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

Figures & data

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 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 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.

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

Type of Cancer	Author (Year)	Type of Study	Intervention	Overall Survival	Recurrence-Free Survival
Breast	Sessler et al (2019)^Citation9	RCT	PVB-GA vs GA	No difference	No difference
Breast	Perez-Gonzalez (2017)^Citation59	SR (6 studies)	PVB-GA vs GA	No difference	1 study showed benefit of PVB-GA, 1 study showed negative impact of PVB-GA, 4 studies showed no difference
Multiple (Breast, prostate, gastroesophageal, and colorectal)	Ma (2014)^Citation90	MA (10 studies)	EA-GA vs GA	Not studied	No difference overall. No difference for colorectal alone. For prostate cancer, an increased survival with EA-GA was found.
Colorectal	Cummings (2012)^Citation61	Retrospective	EA-GA vs GA	No difference	Increased with GA-EA
Colorectal	Gottschalk (2010)^Citation62	Retrospective	EA-GA vs GA	Not studied	No difference
Colorectal	Gupta (2011)^Citation63	Retrospective	EA-GA vs Spinal vs GA	Increased for rectal cancer, no difference for colon cancer	Not studied
Colorectal	Day (2012)^Citation64	Retrospective	EA-GA vs Spinal vs GA	No difference	No difference
Colorectal	Kim (2016)^Citation65	RCT	LA wound infiltration vs IVPCA	Not studied	No difference
Colorectal liver metastasis	Zimmitti (2016)^Citation66	Retrospective	EA-GA vs GA	No difference	Increased with EA-GA
Colorectal liver metastasis	Gao (2019)^Citation67	Retrospective	EA-GA vs GA	Not studied	Increased with GA
Gastroesophageal	Perez-Gonzalez (2018)^Citation69	SR (6 studies)	EA-GA vs GA	3 studies showed benefit of EA-GA	1 study showed benefit of EA-GA
Glioblastoma	Zheng (2017)^Citation70	Retrospective	Scalp block vs No block	Not studied	Increased with scalp block
Glioblastoma	Cata (2018)^Citation71	Retrospective	Scalp block vs No block	No difference	No difference
Hepatocellular	Lai (2012)^Citation72	Retrospective	EA vs GA	Not studied	Increased with GA
Multiple (Intra-abdominal, Prostate and Colorectal)	Cakmakkaya (2014)^Citation89	MA (4 RCTs subanalysis studies)	EA-GA vs GA	No difference	No difference
Laryngeal and Hypopharyngeal	Merquiol (2013)^Citation73	Retrospective	EA-GA vs GA	Increased with EA	Increased with EA
Lung	Cata (2013)^Citation74	Retrospective	EA vs PCA vs EA-IVPCA	No difference	No difference
Lung	Lee (2017)^Citation75	Retrospective	EA vs PVB vs IVPCA	Increased with PVB than any other technique. EA and PCA were not different.	No difference
Melanoma	Schlagenhauff (2000)^Citation56	Retrospective	LA vs GA	Decreased with GA	Not studied
Melanoma	Gottschalk (2012)^Citation78	Retrospective	Spinal vs GA	No difference	Not studied
Ovarian	De Oliveira (2011)^Citation79	Retrospective	EA (intra and postop)-GA vs Postop-only EA vs IVPCA	Not studied	Increased with EA-GA
Ovarian	Lin (2011)^Citation80	Retrospective	EA vs GA-IVPCA	Increased with EA	Not studied
Ovarian	Capmas (2012)^Citation81	Retrospective	EA vs No EA	No difference	No difference
Ovarian	Lacassie (2013)^Citation82	Retrospective	EA vs No EA	No difference	No difference
Ovarian	Tseng (2018)^Citation83	Retrospective	EA vs IV-PCA	Increased with EA	Increased with EA
Ovarian	Zhong (2019)^Citation84	Retrospective	EA vs GA-IVPCA	No difference	Not studied
Ovarian	Elias (2015)^Citation85	Retrospective	EA-GA vs GA	Not studied	No difference
Multiple (Ovarian, Gastrointestinal, Prostate, Breast)	Grandhi (2017)^Citation86	MA (28 observational studies)	RA vs GA	No difference	No difference
Prostate	Lee (2015)^Citation87	MA (10 retrospective studies)	EA vs Opioid-based analgesia	Increased with EA	No difference

Abbreviations: EA, epidural anesthesia/analgesia; IV-PCA, intravenous patient-controlled analgesia; GA, general anesthesia; RA, regional anesthesia/analgesia; RCT, randomized-controlled trial; LA, local anesthetic; PVB, paravertebral block; MA, meta-analysis; SR, systematic review.

