Preparing for cancer surgery: what you need to know to maximize the success of your treatment

Preparing for cancer surgery: what you need to know to maximize the success of your treatment

A cancer diagnosis hits hard, but despite the stress all patients must learn about their treatment options in order to have fully informed discussions with an oncologist and other specialists on treatment options. If your treatment plan includes surgery to remove a tumor there are a few things you should know to ensure success. The surgeon’s skill and experience are certainly important factors, but the type of anesthesia used can impact the risk of cancer recurrence. Adequate pain control can also affect your recovery and the risk of permanent disability. Effective nausea management will have a significant impact on your quality of life. Here we will discuss how pharmacogenetic testing prior to surgery can assist your doctors to optimize your treatment and maximize the chances of full recovery.

Your surgery might be scheduled before or after several rounds of chemotherapy, depending on the tumor type and stage of disease. Regardless of chemotherapy, cancer surgery by itself carries several risks that can be reduced. Surgery-induced tissue damage, physical and emotional stress, and pain all impact inflammation and your immune system function. The wound-healing process can promote the formation of new blood vessels and alter the risk of metastatic cancer recurrence. Stress-induced suppression of your immune system can influence your body’s ability to identify and kill the remaining micro metastasis and has been shown to negatively affect long term survival rates.

Anesthesia and risk of cancer recurrence:

Recent studies have shown that the type of anesthesia used during the surgery can affect the risk of metastasis. Two major types of general anesthetics used today are:

  • Inhalational: such as desflurane, enflurane, halothane, isoflurane, sevoflurane, and similar compounds
  • Intravenous: propofol, etomidate, ketamine, and barbiturates

Recent clinical studies have shown a relationship between the type of anesthesia and long-term survival in patients with cancer. Patients who received inhaled anesthesia had a lower survival rate compared to patients with similar diagnoses and types of cancer who received propofol-based anesthesia. The largest UK study analyzed the outcomes of 7,030 patients with more than 20 different types of cancer and, after adjustment for other confounding factors, showed  that patients who received inhaled anesthetic with isoflurane or sevoflurane were 1.46 times more likely to die at 5 years, compared with patients who received intravenous propofol and the ultra–short-acting opioid drug remifentanil.

Inhalational anesthetics are most commonly used, but studies have shown that these drugs enhance development of new blood vessels (angiogenesis), proliferation, migration, and metastatic invasion of cancer cells. Although the exact mechanisms are still unknown, it is thought that inhalational anesthetics affect oxygen sensing factors for several hours after administration which can be one reason for the negative impact. Also, inhalational anesthetics suppress immune cells that play a key role in tumor cell surveillance and destruction, leading to increased risk of metastasis.

Intravenous anesthetics, specifically propofol, are commonly used to maintain sedation with continuous intravenous infusion. Propofol has been shown to have the opposite effect to inhaled anesthetics on risk of cancer recurrence. Propofol inhibits cancer cell migration, invasion, and metastasis. Propofol also does not suppress immune response and has anti-inflammatory and antioxidant properties, which are beneficial for cancer patients.

As part of your preparation for cancer surgery you should discuss with your anesthesiologist which type of anesthesia is planned for your surgery to ensure that propofol or another intravenous anesthetic will be used.

Propofol metabolism and clearance is controlled by an enzyme in your liver, the CYP2B6 enzyme. Up to 50% of people in North America have inherently reduced function of this enzyme and have slower propofol elimination rate, prolonging recovery from anesthesia and increasing the risk of propofol-induced side effects such as numbness and confusion. Elderly patients with a low function of this enzyme may benefit from lower a propofol dose to facilitate recovery. A pharmacogenetic test can assist your anesthesiologist to assess the clinically effective propofol dose for you. Remember, pharmacogenetic tests take a week or two before results are available – consider getting a test as soon as possible so the test results will be available for your pre-surgery appointment with your anesthesiologist.

Pain control post-surgery

To control pain during surgery, fast-acting injected opioids such as remifentanil, fentanyl, and morphine are commonly used. Potent opioids are needed to control pain in the post-surgery period as well. Some people want to “tough through” the pain due to fear of developing opioid dependence and refuse to take opioids or intentionally reduce the drug dose. However, multiple studies have shown that poor pain control before, during, and after surgery greatly increases the risk of developing chronic pain. Chronic pain has significant impact not only on quality of life for many years, but also reduces the survival rate for cancer patients. When your body is under constant stress triggered by pain, high levels of stress hormones like cortisol suppress immune system and increase the risk of cancer recurrence. Hence, adequate pain control in the first 2-3 days after the surgery is very important for long term survival, and quality of life. Patients who take opioids to control high levels of pain do not become addicted if the opioids can be reduced or stopped entirely a few days after the surgery. However, patients discharged home with high opioid doses are at much greater risk of developing opioid dependence. Long term use of opioids also reduces their effectiveness due to tolerance development and an increased sensitivity to pain – a phenomenon called opioid-induced hyperalgesia. Therefore, it is prudent to control pain right after the surgery.

