– Melanoma staging in the American Joint Committee on Cancer Eighth Edition Cancer Staging Manual implements better stratification of stage III melanoma patients, resulting in an evidence-based improved prognosis for many of them, Laura Korb Ferris, MD, PhD, said at the Hawaii Dermatology Seminar provided by Skin Disease Education Foundation/Global Academy for Medical Education.

Dr. Ferris, of the department of dermatology, University of Pittsburgh, highlighted some of the key changes in the eighth edition of the AJCC staging manual, which is now in effect. She also described the clinical implications of important updates introduced in the 2018 National Comprehensive Cancer Network (NCCN) guidelines for the diagnosis and management of melanoma.

The AJCC eighth edition

The eighth edition is built upon an AJCC database of more than 46,000 patients with stage I-III melanoma diagnosed since 1998 at 10 academic medical centers. The AJCC panel made no changes in stage IV melanoma guidance because the newer targeted therapies have rapidly changed treatment outcomes in that setting and longer follow-up is needed to assess the full impact.

Melanoma Courtesy RegionalDerm.com

The current edition of the AJCC melanoma staging manual creates a new subcategory within pathologic stage III. In the melanoma staging world, that’s exciting news, especially because this change has important implications for prognosis.

This fourth subcategory, stage IIID, is for melanomas, which in the Tumor, Nodes, Metastasis (TNM) classification scheme, are primary tumor stage T4b, meaning greater than 4.0 mm in thickness and with ulceration; regional lymph node N3a, b, or c, based upon the number of metastatic nodes involved and whether they were clinically occult nodal metastases detected by sentinel lymph node biopsy (SLNB) or clinically detected; and M0, meaning no distant metastatic disease. In the 8th edition, the AJCC staging system can be applied in patients with T2 through T4 primary melanoma only if they have undergone SLNB.

Melanoma Courtesy RegionalDerm.com

This new approach to stage III disease makes for more homogeneous patient subgroups, which in turn provides much better stratification of prognosis than was possible in the seventh edition of the AJCC staging manual, which dates back to 2010. Most strikingly, the 5-year melanoma-specific survival rate for patients with stage IIIA disease was 78% in the seventh edition of AJCC, but it climbs to 93% in the eighth edition. For patients with stage IIIB melanoma, 5-year melanoma-specific survival improved from 59% in the seventh edition to 83% in the current iteration, while in stage IIIC, the jump is from 40% to 69%. All this is made possible because the eighth edition separates out patients with the new stage IIID, whose 5-year melanoma-specific survival is only 32%, Dr. Ferris explained.

Among the other key points to remember about the eighth edition of AJCC:

  • Tumor thickness is now measured to the nearest 0.1 mm rather than to the nearest 0.01 mm, as previously. Thus, a 0.75-mm-thick melanoma is now rounded up to 0.8 mm, while a 0.74-mm melanoma becomes a 0.7-mm tumor.
  • Based upon recent evidence, tumors that are 0.8-1.0 mm thick, with or without ulceration, are now classified at T1b. So are ulcerated lesions that are less than 0.8 mm.
  • Dermal mitotic rate is no longer used in staging T1 tumors, although it’s still supposed to be included in pathology reports.
  • The T category definitions of primary tumors have been clarified in the eighth edition. A tumor is now classified as T0 only if there is no evidence of a primary tumor. Tx is employed when the primary tumor thickness can’t be determined, as for example when the biopsy specimen was obtained by curettage. Tis is utilized for melanoma in situ.
  • The N subcategory definitions of regional nodal status have been revised. Microsatellites, clinical satellites, and in-transit metastases are now categorized as N1c, N2c, or N3c based upon the number of tumor-involved regional lymph nodes. These features are no longer defined by their size or distance from the primary tumor.

2018 NCCN melanoma guidelines

The guidelines have been revised to recommend against SLNB if a patient’s pretest probability of finding a positive SLN is less than 5%. This includes patients who have a clinical stage IA/T1a melanoma with a Breslow thickness of less than 0.8 mm without ulceration.

Melanoma Courtesy RegionalDerm.com
If the pretest risk is 5%-10%, the NCCN recommends “discussing and considering” SLNB with the patient. This includes melanomas that are clinical stage IB/T1b or IB/T1a lesions less than 0.8 mm with adverse features such as a high mitotic index of at least 2 per mm2, especially in a younger patient.

There is to be no SLNB in patients with microsatellites, clinical satellites, or in-transit metastases because SLN status has no prognostic significance in this situation.

Dr. Laura Korb Ferris, a dermatologist at the University of Pittsburgh Bruce Jancin/MDedge News

Dr. Laura Korb Ferris

“You basically have already upstaged them once you have found one of these factors,” Dr. Ferris observed. “Microsatellitosis, clinical satellites, and in-transit metastases have all been shown to portend a poor prognosis, but we can’t say that one is worse than the others. So we basically lump them all together and use them in N staging based on the number of involved nodes.”

Routine ordering of prognostic genetic tests for BRAF or the multigene test panels that are now commercially available is not recommended except to guide systemic therapy or to determine if a patient is a candidate for a specific clinical trial. “Basically, there is not a place to use this information in the NCCN guidelines,” according to the dermatologist.

What about completion lymphadenectomy in the SLN-positive melanoma patient?

Completion lymph node dissection looks increasingly like a procedure in search of an indication. Results of the National Cancer Institute–sponsored Multicenter Selective Lymphadenectomy Trial–II (MSLT-II) demonstrated not even a hint of a difference in 3-year melanoma-specific survival in 1,934 melanoma patients with sentinel lymph node metastases regardless of whether they were randomized to immediate completion lymph node dissection or ultrasound-based nodal monitoring. Moreover, completion lymphadenectomy was associated with significant morbidity: a 24.1% incidence of lymphedema, compared with a 6.3% rate in the observation group (N Engl J Med. 2017 Jun 8;376[23]:2211-22).

On the other hand, Dr. Ferris noted that many newer drugs are being approved for the treatment of stage III melanoma, and in all the pivotal clinical trials, patients had to have undergone completion lymph node dissection as a condition of participation. So the surgery becomes a consideration if physicians want to use the newer agents the way they were used successfully in the trials.

The full eighth edition of the AJCC cancer staging manual is available for purchase. For physicians with a specific interest in melanoma, Dr. Ferris recommended as an extremely useful alternative the AJCC expert writing panel’s free downloadable summary of the evidence-based changes made in melanoma staging (CA Cancer J Clin. 2017 Nov;67[6]:472-92). The 2018 NCCN guidelines (Melanoma. Version 1.2018 Oct. 11, 2017) are available for free (www.NCCN.org).

Dr. Ferris reported serving as a consultant to DermTech.

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