The Role of Anesthetic Drugs and Statins in Prostate Cancer Recurrence: Starting at the Actual Knowledge and Walking through a New Paradigm

Simple Summary The relationship between an anesthetic procedure and cancer is a common theme of various research papers and systematic reviews. Prostate cancer, although it has a high incidence, is one example for which we currently do not know the possible benefits of anesthetic techniques. Our article starts from the current knowledge of the influence of anesthetic drugs and anesthetic techniques, and we propose where we should go in the future to elucidate its role in prostate cancer recurrence. Abstract Prostate cancer has become a major health problem in men. Its incidence is increasing as the average age of the affected population tends to be higher. Of all the possible treatments, surgery is the gold standard in its treatment. Surgery produces a deregulation in the immune system that can favour the development of distant metastases. Different anesthetic techniques have raised the hypothesis that different anesthetic drugs influence tumor recurrence and prognosis. Some mechanisms are beginning to be understood by which halogenated agents in cancer patients and the use of opioids may negatively affect patients. In this document, we group together all the available evidence on how the different anesthetic drugs affect tumor recurrence in prostate cancer.

[1]  A. Jemal,et al.  Cancer statistics, 2023 , 2023, CA: a cancer journal for clinicians.

[2]  S. Mashele,et al.  Prostate Cancer Review: Genetics, Diagnosis, Treatment Options, and Alternative Approaches , 2022, Molecules.

[3]  W. Hwang,et al.  Perioperative Inflammatory Response and Cancer Recurrence in Lung Cancer Surgery: A Narrative Review , 2022, Frontiers in Surgery.

[4]  Yuzhuo Wang,et al.  Molecular Landscape of LncRNAs in Prostate Cancer: A focus on pathways and therapeutic targets for intervention , 2022, Journal of experimental & clinical cancer research : CR.

[5]  Qi-Dong Xia,et al.  Statin Use and the Risk of Prostate Cancer Biochemical Recurrence Following Definitive Therapy: A Systematic Review and Meta-Analysis of Cohort Studies , 2022, Frontiers in Oncology.

[6]  A. Kaye,et al.  The Influence of Analgesic Modalities on Postoperative Cancer Recurrence , 2022, Anesthesiology and pain medicine.

[7]  Qingfeng Hu,et al.  The association of statin use and biochemical recurrence after curative treatment for prostate cancer , 2022, Medicine.

[8]  D. Berney,et al.  What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment , 2021, International journal of molecular sciences.

[9]  J. Cruz Mañas,et al.  Breast Cancer and Anaesthesia: Genetic Influence , 2021, International journal of molecular sciences.

[10]  S. Yun,et al.  Adjuvant Low-dose Statin Use after Radical Prostatectomy: The PRO-STAT Randomized Clinical Trial , 2021, Clinical Cancer Research.

[11]  Jing Yang,et al.  Propofol enhanced the cell sensitivity to paclitaxel (PTX) in prostatic cancer (PC) through modulation of HOTAIR , 2021, Genes & Genomics.

[12]  Chao Ma,et al.  Knockdown of lncRNA MIR4435-2HG and ST8SIA1 expression inhibits the proliferation, invasion and migration of prostate cancer cells in vitro and in vivo by blocking the activation of the FAK/AKT/β-catenin signaling pathway , 2021, International journal of molecular medicine.

[13]  D. Ma,et al.  Anesthetics may modulate cancer surgical outcome: a possible role of miRNAs regulation , 2021, BMC Anesthesiology.

[14]  W. Nahas,et al.  Opioids and premature biochemical recurrence of prostate cancer: a randomised prospective clinical trial. , 2021, British journal of anaesthesia.

[15]  T. Kinoshita,et al.  Links between Inflammation and Postoperative Cancer Recurrence , 2021, Journal of clinical medicine.

[16]  J. Hallas,et al.  Inhalation or total intravenous anaesthesia and recurrence after colorectal cancer surgery: a propensity score matched Danish registry-based study. , 2020, British journal of anaesthesia.

[17]  G. Sethi,et al.  LDL cholesterol promotes the proliferation of prostate and pancreatic cancer cells by activating the STAT3 pathway , 2020, Journal of cellular physiology.

