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The Cochrane Database of Systematic... Jan 2017Axillary surgery is an established part of the management of primary breast cancer. It provides staging information to guide adjuvant therapy and potentially local... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Axillary surgery is an established part of the management of primary breast cancer. It provides staging information to guide adjuvant therapy and potentially local control of axillary disease. Several alternative approaches to axillary surgery are available, most of which aim to spare a proportion of women the morbidity of complete axillary dissection.
OBJECTIVES
To assess the benefits and harms of alternative approaches to axillary surgery (including omitting such surgery altogether) in terms of overall survival; local, regional and distant recurrences; and adverse events.
SEARCH METHODS
We searched the Cochrane Breast Cancer Group Specialised Register, MEDLINE, Pre-MEDLINE, Embase, CENTRAL, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov on 12 March 2015 without language restrictions. We also contacted study authors and checked reference lists.
SELECTION CRITERIA
Randomised controlled trials (RCTs) including women with clinically defined operable primary breast cancer conducted to compare axillary lymph node dissection (ALND) with no axillary surgery, axillary sampling or sentinel lymph node biopsy (SLNB); RCTs comparing axillary sampling with SLNB or no axillary surgery; RCTs comparing SLNB with no axillary surgery; and RCTs comparing ALND with or without radiotherapy (RT) versus RT alone.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed each potentially relevant trial for inclusion. We independently extracted outcome data, risk of bias information and study characteristics from all included trials. We pooled data according to trial interventions, and we used hazard ratios (HRs) for time-to-event outcomes and odds ratios (OR) for binary outcomes.
MAIN RESULTS
We included 26 RCTs in this review. Studies were at low or unclear risk of selection bias. Blinding was not done, but this was only considered a source of bias for outcomes with potential for subjectivity in measurements. We found no RCTs of axillary sampling versus SLNB, axillary sampling versus no axillary surgery or SLNB versus no axillary surgery. No axillary surgery versus ALND Ten trials involving 3849 participants compared no axillary surgery versus ALND. Moderate quality evidence showed no important differences between overall survival of women in the two groups (HR 1.06, 95% confidence interval (CI) 0.96 to 1.17; 3849 participants; 10 studies) although no axillary surgery increased the risk of locoregional recurrence (HR ranging from 1.10 to 3.06; 20,863 person-years of follow-up; four studies). It was uncertain whether no surgery increased the risk of distant metastasis compared with ALND (HR 1.06, 95% CI 0.87 to 1.30; 946 participants; two studies). Low-quality evidence indicated no axillary surgery decreased the risk of lymphoedema compared with ALND (OR 0.31, 95% CI 0.23 to 0.43; 1714 participants; four studies). Axillary sampling versus ALND Six trials involving 1559 participants compared axillary sampling versus ALND. Low-quality evidence indicated similar effectiveness of axillary sampling compared with ALND in terms of overall survival (HR 0.94, 95% CI 0.73 to 1.21; 967 participants; three studies) but it was unclear whether axillary sampling led to increased risk of local recurrence compared with ALND (HR 1.41, 95% CI 0.94 to 2.12; 1404 participants; three studies). The relative effectiveness of axillary sampling and ALND for locoregional recurrence (HR 0.74, 95% CI 0.46 to 1.20; 406 participants; one study) and distant metastasis was uncertain (HR 1.05, 95% CI 0.74 to 1.49; 406 participants; one study). Lymphoedema was less likely after axillary sampling than after ALND (OR 0.32, 95% CI 0.13 to 0.81; 80 participants; one study). SLNB versus ALND Seven trials involving 9426 participants compared SLNB with ALND. Moderate-quality