Different localization techniques during surgery of non-palpable breast lumps

Review question
We reviewed the evidence on new localization techniques against the gold standard (wire-guided) for the surgical removal of non-palpable breast lumps.

Background
Breast cancer screening has brought a shift towards earlier detection of non-palpable breast lumps (i.e. lumps that cannot be felt by palpation by a doctor). Surgical removal of non-palpable lumps can be challenging as it involves locating and removing the entire lump while removing the smallest amount of healthy tissue possible and maintaining optimal breast appearance. The commonly used technique in guiding the surgical removal of non-palpable breast lumps is wire-guided localization (WGL; inserting a wire to the centre of the lump). We wanted to examine whether WGL was better or worse than other newer alternatives.

Study characteristics
The evidence is current to 30 March 2015. Eleven trials met the inclusion criteria of this Cochrane review but we included only eight in our analyses. Six studies compared WGL to radio-guided occult lesion localization (ROLL; it uses a radioactive tracer injected into the lump) and two studies compared WGL to radioactive seed localization (RSL; it involves implanting an Iodine seed in the centre of the tumour). We included a total of 1273 participants with non-palpable breast lumps (627 participants (WGL), 443 participants (ROLL), 203 participants (RSL)). There was considerable variation in the participants' tumours in the studies. The included studies did not report any long-term outcomes.

Key results
People who had WGL and ROLL treatment gave similar results in being able to successfully localize and remove the lump as planned, and also similar postoperative complication rates. ROLL resulted in slightly fewer positive tumour margins (that is, the when the tumour is removed, some surrounding tissue is removed and cancer cells extend out into the margins) compared to WGL, and ROLL also had lower re-intervention rates (that is, less likely to require further surgery) over WGL, but neither differences were statistically significant.

WGL was superior to RSL in successfully locating the lump, but both techniques seemed equally effective in successfully removing the lump. Similarly, RSL provided fewer positive tumour margins compared to WGL (though not statistically significant). However only one study reported on re-intervention rates where the rates were comparable for RSL and WGL.

The studies either did not report or inconsistently reported information on the operation time, length of hospital stay, recurrence, breast appearance, and participant preference when using these different techniques.

Quality of the evidence
The overall quality of the evidence was good. There was no clear evidence to support one guided technique for surgically removing a non-palpable breast lesion over another. The results from this Cochrane review support the continuing use of WGL as a safe and tested technique. ROLL and RSL could be offered to participants as a comparable replacement for WGL. This Cochrane review highlights the need for more fully-powered trials (that is, trials large enough to detect intervention differences) to evaluate the best localization techniques.

Authors' conclusions: 

Owing to a lack of trials in certain localization techniques, we could only draw conclusions about ROLL and RSL versus WGL. There is no clear evidence to support one guided technique for surgically excising a non-palpable breast lesion over another. Results from this Cochrane review support the continued use of WGL as a safe and tested technique that allows for flexibility in selected cases when faced with extensive microcalcification. ROLL and RSL could be offered to patients as a comparable replacement for WGL as they are equally reliable. Other techniques such as IOUS, RCML, and CAL are of academic interest, but recommendation for routine use in the clinical environment and oncological outcomes require further validation. The results of this Cochrane review also stress the need for more fully powered RCTs to evaluate the best technique according to the comprehensive criteria described, with a more consistent and standardized approach in outcome reporting.

Read the full abstract...
Background: 

Breast cancer is the most common form of cancer and the second leading cause of death amongst women in Europe. Amongst five invasive cancers per 1000 women detected in screening, 2.7 were < 15 mm in diameter; and others reported that over one third of excised breast lesions were clinically occult. The challenge is to accurately locate small non-palpable lesions intraoperatively for optimal therapeutic outcome. A secondary important goal is to remove the smallest amount possible of healthy glandular tissue for optimal cosmesis. Currently the most widely adopted approach (80% in one survey) in guided breast-conserving surgery for excising non-palpable breast lesions is wire-guided localization (WGL). With the clinical setting shifting towards earlier non-palpable breast lesions being detected through screening, we investigated whether the current standard in assisting surgical excision of these lesions, WGL, yields the best therapeutic outcome for women with breast cancer.

