An inexpensive peritumoral injection of a local anaesthetic before breast cancer surgery significantly increased disease-free survival (DFS) and overall survival (OS) in women with early breast cancer, a randomised trial from India showed.
The open-label multicentre study included 1 583 women from 11 centres across India.
MedPage Today reports that eligible patients included those with operable breast cancer with clinical N0 or N1 lymph node status, no evidence of distant metastasis, and an Eastern Co-operative Oncology Group score of zero.
Of these women, mean age was 51.3, and 60.2% were postmenopausal. Mean tumour 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 tumour surfaces (superior, inferior, anterior, posterior, medial and lateral) of the primary tumour, after administration of general anaesthesia.
Randomisation was stratified by menopausal status, tumour size and centre. All participants received standard post-operative adjuvant treatment.
At a median follow-up of 68 months, the five-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 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 Journal of Clinical Oncology.
“Peritumoral injection of lidocaine is easily implementable as a one-time procedure,” Badwe and colleagues wrote.
“It is inexpensive and can be practised 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 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), tumour 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 peritumoral injection also resulted in a trend towards a reduction in locoregional recurrences, with a five-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 five-year cumulative incidence of 8.1% versus 10.9% (subdistribution HR 0.74, 95% CI 0.54-1.01).
The researchers 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, known to have several pro-metastatic effects, and various other anti-metastatic effects of local anaesthetic 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 evidence supporting the perioperative use of local anaesthetics for multiple reasons… 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 Dr Elizabeth Mittendorf of Dana-Farber Brigham Cancer Centre and Harvard Medical School, in an accompanying editorial.
Study details
Effect of peritumoral infiltration of local anaesthetic before surgery on survival in early breast cancer
Rajendra A. Badwe, Vani Parmar, Nita Nair, Shalaka Joshi, Rohini Hawaldar, Suraj Pawar, et al.
Published in the Journal of Clinical Oncology on 6 April 2023
Abstract
Purpose
Preventing metastases by using perioperative interventions has not been adequately explored. Local anaesthesia blocks voltage-gated sodium channels and thereby prevents activation of prometastatic pathways. We conducted an open-label, multicentre randomised trial to test the impact of presurgical, peritumoral infiltration of local anaesthesia on disease-free survival (DFS).
Methods
Women with early breast cancer planned for upfront surgery without prior neoadjuvant treatment were randomly assigned to receive peritumoral injection of 0.5% lidocaine, 7-10 minutes before surgery (local anaesthetics [LA] arm) or surgery without lidocaine (no LA arm). Random assignment was stratified by menopausal status, tumour size, and centre. Participants received standard postoperative adjuvant treatment. Primary and secondary end points were DFS and overall survival (OS), respectively.
Results
Excluding eligibility violations, 1,583 of 1,600 randomly assigned patients were included in this analysis (LA, 796; no LA, 804). At a median follow-up of 68 months, there were 255 DFS events (LA, 109; no LA, 146) and 189 deaths (LA, 79; no LA, 110). In LA and no LA arms, 5-year DFS rates were 86.6% and 82.6% (hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.95; P = .017) and 5-year OS rates were 90.1% and 86.4%, respectively (HR, 0.71; 95% CI, 0.53 to 0.94; P = .019). The impact of LA was similar in subgroups defined by menopausal status, tumour size, nodal metastases, and hormone receptor and human epidermal growth factor receptor 2 status. Using competing risk analyses, in LA and no LA arms, 5-year cumulative incidence rates of locoregional recurrence were 3.4% and 4.5% (HR, 0.68; 95% CI, 0.41 to 1.11), and distant recurrence rates were 8.5% and 11.6%, respectively (HR, 0.73; 95% CI, 0.53 to 0.99). There were no adverse events because of lidocaine injection.
Conclusion
Peritumoral injection of lidocaine before breast cancer surgery significantly increases DFS and OS. Altering events at the time of surgery can prevent metastases in early breast cancer (CTRI/2014/11/005228).
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