evidence showed similar overall survival following SLNB compared with ALND (HR 1.05, 95% CI 0.89 to 1.25; 6352 participants; three studies; moderate-quality evidence). Differences in local recurrence (HR 0.94, 95% CI 0.24 to 3.77; 516 participants; one study), locoregional recurrence (HR 0.96, 95% CI 0.74 to 1.24; 5611 participants; one study) and distant metastasis (HR 0.80, 95% CI 0.42 to 1.53; 516 participants; one study) were uncertain. However, studies showed little absolute difference in the aforementioned outcomes. Lymphoedema was less likely after SLNB than ALND (OR ranged from 0.04 to 0.60; three studies; 1965 participants; low-quality evidence). Three studies including 1755 participants reported quality of life: Investigators in two studies found quality of life better after SLNB than ALND, and in the other study observed no difference. RT versus ALND Four trials involving 2585 participants compared RT alone with ALND (with or without RT). High-quality evidence indicated that overall survival was reduced among women treated with radiotherapy alone compared with those treated with ALND (HR 1.10, 95% CI 1.00 to 1.21; 2469 participants; four studies), and local recurrence was less likely in women treated with radiotherapy than in those treated with ALND (HR 0.80, 95% CI 0.64 to 0.99; 22,256 person-years of follow-up; four studies). Risk of distant metastasis was similar for radiotherapy alone as for ALND (HR 1.07, 95% CI 0.93 to 1.25; 1313 participants; one study), and whether lymphoedema was less likely after RT alone than ALND remained uncertain (OR 0.47, 95% CI 0.16 to 1.44; 200 participants; one study). Less surgery versus ALND When combining results from all trials, treatment involving less surgery was associated with reduced overall survival compared with ALND (HR 1.08, 95% CI 1.01 to 1.17; 6478 participants; 18 studies). Whether local recurrence was reduced with less axillary surgery when compared with ALND was uncertain (HR 0.90, 95% CI 0.75 to 1.09; 24,176 participant-years of follow up; eight studies). Locoregional recurrence was more likely with less surgery than with ALND (HR 1.53, 95% CI 1.31 to 1.78; 26,880 participant-years of follow-up; seven studies). Whether risk of distant metastasis was increased after less axillary surgery compared with ALND was uncertain (HR 1.07, 95% CI 0.95 to 1.20; 2665 participants; five studies). Lymphoedema was less likely after less axillary surgery than with ALND (OR 0.37, 95% CI 0.29 to 0.46; 3964 participants; nine studies).No studies reported on disease control in the axilla.
AUTHORS' CONCLUSIONS
This review confirms the benefit of SLNB and axillary sampling as alternatives to ALND for axillary staging, supporting the view that ALND of the clinically and radiologically uninvolved axilla is no longer acceptable practice in people with breast cancer.
Topics: Axilla; Breast Neoplasms; Female; Humans; Lymph Node Excision; Lymphedema; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Sentinel Lymph Node Biopsy
PubMed: 28052186
DOI: 10.1002/14651858.CD004561.pub3 -
PloS One 2016With the increased use of neoadjuvant chemotherapy (NAC) in breast cancer, the timing of sentinel lymph node biopsy (SLNB) has become increasingly important. In this... (Meta-Analysis)
Meta-Analysis Review
The Feasibility and Accuracy of Sentinel Lymph Node Biopsy in Initially Clinically Node-Negative Breast Cancer after Neoadjuvant Chemotherapy: A Systematic Review and Meta-Analysis.
BACKGROUND
With the increased use of neoadjuvant chemotherapy (NAC) in breast cancer, the timing of sentinel lymph node biopsy (SLNB) has become increasingly important. In this study, we aimed to evaluate the feasibility and accuracy of SLNB for initially clinically node-negative breast cancer after NAC by conducting a systematic review and meta-analysis.
METHODS
We searched PubMed, Embase, and the Cochrane Library from January 1, 1993 to November 30, 2015 for studies on initially clinically node-negative breast cancer patients who underwent SLNB after NAC followed by axillary lymph node dissection (ALND).
