NEW YORK (Reuters Health) – A modified prognostic nodal classification system improved mortality risk stratification for cutaneous melanoma when contrasted with the current American Joint Committee on Cancer (AJC) system, researchers say.

“The management paradigm has changed significantly over the past several years” for patients with cutaneous melanomas with lymph node metastases, Dr. Zachary Zumsteg of Cedars-Sinai Medical Center in Los Angeles told Reuters Health by email. “Many now receive relatively limited lymph node surgeries, consisting of sentinel lymph node biopsy only, and most now receive post-operative systemic therapy. Accurately understanding the prognosis of this relatively heterogenous group is important for optimizing the risks and benefits of treatment, in addition to designing clinical trials.”

“Using recursive partitioning analysis (RPA), a statistical clustering algorithm, we were able to separate patients into distinct groups with widely divergent prognoses based on the characteristics of their nodal metastases,” he explained. “Our system was more accurate than the current staging system, which has several staging groups with overlapping prognoses. It remained accurate even in patients undergoing sentinel lymph node biopsy without completion dissection, consistent with the current standard of care.”

“We further validated that our system accurately predicted both overall survival and melanoma-specific survival in a distinct cancer registry database,” he said.

As reported in JAMA Surgery, Dr. Zumsteg and colleagues developed the tool by analyzing data on close to 106,000 patients in the US National Cancer Database mean age, 60; 59% men) who underwent surgery and nodal evaluation from 2004 through 2015. The extent of lymph node dissection was available for patients diagnosed in 2012 and onward.

The proposed lymph node classification system was validated in an analysis of data on more than 85,000 patients the SEER-18 database.

Variables independently associated with mortality included: the number of positive lymph nodes (hazard ratio per lymph node for 0 to 2 positive nodes, 2.48; HR per lymph node for 3 positive nodes, 1.10); clinically detected metastases (HR, 1.35); and in-transit metastases (HR, 1.48).

The RPA-derived system using these variables showed continuously increasing mortality for each proposed lymph node classification group, with the following HRs: 1.83 for N1a; 2.72 for N1b; 3.79 for N2a; 4.56 for N2b; 6.15 for N3a; and 8.25 for N3b.

By contrast, the AJCC nodal classification system produced a more haphazard mortality profile, with the following HRs: 1.83 for N1a; 3.81 for N1b; 2.59 for N1c; 2.71 for N2a; 4.51 for N2b; 3.44 for N2c; 6.06 for N3a; 8.15 for N3b; and 6.90 for N3c.

As a sensitivity analysis, the proposed system continued to accurately stratify patients when excluding those undergoing completion lymph node dissection (CLND) for microscopic metastases.

As Dr. Zumsteg noted, the system was validated for overall survival and cause-specific mortality in SEER-18.

The authors conclude, “The findings of this cohort study suggest that a modified nodal classification system can accurately stratify mortality risk in cutaneous melanoma in an era of increasing use of sentinel lymph node biopsy without CLND and should be considered for future staging systems.”

Dr. Jeffrey Farma, co-director of the melanoma and skin cancer program at Fox Chase Cancer Center in Philadelphia, commented by email that staging systems must be continually modified based on evolving treatment standards. For example, he noted, “We are currently performing less completion lymph node dissections for node positive disease in patients with melanoma.”

“This study utilized … recursive partitioning analysis to modify the lymph node classification system,” he said. “Overall, the data suggest that this modified lymph node classification can stratify mortality risk in melanoma in our new treatment era. Further studies will be needed to confirm these findings and ultimately determine if the American Joint Committee on Cancer (AJCC) staging system should be changed based on their findings.”

SOURCE: https://bit.ly/3tkCe4Y and https://bit.ly/38PLzbQ JAMA Surgery, online September 1, 2021.

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