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Background: Identifying factors associated with nonsentinel lymph node (NSN) metastases in melanoma patients with a single positive sentinel lymph node (SLN) could aid decision making regarding adjuvant therapy. We describe a model for identifying patients with a single positive SLN at low risk for NSN metastasis., Methods: Factors associated with NSN metastasis in patients with a primary cutaneous melanoma and a single positive SLN who underwent completion lymph node dissection (CLND) were identified. These factors were used to construct a model for predicting the NSN status. The model was validated using a separate data set from another tertiary referral cancer center., Results: In the training data set, 111 patients had a single positive SLN. Of these, 27 had positive NSN. SLN tumor deposit diameter ≥0.75 mm (OR, 3.43; P = 0.047), age ≥40 (OR, 12.14; P = 0.024), and multifocal SLN tumor deposit location (OR, 4.16; P = 0.0096) were independently associated with NSN positivity. Patients with 0 to 1 of these risk factors had a low risk of NSN metastasis in both the training (7.5%) and validation (4.6%) data sets., Conclusions: A combination of patient and SLN tumor burden characteristics can help to identify patients with a single positive SLN who are at a low risk of NSN metastasis., (© 2018 Wiley Periodicals, Inc.)

Background: Prognostic models are increasingly being made available online, where they can be publicly accessed by both patients and clinicians. These online tools are an important resource for patients to better understand their prognosis and for clinicians to make informed decisions about treatment and follow-up. The goal of this analysis was to highlight the possible variability in multiple online prognostic tools in a single disease., Methods: To demonstrate the variability in survival predictions across online prognostic tools, we applied a single validation dataset to three online melanoma prognostic tools. Data on melanoma patients treated at Memorial Sloan Kettering Cancer Center between 2000 and 2014 were retrospectively collected. Calibration was assessed using calibration plots and discrimination was assessed using the C-index., Results: In this demonstration project, we found important differences across the three models that led to variability in individual patients' predicted survival across the tools, especially in the lower range of predictions. In a validation test using a single-institution data set, calibration and discrimination varied across the three models., Conclusions: This study underscores the potential variability both within and across online tools, and highlights the importance of using methodological rigor when developing a prognostic model that will be made publicly available online. The results also reinforce that careful development and thoughtful interpretation, including understanding a given tool's limitations, are required in order for online prognostic tools that provide survival predictions to be a useful resource for both patients and clinicians.

Background: Sentinel lymph node (SLN) biopsy for melanoma results in accurate nodal staging, which guides treatment decisions. Patients with a negative SLN biopsy in general have a favorable prognosis, but certain subsets are at increased risk for recurrence and death. This study aimed to identify risk factors predictive of prognosis in patients with a tumor-negative SLN biopsy for cutaneous melanoma., Methods: In this post-hoc analysis of data from a multicenter prospective randomized trial, clinicopathologic data of patients with cutaneous melanoma ≥1.0 mm Breslow thickness and tumor-negative SLN were analyzed. Disease-free survival, overall survival (OS), and local and in-transit recurrence-free survival were compared by Kaplan-Meier analysis. Risk factors for worse survival were identified with Cox proportional hazard models., Results: This analysis included 1,998 patients with tumor-negative SLN with a median follow-up of 70 months. Ulceration, Breslow thickness, nonextremity tumor location, and age ≥45 years were independent risk factors for worse disease-free survival and OS. Breslow thickness and ulceration were the only factors on multivariate analysis that predicted local and in-transit recurrence-free survival. Estimated 5-year OS rates ranged from 55.5 to 95.4% on the basis of the defined risk factors., Conclusion: There is a wide range of prognosis among patients with tumor-negative SLN. Breslow thickness, ulceration, age, and anatomic location of the primary melanoma are important independent factors predicting survival and recurrence among such patients. These factors can be used to stratify prognosis among patients with tumor-negative SLN to formulate rational long-term follow-up strategies as well as identify high-risk, SLN-negative patients for clinical trials of adjuvant therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: The Sunbelt Melanoma Trial is a prospective randomized trial evaluating the role of high-dose interferon alfa-2b therapy (HDI) or completion lymph node dissection (CLND) for patients with melanoma staged by sentinel lymph node (SLN) biopsy., Patients and Methods: Patients were eligible if they were age 18 to 70 years with primary cutaneous melanoma ≥ 1.0 mm Breslow thickness and underwent SLN biopsy. In Protocol A, patients with a single tumor-positive lymph node after SLN biopsy underwent CLND and were randomly assigned to observation versus HDI. In Protocol B, patients with tumor-negative SLN by standard histopathology and immunohistochemistry underwent molecular staging by reverse transcriptase polymerase chain reaction (RT-PCR). Patients positive by RT-PCR were randomly assigned to observation versus CLND versus CLND+HDI. Primary end points were disease-free survival (DFS) and overall survival (OS)., Results: In the Protocol A intention-to-treat analysis, there were no significant differences in DFS (hazard ratio, 0.82; P = .45) or OS (hazard ratio, 1.10; P = .68) for patients randomly assigned to HDI versus observation. In the Protocol B intention-to-treat analysis, there were no significant differences in overall DFS (P = .069) or OS (P = .77) across the three randomized treatment arms. Similarly, efficacy analysis (excluding patients who did not receive the assigned treatment) did not demonstrate significant differences in DFS or OS in Protocol A or Protocol B. Median follow-up time was 71 months., Conclusion: No survival benefit for adjuvant HDI in patients with a single positive SLN was found. Among patients with tumor-negative SLN by conventional pathology but with melanoma detected in the SLN by RT-PCR, there was no OS benefit for CLND or CLND+HDI., (© 2016 by American Society of Clinical Oncology.)

