The sentinel node negative axilla: is it a no-go zone?

The technique of sentinel node biopsy (SNB) presents a great opportunity to reduce the morbidity of surgical treatment of breast cancer. Using either dye, isotope or a combination, after completing a learning process a sensitivity of 80-99% may be achieved. Most surgeons would aim for a sensitivity of 95% but this will mean that 5% of patients will be under-staged, with disease within the axilla and possibly inappropriate advice with regard to adjuvant systemic therapy. Injudicious use of sentinel biopsy will lead to more local relapses and may diminish or neutralize gains from systemic therapy.     

What's new in sentinel node biopsy?

Sentinel node (SN) biopsy is become a standard of care in breast cancer surgical practice. However, the advent of this technique, recently discussed during the 29th San Antonio Breast Cancer Symposium 2006, revealed new questions, which the concept of the SN procedure raises: can we increase the current indications? Could be axillary lymph node dissection avoided in patients with metastatic SN? the morbidity of the biopsy of the SN, which is the prognostic value of micrometastatis discovered by the diffusion of the ultra-stadification of the SNs?     

Predictive factors for non-sentinel lymph node involvement in breast cancer patients with a positive sentinel node: should we consider sentinel node-related factors?

Introduction  Sentinel node (SN) biopsy to predict axillary involvement in breast cancer patients is a common practice. After a positive SN, additional metastases are present in an unpredictable percentage, as variable as 13–66%, of axillary clearances. Our aim is to define variables associated with non-sentinel node (NSN) metastases and to determine the predictive value of a derived clinical decision rule. Methods  A consecutive series of patients with a positive SN submitted to SN biopsy plus axillary dissection was evaluated from June 1999 to December 2004 (n=143). Patient-, tumour- and SN-related variables were analysed in relation to the presence of additional metastasis. Univariate and multivariate analyses were done and predictive values of a clinical decision rule based on significant variables were estimated. Results  A total of 66 patients had metastasis in non-sentinel axillary nodes. No significant differences were present between this group and those with only the SN metastasised. Significant and independent association was found between NSN positivity and increasing tumour size, the presence of multifocality and the presence of peritumoral lymph channel invasion. Conclusions  A first derivation of a simple rule based on tumour-related variables concurs to define the presence of NSN metastasis. Care should be taken when including SN-related variables in these algorithms.     

Can axillary dissection be avoided in patients with sentinel lymph node metastasis?

BACKGROUND: Who should undergo a completion dissection following identification of a +sentinel lymph node (SLN) is controversial. METHODS: The records of 1,133 patients who underwent SLN mapping were reviewed. The association between patient, tumor, and treatment characteristics and the presence of +SLNs and +nonSLNs was analyzed using two-way tables of frequency counts and Pearson chi2 test. Possible predictors of +SLNs and +nonSLNs were analyzed using simple and multiple logistic regression. RESULTS: One thousand one hundred forty-eight SLN procedures were performed. 367 procedures (32%) yielded +SLNs. For patients with a +SLN, on multiple logistic regression analysis LVSI, increasing numbers of +SLNs, decreasing numbers of negative SLNs, and increasing size of the largest SLN metastasis were statistically significantly associated with increased likelihood of nonSLN involvement. No subgroup was identified that did not have a significant rate of nonSLN involvement on completion axillary dissection, except those who had a large number of negative SLNs (> or =3) and small size of the largest SLN metastasis (<10 mm). CONCLUSIONS: A definitive answer to the question of who needs a completion axillary dissection awaits the results of ongoing trials. In the interim, our data does not support eliminating dissection for any subgroup of patients with +SLNs.     

Should all patients with melanoma between 1 and 2 mm Breslow thickness undergo sentinel lymph node biopsy?

BACKGROUND:

Sentinel lymph node (SLN) biopsy generally is recommended for patients who have melanoma with a Breslow thickness ≥1 mm. Most patients with melanoma between 1 mm and 2 mm thick have tumor‐negative SLNs and an excellent long‐term prognosis. The objective of the current study was to evaluate prognostic factors in this subset of patients and determine whether all such patients require SLN biopsy.

METHODS:

Patients with melanoma between 1 mm and 2 mm in Breslow thickness were evaluated from a prospective multi‐institutional study of SLN biopsy for melanoma. Disease‐free survival (DFS) and overall survival (OS) were evaluated by Kaplan‐Meier analysis to compare patients with melanoma that measured from 1.0 mm to 1.59 mm (Group A) versus patients with melanoma that measured from ≥1.6 mm to 2.0 mm thick (Group B). Univariate and multivariate analyses were performed to evaluate factors predictive of tumor‐positive SLN status, DFS, and OS.

