Sentinel node tumor burden in prediction of prognosis in melanoma patients

Abstract

Recent data have demonstrated no survival benefit to immediate completion lymph node dissection (CLND) for positive sentinel node (SN) disease in melanoma. It is important to identify parameters in positive SNs, which predict prognosis in melanoma patients. These might provide prognostic value in staging systems and risk models by guiding high-risk patients' adjuvant therapy in clinical practice. In this retrospective study of university hospital melanoma database we analyzed tumor burden and prognosis in patients with positive SNs. Patients were stratified by the diameter of tumor deposit, distribution of metastatic focus in SN, ulceration and number of metastatic SNs. These were incorporated in Cox proportional hazard regression models. Predictive ability was assessed using Akaike information criterion and Harrell's concordance index. A total of 110 patients had positive SN and 104 underwent CLND. Twenty-two (21%) patients had non-SN metastatic disease on CLND. The 5-year melanoma specific survival for CLND-negative patients was 5.00 years (IQR 3.23-5.00, range 0.72-5.00) compared to 3.69 (IQR 2.28-4.72, range 1.01-5.00) years in CLND-positive patients (HR 2.82 (95% CI 1.17-6.76, p = 0.020).The models incorporating distribution of metastatic focus and the largest tumor deposit in SN had highest predictive ability. According to Cox proportional hazard regression models, information criterions and c-index, the diameter of tumor deposit > 4 mm with multifocal location in SN despite of number of metastatic SN were the most important parameters. According to the diameter of tumor deposit and distribution of metastatic focus in SN, adequate stratification of positive SN patients was possible and risk classes for patients were identified.

The Role Of Sentinel Node Tumor Burden In Modeling The Prognosis Of Melanoma Patients With Positive Sentinel Node Biopsy: An Italian Melanoma Intergroup Study (N=2,086)

“…In our opinion, CLND adds prognostic information as the status of non-sentinel nodes is an independent prognostic feature, as we have demonstrated not only in the present analysis but also previously (6,11) . Therefore, CLND not only improves regional relapse-free survival (as demonstrated by the results of the MSLT-II) but also provides physicians with useful prognostic information (6)(7)(8) .…”

“…Another study analyzing 104 SN positive patients who underwent CLND demonstrated that the 5year melanoma specific survival for CLND-negative patients was 5 years as compared to 3.69 years in CLND positive patients. In this analysis, clinico-pathological parameters such as diameter of tumor deposit, distribution of metastatic focus within the sentinel node, ulceration and number of metastatic sentinel nodes were evaluated and the investigators found that TB >4 mm and multifocal metastatic disease within the sentinel node were the most important variables that allowed an accurate prognostic stratification of patients (11) .…”

“…However, these trials, the results of which might lead to abandon the practice of CLND, had some limitations. First, retrospective series produced varied results and were subject to a considerable risk of select bias; next, there were differences in clinic-pathologic features of the patient cohorts between centers; moreover, most patients, enrolled in these studies, had a low-volume nodal tumor burden (5,7,(9)(10)(11) . In the end, international guidelines such as those issued by the National Comprehensive Cancer Network, recommend to discuss with the patient the benefit of CLND mainly based on the risk of harboring additional lymph node metastatic disease.…”

“…In this challenging landscape, adjuvant therapy decision making would greatly benefit from the identification independent prognostic factors improving the risk stratification, which ultimately would enable physicians to optimize the management of melanoma patients with positive SNB (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) .…”

The role of sentinel node tumor burden in modeling the prognosis of melanoma patients with positive sentinel node biopsy: an Italian melanoma intergroup study (N = 2,086)

“…However, these trials, the results of which might lead to abandon the practice of CLND, had some limitations. First, retrospective series produced varied results and were subject to a considerable risk of select bias; next, there were differences in clinic-pathologic features of the patient cohorts between centers; moreover, most patients, enrolled in these studies, had a low-volume nodal tumor burden [ 5 , 7 , 9 – 11 ]. In the end, international guidelines such as those issued by the National Comprehensive Cancer Network, recommend to discuss with the patient the benefit of CLND mainly based on the risk of harboring additional lymph node metastatic disease.…”