Background: Molecular staging of sentinel lymph nodes (SLNs) may identify patients who are node-negative by standard microscopic staging but are at increased risk for regional nodal recurrence; such patients may benefit from completion lymph node dissection (CLND)., Study Design: In a multicenter, randomized clinical trial, patients with tumor-negative SLNs by standard pathology (hematoxylin and eosin [H and E] serial sections and immunohistochemistry [IHC]) underwent reverse transcriptase polymerase chain reaction (PCR) analysis of SLNs for melanoma-specific mRNA. Microscopically negative/PCR+ patients were randomized to observation, CLND, or CLND with high-dose interferon (HDI). For this post-hoc analysis, clinicopathologic features and survival outcomes, including overall survival (OS) and disease-free survival (DFS), were compared between PCR+ patients who underwent CLND vs observation. Microscopic and molecular node-negative (PCR-) patients were included for comparison., Results: A total of 556 patients were PCR+: 180 underwent observation, and 376 underwent CLND. An additional 908 PCR- patients were observed. Median follow-up was 72 months. Disease-free survival (DFS) was significantly better for PCR+ patients who underwent CLND compared with observation (p = 0.0218). No statistically significant differences in OS or distant disease-free survival (DDFS) were seen. Regional lymph node recurrence-free survival (LNRFS) was improved in PCR+ patients with CLND compared to observation (p = 0.0065). The PCR+ patients in the observation group had the worst DFS; those with CLND had similar DFS to that in the PCR- group (p = 0.9044)., Conclusions: Patients with microscopically negative/PCR+ SLN have an increased risk of nodal recurrence that was mitigated by CLND. Although CLND did not affect OS, these data suggest that molecular detection of melanoma-specific mRNA in the SLN predicts a greater risk of nodal recurrence and deserves further study., (Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Quality of life (QOL) and physical condition (PC) outcomes after sentinel lymph node biopsy (SLNB), completion lymph node dissection (CLND), and adjuvant therapy with interferon alfa-2b (IFN) were evaluated in this study., Methods: Self-reported QOL and PC scores were evaluated in patients enrolled in a prospective, multicenter, randomized, clinical trial evaluating adjuvant IFN. After SLN biopsy, patients with a positive SLN underwent CLND then were randomized to adjuvant IFN or observation. QOL and PC scores were compared between patients who underwent SLNB alone, CLND without IFN, and CLND with IFN. Time to return to baseline QOL and PC scores reported at the time of SLNB was recorded and compared., Results: There were statistically significant differences in time to return to baseline QOL (p = 0.0018) and PC (p = 0.0018) scores across the three treatment groups. The time to return to baseline QOL and PC scores was similar for SLND and CLND alone. Differences in time to return to baseline QOL and PC were sustained when stratified by recurrence status but did not differ significantly for different lymph node regions. There was a delay in return to baseline QOL and PC condition scores that was sustained beyond the cessation of IFN therapy., Conclusions: CLND is well-tolerated with a similar effect on self-reported QOL outcomes in both the short- and long-term compared with SLNB alone. IFN therapy is associated with worse QOL outcomes compared with SLNB and CLND, an effect that may be sustained following cessation of adjuvant IFN.

