To evaluate the impact of axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) on upper limb (UL) morbidity in breast cancer patients.
Axillary de-escalation is motivated by a ...desire to reduce harm of ALND. Understanding the impact of axillary surgery and disparities in operative procedures on postoperative arm morbidity would better direct resources to the point of need and cement the need for de-escalation strategies.
Embase, MEDLINE, CINAHL, and PsychINFO were searched from 1990 until March 2020. Included studies were randomized-controlled and observational studies focusing on UL morbidities, in breast surgery patients. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The prevalence of UL morbidity comparing SLNB and ALND at <12 months, 12 to 24 months, and beyond 24 months were analyzed.
Sixty-seven studies were included. All studies reported a higher rate of lymphedema and pain after ALND compared with SLNB. The difference in lymphedema and pain prevalence between SLNB and ALND was 13.7% (95% confidence interval: 10.5-16.8, P <0.005) and 24.2% (95% confidence interval: 12.1-36.3, P <0.005), respectively. Pooled estimates for prevalence of reduced strength and range of motion after SLNB and ALND were 15.2% versus 30.9% and 17.1% versus 29.8%, respectively. Type of axillary surgery, greater body mass index, and radiotherapy were some of the predictors for UL morbidities.
Prevalence of lymphedema after ALND was higher than previously estimated. ALND patients experienced greater rates of lymphedema, pain, reduced strength, and range of motion compared with SLNB. The findings support the continued drive to de-escalate axillary surgery.
Background
Pelvic lymphadenectomy provides prognostic information for those diagnosed with endometrial (womb) cancer and provides information that may influence decisions regarding adjuvant ...treatment. However, studies have not shown a therapeutic benefit, and lymphadenectomy causes significant morbidity. The technique of sentinel lymph node biopsy (SLNB), allows the first draining node from a cancer to be identified and examined histologically for involvement with cancer cells. SLNB is commonly used in other cancers, including breast and vulval cancer. Different tracers, including colloid labelled with radioactive technetium‐99, blue dyes, e.g. patent or methylene blue, and near infra‐red fluorescent dyes, e.g. indocyanine green (ICG), have been used singly or in combination for detection of sentinel lymph nodes (SLN).
Objectives
To assess the diagnostic accuracy of sentinel lymph node biopsy (SLNB) in the identification of pelvic lymph node involvement in women with endometrial cancer, presumed to be at an early stage prior to surgery, including consideration of the detection rate.
Search methods
We searched MEDLINE (1946 to July 2019), Embase (1974 to July 2019) and the relevant Cochrane trial registers.
Selection criteria
We included studies that evaluated the diagnostic accuracy of tracers for SLN assessment (involving the identification of a SLN plus histological examination) against a reference standard of histological examination of removed pelvic +/‐ para‐aortic lymph nodes following systematic pelvic +/‐ para‐aortic lymphadenectomy (PLND/PPALND) in women with endometrial cancer, where there were sufficient data for the construction of two‐by‐two tables.
Data collection and analysis
Two review authors (a combination of HN, JM, NW, RG, and WH) independently screened titles and s for relevance, classified studies for inclusion/exclusion and extracted data. We assessed the methodological quality of studies using the QUADAS‐2 tool. We calculated the detection rate as the arithmetic mean of the total number of SLNs detected out of the total number of women included in the included studies with the woman as the unit of analysis, used univariate meta‐analytical methods to estimate pooled sensitivity estimates, and summarised the results using GRADE.
Main results
The search revealed 6259 unique records after removal of duplicates. After screening 232 studies in full text, we found 73 potentially includable records (for 52 studies), although we were only able to extract 2x2 table data for 33 studies, including 2237 women (46 records) for inclusion in the review, despite writing to trial authors for additional information.
We found 11 studies that analysed results for blue dye alone, four studies for technetium‐99m alone, 12 studies that used a combination of blue dye and technetium‐99m, nine studies that used indocyanine green (ICG) and near infra‐red immunofluorescence, and one study that used a combination of ICG and technetium‐99m. Overall, the methodological reporting in most of the studies was poor, which resulted in a very large proportion of 'unclear risk of bias' ratings.
