoflurane (1%-2%) increases migration and invasion of lung cancer cells by promoting Akt/mTOR activation and by promoting the release of MMPs.Citation97 In ovarian cancer cells, two-hour exposure to isoflurane (1.7 MAC), sevoflurane (1.7 MAC), or desflurane (1.7 MAC) stimulated the mRNA expression of VEGF-A, CXCR2, TGF-β and MMP-11, which correlated with increased cell migration.Citation98 Also, in ovarian cancer cells, isoflurane (2%) increased the release of VEGF, angiopoietin-1 and MMP-2, and 9.Citation99 Sevoflurane (3.6%) stimulated the metastatic potential of renal cancer cells and induced their chemo-resistance to cisplatin. These pro-metastatic effects were linked to an increase in the expression of TGF-B1, TGF-BRII and downregulation of Smad3.Citation100 In a melanoma mice model, isoflurane (1.3 MAC) anesthesia promoted pulmonary metastasis.Citation101

As mentioned previously, platelets may play a critical role in CTCs’ ability to survive in the bloodstream and attached the endothelium. Lung cancer cells co-cultured with platelets obtained from patients anesthetized with sevoflurane or isoflurane showed increased invasive properties compared to cancer cells incubated with control platelets.Citation102 Similarly, the culture of colorectal or breast cancer cells with serum obtained from patients receiving sevoflurane anesthesia promoted cell survival in comparison to the serum from propofol-treated patients.Citation103,Citation104

Volatile anesthetics can also impair the immune surveillance system. In animals, volatile anesthetics inhibit the function of NK cells, which correlates with an increased metastatic burden.Citation105 A reduction in the expression of the adhesion molecule leukocyte-associated antigen-1 and decrease in cell-to-cell contact with their target cancer cells has been implicated in the suppressive effects of isoflurane and sevoflurane on NK cells’ activity.Citation106 Interestingly, Meier et al suggested that the impact of volatile anesthetics such as isoflurane on the immune system are sex-depended.Citation107 For instance, when male mice were treated with isoflurane, the author observed not only faster tumor growth compared to controls but also faster tumor growth compared to female counterparts.Citation107 The investigators demonstrated that an immune-mediated mechanism was implicated in their findings since melanoma growth was absent in mice lacking functional T and B cells.Citation107

In vitro and animal studies have also demonstrated that general anesthetics may have anti-metastatic effects.Citation108,Citation109 High concentrations (5% and 10%) of sevoflurane inhibited migration and invasion of osteosarcoma cells, which was associated with the inhibition of EMT markers, including fibronectin and N-cadherin.Citation108 Similarly, sevoflurane (4.1%) inhibited glioma cell migration by inducing the expression of miR-124-3p and suppressing ROCK signaling.Citation109 Colorectal cancer cells also exposed to 1% of sevoflurane showed impaired migration and invasion; an effect that was mediated by inhibition of both, miR-203 expression and ERK signaling.Citation110 Under in vitro hypoxic conditions, sevoflurane (3.5%) suppressed the ability of lung cancer cells to migrate and invade the extracellular matrix by inhibiting the expression of (hypoxia-inducible factor) HIF-1α, which resulted in low levels of XIAP and survivin.Citation111 However, Gallyas et al could not demonstrate that isoflurane influenced the expression of HIF-1α in renal cancer cells.Citation112

Propofol

Propofol is the most common hypnotic used for TIVA. Most in vitro and in vivo animal studies indicate that propofol has significant anti-metastatic effects.Citation113,Citation114 One of the proposed mechanisms is the downregulation of the STAT3/HOTAIR signaling pathway, which suppresses transcription factors Slug and HIF-1α and induces silencing of the NET1 gene; all changes associated with decreased migration and invasion in cancer cells. A second mechanism involves the upregulation of miR-124-3p.1, miR-135b, miR-361, miR-410-3p, miR-328, and lncRNA DGCR5. A consequence of those epigenetic changes is in vitro inhibition of EMT, which correlates with low levels of N-cadherin and MMPs.Citation113

Adhesion molecules located on the surface of endothelial cells are needed to initiate TEM. HUVEC cells treated with different concentrations (5, 25, and 50 µM) of propofol showed low levels of the adhesion molecules E-selectin, VCAM-1, and ICAM-1. These changes in the expression of the adhesion molecules correlated with a reduction in the expression of HIF-1α, and inhibition of Akt and CaMKII phosphorylation.Citation114 Propofol also has anti-angiogenesis effects as demonstrated in experiments in which it suppressed the invasion of endothelial cells and vessel formation.Citation115

The proposed mechanisms behind the anti-angiogenic effects of propofol include the downregulation of S100A4 in endothelial cells and inhibition of the release of VEGF from cancer cells.Citation115,Citation116 Sen et al conducted an RCT to investigate the effect of propofol in combination with regional analgesia (in comparison to sevoflurane anesthesia) on serum concentrations of VEGF in patients having lung cancer surgery.Citation117 Patients receiving sevoflurane had significantly higher concentrations of VEGF.Citation117 Lastly, a proteomic analysis from head and neck cancers demonstrated that the tumors from patients who received sevoflurane anesthesia had higher expression HIF-2α and phosphorylated p38 MAPK in comparison to those receiving propofol.Citation118