Background: Controversy exists regarding the value and indications for inguinal dissection alone or in combination with an iliac/obturator lymph node dissection for melanoma., Study Design: We reviewed patients from a multicenter prospective clinical trial and a single center who underwent inguinal dissection alone or combined with an iliac/obturator dissection for cutaneous melanoma. Analyses were stratified and compared by microscopic or macroscopic (palpable or detected by imaging) disease., Results: The study was composed of 134 patients with a median follow-up of 39 months. Indications for inguinal dissection were microscopic disease in 94 (70%) patients and macroscopic nodal disease in 40 (30%) patients. An iliac/obturator dissection yielded tumor-positive pelvic nodes in 25% vs 55% in the microscopic vs macroscopic groups, respectively (p = 0.10). No risk factors for positive pelvic nodes were identified. For both microscopic and macroscopic disease, addition of an iliac/obturator dissection to an inguinal dissection did not significantly reduce the risk of pelvic nodal recurrence. Five-year overall survival rates for 4 groups were compared: microscopic disease, inguinal dissection alone (72%); microscopic disease, iliac/obturator dissection (68%); macroscopic disease, inguinal dissection alone (51%); and macroscopic disease, iliac/obturator dissection (44%) (p = 0.0163). On survival analysis, addition of an iliac/obturator dissection in either microscopic or macroscopic disease did not affect disease-free survival or regional lymph node recurrence-free survival., Conclusions: The addition of an iliac/obturator dissection to an inguinal dissection for both microscopic and macroscopic nodal disease did not significantly affect lymph node recurrence rates, disease-free survival, or overall survival., (Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Multiple methods have been proposed to classify the micrometastatic tumor burden in sentinel lymph nodes (SLN) for melanoma. The purpose of this study was to determine the classification scheme that best predicts nonsentinel node (NSN) metastasis, disease-free survival (DFS), and overall survival (OS)., Study Design: A single reviewer reanalyzed tumor-positive SLN from a multicenter, prospective clinical trial of patients with melanoma ≥ 1.0 mm Breslow thickness who underwent SLN biopsy. The following micrometastatic disease burden measurements were recorded: Starz classification, Dewar classification (microanatomic location), maximum diameter of the largest focus of metastasis, maximum tumor area, and sum of all diameters. Univariate and multivariate models and Kaplan-Meier analysis were used to evaluate each classification system., Results: We reviewed 204 tumor-positive SLNs from 157 patients. On univariate analysis, all criteria except Starz classification were statistically significant risk factors for NSN metastasis. On multivariate analysis, including Breslow thickness, ulceration, age, sex, and NSN status, maximum diameter (using a cut-off of 3 mm) was the only classification system that was an independent risk factor predicting DFS (hazard ratio 2.31, p = 0.0181) and OS (hazard ratio 3.53, p = 0.0005). By Kaplan-Meier analysis, DFS and OS were significantly different among groups using maximum diameter cut-offs of 1 and 3 mm., Conclusions: Maximum tumor diameter outperformed other measurements of metastatic tumor burden, including microanatomic tumor location (Dewar classification), Starz classification, maximum tumor area, and sum of all diameters for prediction of survival. Maximum tumor diameter is a simple method of assessing micrometastatic tumor burden that should be reported routinely., (Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Gender is an established prognostic factor in cutaneous melanoma; women as a group have a better overall prognosis than men. However, the investigators hypothesized that melanoma in young women may have distinct clinicopathologic features and biologic behavior compared with melanoma in older women, possibly related to tanning bed use and excessive acute episodes of sun exposure., Methods: A retrospective analysis was performed of a large multicenter study that accrued patients between 1996 and 2003 and included patients aged 18 to 70 years with cutaneous melanoma ≥1 mm Breslow thickness and no evidence of regional or distant metastatic disease. All women with follow-up data were included. Univariate and multivariate analyses as well as Kaplan-Meier (KM) analysis were performed to test for differences in clinicopathologic variables, disease-free survival (DFS), and overall survival (OS) between female patients ≤40 and >40 years of age., Results: A total of 1,056 female patients were divided into 2 groups: those >40 years of age (n = 757 [71.7%]) and those ≤40 years of age (n = 299 [28.3%]). Overall, there were no differences in Breslow thickness, ulceration, or sentinel lymph node status between groups. Compared with older women, younger women were more likely to have truncal melanomas (39.5% vs 29.5%, P = .0017) and less likely to have regression of the primary tumor (6.4% vs 11.5%, P = .0208). The mean number of sentinel lymph nodes removed was 2.82 for younger women and 2.29 for older women (P < .0001). Multivariate analysis revealed that Breslow thickness, ulceration, and tumor-positive sentinel lymph node were associated with worse DFS in both the younger and