RESULTS
A total of 1,456 patients from 16 studies were included in this review. The pooled identification rate (IR) for SLNB was 96% [95% confidence interval (CI): 95%-97%], and the false negative rate (FNR) was 6% (95% CI: 3%-8%). The pooled sensitivity, negative predictive value (NPV) and accuracy rate (AR) were 94% (95% CI: 92%-97%, I2 = 27.5%), 98% (95% CI: 98%-99%, I2 = 42.7%) and 99% (95% CI: 99%-100%, I2 = 32.6%), respectively. In the subgroup analysis, no significant differences were found in either the IR of an SLNB when different mapping methods were used (P = 0.180) or in the FNR between studies with and without immunohistochemistry (IHC) staining (P = 0.241).
CONCLUSION
Based on current evidence, SLNB is technically feasible and accurate enough for axillary staging in initially clinically node-negative breast cancer patients after NAC.
Topics: Breast Neoplasms; False Negative Reactions; Feasibility Studies; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Neoadjuvant Therapy; Predictive Value of Tests; Publication Bias; Sentinel Lymph Node Biopsy
PubMed: 27606623
DOI: 10.1371/journal.pone.0162605 -
Breast Cancer (Tokyo, Japan) Jan 2022The effectiveness of sentinel lymph node (SLN) mapping and biopsy following neoadjuvant chemotherapy (NAC) in axillary lymph node staging of breast cancer (BCa) patients... (Meta-Analysis)
Meta-Analysis
Sentinel lymph node mapping in breast cancer patients following neoadjuvant chemotherapy: systematic review and meta-analysis about head to head comparison of cN0 and cN + patients.
PURPOSE
The effectiveness of sentinel lymph node (SLN) mapping and biopsy following neoadjuvant chemotherapy (NAC) in axillary lymph node staging of breast cancer (BCa) patients with initial clinical node positive status (cN +) compared to clinical node negative status (cN0) is not yet known. The aim of this meta-analysis was to compare the accuracy of SLN mapping following NAC in cN + and cN0 BCa patients.
METHODS
PubMed and Scopus were comprehensively reviewed to retrieve all the studies that performed SLN mapping/biopsy and standard axillary lymph node dissection on cN0 and cN + BCa patients following NAC. Pooled detection and false negative rates for N0 and N + patients including 95% confidence interval values (95% CI) were evaluated. Odds ratio (OR) and risk difference (RD) of SLN detection failure and false negative results were compared between two groups.
RESULTS
A total of 27 articles were included for SLN detection rate evaluation and 17 for false negative assessment. The OR and RD of detection failure in N + group compared with N0 group following NAC were 2.22 (p = 0.00, 95% CI 1.4-3.4) and 4% (p = 0.00, 95% CI 2-6%), respectively. The OR and RD of false negative rate were 1.6 (p = 0.01, 95% CI 1-2.6) and 8% (p = 0.02, 95% CI 1-14%), respectively.
CONCLUSION
SLN mapping in BCa patients following NAC shows high risk of detection failure and high false negative rate of SLN biopsy in cN + patients. In comparison with cN0 BCa patients, SLN mapping and biopsy after NAC was associated with almost two times higher odds of detection failure and false negative results in cN + patients; therefore, this method should not be recommended in this group of patients.
Topics: Breast Neoplasms; Chemotherapy, Adjuvant; Female; Humans; Neoadjuvant Therapy; Sentinel Lymph Node; Sentinel Lymph Node Biopsy
PubMed: 34341902
DOI: 10.1007/s12282-021-01280-7 -
International Journal of Surgical... Dec 2012Intramammary lymph nodes (IntraMLNs) are frequent mostly benign incidental findings. However, they are clinically important because they can be the primary sites of... (Meta-Analysis)
Meta-Analysis Review
Intramammary lymph nodes (IntraMLNs) are frequent mostly benign incidental findings. However, they are clinically important because they can be the primary sites of metastasis and sentinel lymph nodes. Literature data regarding the clinical significance of IntraMLNs metastasis, however, remains controversial. This study aimed to perform a systematic review and meta-analysis to better define the prognostic value of positive IntraMLNs in patients with breast cancer. A systematic review of the literature without date restrictions was conducted. Five electronic medical databases were searched, and a hand-search of the reference lists of the collected articles was also performed. Studies with sufficient and relevant pathologic and clinical survival data were included. Other studies with insufficient data or normal findings were excluded. This study found 18 studies eligible for systematic review, 3 of which were eligible for outcome meta-analysis. IntraMLNs metastases were strongly correlated with axillary lymph nodes involvement. Positive IntraMLNs are reliable predictors of axillary lymph node involvement and therefore a guide for further surgical management of the axillary nodes. Even though it could be concluded that IntraMLNs metastasis is an independent predictor of outcome, this meta-analysis was limited because of the scarcity of data and the inconsistencies and heterogeneity of the outcome studies.