Propofol can protect against immunosuppression by promoting cytotoxicity activity of NK cells, decreasing pro-inflammatory cytokines and inhibiting prostaglandin E2 (PGE2) and cyclooxygenase (COX) activity. In vitro, propofol stimulated the function and triggered the proliferation of NK cells obtained from healthy subjects and patients with cancer. Such effect on NK cells has been linked to an increase in the expression of granzyme B, IFNγ, and activating surface receptors (CD16, NKp30, NKp44, and NKG2D) as well as a reduction in the formation of PGE2.Citation119Citation121 The beneficial effect of propofol in tumor metastasis has been demonstrated in animals. When rats having surgery were anesthetized with propofol the function of NK cells remained unchanged and metastatic formation was lower than animals receiving volatile anesthetics.Citation105

In women undergoing breast or cervical cancer surgery, the use of propofol for TIVA in combination with regional anesthesia increased the number of NK and T helper cells in the primary tumor tissue and it was associated with significantly less lymphopenia.Citation96 Similar findings were observed in circulating lymphocytes of surgical patients with tongue cancer who received TIVA in comparison to sevoflurane.Citation122,Citation123 In contrast two independent groups of investigators, did not observe any significant changes cytokines (IL-6, IL-10, and IL-12 TGF- β) and in regulatory T cell cluster differentiation in women randomized to have breast cancer surgery under TIVA or sevoflurane general anesthesia.Citation124,Citation125 Similarly, inflammatory and immune scores were not different between patients who received general volatile versus TIVA for pancreatic cancer surgery or during cytoreduction with hyperthermic intraperitoneal chemotherapy.Citation126,Citation127

TIVA vs Volatile Anesthesia: Human Studies

Because of the anti-metastatic effects of TIVA in experimental conditions, there has been a growing interest in translating such beneficial effects into human studies.Citation6,Citation9,Citation85,Citation125,Citation128Citation142 The most extensive study was conducted by Wigmore et al, who retrospectively reviewed the impact of propofol-based general anesthesia vs volatile anesthesia in more than 7000 patients.Citation6 The authors reported a significant benefit in overall survival (HR 95% CI: 1.59, 1.30–1.95) in patients receiving propofol, even after adjusting for metastatic disease.Citation6 Several much smaller retrospective studies have demonstrated similar results (). In 2019, a meta-analysis of 10 retrospective studies concluded that the use of TIVA during cancer surgery is associated with significant improvements in recurrence-free and overall survival.Citation140 However, TIVA was associated with the most significant impact on the survival of patients with gastrointestinal malignancies.Citation140 Since the meta-analysis publication, two retrospective studies that included over 2000 patients did not show any association between TIVA and longer survival. Also, data from an RCT (TIVA vs sevoflurane anesthesia) of patients undergoing breast cancer surgery could not demonstrate differences in 2 years recurrence-free and overall survival. However, survival was not the primary endpoint of the study, which also lacked significant statistical power.Citation125 Our group investigated differences in survival in patients receiving different volatile anesthetics during glioblastoma surgery.Citation136 We observed no association between the use of desflurane or isoflurane in progression-free and overall survival.Citation136

Table 2 Summary of Clinical Studies Comparing TIVA vs Inhalational Anesthesia with Respect to Cancer Outcomes

The VAPOR-C trial (NCT04074460) is a RCT designed to investigate the effect of TIVA versus sevoflurane anesthesia on cancer recurrence in patients having surgery for lung or colorectal cancers.Citation143 The GA-CARES (NCT03034096) study is also a large clinical trial that will randomize patients to TIVA versus volatile anesthesia. The primary endpoint is all-cause mortality. Similar studies also being conducted in patients with pancreatic (NCT03447691) and breast (NCT02839668) cancers.

Conclusion

The perioperative period is a time of vulnerability for patients with cancer because it can promote the seeding of CTCs or the growth of micrometastatic tumors. The evidence from experimental laboratory studies demonstrates that anesthetics can modulate the metastatic behaviors of cancer cells. Anesthetics can also affect immune surveillance and inflammatory responses. Nevertheless, it is less clear about the actual clinical relevance of such changes in patients with cancer progression and patient’s survival.

We think that the strength of evidence is weak to recommend the use of TIVA to improve cancer-related or overall survival after oncologic surgery. As for regional anesthesia, there is strong evidence to conclude that the impact of paravertebral blocks does not influence cancer recurrence after breast cancer surgery. The findings of ongoing and future randomized control trials will bring light on whether an anesthetic technique modifies the long-term survival of patients who had surgery for cancer.

Disclosure

The authors declare no conflicts of interest.

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