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| EDITORIAL |
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| Year : 2023 | Volume
: 2
| Issue : 1 | Page : 5-6 |
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The impact of analgesics and anesthetics on cancer outcomes: Exploring the evidence
Lalit Gupta, Kirti N Saxena
Department of Anaesthesia and Critical Care, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India
| Date of Submission | 27-Apr-2023 |
| Date of Acceptance | 01-May-2023 |
| Date of Web Publication | 25-May-2023 |
Correspondence Address:
Dr. Lalit Gupta
Department of Anaesthesia and Critical Care, Maulana Azad Medical College and Lok Nayak Hospital, Bahadur Shah Zafar Marg, New Delhi - 110 002
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jica.jica_10_23
How to cite this article:
Gupta L, Saxena KN. The impact of analgesics and anesthetics on cancer outcomes: Exploring the evidence. J Ind Coll Anesth 2023;2:5-6 |
As medical professionals continue to seek ways to improve patient outcomes in cancer care, the role of anesthesia in cancer recurrence has become an increasingly important topic of discussion. A number of studies in recent years have looked at the possibility that the anesthetic method used during cancer surgery may affect cancer recurrence rates. Multiple studies have shown that anesthetic and analgesic techniques can affect the immune system, inflammation, and tumor biology, which may contribute to cancer recurrence.[1] Particularly, intriguing is the potential effects of endogenous and exogenous opioids on cancer biology, as well as the potential effects of regional anesthesia or general anesthetics used during cancer surgery on long-term survival.[2] Understanding the underlying processes of these potential interactions is critical to provide patients with the highest chance of pain-free life.
A retrospective study conducted by Gupta et al. found that morphine, a commonly used opioid analgesic during surgery, stimulated angiogenesis, leading to increased breast tumor growth.[3] Similarly, a study by Benzonana et al. found that isoflurane, a commonly used volatile anesthetic, enhanced renal cancer growth, and malignant potential through the hypoxia-inducible factor cellular signaling pathway in vitro.[4] Another retrospective cohort study by Xu et al. suggested that the use of sevoflurane, another commonly used volatile anesthetic, was allied with a significantly higher risk of recurrence in patients with cervical cancer undergoing radical hysterectomy.[5] These retrospective studies suggest that the choice of anesthesia may play a role in cancer recurrence.
In contrast, some prospective studies have reported no significant association between anesthesia and cancer recurrence. For example, a study by Kim and Kin found that the type of anesthetic technique used during breast cancer surgery had no significant impact on the levels of cytokines or matrix metalloproteinases associated with cancer recurrence.[6] Similarly, other prospective randomized trials also observed no significant association between epidural analgesia, a commonly used anesthesia technique for cancer surgery, and cancer recurrence or survival after surgery.[7] These prospective studies suggest that the selection of anesthesia may not have a substantial impact on the recurrence of cancer.
The reasons for the conflicting results among different studies are not entirely clear. One possibility is that the impact of anesthesia on cancer recurrence may vary depending on the type and stage of cancer, as well as other individual patient factors. These processes are complex and most likely multifactorial. In the short and long term, drugs have the potential to influence the immune response and cellular pathways critical to cancer cell survival and dissemination. Cancer prognosis is heavily influenced by the host immune system, the tumor (including its kind, stage, and location), and their interplay. Opioids, local anesthetics, ketamine, and nonsteroidal anti-inflammatory medicines have all been the subject of research into how they influence host defenses through altering cell-mediated immunity and/or natural killer cell activity. In addition, they could have an impact on cancer development and metastasis. Opioids have been associated with cancer progression and decreased overall survival in preclinical studies[8] and in patients with cancer.[9] As a result of immunosuppression, cancer cell migration, and enhanced vascular endothelial growth factor activity, it has been hypothesized that opioids have protumor action.[8] In particular, using opioids during immunotherapy have been found to be linked with early progression, which could serve as a predictor for reduced progression-free survival and have a negative impact on overall survival.[10]
Second, the μ-opioid receptor (MOR), which is expressed in both cancer cells and noncancerous cells in the tumor microenvironment, is affected by opioids.[11] The MOR can participate in an important mechanism of cancer spread, such as perineural invasion.[12] In addition, studies have shown links between survival and intratumoral opioid receptor gene alterations.[13] Finally, opioids have the potential to influence tumor immune surveillance mechanisms. Studies have shown that opioids possess protumor activity secondary to immunosuppression, which can negatively affect the immune response to anti-PD-1/PD-L1 agents and impair the immune response to cancer.[10]
General anesthesia and volatile anesthesia have been shown to suppress the immune system, while regional anesthesia and intravenous anesthesia have been shown to have less of an impact on immune function.[14] A compromised immune system may be less able to detect and eliminate cancer cells, leading to an increased risk of cancer recurrence. It is also possible that different types of anesthesia may have different effects on the immune system, which plays an important role in cancer surveillance and control. Some studies have suggested that volatile anesthesia may have immunosuppressive effects, while total intravenous anesthesia may have immunostimulatory effects.[15] Studies suggest that fascial plane blocks, such as paravertebral block, combined with opioid-free anesthesia offer superior postoperative pain management and may improve long-term survival with lower cancer recurrence rates after potentially curative surgery when using regional anesthesia–analgesia instead of general anesthesia and opioids.[16],[17]
While the evidence on the link between anesthesia and cancer recurrence is still evolving, it is clear that this is an important area of research that deserves further investigation. If certain types of anesthesia are found to increase the risk of cancer recurrence, it may be possible to modify anesthesia practices to improve patient outcomes. For example, it may be possible to develop new anesthesia techniques that minimize the risk of cancer recurrence or to identify patients who are at higher risk of recurrence and tailor anesthesia practices accordingly. It is premature to conclude that opioids can be fully removed from anesthetic practice, particularly when they are the predominant medication in intravenous patient-controlled analgesia, where their rapid onset of action and predictable duration offer them a clear advantage over opioid-free anesthesia. The unwarranted side effects and impacts on multiple organ systems limit the use of nonopioid analgesics. Until more evidence is available, clinicians should use the best available evidence to guide their choices of anesthesia and analgesia techniques during cancer surgery. Factors such as the type and stage of cancer, the patient's medical history, and the surgical procedure should all be taken into account when making decisions about perioperative management. Ultimately, the goal of perioperative management should be to optimize patient outcomes while minimizing the risk of cancer recurrence.