Topics: Adenocarcinoma; Axilla; Breast Neoplasms; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Neoplasm Staging; Predictive Value of Tests; Prognosis; Sentinel Lymph Node Biopsy
PubMed: 22649167
DOI: 10.1177/1066896912448425 -
The Breast Journal Feb 2021Axillary lymph node dissection (ALND) in early-stage breast cancer with limited sentinel node metastasis may not be superior to sentinel lymph node dissection (SLND). We... (Meta-Analysis)
Meta-Analysis
Axillary lymph node dissection (ALND) in early-stage breast cancer with limited sentinel node metastasis may not be superior to sentinel lymph node dissection (SLND). We performed a meta-analysis comparing SLND/Radiotherapy (RT) with ALND. All data were analyzed using Review Manager Software 5.3. Five randomized controlled trials (RCTs) were included. Overall survival, death, and disease-free survival were estimated higher in the SLND group compared to the ALND group. Statistically significant differences in axillary recurrence were observed in favor of ALND. Omission of ALND in patients with <3 positive SLNs is indicated.
Topics: Axilla; Breast Neoplasms; Female; Humans; Lymph Node Excision; Lymphatic Metastasis; Neoplasm Recurrence, Local; Sentinel Lymph Node Biopsy
PubMed: 33368762
DOI: 10.1111/tbj.14140 -
The Cochrane Database of Systematic... May 2013Fibrin glue (FG) combines fibrinogen and thrombin, under the presence of factor XIII and calcium chloride, and produces a 'fibrin clot' as would occur through the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fibrin glue (FG) combines fibrinogen and thrombin, under the presence of factor XIII and calcium chloride, and produces a 'fibrin clot' as would occur through the natural clotting cascade. FG is thought to close over any small vessels including lymphatics that are too small for conventional surgical closure, thereby reducing seroma formation, seroma incidence and related comorbidities.
OBJECTIVES
To assess the evidence on the effectiveness of FG in people undergoing breast and axillary surgery and to establish whether FG is an efficient modality to prevent postoperative seroma and seroma-related outcomes.
SEARCH METHODS
We searched the Cochrane Breast Cancer Group's (CBCG) Specialised Register (9 December 2011), the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1 2012), MEDLINE (9 December 2011), EMBASE (9 December 2011), LILACS (22 October 2012), SCI-E (22 October 2012), the World Health Organization's International Clinical Trial Registry (9 December 2011) and ClinicalTrials.gov (22 October 2012).
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing the effectiveness of FG in terms of reducing the postoperative seroma incidence and related comorbidities in people undergoing breast and axillary surgery.
DATA COLLECTION AND ANALYSIS
At least two review authors independently scrutinised search results, selected eligible studies and extracted the data. The pooled analysis of the extracted data was achieved by the statistical analysis on Review Manager software. The quality of studies was assessed using The Cochrane Collaboration's 'Risk of bias' tool.