[18]  A. Tsung,et al.  Surgical Stress Promotes Tumor Progression: A Focus on the Impact of the Immune Response , 2020, Journal of clinical medicine.

[19]  H. Hua,et al.  Complex roles of cAMP–PKA–CREB signaling in cancer , 2020, Experimental Hematology & Oncology.

[20]  M. Kao,et al.  Anesthesia and Long-Term Oncological Outcomes: A Systematic Review and Meta-analysis. , 2020, Anesthesia and analgesia.

[21]  A. Figueiredo,et al.  Statins Prevent Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy: A Single-center Retrospective Study with a Median Follow-up of 51.20 Months , 2020, Research and reports in urology.

[22]  K. Ng,et al.  Effect of perioperative regional anesthesia on cancer recurrence: A meta-analysis of randomized controlled trials. , 2020, International journal of surgery.

[23]  A. Lenis,et al.  The Role of Opioids and Their Receptors in Urologic Malignancy: A Review. , 2020, The Journal of urology.

[24]  V. Koyyala,et al.  The tumor microenvironment , 2020, Current Biology.

[25]  James D. Murphy,et al.  Associations among statins, preventive care, and prostate cancer mortality , 2020, Prostate Cancer and Prostatic Diseases.

[26]  Na Young Kim,et al.  Comparison of Biochemical Recurrence After Robot-assisted Laparoscopic Radical Prostatectomy with Volatile and Total Intravenous Anesthesia , 2020, International journal of medical sciences.

[27]  B. Herrera Imbroda,et al.  Anesthesia in Combination with Propofol Increases Disease-Free Survival in Bladder Cancer Patients Who Undergo Radical Tumor Cystectomy as Compared to Inhalational Anesthetics and Opiate-Based Analgesia , 2020, Oncology.

[28]  Gonghui Li,et al.  lncRNA UCA1 Functions as a ceRNA to Promote Prostate Cancer Progression via Sponging miR143 , 2019, Molecular therapy. Nucleic acids.

[29]  E. Mascha,et al.  Recurrence of breast cancer after regional or general anaesthesia: a randomised controlled trial , 2019, The Lancet.

[30]  D. Siemens,et al.  Anesthetic technique and oncological outcomes in urology: A clinical practice review. , 2019, Urologic oncology.

[31]  D. Ma,et al.  Influence of perioperative anaesthetic and analgesic interventions on oncological outcomes: a narrative review. , 2019, British journal of anaesthesia.

[32]  M. Kao,et al.  Comment on “Anesthetic technique and cancer outcomes: a meta-analysis of total intravenous versus volatile anesthesia” , 2019, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[33]  D. Ma,et al.  Can Anesthesia Influence Cancer Outcomes After Surgery? , 2019, JAMA surgery.

[34]  Ł. Łaczmański,et al.  Blood Circulating miRNAs as Cancer Biomarkers for Diagnosis and Surgical Treatment Response , 2019, Front. Genet..

[35]  B. Riedel,et al.  Anesthetic technique and cancer outcomes: a meta-analysis of total intravenous versus volatile anesthesia , 2019, Canadian Journal of Anesthesia/Journal canadien d'anesthésie.

[36]  Yue Yu,et al.  Propofol Reduced Mammosphere Formation of Breast Cancer Stem Cells via PD-L1/Nanog In Vitro , 2019, Oxidative medicine and cellular longevity.

[37]  Yang Wang,et al.  Propofol inhibits proliferation, migration and invasion of gastric cancer cells by up-regulating microRNA-195. , 2018, International journal of biological macromolecules.

[38]  Hu Zhao,et al.  Positive surgical margin is associated with biochemical recurrence risk following radical prostatectomy: a meta-analysis from high-quality retrospective cohort studies , 2018, World Journal of Surgical Oncology.

[39]  Sufang Jiang,et al.  Effects of propofol on cancer development and chemotherapy: Potential mechanisms , 2018, European journal of pharmacology.

[40]  J. Qian,et al.  Propofol Reversed Hypoxia-Induced Docetaxel Resistance in Prostate Cancer Cells by Preventing Epithelial–Mesenchymal Transition by Inhibiting Hypoxia-Inducible Factor 1α , 2018, BioMed research international.