Objectives: 

To assess the therapeutic outcomes of any new form of guided surgical intervention for non-palpable breast lesions against wire-guided localization, the current gold standard.

Search strategy: 

We searched the Cochrane Breast Cancer Group's (CBCG) Specialized Register, MEDLINE (via PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal from the earliest available date up to 30 March 2015. We also handsearched recent conference proceedings and sought information from experts in the field.

Selection criteria: 

Two review authors, BC and RJ, independently screened by title and abstract the studies we had identified through the search strategy; when this was inconclusive, they examined the full-text article for inclusion. We resolved any discrepancies regarding eligibility by discussion with a third review author, RA.

Data collection and analysis: 

Three review authors, BC, JW, and RJ, independently extracted data using a standardized data sheet. We performed all analyses using Review Manager (RevMan) or the R meta package, and in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. We reported results via a graphical assessment using forest plots showing the study estimates. We considered and discussed additional subgroup and sensitivity analyses.

Main results: 

We identified 11 randomized controlled trials (RCTs) that met the inclusion criteria of this Cochrane review and included eight trials in the meta-analyses. Six RCTs compared radioguided occult lesion localization (ROLL) versus WGL, and two RCTs compared radioactive iodine (125I) seed localization (RSL) versus WGL. Of the three remaining trials, one RCT compared cryo-assisted techniques (CAL) versus WGL, one compared intraoperative ultrasound-guided lumpectomy (IOUS) versus WGL, and one compared modified ROLL technique in combination with methylene dye (RCML) versus WGL. Of the trials we included in the meta-analysis, there were a total of 1273 participants with non-palpable breast lesions (627 participants (WGL); 443 participants (ROLL); and 203 participants (RSL)). The participant population varied considerably between included trials, which included participants with both non-palpable benign and malignant lesions, and varied in defining clear margins. The included trials did not report any long-term outcomes.

In general, the outcomes of WGL, ROLL and RSL were comparable.

ROLL demonstrated favourable results in successful localization (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.16 to 2.28; 869 participants; six trials), positive excision margins (RR 0.74, 95% CI 0.42 to 1.29; 517 participants; five trials), and re-operation rates (RR 0.51, 95% CI 0.21 to 1.23; 583 participants; four trials) versus WGL, but none were statistically significant. WGL was significantly superior to RSL in successfully localizing non-palpable lesions (RR 3.85, 95% CI 1.21 to 12.19; 402 participants; two trials). However, for successful excision, ROLL and RSL have comparable outcomes versus WGL (ROLL versus WGL: RR 1.00, 95% CI 0.99 to 1.01; 871 participants; six trials; RSL versus WGL: RR 1.00, 95% CI 0.99 to 1.01; 402 participants; two trials). These findings were similar in that RSL demonstrated favourable results over WGL in positive tumour margins (RR 0.67, 95% CI 0.43 to 1.06; 366 participants; two trials), and re-operation rates (RR 0.80, 95% CI 0.48 to 1.32; 305 participants; one trial) but neither reached statistical significance. In contrast, WGL had fewer postoperative complications to both ROLL (RR 1.18, 95% CI 0.71 to 1.98; 642 participants; four trials) and RSL (RR 1.51, 95% CI 0.75 to 3.03; 305 participants; one trial), although this was also not statistically significant.

The overall quality of evidence was good. The main risk of bias amongst included studies consisted of incomplete data sets, selective reporting, and allocation concealment. Interpretation and applicability of this meta-analysis was hindered by the mixed indication of diagnostic versus therapeutic purposes when undertaking WGL, ROLL, or RSL, leading to a high level of mixed pathology in numerous trials. Other limitations include underpowered studies, lack of data in standardized format for meta-analysis, lack of complete data amongst the trials, and absence of long-term data.

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