Some patients have an inherently reduced response to opioids due to inherited variations in the OPRM1 gene, which controls how your body processes them. Multiple studies have shown that carriers of OPRM1 variants require higher doses to achieve adequate pain relief, when compared to people who do not carry such variations.

Furthermore, when patients are discharged from the recovery room to a regular unit, they are switched to oral opioids such as tramadol, hydrocodone, or oxycodone – these require activation by a liver enzyme called CYP2D6 to become effective. Patients who cannot process these medications should avoid them altogether (See CPIC guidelines,  CPIC publishes pharmacogenetic prescribing information). To provide effective pain control in patients who are Poor CYP2D6 metabolizers, CPIC recommends avoiding tramadol, codeine, or oxycodone – these could be treated with alternative drugs (high doses of NSAIDs like Advil) or morphine if stronger pain relief is needed. People who process oral opioids more slowly due to reduced liver enzyme activity (12-20% of population) may require higher tramadol or oxycodone doses to compensate for slower drug activation.

Additionally, 5-10% of people are ultrarapid metabolizers of oral opioids and convert tramadol, codeine, and oxycodone too fast, leading to nausea and delirium. They are even at risk for breathing issues at higher doses. Ultrarapid metabolizers also experience shorter pain relief at standard doses and are at an elevated risk of addiction with continued use of these opioids. Ultrarapid metabolizers can also benefit from NSAIDs or morphine for pain control in the post-surgery period.

A pharmacogenetic test for CYP2D6 and OPRM1 function can help your doctors to optimize your pain management and select appropriate pain relief therapy. But once again, remember to have your pharmacogenetic test done several weeks in advance so you’ll be able to show your results to your doctor and anesthesiologist.

Nausea management

Recovery from anesthesia frequently causes severe nausea in a few hours in the post- operative period. Intravenous administration of fluids helps to clear the remaining anesthetic drug from bloodstream and reduce nausea symptoms. However, some patients need additional anti-nausea medications such as dolasetron, ondansetron, palonosetron, or tropisetron. Ultrarapid CYP2D6 metabolizers clear these four commonly used anti-nausea drugs too fast and do not get relief from them. The CPIC guideline recommends use of alternative drugs not predominantly metabolized by CYP2D6 for example, granisetron.

A pharmacogenetic test prior to surgery for CYP2D6 can help your anesthesiologist to select appropriate treatment.

If chemotherapy is scheduled after the surgery, a pharmacogenetic test for TPMT and DPD genes can also help to identify appropriate dose and type of chemotherapy. You can read more about role of these genes in chemotherapy here.

Broad pharmacogenetic tests such as Pillcheck can provide insights on your body’s ability to metabolize different drugs and optimize cancer surgery, improve pain and nausea management, as well as chemotherapy. You can order Pillcheck today to get your results before the planned cancer surgery to maximize success of your treatment.

The key points to remember:

  1. Different types of anesthesia used during cancer surgery can affect the survival rate of cancer patients; in general, propofol and other types of anesthesia that are not inhaled are preferable.  Based on the results of a study, patients who receive inhaled sevoflurane and isoflurane were 1.46 times more likely to die at 5 years than those who received intravenous propofol or remifentanil
  2. Pain management is extremely important after cancer surgery as well as before it.  People whose cancer pain is not well-controlled run a higher risk of developing chronic pain. Studies have shown that effective pain management can make a difference in cancer survival rates as well.
  3. Effective anti-nausea management makes a big difference to patient comfort after surgery as well as during chemotherapy treatment if you require it.
  4. Complete your pharmacogenetic test well in advance of your surgery so that you have time to share your results with your doctor and anesthesiologist.

Selected references:

Perry NJS, et al., Can Anesthesia Influence Cancer Outcomes After Surgery? JAMA Surg. 2019;154(4):279-280. doi:10.1001/jamasurg.2018.4619

Eugene AR CYP2B6 Genotype Guided Dosing of Propofol Anesthesia in the Elderly based on Nonparametric Population Pharmacokinetic Modeling and Simulations. Int J Clin Pharmacol Toxicol. 2017;6(1):242-249.

Crews KR., et al., Clinical Pharmacogenetics Implementation Consortium Guidelines for Cytochrome P450 2D6 Genotype and Codeine Therapy: 2014 Update CLINICAL PHARMACOLOGY & THERAPEUTICS 2014; 95(4): 376-382

Hwang IC., et al., OPRM1 A118G Gene Variant and Postoperative Opioid Requirement: A Systematic Review and Meta-analysis Anesthesiology 2014;121:825-834

Bell GC, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 Genotype and Use of Ondansetron and Tropisetron CLINICAL PHARMACOLOGY & THERAPEUTICS 2017; 102(2):213-218

Gaedigk A, et al., Prediction of CYP2D6 phenotype from genotype across world populations Genet Med. 2017 Jan; 19(1): 69–76.

Share this post