[41]  Jai-hyun Hwang,et al.  Comparison of the effect of spinal anesthesia and general anesthesia on 5-year tumor recurrence rates after transurethral resection of bladder tumors , 2017, Oncotarget.

[42]  N. Terada,et al.  Effect of propofol on androgen receptor activity in prostate cancer cells , 2017, European journal of pharmacology.

[43]  Hailin Zhao,et al.  Local anesthetic bupivacaine induced ovarian and prostate cancer apoptotic cell death and underlying mechanisms in vitro , 2016, Scientific Reports.

[44]  Yan Qian,et al.  CD4+CD25+ regulatory T cells in tumor immunity. , 2016, International immunopharmacology.

[45]  A. Raval,et al.  Association between statins and clinical outcomes among men with prostate cancer: a systematic review and meta-analysis , 2016, Prostate Cancer and Prostatic Diseases.

[46]  J. Karam,et al.  Regional anesthesia/analgesia and the risk of cancer recurrence and mortality after prostatectomy: a meta-analysis. , 2015, Pain management.

[47]  G. Scheffer,et al.  A systematic review and meta-analysis of the ability of analgesic drugs to reduce metastasis in experimental cancer models , 2015, Pain.

[48]  G. Strichartz,et al.  Cancer surgery: how may anesthesia influence outcome? , 2015, Journal of clinical anesthesia.

[49]  M. Narita,et al.  κ Opioid receptor ligands regulate angiogenesis in development and in tumours , 2015, British journal of pharmacology.

[50]  T. Schlomm,et al.  Oncological long-term outcome of 4772 patients with prostate cancer undergoing radical prostatectomy: does the anaesthetic technique matter? , 2014, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[51]  M. Terris,et al.  Postoperative statin use and risk of biochemical recurrence following radical prostatectomy: Results from the SEARCH database , 2014 .

[52]  T. Murtola Statins and biochemical recurrence after radical prostatectomy – who benefits? , 2014, BJU international.

[53]  D. Schroeder,et al.  Outcomes After Radical Prostatectomy for Cancer: A Comparison Between General Anesthesia and Epidural Anesthesia with Fentanyl Analgesia A Matched Cohort Study , 2014, Anesthesia and analgesia.

[54]  P. Scardino,et al.  Association of anesthesia technique for radical prostatectomy with biochemical recurrence: a retrospective cohort study , 2014, Canadian Journal of Anesthesia/Journal canadien d'anesthésie.

[55]  A. Masson-Lecomte,et al.  Conditional survival after radical cystectomy for bladder cancer: evidence for a patient changing risk profile over time. , 2014, European urology.

[56]  R. Brown,et al.  Prostate cancer cell malignancy via modulation of HIF-1α pathway with isoflurane and propofol alone and in combination , 2014, British Journal of Cancer.

[57]  L. Bergkvist,et al.  The choice of anaesthetic—sevoflurane or propofol—and outcome from cancer surgery: A retrospective analysis , 2014, Upsala journal of medical sciences.

[58]  D. Schroeder,et al.  Association between neuraxial analgesia, cancer progression, and mortality after radical prostatectomy: a large, retrospective matched cohort study. , 2014, British journal of anaesthesia.

[59]  R. Salgia,et al.  Increased μ-opioid receptor expression in metastatic lung cancer. , 2014, British journal of anaesthesia.

[60]  Ji-Xin Cheng,et al.  Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. , 2014, Cell metabolism.

[61]  Christopher L. Wu,et al.  Spinal Anesthesia Does Not Impact Prostate Cancer Recurrence in a Cohort of Men Undergoing Radical Prostatectomy: An Observational Study , 2014, Regional Anesthesia & Pain Medicine.

[62]  D. Ma,et al.  Isoflurane, a Commonly Used Volatile Anesthetic, Enhances Renal Cancer Growth and Malignant Potential via the Hypoxia-inducible Factor Cellular Signaling Pathway In Vitro , 2013, Anesthesiology.

[63]  F. Burkhard,et al.  Epidural Analgesia during Open Radical Prostatectomy Does Not Improve Long-Term Cancer-Related Outcome: A Retrospective Study in Patients with Advanced Prostate Cancer , 2013, PloS one.