older groups; truncal location was associated with worse DFS in the younger group only. The same factors were predictive of OS in both groups, except that ulceration was not significant in the younger patient group. In the younger patient group, the 5-year KM DFS rates were 78.1% for truncal melanomas and 92.5% for nontruncal melanoma locations (P = .0009); the corresponding 5-year KM OS rates were 76.6% and 93.9% (P = .0003). In the older patient group, the 5-year KM DFS rates were 84.1% for truncal and 82.8% for nontruncal melanomas (P = NS), and the corresponding 5-year KM OS rates were 81.6% and 87.5% (P = .0049)., Conclusions: Although women with cutaneous melanoma tend to have a better prognosis than men, women ≤40 years of age with primary melanoma of the trunk may represent a subgroup at higher risk for disease recurrence and metastasis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Prognostic factors and risk factors for positive sentinel lymph node (SLN) biopsy results are important to identify in superficial spreading melanoma (SSM)., Methods: A single-center database and a prospective clinical trial database were reviewed for all patients with diagnoses of SSM. Logistic regression, Kaplan-Meier survival analysis, and univariate and multivariate Cox models were used., Results: A total of 1,643 patients with SSM were identified. Independent risk factors for positive SLN biopsy results were Breslow thickness (BT) ≥2.0 mm, age <60 years, and presence of ulceration. BT ≥2.0 mm, ulceration, lymphovascular invasion, and positive SLN and positive non-SLN biopsy results were independent risk factors for worse disease-free survival. Independent overall survival risk factors included BT ≥2.0 mm, age ≥60 years, ulceration, nonextremity tumor location, lymphovascular invasion, and positive SLN biopsy results., Conclusions: BT, ulceration, lymphovascular invasion, and SLN and non-SLN status are important risk factors for SSM., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Recent studies have suggested that sentinel lymph node (SLN) biopsy is of limited value in desmoplastic melanoma. This study was performed to compare the rate of positive SLN biopsy in the Surveillance, Epidemiology, and End Results (SEER) database with that of a multi-institutional clinical trial and to investigate relevant prognostic factors in desmoplastic melanoma., Study Design: Patients with desmoplastic melanoma ≥1.0 mm Breslow thickness, who underwent SLN biopsy in a multi-institutional prospective clinical trial, were combined with a single institution melanoma database (combined database) and compared with patients from the SEER database (1998 to 2009). Disease-free survival (DFS) and overall survival (OS) were summarized using Kaplan-Meier curves and compared using Cox proportional hazard models., Results: The rate of positive SLN in the combined database was 17.0% (8 of 47). By comparison, the rate of positive SLN in SEER was lower: 2.5% (15 of 594). On multivariable analysis, Breslow thickness ≥2.6 mm (hazard ratio 8.17, 95% CI 1.26 to 160.1; p = 0.0259) and an interaction between SLN status and ulceration (p = 0.0013) were independent risk factors for worse OS in the combined database; patients with ulceration and a positive SLN had significantly worse OS. In the combined database on multivariable analysis, SLN positivity (p = 0.0161) and ulceration (p = 0.0004) were independent risk factors for worse DFS., Conclusions: The rate of positive SLN in desmoplastic melanoma may be higher than that reported in the SEER database. Sentinel lymph node biopsy may be considered as part of the comprehensive staging of desmoplastic melanoma ≥1.0 mm Breslow thickness., (Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Sentinel lymph node (SLN) biopsy for melanoma often detects minimal nodal tumor burden. Although all node-positive patients are considered stage III, there is controversy regarding the necessity of adjuvant therapy for all patients with tumor-positive SLN., Methods: Post hoc analysis was performed of a prospective multi-institutional study of patients with melanoma ≥ 1.0 mm Breslow thickness. All patients underwent SLN biopsy; completion lymphadenectomy was performed for patients with SLN metastasis. Kaplan-Meier analysis of disease-free survival (DFS) and overall survival (OS) was performed. Univariate and multivariate Cox regression analyses were performed. Classification and regression tree (CART) analysis also was performed., Results: A total of 509 patients with tumor-positive SLN were evaluated. Independent risk factors for worse OS included thickness, age, gender, presence of ulceration, and tumor-positive non-SLN (nodal metastasis found on completion lymphadenectomy). As the number of tumor-positive SLN and the total number of tumor-positive nodes (SLN and non-SLN) increased, DFS and OS worsened on Kaplan-Meier analysis. On CART analysis, the 5-year OS rates ranged from 84.9% (women with thickness < 2.1 mm, age < 59 years, no ulceration, and tumor-negative non-SLN) to 14.3% (men with thickness ≥ 2.1 mm, age ≥ 59 years, ulceration present, and tumor-positive non-SLN). Six distinct subgroups were identified with 5-year OS in excess of 70%., Conclusions: Stage III melanoma in the era of SLN is associated with a very wide range of prognosis. CART analysis of prognostic factors allows discrimination of low-risk subgroups for which adjuvant therapy may not be warranted.