| References | |  |
| 1. | Evans MT, Wigmore T, Kelliher LJ. The impact of anaesthetic technique upon outcome in oncological surgery. BJA Educ 2019;19:14-20.  |
| 2. | Mao L, Lin S, Lin J. The effects of anesthetics on tumor progression. Int J Physiol Pathophysiol Pharmacol 2013;5:1-10. |
| 3. | Gupta K, Kshirsagar S, Chang L, Schwartz R, Law PY, Yee D, et al. Morphine stimulates angiogenesis by activating proangiogenic and survival-promoting signaling and promotes breast tumor growth. Cancer Res 2002;62:4491-8. |
| 4. | Benzonana LL, Perry NJ, Watts HR, Yang B, Perry IA, Coombes C, 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. Anesthesiology 2013;119:593-605. |
| 5. | Xu Y, Jiang W, Xie S, Xue F, Zhu X. The role of inhaled anesthetics in tumorigenesis and tumor immunity. Cancer Manag Res 2020;12:1601-9. |
| 6. | Kim R, Kin T. Anesthetic techniques and recurrence of breast cancer: Unanswered questions. Gland Surg 2020;9:490-4. |
| 7. | Yen FY, Chang WK, Lin SP, Lin TP, Chang KY. Association between epidural analgesia and cancer recurrence or survival after surgery for renal cell carcinoma: A propensity weighted analysis. Front Med (Lausanne) 2021;8:782336. |
| 8. | Amaram-Davila J, Davis M, Reddy A. Opioids and cancer mortality. Curr Treat Options Oncol 2020;21:22. |
| 9. | Boland JW. Effect of opioids on survival in patients with cancer. Cancers (Basel) 2022;14:5720. |
| 10. | Botticelli A, Cirillo A, Pomati G, Cerbelli B, Scagnoli S, Roberto M, et al. The role of opioids in cancer response to immunotherapy. J Transl Med 2021;19:119. |
| 11. | Ramirez MF, Gorur A, Cata JP. Opioids and cancer prognosis: A summary of the clinical evidence. Neurosci Lett 2021;746:135661. |
| 12. | Cata JP, Uhelski ML, Gorur A, Bhoir S, Ilsin N, Dougherty PM. The μ-Opioid receptor in cancer and its role in perineural invasion: A short review and new evidence. Adv Biol (Weinh) 2022;6:e2200020. |
| 13. | Connolly JG, Tan KS, Mastrogiacomo B, Dycoco J, Caso R, Jones GD, et al. Intraoperative opioid exposure, tumour genomic alterations, and survival differences in people with lung adenocarcinoma. Br J Anaesth 2021;127:75-84. |
| 14. | Sessler DI. Does regional analgesia reduce the risk of cancer recurrence? A hypothesis. Eur J Cancer Prev 2008;17:269-72. |
| 15. | Sofra M, Fei PC, Fabrizi L, Marcelli ME, Claroni C, Gallucci M, et al. Immunomodulatory effects of total intravenous and balanced inhalation anesthesia in patients with bladder cancer undergoing elective radical cystectomy: Preliminary results. J Exp Clin Cancer Res 2013;32:6. |
| 16. | Buggy DJ, Wall T. Can anaesthetic-analgesic technique during cancer surgery of curative intent influence recurrence or metastasis? An update. Br J Anaesth 2019;123:e525-6. |
| 17. | Gupta L, Agarwal J, Saxena KN. Opioid-free anaesthesia: The conundrum and the solutions. Indian J Anaesth 2022;66:S91-4. |
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