Abstract and Background
Abstract
Background: The benefits of sentinel lymph node biopsy (SLNB) for breast cancer patients with histologically negative axillary nodes, in whom axillary lymph node dissection (ALND) is thereby avoided, are now established. Low false negative rate, certainly with blue dye technique, mostly reflects the established high inherent accuracy of SLNB and low axillary nodal metastatic load (subject to patient selection). SLN identification rate is influenced by volume, injection site and choice of mapping agent, axillary nodal metastatic load, SLN location and skill at axillary dissection. Being more subject to technical failure, SLN identification seems to be a more reasonable variable for learning curve assessment than false negative rate.
Methylene blue is as good an SLN mapping agent as Isosulfan blue and is much cheaper. Addition of radio-colloid mapping to blue dye does not achieve a sufficiently higher identification rate to justify the cost. Methylene blue is therefore the agent of choice for SLN mapping in developing countries.
The American Society of Breast Surgeons recommends that, for competence, surgeons should perform 20 SLNB but admits that the learning curve with a standardized technique may be "much shorter". One appropriate remedy for this dilemma is to plot individual learning curves.
Methods: Using methylene blue dye, experienced breast surgeons performed SLNB in selected patients with breast cancer (primary tumor < 5 cm and clinically negative ipsilateral axilla). Intraoperative assessment and completion ALND were performed for standardization on the first 13 of 24 cases. SLN identification was plotted for each surgeon on a tabular cumulative sum (CUSUM) chart with sequential probability ratio test (SPRT) limits based on a target identification rate of 85%.
Results: The CUSUM plot crossed the SPRT limit line after 8 consecutive, positively identified SLN, signaling achievement of an acceptable level of competence.
Conclusion: Tabular CUSUM charting, based on a justified choice of parameters, indicates that the learning curve for SLNB using methylene blue dye is completed after 8 consecutive, positively identified SLN. CUSUM charting may be used to plot individual learning curves for trainee surgeons by applying a proxy parameter for failure in the presence of a mentor (such as failed SLN identification within 15 minutes).
Background
The benefits of sentinel lymph node biopsy (SLNB) in breast cancer patients with histologically negative axillary nodes, in whom axillary lymph node dissection (ALND) is thereby avoided, have now been well established. The risks of lymphedema of the ipsilateral upper limb and distressing paraesthesiae and pain syndromes associated with ALND are reduced with consequential improved quality of life. SLNB is an accurate test of the metastatic status of axillary nodes, particularly when adjacent, palpably abnormal nodes are also reaped, with a false negative rate not exceeding 5% in properly selected patients (those with primary breast tumors not exceeding 5 cm and clinically negative axillae) and therefore, not surprisingly, has also been established as an oncologically safe and adequate procedure with disease free and overall survival similar to stage-matched patients having ALND.
Methylene blue dye is much cheaper than Isosulfan blue, does not cause hypersensitivity reactions nor other significant complications (except skin necrosis, avoidable by meticulous injection technique when performing breast conserving surgery) and, most importantly, is as good as and possibly better at SLN mapping than Isosulfan blue. Side effects such as blue discoloration of urine, stool and skin (does not cause tattooing) over the injection site are temporary and benign. In North America and Europe, it is recommended that blue dye and radio-tracer mapping be combined as this approach may yield a higher SLN identification rate than blue dye alone, although some studies have not confirmed this advantage. Radio-tracer mapping is very expensive (prohibitively so in most developing countries), cumbersome (requiring time-consuming preoperative preparation and increased operating time), has no significant SLN detection advantage as single agent over blue dye (except detection of internal mammary SLN, an uncommon finding of doubtful clinical and therapeutic significance) and may pose radiation risk to pathologists handling the nodes. Combination of the two techniques achieves a range of 0% to 18% increase in SLN identification rate over blue dye alone. Since 60% of clinically negative axillae are also pathologically negative, combining the radio-labeled tracer technique with the blue dye technique stands to benefit only an additional 0 to 11 per 100 women (by way of avoidance of ALND). This seems to be an unjustifiably high price to pay for such a small additional benefit, especially since SLNB is not a therapeutic procedure and does not offer any survival advantage to patients. Methylene blue dye as a single agent is therefore well suited to enable surgeons in developing countries to offer the important technique of SLNB without significantly compromising the quality of the test.
The American Society of Breast Surgeons recommends that, for competence, surgeons should perform 20 SLNB procedures either under supervised mentoring by an experienced colleague or followed immediately by completion ALND. It is also recommended that the false negative rate not exceed 5% and the SLN identification rate not be less than 85%. Low false negative rate is a reflection of the high inherent accuracy with which the sentinel node reflects the metastatic status of axillary nodes, now an established fact, as well as a function of selection of patients for the procedure who are less likely to harbor lymph node metastases. SLN identification rate is, like false negative rate, subject to axillary nodal metastatic load (patient selection) but also to injection site, volume and choice of mapping agent, location of the SLN, and, importantly, the surgeon's skill at dissecting the axilla. Being more susceptible to technical failure, SLN identification therefore seems to be a more reasonable target for learning curve analysis than false negative rate. Others agree that SLN identification should be the objective of the learning process, especially since failure to find the SLN does not have therapeutically deleterious consequences, ALND being performed in those cases.
The American Society of Breast Surgeons admits that the learning curve for surgeons using a standardized technique may be "much shorter" than 20 cases but does not suggest a remedy by way of a reliable method for assessing individual learning curves. It should hardly be surprising that experienced breast surgeons can be expected to master this technique after just a few cases since, being skilled at ALND, they know how to find the nodes draining the breast and should therefore have little difficulty locating a blue sentinel node (radio-tracer mapping adds another level of difficulty), as long as patients are properly selected and the SLN resides within levels I and II of the axilla. Clearly a method is needed for plotting learning curves with the capacity to test and predict individual performance with reference to a standardized level of competence.
Cumulative sum (CUSUM) charting is one of a group of statistical process control methods used by engineers, particularly in manufacturing, to monitor quality of output and, with boundary limits set by the sequential probability ratio test (SPRT), to indicate when a process is out of control. Statistical process control methods are now being used in medicine predominantly for quality control monitoring but more recently, for learning curve analysis. CUSUM plots are an excellent method for determining learning curves for any procedure with output variables that can be dichotomized and hold the promise of individualizing credentialing and competency certification requirements and ending what has been called the tyranny of mandatory case numbers.
CUSUM analysis has been applied to the learning curve for SLNB as a retrospective quality control tool but not for prospective learning curve analysis. Other learning curve methodologies have also been applied for SLNB. In this study, using methylene blue dye as the mapping agent, tabular CUSUM control charting is used to prospectively evaluate the learning curve of individual surgeons for SLNB and signal achievement of an acceptable, predetermined level of competence.