Background: The importance of the lymph node ratio (LNR) after regional lymphadenectomy for cutaneous melanoma is unknown., Materials and Methods: A post hoc analysis was performed for patients after the completion of lymphadenectomy for cutaneous melanoma. LNR was calculated as the number of tumor-positive nodes divided by the total number of lymph nodes. Comparison of disease-free survival (DFS) and overall survival (OS) and univariate and multivariate analyses with regard to LNR was performed. Comparison of the performance of LNR to other measurements of lymph node disease was performed., Results: A LNR of 0.10 was a significant cutoff point for determining DFS and OS. On multivariate analysis, LNR >0.10 was an independent predictor of DFS and OS without other measures of lymph node disease burden. Patients with LNR >0.10 had worse DFS and OS. Absolute counts of tumor-positive lymph nodes differentiated survival differences better than LNR. LNR was not a significant predictor of survival in patients with neck or axillary dissections but was for inguinal dissections. In multivariate analysis of alternative nodal measures, LNR was an inferior prognostic factor., Conclusions: A LNR >0.10 has a negative prognostic significance when it is the only measurement of lymph node disease considered but is an inferior prognostic factor to alternative measures of lymph node disease., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: This study was performed to identify clinicopathologic factors associated with survival in acral lentiginous melanoma., Methods: A post hoc analysis of a prospective clinical trial and local database was performed in all patients with acral lentiginous melanomas. Multivariate analyses of factors associated with a tumor-positive sentinel lymph node (SLN) biopsy, disease-free survival (DFS), overall survival (OS), and local and in-transit recurrence-free survival (LITRFS) were performed. Kaplan-Meier survival analyses were performed., Results: Eighty-five patients were identified. Age younger than 59 years and Breslow thickness (BT) of 2.0 mm or greater were independent risk factors for a positive SLN. SLN status was the only independent risk factor for DFS and LITRFS on multivariate analysis. A BT of 2.0 mm or greater was the only independent risk factor for OS. SLN status distinguished differences in DFS, OS, and LITRFS on Kaplan-Meier analysis., Conclusions: SLN status is the dominant factor for recurrence and survival in acral lentiginous melanoma. BT and ulceration are less important in this histologic subtype., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: In patients with cutaneous melanoma, mitotic rate (MR) historically has been reported as the number of mitoses per high-power field (hpf) or per 10 hpf. The most recent revision of the American Joint Committee on Cancer melanoma staging system now incorporates MR and specifies that MR should be reported as mitoses per mm(2), with a conversion factor of 1 mm(2) equaling 4 hpf. However, because many pathologists continue to report MR in hpf units, we sought to compare the 2 conventions for reporting MR; this is important now that MR is used for staging and prognostic information., Methods: A retrospective analysis was performed of a database that combined patients from a large multicenter study and our single-institution melanoma database. All patients with pathology reports that included MR were included. For patients with MR reported in hpf units, MR was converted to mitoses per 10 hpf. Statistical analysis was performed to test differences in Breslow thickness (BT), ulceration, sentinel lymph node (SLN) status, and overall survival (OS) (log-rank test) between the mitoses per mm(2) group versus the mitoses per 10-hpf group., Results: A total of 1,148 patients were identified; of these, 759 were reported as per mm(2) and 389 were reported in hpf units. When patients were subdivided into categories of MR of 0, 1, or more than 1, there was no statistically significant difference in mean or median BT, ulceration, or SLN positivity within categories between patients with MR per mm(2) versus patients with MR reported per 10 hpf. There was also no difference in OS between groups. Subdividing into smaller categories of MR of 0, 1, 2, 3, 4, 5, or more than 5 did not yield different results., Conclusions: Although the American Joint Committee on Cancer staging system reports a conversion factor for MR of 1 mm(2) equals 4 hpf, no clinically meaningful differences in predictors of prognosis (BT, ulceration, SLN positivity) or OS were seen between groups when a conversion factor of 1 mm(2) equaling 10 hpf was used. Therefore, for practical purposes, MR reported per 10 hpf approximates MR per mm(2)., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The nodular subtype of cutaneous melanoma has a more pronounced vertical phase and less of a radial growth phase compared with other histologic subtypes. This study was performed to determine prognostic factors and outcomes for nodular melanomas., Methods: A post hoc analysis of a prospective clinical trial was performed in all patients with nodular histologic subtype. Univariate and multivariate analyses of factors associated with disease-free survival (DFS), overall survival (OS), and local and in-transit recurrence-free survival (LITRFS) were performed. Kaplan-Meier survival analyses were performed., Results: There were 736 patients available for analysis, and 189 (25.7%) were sentinel lymph node (SLN) positive. Breslow thickness of ≥2.3 mm, presence of ulceration, nonextremity tumor location, positive SLN, and non-SLN-positive status were independent risk factors for worse OS and DFS. Kaplan-Meier analysis demonstrated that ulceration predicted worse OS and DFS in all nodular melanoma patients, and in both SLN-positive and -negative subsets. The presence of ulceration and a positive SLN together predicted significantly worse DFS and OS., Conclusion: The most important risk factors that determine prognosis in nodular melanomas are SLN status and ulceration. The presence of both a positive SLN and ulceration significantly affect DFS and OS, and to a lesser degree LITRFS., (Copyright © 2012 Mosby, Inc. All rights reserved.)