RESULTS:

The current analysis included 1110 patients with a median follow‐up of 69 months. SLN status was tumor‐positive in 133 of 1110 patients (12%) including 66 of 762 patients (8.7%) in Group A and 67 of 348 patients (19.3%) in Group B (P < .0001). On multivariate analysis, age, Breslow thickness, and lymphovascular invasion were independently predictive of a tumor‐positive SLN (P < .05). DFS (P < .0001) and OS (P = .0001) were significantly better for Group A than for Group B. When tumor thickness was treated as either a continuous variable (P < 0.0001) or a categorical variable (P < .0001), it was significantly predictive of DFS and OS. On multivariate analysis, Breslow thickness, age, ulceration, histologic subtype, regression, Clark level, and SLN status were significant factors predicting DFS; and Breslow thickness, age, primary tumor location, sex, ulceration, and SLN status were significant factors predicting OS (P < .05). A subgroup of patients who had tumors <1.6 mm in Breslow thickness, had no lymphovascular invasion, and were aged ≥59 years had a low risk (5%) of tumor‐positive SLN.

CONCLUSIONS:

The current findings indicated that there is significant diversity in the biologic behavior of melanoma between 1 mm and 2 mm in Breslow thickness. SLN biopsy is recommended for all such patients to identify those with lymph node metastasis who are at the greatest risk of recurrence and mortality. Cancer 2010. © 2010 American Cancer Society.     

What is a sentinel node? Re‐evaluating the 10% rule for sentinel lymph node biopsy in melanoma

INTRODUCTION: Many surgeons use the "10% rule" to define whether a lymph node is a sentinel node (SLN) when staging malignant melanoma. However, this increases the number of SLN removed and the time and cost of the procedure. We examined the impact of raising this threshold on the accuracy of the procedure. METHODS: We reviewed the records of 561 patients with melanoma (624 basins) who underwent SLN with technetium Tc99 labeled sulfur colloid using a definition of a SLN as 10% of that of the node with the highest counts per minute (CPM). RESULTS: Of the 624 basins, 154 (25%) were positive for metastases. An average of 1.9 nodes per basin were removed (range 1-6). Metastases were found in the hottest node in 137 cases (89% of positive basins, 97% of basins overall). Increasing the threshold above 10% decreased the number of nodes excised and the costs involved, but incrementally raised the number of false negative cases above baseline (a 4% increase for a "20% rule," 5% for a "30% rule," 6% for a "40% rule," and 7% for a "50% rule"). Taking only the hottest node would raise the false negative rate by 11%. CONCLUSIONS: Although using thresholds higher than 10% for the definition of a SLN will minimize the extent of surgery and decrease the costs associated with the procedure, it will compromise the accuracy of the procedure and is not recommended.     

Breast sentinel lymph node navigation with three-dimensional computed tomography–lymphography: a 12-year study

Purpose

To evaluate the utility of three-dimensional (3D) computed tomography (CT)?lymphography (LG) breast sentinel lymph node navigation in our institute.

Patients and methods

Between 2002 and 2013, we preoperatively identified sentinel lymph nodes (SLNs) in 576 clinically node-negative breast cancer patients with T1 and T2 breast cancer using 3D CT–LG method. SLN biopsy (SLNB) was performed in 557 of 576 patients using both the images of 3D CT–LG for guidance and the blue dye method.

Results

Using 3D CT–LG, SLNs were visualized in 569 (99 %) of 576 patients. Of 569 patients, both lymphatic draining ducts and SLNs from the peritumoral and periareolar areas were visualized in 549 (96 %) patients. Only SLNs without lymphatic draining ducts were visualized in 20 patients. Drainage lymphatic pathways visualized with 3D CT–LG (549 cases) were classified into four patterns: single route/single SLN (355 cases, 65 %), multiple routes/single SLN (59 cases, 11 %) single route/multiple SLNs (62 cases, 11 %) and multiple routes/multiple SLNs (73 cases, 13 %). SLNs were detected in 556 (99.8 %) of 557 patients during SLNB.