Overall, the mean SLN detection rate was 86.9% (95% CI 82.9% to 90.8%; 2237 women; 33 studies; moderate‐certainty evidence). In studies that reported bilateral detection the mean rate was 65.4% (95% CI 57.8% to 73.0%) . When considered according to which tracer was used, the SLN detection rate ranged from 77.8% (95% CI 70.0% to 85.6%) for blue dye alone (559 women; 11 studies; low‐certainty evidence) to 100% for ICG and technetium‐99m (32 women; 1 study; very low‐certainty evidence). The rates of positive lymph nodes ranged from 5.2% to 34.4% with a mean of 20.1% (95% CI 17.7% to 22.3%).
The pooled sensitivity of SLNB was 91.8% (95% CI 86.5% to 95.1%; total 2237 women, of whom 409 had SLN involvement; moderate‐certainty evidence). The sensitivity for of SLNB for the different tracers were: blue dye alone 95.2% (95% CI 77.2% to 99.2%; 559 women; 11 studies; low‐certainty evidence); Technetium‐99m alone 90.5% (95% CI 67.7% to 97.7%; 257 women; 4 studies; low‐certainty evidence); technetium‐99m and blue dye 91.9% (95% CI 74.4% to 97.8%; 548 women; 12 studies; low‐certainty evidence); ICG alone 92.5% (95% CI 81.8% to 97.1%; 953 women; 9 studies; moderate‐certainty evidence); ICG and blue dye 90.5% (95% CI 63.2.% to 98.1%; 215 women; 2 studies; low‐certainty evidence); and ICG and technetium‐99m 100% (95% CI 63% to 100%; 32 women; 1 study; very low‐certainty evidence). Meta‐regression analyses found that the sensitivities did not differ between the different tracers used, between studies with a majority of women with FIGO stage 1A versus 1B or above; between studies assessing the pelvic lymph node basin alone versus the pelvic and para‐aortic lymph node basin; or between studies that used subserosal alone versus subserosal and cervical injection. It should be noted that a false‐positive result cannot occur, as the histological examination of the SLN is unchanged by the results from any additional nodes removed at systematic lymphadenectomy.
Authors' conclusions
The diagnostic test accuracy for SLNB using either ICG alone or a combination of a dye (blue or ICG) and technetium‐99m is probably good, with high sensitivity, where a SLN could be detected. Detection rates with ICG or a combination of dye (ICG or blue) and technetium‐99m may be higher. The value of a SLNB approach in a treatment pathway, over adjuvant treatment decisions based on uterine factors and molecular profiling, requires examination in a high‐quality intervention study.
To provide evidence-based recommendations to practicing oncologists, surgeons, and radiation therapy clinicians to update the 2005 clinical practice guideline on the use of sentinel node biopsy (SNB) ...for patients with early-stage breast cancer.
The American Society of Clinical Oncology convened an Update Committee of experts in medical oncology, pathology, radiation oncology, surgical oncology, guideline implementation, and advocacy. A systematic review of the literature was conducted from February 2004 to January 2013 in Medline. Guideline recommendations were based on the review of the evidence by Update Committee.
This guideline update reflects changes in practice since the 2005 guideline. Nine randomized clinical trials (RCTs) met systematic review criteria for clinical questions 1 and 2; 13 cohort studies informed clinical question 3.
Women without sentinel lymph node (SLN) metastases should not receive axillary lymph node dissection (ALND). Women with one to two metastatic SLNs planning to undergo breast-conserving surgery with whole-breast radiotherapy should not undergo ALND (in most cases). Women with SLN metastases who will undergo mastectomy should be offered ALND. These three recommendation are based on RCTs. Women with operable breast cancer and multicentric tumors, with ductal carcinoma in situ (DCIS) who will undergo mastectomy, who previously underwent breast and/or axillary surgery, or who received preoperative/neoadjuvant systemic therapy may be offered SNB. Women who have large or locally advanced invasive breast cancer (tumor size T3/T4), inflammatory breast cancer, or DCIS (when breast-conserving surgery is planned) or are pregnant should not undergo SNB. These recommendations are based on cohort studies and/or informal consensus. In some cases, updated evidence was insufficient to update previous recommendations.
Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in clinically node-negative (cN0) breast cancer patients without neoadjuvant chemotherapy (NAC). The application of SLNB ...in patients receiving NAC has also been explored. Evidence supports its use after NAC in pretreatment cN0 patients. Nonetheless, its routine use in all the pretreatment node-positive patients who become cN0 after NAC is unjustified due to the unacceptably high false-negative rate, which can be improved in a subset of patients. Axillary surgery omission in selected patients with a low risk of ALN metastasis has gained more and more research interest because the SLNs are tumor-free in more than 70% of all patients. To avoid drawbacks of conventional mapping methods, novel techniques for SLN detection have been developed and shown to be highly accurate in patients with early breast cancer. This article reviews the progress in SLNB in patients with breast cancer.
Ever since Kitai first performed fluorescent navigation of sentinel lymph nodes (SLNs) using indocyanine green (ICG) dye with a charge-couple device and light emitting diodes, the intraoperative use ...of near infrared fluorescence has served a critical role in increasing our understanding in various fields of surgical oncology. Here the authors review the emerging role of the ICG fluorophore in the development of our comprehension of the lymphatic system and its use in SLN mapping and biopsy in various cancers. In addition, they introduce the novel role of ICG-guided video angiography as a new intraoperative method of assessing microvascular circulation. The authors attempt to discuss the promising potential in addition to assessing several challenges and limitations in the context of specific surgical procedures and ICG as a whole. PubMed and Medline literature databases were searched for ICG use in clinical surgical settings. Despite ICG's significant impact in various fields of surgical oncology, ICG is still in its nascent stages, and more in-depth studies need to be carried out to fully evaluate its potential and limitations.
The use of sentinel lymph node biopsy (SLNB) following neoadjuvant chemotherapy (NAC) in patients presenting with clinically positive lymph nodes remains controversial.
A computer-aided search of the ...literature regarding SLNB in clinically node-positive breast cancer treated with NAC was carried out to identify the false negative rate (FNR), sentinel lymph node identification rate (IR), and axillary pathological complete response (pCR).
Nineteen articles were used in the analysis yielding 3,398 patients. The pooled estimate of the FNR was 13% and that of the IR was 91%. The adjusted pCR rate was 47%. A trend toward significance was observed with only clinical stage N1 (cN1) disease whereby clinical stage N1 was associated with an increased pCR rate when compared to N2 or N3 disease (P = .06).
SLNB after NAC in biopsy-proven node-positive patients results in reasonably acceptable FNR and IR, making it a valid alternative management strategy to axillary dissection. More refined patient selection and optimal techniques can improve the FNR and IR in this patient population.
•The pooled estimate of false negative rate was 13%.•The pooled estimate of identification rate was 91%.•The adjusted pathological complete response rate was 47%.•There was a trend toward significance with only cN1 disease.•SLNB post NAC in node-positive patients is a valid alternative strategy to ALND.
Due to a series of complications associated with traditional axillary lymph node dissection, sentinel lymph node biopsy has now replaced axillary lymph node dissection as the standard axillary ...staging procedure for patients with negative axillary lymph nodes in both domestic and international clinical practice. With the increased application of breast-conserving surgery and the subsequent increase in the number of patients with ipsilateral breast recurrence after breast-conserving surgery, the appropriate axillary evaluation of such patients has become a new topic of clinical concern, and the application of repeat sentinel lymph node biopsy has become one of the focal points of this topic. It has been shown that repeat sentinel lymph node biopsy is a feasible and safe method for axillary evaluation in patients with ipsilateral breast tumor recurrence after breast-conserving surgery, and that treatment can be adjusted for some patients depending on axillary lymph node status. However, due to the relative lack of studies on the prognostic impact of repeat sentinel lymph node biopsy results and with the development of non-invasive screening techniques, the necessity of repeat sentinel lymph node biopsy in this group of patients remains controversial and needs to be explored in future high-quality prospective trials. This article compiled and summarized the previous literature related to repeat sentinel lymph node biopsy, and focused on its feasibility, safety and clinical application value for clinical reference.
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 1.16; 12,864 participants; 19 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.
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