This analysis was performed to compare differences in clinicopathologic factors, sentinel lymph node (SLN) status, and survival between upper extremity (UE) and lower extremity (LE) melanoma patients. Post hoc analysis of a prospective clinical trial was performed of all patients with extremity melanomas with complete data. Survival was evaluated with Kaplan-Meier analysis. Univariate and multivariate analyses were performed. A total of 1115 patients aged 18 to 70 years with extremity melanomas ≥ 1.0 mm Breslow thickness were analyzed; all underwent SLN biopsy with completion lymphadenectomy for a tumor-positive SLN. Compared with UE patients, LE melanoma patients were younger, predominantly female, and had a higher rate of SLN metastasis. Kaplan-Meier analysis revealed worse 5-year disease-free survival (DFS) and worse local and in-transit recurrence-free survival in LE versus UE melanoma patients, but no difference in overall survival (OS). Subgroup analysis revealed that older patients (age > 51 years) with LE melanomas had worse DFS, local and in-transit recurrence-free-survival, and OS. LE tumor location was not an independent risk factor for OS or DFS. Compared with UE melanoma patients, those with LE melanomas have a greater risk of tumor-positive SLN and local/in-transit recurrence.

Background: We found that a computer model developed by the American Joint Committee on Cancer (AJCC) melanoma staging committee had limitations for predicting prognosis of patients staged by sentinel lymph node (SLN) biopsy. We sought to develop a model that more accurately predicts prognosis in this population., Study Design: Using a data set obtained from a prospective multi-institutional study of 2,507 patients with clinically node-negative melanomas ≥1.0 mm Breslow thickness, we developed a prognostic model using a Cox regression formula incorporating a number of significant clinicopathologic factors. The AJCC model and our model were used to predict 5-year survival from this test data set. The concordance correlation coefficient (CCC) was determined and chi-square tests were performed. Our new prognostic model was validated using an independent data set of 1,001 patients., Results: Using the test data set, the CCC for the AJCC model was 0.875; chi-square tests demonstrated statistically significant differences between observed and predicted survivals for numerous clinicopathologic factors. The CCC for our model was 0.976 and none of the chi-square tests was statistically significant. Our model performed similarly well in SLN-negative patients (CCC 0.929) and SLN-positive patients (CCC 0.889). The AJCC model performed well in SLN-negative patients (CCC 0.854), but not in SLN-positive patients (CCC 0.626). Using the validation data set, similar findings were obtained., Conclusions: Our prognostic model provides superior survival estimates compared with the AJCC model for patients undergoing SLN biopsy. This online tool is available at www.melanomacalculator.com, and will provide important information that can be used to guide adjuvant therapy decisions and stratification in clinical trials., (Copyright © 2012 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Breslow thickness, ulceration, and sentinel lymph node (SLN) status are well established as the most important prognostic factors for patients with cutaneous melanoma. Anatomic location of the primary tumor is generally considered to play a minor role in determining prognosis compared with these other factors. This analysis was performed to better define the influence of anatomic location of the primary melanoma on prognosis., Methods: In this post hoc analysis of a prospective randomized trial that included patients ages 18 to 70 years with melanomas 1 mm or greater in Breslow thickness, all patients underwent SLN biopsy and completion lymphadenectomy if tumor-positive SLN were found. Kaplan-Meier survival analysis and univariate and multivariate analyses were performed to evaluate factors predictive of disease-free survival (DFS), local and in-transit recurrence-free survival (LITRFS), and overall survival (OS)., Results: A total of 2,500 patients were included in this analysis with a median follow-up period of 68 months. Anatomic locations included head, neck, trunk, upper extremity, and lower extremity. Age, Breslow thickness, and percentage of patients with a positive SLN were significantly different by anatomic location on univariate analysis, as were positive SLN status, presence of regression, sex, and histologic subtype (P < .0001). On multivariate analysis, anatomic location was an independent predictor of SLN status (P < .0001), DFS (P = .045), LITRFS (P = .023), and OS (P < .0001). By Kaplan-Meier analysis, anatomic location was associated significantly with DFS, LITRFS, and OS., Conclusions: Anatomic location of the primary melanoma is an important independent predictor of SLN status and