Cite as: Nunez-Rodriguez E, Cata JP. Curb your enthusiasm: numbing the pain, not the cancer—rethinking regional anesthesia role in recurrence. ASRA Pain Medicine News 2025;50. https://doi.org/10.52211/asra110125.017.

Curb Your Enthusiasm

More than 500,000 patients undergo cancer surgery with curative intent each year in the United States.^1,2 Despite advancements in surgical techniques and the development of novel oncological therapies, the risk of recurrence and disease progression remains high with rates ranging from 30%- 80% depending on the cancer type.^3-5 Consequently, there is an unmet need for identifying interventions that can halt cancer spread and progression during the perioperative period when patients are physiologically vulnerable.

There is substantial evidence that regional anesthesia can provide adequate pain relief for hours after cancer surgery. However, for nearly two decades, regional anesthesia has been at the center of a scientific debate to determine whether anesthetics, and especially regional anesthesia, influence oncological outcomes. Building on preclinical evidence,⁶ Exadaktylos et al. published a 2006 clinical investigation suggesting a strong association between the use of paravertebral blocks during breast cancer surgery and reduced cancer recurrence.⁷ In their retrospective analysis of 129 patients undergoing breast cancer surgery, paravertebral block was associated with a 57% reduction in recurrence, particularly local and axillary nodal disease, compared with general anesthesia. The authors speculated that avoidance of volatile anesthetics, attenuation of the inflammatory response during the high-stress perioperative period, and reduced perioperative opioid consumption were the mechanisms behind the observed findings.⁸

However, the enthusiasm these findings generated was not substantiated by subsequent randomized clinical trials (RCTs). In a study including 2,108 women, Sessler et al. found no differences in local or metastatic breast cancer recurrence in their 36 months of follow-up between patients allocated to receive paravertebral blocks and those assigned to general anesthesia only.⁹ Similarly, another RCT of 526 patients comparing general anesthesia plus pectoral nerve blocks versus general anesthesia alone showed no improvement in 5-year oncological outcomes.¹⁰ Two additional studies in women with breast cancer evaluating thoracic epidural anesthesia also reported no significant differences in mortality or local or metastatic recurrence rates.^11,12

When examining prostate cancer, similar findings are observed. Retrospective studies have yielded mixed results with some reports associating neuraxial anesthesia with reduced recurrence rates.^13,14 For instance, an observational study including 225 patients that underwent radical prostatectomy described a 57% lower risk of recurrence in patients receiving epidural plus general anesthesia compared with general anesthesia alone.¹⁴ In contrast, a follow-up observation of an RCT (n=99), comparing combined epidural and general anesthesia versus general anesthesia alone, revealed no differences in disease-free survival.¹⁵ However, the interpretation of that study is limited by the small sample size.

The case of non-muscle invasive bladder cancer deserves careful interpretation. Findings from initial retrospective studies associated spinal anesthesia with lower recurrence.^16-18 Similarly, in a recent RCT including 287 patients with clinical non-muscle invasive bladder cancer, spinal anesthesia showed statistically significantly lower recurrence (27% versus 40%) and disease progression rates (8% versus 15%) compared with general anesthesia.¹⁸ However, this study presented significant methodological limitations, such as the absence of blinding, a small sample size, and a low number of events, which introduce statistical frailty and limit the interpretability of the results.¹⁹ In addition, this study failed to include critical factors that influence recurrence, such as the quality of surgical resection, the presence of carcinoma in situ, or the histological subtype.¹⁹

More than 500,000 patients undergo cancer surgery with curative intent each year in the United States.Despite advancements in surgical techniques and the development of novel oncological therapies, the risk of recurrence and disease progression remains high with rates ranging from 30%- 80% depending on the cancer type.

Other trials evaluating the impact of regional/neuraxial anesthesia and cancer outcomes have not shown positive results. Christopherson et al. and Falk et al. observed that epidural anesthesia had no effect on cancer recurrence following 2 and 5 years, respectively, of colon cancer surgery.^20,21 Du et al. reported no differences in cancer-specific survival or recurrence-free survival in their follow-up study of 1,712 patients with gastrointestinal, genitourinary, and lung cancer, who were randomized to receive combined epidural and general anesthesia or general anesthesia alone.²² In an RCT including 400 patients with lung cancer randomized to receive general anesthesia or combined epidural-general anesthesia, the 3-year recurrence-free survival or cancer-specific survival rate was not different.²³

Overall, there is robust evidence from adequately powered RCTs to suggest that regional anesthesia does not cause a clinically relevant reduction in cancer recurrence. The failure to translate evidence from preclinical research into clinical trials for regional anesthesia may be attributed to the use of toxic doses or unusual dosing regimens in some in vivo and in vitro experiments, which are not applicable to patient care, or the limitations of preclinical models in accurately reflecting human tumor behavior.²⁴

Yet, evidence from pre-clinical research on the anti-cancerous effect of local anesthetics should prompt us to explore alternative interventions in which they might have an impact on cancer perioperatively.⁶ One interesting alternative involves the administration of lidocaine intravenously.²⁵ However, an RCT of 563 patients undergoing pancreatic cancer surgery with curative intent showed no differences in overall disease-free survival in 3 years of follow-up.²⁶ The 10-year follow-up of the Allegro trial, studying intravenous lidocaine infusion in patients undergoing colon cancer surgery, will shed light on the role of an intravenous lidocaine infusion in colon cancer recurrence.²⁷

Another alternative is the administration of local anesthetics around the tumors. Badwe et al. examined the effect of peritumoral administration of lidocaine 0.5% in an RCT including 1,583 patients undergoing breast cancer surgery and followed them for 5 years.²⁸ In their report, patients receiving lidocaine experienced statistically significant increased disease-free survival (86.6% versus 72.6%; p = 0.02) and overall survival rates (90.1% versus 86.4%; p = 0.02). These findings were mainly attributed to reduced distant recurrence rates as there was no statistically significant difference in locoregional recurrence rates. Unfortunately, the study had several limitations, such as a lack of adequate placebo, no specification on the volume used.

In summary, regional anesthesia should be used to block nerves and thus to provide adequate postoperative pain control.^29-31 Evidence from clinical trials suggests that we reconsider the role of regional blocks in mitigating cancer spread. Future trials should clarify the role of local administration of local anesthetics in cancer recurrence.

References

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