Conclusion

CT–LG is useful for preoperative visualization of SLNs and breast lymphatic draining routes. This preoperative method should contribute greatly to the easy detection of SLNs during SLNB.

     

When is sentinel node biopsy for breast cancer contraindicated?

Sentinel node biopsy is an exciting new tool for staging the axilla in an accurate and less morbid way. It is becoming more apparent that sentinel node biopsy is appropriate in a variety of settings. When an experienced multidisciplinary team is present and patients are properly selected sentinel node biopsy can be performed with greater than 95% accuracy. The current data regarding contraindications for the use of sentinel lymph node biopsy and lymphatic mapping is reviewed.     

Is there a benefit to sentinel lymph node biopsy in patients with T4 melanoma?

BACKGROUND:

Controversy exists as to whether patients with thick (Breslow depth >4 mm), clinically lymph node‐negative melanoma require sentinel lymph node (SLN) biopsy. The authors examined the impact of SLN biopsy on prognosis and outcome in this patient population.

METHODS:

A review of the authors' institutional review board‐approved melanoma database identified 293 patients with T4 melanoma who underwent surgical excision between 1998 and 2007. Patient demographics, histologic features, and outcome were recorded and analyzed.

RESULTS:

Of 227 T4 patients who had an SLN biopsy, 107 (47%) were positive. The strongest predictors of a positive SLN included angiolymphatic invasion, satellitosis, or ulceration of the primary tumor. Patients with a T4 melanoma and a negative SLN had a significantly better 5‐year distant disease‐free survival (DDFS) (85.3% vs 47.8%; P < .0001) and overall survival (OS) (80% vs 47%; P < .0001) compared with those with metastases to the SLN. For SLN‐positive patients, only angiolymphatic invasion was a significant predictor of DDFS, with a hazard ratio of 2.29 (P = .007). Ulceration was not significant when examining SLN‐positive patients but the most significant factor among SLN‐negative patients, with a hazard ratio of 5.78 (P = .02). Increasing Breslow thickness and mitotic rate were also significantly associated with poorer outcome. Patients without ulceration or SLN metastases had an extremely good prognosis, with a 5‐year OS >90% and a 5‐year DDFS of 95%.

CONCLUSIONS:

Clinically lymph node‐negative T4 melanoma cases should be strongly considered for SLN biopsy, regardless of Breslow depth. SLN lymph node status is the most significant prognostic sign among these patients. T4 patients with a negative SLN have an excellent prognosis in the absence of ulceration and should not be considered candidates for adjuvant high‐dose interferon. Cancer 2009. © 2009 American Cancer Society.     

Is axillary clearance the standard of care for breast cancer patients with sentinel node involvement?

Sentinel node biopsy (SNB) has become accepted for staging the axilla in early breast cancer with avoidance of axillary lymph node dissection (ALND) in patients with negative SNB. For those with positive SNB, the standard surgical management is ALND; however, this approach is increasingly being challenged. The central problem is that it is not possible to preoperatively predict whether the SNB will be positive, and it is even more difficult to determine the likelihood of nonsentinel node positivity. Various histopathological features indicate increased risk of nonsentinel node metastasis, including size of SNB metastasis, presence of lymphovascular invasion, multifocality, number of involved sentinel nodes and, conversely, the number of negative sentinel nodes. These features have been combined to produce predictive nomograms but, understandably, these still lack precision. Presently, the decision to avoid ALND will depend upon both the clinician and the patient's impression of risk, but if either requires assurance that no residual axillary disease remains, a completion clearance will be required.     

Should all melanoma patients undergo sentinel lymph node biopsy?

PURPOSE OF REVIEW: It is now well established that sentinel lymph node biopsy is a powerful test to predict prognosis for melanoma patients. Controversy exists, however, regarding the appropriate selection of patients for sentinel lymph node biopsy, especially among patients with thin melanomas (< 1 mm Breslow thickness), thick melanomas (> 4 mm Breslow thickness), or locally recurrent melanoma. RECENT FINDINGS: The majority of the studies in the past 2 years regarding sentinel lymph node biopsy have been concerned with identifying factors that can better predict regional nodal metastasis and survival. Other studies have proposed a better risk stratification model, which includes these factors, to best select those patients at increased risk of nodal positivity. SUMMARY: Although much research has been done to select appropriate patients for sentinel lymph node biopsy based on multiple prognostic factors, further studies are necessary to completely define the indications for this procedure in patients with thin, thick and locally recurrent melanomas.