Melanoma staging updates

Dermatologists should be aware that the American Joint Committee on Cancer (AJCC) 8^th Edition Melanoma Staging System contains a number of revisions pertaining to primary cutaneous melanoma and should stay tuned for new information about the role of sentinel lymph node biopsy (SLNB) in the evaluation of patients with thin tumors and the availability of electronic tools for personalized prognostication.

Jeffrey E. Gershenwald, M.D., spoke about these topics at the 16^th World Congress on Cancers of the Skin. He is the Dr. John M. Skibber Professor, Department of Surgical Oncology at the University of Texas MD Anderson Cancer Center, and serves as chair of the 8^th Edition melanoma expert panel of the AJCC.

Evolving recommendations for SLNB

Currently, SLNB in patients with a clinically negative nodal basin is considered standard of care for those with an intermediate thickness melanoma and for most patients who have a thick tumor. The majority of patients who are diagnosed with melanoma in the United States, however, have a thin melanoma (<1 mm).

“In general, the prognosis is very favorable for thin melanomas, but a fraction of these patients will develop clinically evident disease in the regional basin after a period of observation. In absolute terms, that minority can represent a significant number of people who are affected by regional disease and further metastasis over time,” Dr. Gershenwald says.

“This background raises consideration of what might be an appropriate threshold for risk of having a positive SLN that would lead a clinician to recommend or offer SLNB to patients with a thin melanoma. The answer will vary depending on features of the primary tumor, as well as patient factors, including the presence and risk for other comorbidities. There are ongoing efforts to address this question by analyzing accumulating data to determine the risk of having a positive SLN in patients with a thin melanoma stratified further by clinical stage and other factors, including mitotic rate.”

AJCC melanoma staging update

The 8^th edition of the AJCC Cancer Staging System was released in October, 2016, and while formal implementation is scheduled for January, 2018, clinicians can now be applying the revisions it contains for patient care, Dr. Gershenwald says.

“Ten cancer centers contributed to the international melanoma database that helped inform the recommended changes to the 8^th edition. In total, the database includes over 40,000 patients diagnosed with stage 1 through 3 melanoma over the last 20 years,” he adds.

A key update in the AJCC 8^th edition melanoma staging system is the subcategorization of T1 tumors by tumor thickness using a cutpoint of 0.8 mm. This change reflects analyses demonstrating that tumor thickness within the T1 category was a strong independent predictor of survival. In addition, mitotic rate was removed as a T1 staging criterion.

Per the updated definitions, T1a tumors include those that are <0.8 mm with no evidence of ulceration. The T1b category encompasses tumors <0.8 mm with ulceration and tumors measuring ≥0.8 to 1.0 mm in thickness with or without ulceration.

Dr. Gershenwald notes that mitotic rate was eliminated from the T1 staging criteria based on the finding that its predictive value as a dichotomous variable was significantly diminished when the thin lesions were subcategorized by thickness.

“Mitotic rate, however, is still important for predicting survival,” he says.

“We know that overall, mitotic rate increases with increasing tumor thickness and that there is a range of mitotic activity at any level of tumor thickness that is likely prognostically important. Therefore, information on mitotic rate should still be collected for all invasive melanomas because we plan to incorporate it as an integer variable when developing more sophisticated clinical prognostic tools.”

Dr. Gershenwald also points out that the AJCC 8^th edition presents a contemporary snapshot of melanoma-specific survival for patients with stage 1/2 disease. While the data seem more favorable than those appearing in the AJCC 7^th edition, the difference likely reflects differences in the analyzed populations.

The 8^th edition calculations for stages 1 and 2 node-negative melanoma include patients diagnosed with melanoma after the introduction of SLNB. Patients with a T2N0 melanoma tumor were included for the 8^th edition analysis only if they had a negative SLN (pN0) and those with a T1 tumor were included either if they did not undergo SLNB or if the biopsy was negative.

“The pool of patients in the 7^th edition included some individuals diagnosed before the SLNB era. As such, it might have included patients who had occult or microscopic regional disease and thereby could have contributed to worse survival,” Dr. Gershenwald explains.

“The 8^th edition analysis places patients with regional disease into the stage 3 dataset where they belong.”

As another change, the AJCC 8^th edition recommends recording primary tumor thickness to the 0.1 mm rather than to the .01 mm. The revision takes into account the challenges in precision and the practicality noted by pathology members of the AJCC melanoma expert panel of measuring to the 0.01 mm, Dr. Gershenwald says.

Outcome predictors

Because the TNM system is constrained as to how much information can be packaged into tabular form, and recognizing the lack of evidence to support the quality of existing prediction models, AJCC established the Precision Medicine Core group in an effort to develop a framework for more clinically relevant, personalized probabilistic prediction tools that harness the capabilities of software-driven platforms. The goals are to develop risk models that will provide accurate prognostic information for patients with melanoma across different stages of disease and potentially for different outcomes, eg, overall survival, disease-specific survival, relapse-free survival, and conditional survival.

“Conditional survival takes into account that the probability of an event occurring by a specific time point after a patient survives a given period of time without reaching the specified outcome. For example, the 5-year recurrence-free survival estimate for an individual would likely be better once that person reaches three years without developing a recurrence compared with the initial prediction at diagnosis,” Dr. Gershenwald explains.

“We believe this is an important theme to introduce in the current era when new effective therapeutic options are changing the landscape for patients with advanced and unresectable melanoma.”
A published article from the AJCC Precision Medicine Core [Kattan MW, et al. CA Cancer J Clin. 2016;66(5):370-374] outlines 13 inclusion and 3 exclusion criteria for AJCC risk model endorsement in cancer. SEE CHART

“These criteria can be used by clinicians to properly evaluate models and by those who are interested in creating quality tools. Going forward, we hope this information will ultimately improve care for patients with melanoma,” Dr. Gershenwald says.

Disclosure: Dr. Gershenwald has no relevant financial interests to disclose.