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Peritumoral injection of a local anesthetic before breast cancer surgery significantly increased disease-free survival (DFS) and overall survival (OS) in women with early breast cancer, a randomized trial from India showed.

At a median follow-up of 68 months, the 5-year DFS rate was 86.6% with peritumoral injection of lidocaine versus 82.6% with no injection (HR 0.74, 95% CI 0.58-0.95, P=0.017), reported Rajendra A. Badwe, MS, of the Homi Bhabha National Institute in Mumbai, India, and colleagues.

Five-year OS rates were 90.1% versus 86.4%, respectively (HR 0.71, 95% CI 0.53-0.94, P=0.019), they noted in the .

"Peritumoral injection of lidocaine is easily implementable as a one-time procedure," Badwe and colleagues wrote. "It is inexpensive and can be practiced in almost all parts of the world. There seem to be no subgroups wherein the results are markedly different from those in the full study population, suggesting that the benefit of this intervention is likely to be applicable to most patients with breast cancer undergoing upfront curative surgery."

In a Cox proportional hazards model that included subgroups stratified by age (≤50 vs >50 years), tumor size (≤2 cm vs >2 cm), hormone receptor status (positive vs negative), lymph node status (negative vs positive), and grade, lidocaine continued to be significantly associated with improved DFS compared with no lidocaine (adjusted HR 0.69, 95% CI 0.53-0.88, P=0.004), in addition to improved OS (adjusted HR 0.64, 95% CI 0.47-0.86, P=0.003).

Competing risk analyses showed that the use of peritumoral injection also resulted in a trend towards a reduction in locoregional recurrences, with a 5-year cumulative incidence of 3.2% in the lidocaine arm versus 4.1% in the no-lidocaine arm (subdistribution HR 0.69, 95% CI 0.42-1.13), as well as distant recurrences, with a 5-year cumulative incidence of 8.1% versus 10.9% (subdistribution HR 0.74, 95% CI 0.54-1.01).

Badwe and team noted that there could be multiple mechanisms underlying the potential benefit seen with lidocaine in this study. "These involve blockage of voltage-gated sodium channel activity, which is known to have several pro-metastatic effects, and a number of other anti-metastatic effects of local anesthetic agents," they wrote. "Whatever the mechanisms, the results of this study suggest the possible role of modulating processes that may confer metastatic potential on breast cancer cells at the time of surgery to reduce the onset of metastases and improve surgical cure rates."

Of note, there were no adverse events related to lidocaine injection.

"These data add to the body of evidence supporting the perioperative use of local anesthetics for multiple reasons to include not just this potential oncologic benefit but for providing pain relief, as well as decreasing intraoperative and postoperative opioid use, thereby reducing postoperative nausea and vomiting and facilitating enhanced recovery after surgery," wrote Tessa Higgins, BA, of Brigham and Women's Hospital in Boston, and Elizabeth A. Mittendorf, MD, PhD, of Dana-Farber Brigham Cancer Center and Harvard Medical School in Boston, in .

"As concluded by the study investigators, it seems reasonable to introduce this intervention as an easy, cost-effective intervention that may reduce the rates of recurrence and death in women with early-stage breast cancer," they added.

Since this trial was planned to detect an absolute DFS improvement of 6% in the lidocaine arm, it was technically a negative study, Higgins and Mittendorf noted. "However, it is hard to suggest that the 4.0% DFS benefit (and 3.7% OS benefit) that was seen is not clinically significant, particularly given the ease of the intervention and the lack of any adverse events attributable to the lidocaine injection," they wrote.

In explaining the rationale behind the trial, Badwe and colleagues said that have suggested improved outcomes after regional or local anesthesia during primary surgery for breast cancer, while other reports have not supported these findings. Thus, they wanted to test this hypothesis in a randomized setting.

This open-label multicenter study included 1,583 women from 11 centers across India. Eligible patients included those with operable breast cancer with clinical N0 or N1 lymph node status, no evidence of distant metastasis, and an Eastern Cooperative Oncology Group score of 0.

Of these women, mean age was 51.3, and 60.2% were postmenopausal. Mean tumor size was 2.97 cm, and 45.2% had pathologic node-positive disease.

Women randomly assigned to the intervention arm received 0.5% lidocaine (not exceeding 4.5 mg/kg body weight) around all six tumor surfaces (superior, inferior, anterior, posterior, medial, and lateral) of the primary tumor, after administration of general anesthesia.

Randomization was stratified by menopausal status, tumor size, and center. All participants received standard postoperative adjuvant treatment.

At the median follow-up of 68 months, there were 255 DFS events (109 in the lidocaine arm vs 146 in the no-lidocaine arm) and 189 deaths (79 vs 110, respectively).

Badwe and team noted that about 20% of the patients had HER2-positive disease, and only 34.6% received HER2-targeted therapy due to financial reasons, potentially limiting the generalizability of results in this subgroup to locations where there is full access to modern adjuvant HER2-targeted therapy.

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