It may be time to update the melanoma staging system, researchers report

Researchers reporting at the American Society of Clinical Oncology annual meeting on June 4 presented a study in which they compared the seventh and eighth editions of the American Joint Committee on Cancer (AJCC) melanoma staging systems. The eighth edition differentiates melanoma survival slightly worse than the previous edition, they said.

Max Fullah Madu, M.D., a physician with the Netherlands Cancer Institute in Amsterdam who led the study, sought to determine if the 8th edition offered an improvement in prognostic accuracy.

The study is based on the treatment outcomes of 640 melanoma cases from a Netherlands Cancer Institute database. The patients were treated between 2000 and 2016 and followed for 59 months.
In terms of survival discrimination, which is a measure of prognostic accuracy, both staging systems performed similarly with no statistical difference between systems.

Researchers analyzed prognostic factors for melanoma-specific survival and distant metastasis-free survival finding a median melanoma-specific survival rate of 138 months and 96 months for patients with distant metastases-free survival.

The findings were mixed for stage IIIA melanoma for both the 7th and 8th editions. In estimating survival, both the 7th and 8th editions were comparable, but the 8th edition failed to differentiate melanoma-specific survival between stage IIIA and IIIB. For patients with sentinel node metastasis of less than one, researchers found excellent melanoma-specific survival and distant metastasis-free survival rates.

In looking at survival differentiation between the stage III subgroups using the eighth edition, they saw an overlap in the three A and three B survival curves over the first four years of follow-up, resulting in a differentiation that reached only borderline statistical significance (P = 0.047). By contrast, the 7th edition criteria produced a clean separation in IIIA and IIIB survival curves, resulting in a significant difference (0.002).

Given the lower proportion of patients in the 8th edition IIIA group, Dr. Madu said the results should be viewed with some caution. By 8th edition classification, 12% of the Netherlands patients were considered IIIA, compared to 25% of patients using 7th edition classification.

CAN SENTINEL NODE TUMOR BURDEN REFINE IIIA STRATIFICATION?
 

Survival within the 8th edition IIIA subgrouping might be stratified further using European Organization for Research and Treatment of Cancer (EORTC) criteria for sentinel node tumor burden, Dr. Madu said.

In a large EORTC study, patients with a maximum diameter of the largest metastatic deposit in the sentinel node of 1 mm or less had much better survival compared with those with a maximum diameter more than 1 mm.
For the Netherlands data set, using 7th edition staging, stage IIIA patients with a maximum diameter of 1 mm or less had a 5-year survival of 89%, versus 65% for those with a maximum diameter greater than 1 mm (P < 0.001). The difference was slightly less, but still significant, using the 8th edition criteria with 5-year survival of 91% versus 72% for 1 mm or less and greater than 1 mm, respectively (P = 0.020).

The finding was corroborated by a study recently published in the European Journal of Cancer that included a multicenter cohort of more than 1,000 sentinel node-positive patients. Comparing four different prognostic models, investigators found that the combination of eighth edition AJCC staging plus sentinel node tumor burden was the best prognostic model.

“The EORTC tumor burden criteria can be a powerful adjunct to AJCC staging, especially in a post-completion lymph node dissection era where less staging information will be available,” Dr. Madu said. “I hope for a future in which AJCC criteria, combined with sentinel node tumor burden without the need for completion lymph node dissection, will allow precise and minimally invasive tumor staging in melanoma patients.”

NEW CRITERIA, NEW QUESTIONS

Dr. Madu highlighted three points about the 8th edition:
1. It's more complex in clinical use.
2. It does not add any new prognostic factors.
3. And, adjuvant therapy trials have all been performed with 7th edition staging criteria.

One of the most significant changes in the eighth edition is having redefined AJCC prognostic stage three A groupings, including the addition of a new ultra-high-risk stage three D subgroup.

In a presentation on re-evaluating the staging and management of stage three melanoma, April K.S. Salama, M.D., director of the melanoma program at Duke Cancer Institute, said: “The way I think of this is that it has essentially become more selective at each end of the spectrum.”

Dr. Salama said three A includes patients who may have a more favorable prognosis versus the previous three A criteria. While three D is designated for patients who are at the highest risk of recurrence.

The AJCC melanoma expert panel also changed the TNM criteria needed to gain entry to the subgroups, making it difficult to translate between versions, Dr. Madu said.

“A patient who was stage three A in the previous edition can now be stage three C in the current edition. This raises a few questions ― especially in this time of rapidly changing melanoma treatments,” Dr. Madu said.

REFERENCES
Madu, MF, Franke V, Van De Wiel B, et al. “External validation of the 8th Edition Melanoma Staging System of the American Joint Committee on Cancer (AJCC): Effect of adding EORTC sentinel node (SN) tumor burden criteria on prognostic accuracy in stage III.” American Society of Clinical Oncology 2018 Annual Meeting. Presented Monday, June 4, 2018. Abstract 9500.

Verver D, van Klaveren D, van Akkooi ACJ, et al. “Risk stratification of sentinel node-positive melanoma patients defines surgical management and adjuvant therapy treatment considerations.” Eur J Cancer. 2018 Jun;96:25-33. doi: 10.1016/j.ejca.2018.02.022. Epub 2018 Apr 13.