[64]  B. Beck-Schimmer,et al.  Volatile Anesthetics Reduce Invasion of Colorectal Cancer Cells through Down-regulation of Matrix Metalloproteinase-9 , 2012, Anesthesiology.

[65]  M. Srougi,et al.  Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer , 2012, BMC Urology.

[66]  R. Salgia,et al.  Overexpression of the &mgr;-Opioid Receptor in Human Non-Small Cell Lung Cancer Promotes Akt and mTOR Activation, Tumor Growth, and Metastasis , 2012, Anesthesiology.

[67]  T. Kessler,et al.  Potential Influence of the Anesthetic Technique Used during Open Radical Prostatectomy on Prostate Cancer-related Outcome: A Retrospective Study , 2010, Anesthesiology.

[68]  P. Boutros,et al.  Dysregulation of the mevalonate pathway promotes transformation , 2010, Proceedings of the National Academy of Sciences.

[69]  D. Schopflocher,et al.  Epidural anesthesia and cancer recurrence rates after radical prostatectomy , 2010, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[70]  E. Mascha,et al.  Anesthetic Technique for Radical Prostatectomy Surgery Affects Cancer Recurrence: A Retrospective Analysis , 2008, Anesthesiology.

[71]  Craig Murdoch,et al.  The role of myeloid cells in the promotion of tumour angiogenesis , 2008, Nature Reviews Cancer.

[72]  T. Tammela,et al.  Cholesterol-Lowering Drugs and Prostate Cancer Risk: A Population-based Case-Control Study , 2007, Cancer Epidemiology Biomarkers & Prevention.

[73]  K. Cho,et al.  Cholesterol level of lipid raft microdomains regulates apoptotic cell death in prostate cancer cells through EGFR‐mediated Akt and ERK signal transduction , 2007, The Prostate.

[74]  E. Mascha,et al.  Can Anesthetic Technique for Primary Breast Cancer Surgery Affect Recurrence or Metastasis? , 2006, Anesthesiology.

[75]  H. Welch,et al.  Statins and the Risk of Colorectal Cancer , 2005, The New England journal of medicine.

[76]  Ronit Almog,et al.  Statins and the risk of colorectal cancer. , 2005, The New England journal of medicine.

[77]  T. Hla,et al.  Role of prostaglandin E2-dependent angiogenic switch in cyclooxygenase 2-induced breast cancer progression. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[78]  T G Cotter,et al.  Excisional surgery for cancer cure: therapy at a cost. , 2003, The Lancet. Oncology.

[79]  M. Minden,et al.  HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis , 2002, Leukemia.

[80]  S B Malkowicz,et al.  Biochemical Outcome After Radical Prostatectomy , External Beam Radiation Therapy , or Interstitial Radiation Therapy for Clinically Localized Prostate Cancer , 2000 .

[81]  A. Renshaw,et al.  Biochemical Outcome after radical prostatectomy, external beam Radiation Therapy, or interstitial Radiation therapy for clinically localized prostate cancer , 1998 .

[82]  E. Castanas,et al.  Opioid alkaloids and casomorphin peptides decrease the proliferation of prostatic cancer cell lines (LNCaP, PC3 and DU145) through a partial interaction with opioid receptors. , 1997, European journal of pharmacology.

[83]  Lyndsay T Wilson,et al.  Observational Study , 2019, Encyclopedia of Behavioral Medicine.

[84]  S. Spampinato,et al.  Opioid Receptors , 2015, Methods in Molecular Biology.

[85]  G. Batist,et al.  Use of statins and the risk of death in patients with prostate cancer. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[86]  J. McDonald,et al.  Opioid Receptors , 2015, Methods in Molecular Biology.

[87]  E. Compérat,et al.  Guidelines on Muscle-invasive and Metastatic Bladder Cancer , 2013 .

[88]  R. Salgia,et al.  Overexpression of the -Opioid Receptor in Human Non- Small Cell Lung Cancer Promotes Akt and mTOR Activation, Tumor Growth, and Metastasis , 2012 .

[89]  T. Hla,et al.  Role of prostaglandin E 2-dependent angiogenic switch in cyclooxygenase 2-induced breast cancer progression , 2004 .

[90]  C. Schaffner Prostatic cholesterol metabolism: regulation and alteration. , 1981, Progress in clinical and biological research.