MAIN RESULTS
The search of four standard electronic databases yielded 119 potentially relevant studies but only 18 RCTs involving 1252 people were found suitable for statistical analysis. There was significant heterogeneity among trials and the majority of trials were of poor quality. The use of FG under skin flaps following breast and axillary surgery failed to reduce the incidence of postoperative seroma (risk ratio (RR) 1.02; 95% Confidence Interval (CI) 0.90 to 1.16, P value = 0.73), mean volume of seroma (standardised mean difference (SMD) -0.25; 95% CI -0.92 to 0.42, P value = 0.46), wound infection (RR 1.05; 95% CI 0.63 to 1.77, P value = 0.84), postoperative complications (RR 1.13; 95% CI 0.63 to 2.04, P value = 0.68) and length of hospital stay (SMD -0.2; 95% CI -0.78 to 0.39, P value = 0.51). FG reduced the total volume of drained seroma (SMD -0.75, 95% CI -1.24 to -0.26, P value = 0.003) and duration of persistent seromas requiring frequent aspirations (SMD -0.59; CI 95% -0.95 to -0.23, P value = 0.001).
AUTHORS' CONCLUSIONS
FG did not influence the incidence of postoperative seroma, the mean volume of seroma, wound infections, complications and the length of hospital stays in people undergoing breast cancer surgery. Due to significant methodological and clinical diversity among the included studies this conclusion may be considered weak and biased. Therefore, a major multicentre and high-quality RCT is required to validate these findings.
Topics: Axilla; Breast Neoplasms; Female; Fibrin Tissue Adhesive; Hemostatics; Humans; Lymph Node Excision; Postoperative Complications; Randomized Controlled Trials as Topic; Seroma; Surgical Flaps; Treatment Failure
PubMed: 23728694
DOI: 10.1002/14651858.CD009557.pub2 -
Cirugia Espanola Nov 2017Sentinel lymph node biopsy and ACOSOG-Z0011 criteria have modified axillary treatment in breast cancer surgery. We performed a systematic review of studies assessing the... (Review)
Review
Sentinel lymph node biopsy and ACOSOG-Z0011 criteria have modified axillary treatment in breast cancer surgery. We performed a systematic review of studies assessing the impact of axillary treatment on survival. The search showed 6891 potentially eligible items. Of them, 23 clinical trials and 12 meta-analyses published between 1980 and 2017 met the study criteria. The review revealed that axillary lymph node dissection (ALND) can be omitted in patients pN0 and pN1mic, without compromising survival. In patients pN1 it is proposed not to treat the axilla or replace ALND for axillary radiotherapy. The main limitations of this study are the inclusion of old tests that do not use therapeutic targets and lack of risk categorization of relapse. In conclusion, axillary treatment can be avoided in patients without metastatic involvement or micrometastases in the sentinel lymph node. However, there is no evidence to make a recommendation of axillary treatment in N1 patients, so individualized analysis of patient risk factors is needed.
Topics: Axilla; Breast Neoplasms; Female; Humans; Sentinel Lymph Node Biopsy; Survival Rate
PubMed: 29033068
DOI: 10.1016/j.ciresp.2017.08.004 -
The British Journal of Surgery Mar 2024In node-positive (cN+) breast cancer treated with neoadjuvant systemic therapy, combining sentinel lymph node biopsy and targeted lymph node excision, that is targeted...
Systematic review of targeted axillary dissection in node-positive breast cancer treated with neoadjuvant systemic therapy: variation in type of marker and timing of placement.
BACKGROUND
In node-positive (cN+) breast cancer treated with neoadjuvant systemic therapy, combining sentinel lymph node biopsy and targeted lymph node excision, that is targeted axillary dissection, increases accuracy. Targeted axillary dissection procedures differ in terms of the targeted lymph node excision technique. This systematic review aimed to provide an overview of targeted axillary dissection procedures regarding definitive marker type and timing of placement: before neoadjuvant systemic therapy (1-step procedure) or after neoadjuvant systemic therapy adjacent to a clip placed before the neoadjuvant therapy (2-step procedure).