prognosis. Patients with primary melanomas of the head/neck and trunk have a worse prognosis than primary melanomas of other anatomic locations., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Controversy exists regarding the prognostic implications of regression in patients with cutaneous melanoma. Some consider regression to be an indication for sentinel lymph node (SLN) biopsy because regression may result in underestimation of the true Breslow thickness. Other data support regression as a favorable prognostic indicator, representing immune system recognition of the primary tumor. This analysis was performed to determine whether regression predicts nodal metastasis, disease-free survival (DFS), or overall survival (OS). Post hoc analysis was performed of a multicenter prospective randomized trial that included patients aged 18 to 70 years with cutaneous melanomas 1 mm or greater Breslow thickness. All patients underwent SLN biopsy; those with tumor-positive SLN underwent completion lymphadenectomy. Kaplan-Meier analysis of survival, univariate analysis, and multivariate analysis were performed. A total of 2220 patients (261 with regression; 1959 without regression) were included in this analysis with a median follow-up of 68 months. Patients with regression were more likely to be male, older than 50 years old, and have lower median Breslow thickness, superficial spreading histologic subtype, and a nonextremity anatomic location (P < 0.05 in all cases). Regression was not significantly associated with Clark level, ulceration, lymphovascular invasion, number of SLNs removed, or SLN metastasis. On multivariate analysis, factors independently predictive of DFS included Breslow thickness, ulceration, and SLN status (P < 0.05 in all cases); the same factors along with age, gender, and anatomic tumor location were significantly associated with OS (P < 0.05 in all cases). Regression was not significantly associated with DFS (risk ratio [RR], 0.94; 95% confidence interval [CI], 0.67-1.27; P = 0.68) or OS (RR, 1.01; 95% CI, 0.76-1.32; P = 0.93). These data suggest that regression is not a significant prognostic factor for patients with cutaneous melanoma and should not be used to guide clinical decision-making for such patients.

The prognostic significance of lymphovascular invasion (LVI) in melanoma remains controversial. Clinicopathologic data from a prospective trial of patients with melanoma were analyzed with respect to LVI. Disease-free survival and overall survival (OS) were evaluated by Kaplan-Meier (KM) analysis. Univariate and multivariate analyses were performed to evaluate factors predictive of tumor-positive sentinel nodes (SLN) and survival. A total of 2183 patients were included in this analysis; 171 (7.8%) had LVI. Median follow-up was 68 months. Factors associated with LVI included tumor thickness, ulceration, and histologic subtype (P < 0.05). LVI was associated with a greater risk of SLN metastasis (P < 0.05). By KM analysis, LVI was associated with worse OS (P = 0.0009). On multivariate analysis, age, gender, thickness, ulceration, anatomic location, and SLN status were predictors of OS; however, LVI was not an independent predictor of OS. Among patients with regression, the 5-year OS rate was 49.4 per cent for patients with LVI versus 81.1 per cent for those with no LVI (P < 0.0001). LVI is associated with a greater risk of SLN metastasis. Although LVI is not an independent predictor of OS in general, it is a powerful predictor of worse OS among patients who have evidence of regression of the primary tumor.

The prognostic significance of tumor infiltrating lymphocyte (TIL) response in cutaneous melanoma is controversial. This analysis of data from a prospective, randomized trial included patients with cutaneous melanoma > or = 1.0 mm Breslow thickness who underwent wide local excision and sentinel lymph node (SLN) biopsy. Univariate and multivariate analyses were performed to determine factors associated with TIL response, disease-free survival (DFS), and overall survival (OS). A total of 515 patients were included; TIL response was classified as "brisk" (n = 100; 19.4%) or "non-brisk" (n = 415; 80.6%). Patients in the nonbrisk TIL group were more likely to have tumor-positive SLN (17.6% vs 7%; P = 0.0087). On multivariate analysis, nonbrisk TIL response, increased tumor thickness, and ulceration were significant independent predictors of tumor-positive SLN. By Kaplan-Meier analysis, 5-year DFS rate was 91 per cent for those with a brisk TIL response compared with 86 per cent in the nonbrisk group (P = 0.41). The 5-year OS rates were 95 per cent versus 84 per cent in the brisk versus nonbrisk TIL groups, respectively (P = 0.0083). However, on multivariate analysis, TIL response was not a significant independent factor predicting DFS or OS. TIL response is a significant predictor of SLN metastasis but is not a major predictor of DFS or OS.

