PracticeUpdate Dermatology May 2019

EDITOR’S PICKS 13

EXPOSURES Patients were grouped together based on year of diagnosis, before and after 2009. MAIN OUTCOMES AND MEASURES To determine the sentinel lymph node biopsy rate before and after the implementation of the AJCC 7. RESULTS A total of 141 280 patients met inclu- sion criteria. Of 86 846 patients diagnosed from 2004 through 2009, 53.7% (49 644) were male and had a mean (SD) age of 57.7 (16.4) years. Of 54 434 patients diagnosed from 2010 through 2013, 54.3% (31 086) were male and had a mean (SD) age of 59.5 (15.9) years. After 2010, there was a 3.8% decrease in the number of nodal evidence, that information is relatively useless. What may be important, though, is SLN status in patients with ulcerated tumors, rather than SLNBx in T1b melanomas. " " …the real discussion shouldnot be related to what features predict any nodal positivity, because, with today’s

surgeries performed (32 485 of 86 846 patients [37.6%] vs 18 379 of 54 434 patients [33.8%]; P < .001). The nodal positivity rate decreased 1.0% from (9.8% [3166 of 86 846] to 8.8% [1618 of 54 434]) (P< .001). An increase in the propor- tion of T1b melanomas being evaluated, from 48.8% to 62.2%, was seen (P< .001). Of T1b mel- anomas that underwent nodal evaluation from 2004 through 2009, 74.0% had Clark level IV (invasion of the reticular dermis) or Clark level V (invasion of the deep, subcutaneous tissue) and 9.5% were ulcerated. From 2010 through 2013, of the T1b melanomas undergoing nodal evaluation, 82.6% had an elevated mitotic rate only, 3.7% were ulcerated, and 13.7% had both ulceration and an elevated mitotic rate. CONCLUSIONS AND RELEVANCE It appears that after the institution of AJCC 7, there was an overall decrease in the number of T1 melanomas under- going nodal biopsy without a clinically relevant change in sentinel lymph node positivity, with an increase in the number of T1b melanomas undergoing nodal evaluation. Early Melanoma Nodal Positivity and Biopsy Rates Before and After Implementation of the 7th Edition of the AJCC Cancer Staging Manual. JAMA Dermatol 2019 Mar 06;[EPub Ahead of Print], C Isom, L Wheless, MA Hooks, RM Kauffmann. www.practiceupdate.com/c/80764

and the distribution of thin melanomas requiring nodal surgery and nodal positivity rates. DESIGN, SETTING, AND PARTICIPANTS Retrospec- tive cross-sectional study from 2004 through 2013 of all adults (≥18 years) diagnosed with a T1 (Breslow depth ≤1.0 mm) melanoma using The National Cancer Database that captures 70% of all newly diagnosed cancers from accredited Commission on Cancer organizations, including both academic and community settings. Data were analyzed in May 2017.

By John Zitelli MD D r. Brodland has summarized the article well, and, at the end, touches on the most important issue: What is the role of SLNBx in managing melanoma? The procedure itself is based on a theory of orderly progression of metastases from the primary tumor, through lymphatics, to the SLN and then into the general circulation. However, published evidence has proven this theory false. Instead, we know that melanoma cells, including mel- anoma stem cells, enter the circulation very early and disseminate widely. Some of those cells may proliferate, whereas many cells will never develop into clinical metastases. The evidence shows: • Lymph nodes are immunologic organs that sample antigens from regional flow in order to mount an immune response. They are not filters, and they do not preferentially receive antigens or cancer cells excluded from the systemic circulation. • There is no evidence that removing lymph nodes containing microscopic deposits of tumor cells before they become clini- cally enlarged will improve survival for any patient with a solid tumor, including renal cell, gastric, colon, breast, ovary, thyroid, squamous cell carcinoma, Merkel cell carcinoma, or melanoma. • For melanoma, SLNBx does not improve survival. SLNBx and nodal dissection for positive nodes do not improve survival, compared with observing and removing clinically enlarged nodes (MSLT I). • For melanoma, there is no benefit to removing microscopically involved nodes even further down the chain of lymph node drainage (MSLT II). • For melanoma, SLNBx is not the most important prognostic test. Stiegel has proven that SLN status does not add any more useful information than we can obtain from Breslow thickness alone.

• For melanoma, SLNBx has limited usefulness in identifying patients who would benefit from adjuvant therapy. Current evidence shows that most patients who benefit from adjuvant therapy have advanced metastatic disease. Patients with micro- scopic disease limited to a positive SLN do not have a survival advantage. • One subgroup that may warrant a SLNBx are patients with ulcerated primary melanomas. These patients are staged IIIB, and may have a survival benefit from immunotherapy such as PD-1 inhibitors. In summary, it appears that the real discussion should not be related to what features predict any nodal positivity, because, with today’s evidence, that information is relatively useless. What may be important, though, is SLN status in patients with ulcerated tumors, rather than SLNBx in T1b melanomas. In the future, we may find other prognostic measures that predict which melanoma patients would benefit from adjuvant therapy, such as nomograms using multiple clinicopathologic features, gene expression profiling of the primary tumor, or circulating can- cer cell DNA. But, for now, we only have evidence to support SLNBx for ulcerated primaries alone.

Dr. Zitelli is Clinical Associate Professor of Dermatology & Otolaryngology, and Interim Chairman of the Department of Dermatology at University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania.

VOL. 3 • NO. 2 • 2019