METHODS
PubMed and Embase were searched, to 4 July 2023, for RCTs, cohort studies, and case-control studies with at least 25 patients. Studies of targeted lymph node excision only (without sentinel lymph node biopsy), or where intraoperative localization of the targeted lymph node was not attempted, were excluded. For qualitative synthesis, studies were grouped by definitive marker and timing of placement. The targeted lymph node identification rate was reported. Study quality was assessed using a National Institutes of Health quality assessment tool.
RESULTS
Of 277 unique records, 51 studies with a total of 4512 patients were included. Six definitive markers were identified: wire, 125I-labelled seed, 99mTc, (electro)magnetic/radiofrequency markers, black ink, and a clip. Fifteen studies evaluated one-step procedures, with the identification rate of the targeted lymph node at surgery varying from 8 of 13 to 47 of 47. Forty-one studies evaluated two-step procedures, with the identification rate of the clipped targeted lymph node on imaging after neoadjuvant systemic therapy varying from 49 to 100%, and the identification rate of the targeted lymph node at surgery from 17 of 24 to 100%. Most studies (40 of 51) were rated as being of fair quality.
CONCLUSION
Various targeted axillary dissection procedures are used in clinical practice. Owing to study heterogeneity, the optimal targeted lymph node excision technique in terms of identification rate and feasibility could not be determined. Two-step procedures are at risk of not identifying the clipped targeted lymph node on imaging after neoadjuvant systemic therapy.
Topics: Humans; Female; Breast Neoplasms; Neoadjuvant Therapy; Iodine Radioisotopes; Lymph Node Excision; Lymph Nodes; Sentinel Lymph Node Biopsy; Axilla; Neoplasm Staging
PubMed: 38531689
DOI: 10.1093/bjs/znae071 -
Breast Cancer Research and Treatment Apr 2021Marking of cytology-proven metastatic axillary lymph node in breast cancer patients before neoadjuvant treatment and its subsequent surgical retrieval have been shown to... (Review)
Review
BACKGROUND
Marking of cytology-proven metastatic axillary lymph node in breast cancer patients before neoadjuvant treatment and its subsequent surgical retrieval have been shown to reduce the false-negative rate of sentinel lymph node biopsy. A systematic review was performed to evaluate different strategies in nodal marking and localization.
METHODS
PubMed, Embase, EBSCOhost, and the Cochrane library literature databases were searched systematically to address the identification rate and retrieval rate of marked axillary lymph nodes. Studies were eligible if they performed nodal marking before neoadjuvant treatment, followed by selective extirpation of these marked axillary lymph nodes in definitive surgery RESULTS: Fifteen studies with a total of 703 patients were included. Index axillary lymph nodes were marked by clips or tattooed prior to the commencement of neoadjuvant treatment. In our pooled analysis, eighty-eight percent of the clipped nodes and ninety-seven percent of the tattooed nodes were successfully retrieved. Among these patients, seventy-seven percent of these marked axillary lymph nodes were also sentinel lymph nodes.
CONCLUSION
Marking and selectively removing cytology-proven metastatic axillary lymph nodes after neoadjuvant treatment is feasible. An acceptably high nodal retrieval rate could be achieved using various methods of nodal marking and localization techniques.
Topics: Axilla; Breast Neoplasms; Female; Humans; Lymph Node Excision; Lymph Nodes; Neoadjuvant Therapy; Neoplasm Staging; Sentinel Lymph Node Biopsy
PubMed: 33611665
DOI: 10.1007/s10549-021-06118-6 -
Health Technology Assessment... Jan 2015In breast cancer patients, sentinel lymph node biopsy is carried out at the same time as the removal of the primary tumour to postoperatively test with histopathology... (Review)
Review
A systematic review and economic evaluation of intraoperative tests [RD-100i one-step nucleic acid amplification (OSNA) system and Metasin test] for detecting sentinel lymph node metastases in breast cancer.