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

Type of Cancer	Author (Year)	Type of Study	Intervention	Overall Survival	Recurrence-Free Survival
Appendiceal (HIPEC)	Cata (2019)^Citation128	Retrospective	TIVA (Opioid-sparing) vs Inhalational-Opioid	No difference	No difference
Breast	Sessler (2019)^Citation9	RCT subanalysis	TIVA vs Inhalational	No difference	No difference
Breast	Lee (2016)^Citation129	Retrospective	TIVA vs Inhalational	No difference	Increased with TIVA
Breast	Yoo (2019)^Citation130	Retrospective	TIVA vs Inhalational	No difference	No difference
Breast	Yan (2018)^Citation125	RCT (Not powered for OS or RFS)	TIVA vs Inhalational	No difference	No difference
Cholangiocarcinoma	Lai (2019)^Citation131	Retrospective	TIVA vs Inhalational	Increased with TIVA	TIVA group showed a decreased rate of metastasis.
Colorectal	Wu (2018)^Citation132	Retrospective	TIVA vs Inhalational (Desflurane-specific)	Increased with TIVA	Not studied
Esophageal	Jun (2017)^Citation133	Retrospective	TIVA vs Inhalational	Increased with TIVA	Increased with TIVA
Gastric	Zheng (2018)^Citation134	Retrospective	TIVA vs Inhalational	Increased with TIVA	Not studied
Gastric	Oh (2019)^Citation135	Retrospective	TIVA vs Inhalational	No difference	No difference
Glioblastoma	Cata (2017)^Citation136	Retrospective	Isoflurane ± Propofol vs Desflurane ± Propofol	No difference	No difference
Hepatocellular	Lai (2019)^Citation137	Retrospective	TIVA vs Inhalational (Desflurane-specific)	Increased with TIVA	Increased with TIVA
Lung	Oh (2018)^Citation138	Retrospective	TIVA vs Inhalational	No difference	No difference
Lung	Xu (2017)^Citation139	RCT (Not powered for OS or RFS)	TIVA vs Epidural/Inhalational	No difference	No difference
Multiple (Breast, Esophageal, Lung)	Yap (2019)^Citation140	MA (10 studies)	TIVA vs Inhalational	Increased with TIVA	Pooled data from 6 studies showed increased with TIVA
Multiple (Breast, Gastrointestinal, Gynecological, Sarcoma, Urologic, Other)	Wigmore (2016)^Citation6	Retrospective	TIVA vs Inhalational	Increased with TIVA	Not studied
Multiple (Breast, Gastrointestinal, Liver, Lung)	Hong (2019)^Citation141	Retrospective	TIVA vs Inhalational	No difference	Not studied
Multiple (Breast, Gastrointestinal, Urologic, Glioma, Lung)	Jin (2019)^Citation142	MA (12 studies)	TIVA vs Inhalational	Pooled effects favor TIVA, not individualized by cancer type.	Pooled data from 5 studies on recurrence showed no significant difference. TIVA is favored in breast cancer. Pooled data specifically on RFS on 3 studies favor TIVA.
Ovarian	Elias (2015)^Citation85	Retrospective	Inhaled Anesthesia (Sevoflurane/Desflurane) vs TIVA	Not studied	Increased with desflurane

Abbreviations: RCT, randomized controlled trial; HIPEC, hyperthermic intraperitoneal chemotherapy; TIVA, total intravenous anesthesia; OS, overall survival; RFS, recurrence-free survival; MA, meta-analysis.

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