BACKGROUND
In breast cancer patients, sentinel lymph node biopsy is carried out at the same time as the removal of the primary tumour to postoperatively test with histopathology for regional metastases in the sentinel lymph node. Those patients with positive test results are then operated on 2-4 weeks after primary surgery to remove the lymph nodes from the axilla (axillary lymph node dissection, ALND). New molecular tests RD-100i [one-step nucleic acid amplification (OSNA); based on messenger RNA amplification to identify the cytokeratin-19 (CK19) gene marker] (Sysmex, Norderstedt, Germany) and Metasin (using the CK19 and mammaglobin gene markers) (Cellular Pathology, Princess Alexandra Hospital NHS Trust, Harlow, UK) are intended to provide an intraoperative diagnosis, thereby avoiding the need for postoperative histopathology and, in positive cases, a second operation for ALND.
OBJECTIVE
To evaluate the clinical effectiveness and cost-effectiveness of using OSNA and Metasin in the NHS in England for the intraoperative diagnosis of sentinel lymph nodes metastases, compared with postoperative histopathology, the current standard.
DATA SOURCES
Electronic databases including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library and the Health Economic Evaluations Database as well as clinical trial registries, grey literature and conference proceedings were searched up to July 2012.
REVIEW METHODS
A systematic review of the evidence was carried out using standard methods. Single-gate studies were used to estimate the accuracy of OSNA with histopathology as the reference standard. The cost-effectiveness analysis adapted an existing simulation model of the long-term costs and health implications of early breast cancer diagnostic outcomes. The model accounted for the costs of an extended first operation with intraoperative testing, the loss of health-related quality of life (disutility) from waiting for postoperative test results, disutility and costs of a second operation, and long-term costs and disutility from lymphoedema related to ALND, adjuvant therapy, locoregional recurrence and metastatic recurrence.
RESULTS
A total of 724 references were identified in the searches, of which 17 studies assessing test accuracy were included in the review, 15 on OSNA and two on Metasin. Both Metasin studies were unpublished. OSNA sensitivity of 84.5% [95% confidence interval (CI) 74.7% to 91.0%] and specificity of 91.8% (95% CI 87.8% to 94.6%) for patient nodal status were estimated in a meta-analysis of five studies [unadjusted for tissue allocation bias (TAB)]. At these values and a 20% node-positive rate, OSNA resulted in lifetime discounted cost-savings of £498 and a quality-adjusted life-year (QALY) loss of 0.048 relative to histopathology, that is, £4324 saved per QALY lost. The most favourable plausible scenario for OSNA in terms of the node-positive rate (range 10-40%), diagnostic accuracy values (91.3% sensitivity and 94.2% specificity, from three reports that adjusted for TAB), the costs of histopathology, OSNA and second surgery, and long-term costs and utilities resulted in a maximum saving per QALY lost of £10,500; OSNA sensitivity and specificity would need to be ≥ 95% for this figure to be ≥ £20,000.
LIMITATIONS
There is limited evidence on the diagnostic test accuracy of intraoperative tests. The quality of information on costs of resource utilisation during the diagnostic pathway is low and no evidence exists on the disutility of waiting for a second surgery. No comparative studies exist that report clinical outcomes of intraoperative diagnostic tests. These knowledge gaps have more influence on the decision than current uncertainty in the performance of postoperative histopathology in standard practice.
CONCLUSIONS
One-step nucleic acid amplification is not cost-effective for the intraoperative diagnosis of sentinel lymph node metastases. OSNA is less accurate than histopathology and the consequent loss of health benefits in this patient group is not compensated for by health gains elsewhere in the health system that may be obtained with the cost-savings made. The evidence on Metasin is insufficient to evaluate its cost-effectiveness.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42012002889.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Axilla; Breast Neoplasms; Cost-Benefit Analysis; England; Humans; Intraoperative Period; Lymph Nodes; Lymphatic Metastasis; Nucleic Acid Amplification Techniques; Quality of Life; Quality-Adjusted Life Years; Sensitivity and Specificity; Sentinel Lymph Node Biopsy; State Medicine
PubMed: 25586547
DOI: 10.3310/hta19020