Background: The significance of mitotic rate (MR) in melanoma remains controversial., Methods: In this retrospective analysis of a prospective randomized trial that included patients with melanoma of 1.0 mm or greater, all patients underwent wide excision and sentinel node (sentinel lymph node [SLN]) biopsy. Univariate and multivariate analyses were performed to evaluate factors predictive of disease-free survival (DFS) and overall survival (OS)., Results: A total of 551 patients had MR reported. A cut-off point of 6 mitoses/mm(2) best discriminated DFS and OS: 455 patients (82.6%) had MR less than 6/mm(2). SLN were tumor-positive in 14.7% of low MR versus 31.3% of high MR patients (P = .0003). There were significant differences in DFS (P = .0014) and OS (P = .0002) between the 2 groups, however, MR failed to remain significant in the multivariate model., Conclusions: MR is weakly predictive of SLN status but it is not an independent predictor of survival for melanomas 1.0 mm or thicker., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: We hypothesized that metastasis beyond the sentinel lymph nodes (SLN) to the nonsentinel nodes (NSN) is an important predictor of survival., Materials and Methods: Analysis was performed of a prospective multi-institutional study that included patients with melanoma ≥ 1.0 mm in Breslow thickness. All patients underwent SLN biopsy; completion lymphadenectomy was performed for all SLN metastases. Disease-free survival (DFS) and overall survival (OS) were computed by Kaplan-Meier analysis; univariate and multivariate analyses were performed to identify factors associated with differences in survival among groups., Results: A total of 2335 patients were analyzed over a median follow-up of 68 months. We compared 3 groups: SLN negative (n = 1988), SLN-only positive (n = 296), and both SLN and NSN positive (n = 51). The 5-year DFS rates were 85.5, 64.8, and 42.6% for groups 1, 2, and 3, respectively (P < 0.001). The 5-year OS rates were 85.5, 64.9, and 49.4%, respectively (P < 0.001). On univariate analysis, predictors of decreased OS included: SLN metastasis, NSN metastasis, increased total number of positive LN, increased ratio of positive LN to total LN, increased age, male gender, increased Breslow thickness, presence of ulceration, Clark level ≥ IV, and axial primary site (in all cases, P < 0.01). When the total number of positive LN and NSN status were evaluated using multivariate analysis, NSN status remained statistically significant (P < 0.01), while the total number of positive LN and LN ratio did not., Conclusions: NSN melanoma metastasis is an independent prognostic factor for DFS and OS, which is distinct from the number of positive lymph nodes or the lymph node ratio.

Background: Current recommendations by the National Comprehensive Cancer Network and other groups suggest that follow-up of cutaneous melanoma may include chest radiography (CXR) at 6- to 12-month intervals. The aim of this study was to determine the clinical efficacy of routine CXR for recurrence surveillance in melanoma., Methods: Post hoc analysis was performed on data from a prospective, randomized, multi-institutional study on melanoma ≥1.0 mm in Breslow thickness. All patients underwent excision of the primary melanoma and sentinel node biopsy with completion lymphadenectomy for positive sentinel nodes. Yearly CXR and clinical assessments were obtained during follow-up. Results of routine CXR were compared with clinical disease states over the course of the study., Results: A total of 1,235 patients were included in the analysis over a median follow-up of 74 months (range, 12-138). Overall, 210 patients (17.0%) had a recurrence, most commonly local or in-transit. Review of CXR results showed that 4,218 CXR were obtained in 1,235 patients either before, or in the absence of, initial recurrence. To date, 88% (n = 3,722) CXR are associated with no evidence of recurrence. Of CXR associated with recurrence, only 7.7% (n = 38) of surveillance CXR were read as "abnormal." Overall, 99% (n = 4,180) of CXR were read as either "normal" or found to be falsely positive (read as "abnormal," but without evidence of recurrence on investigation). Only 0.9% (n = 38) of all CXR obtained were true positives ("abnormal" CXR, with confirmed first known recurrence). Among these 38 patients with true positive CXR, 35 revealed widely disseminated disease (multiorgan or bilateral pulmonary metastases); only 3 (0.2%) had isolated pulmonary metastases amenable to resection. Sensitivity and specificity for surveillance CXR in detecting initial recurrence were 7.7% and 96.5%, respectively., Conclusion: The routine use of surveillance CXR provides no clinically useful information in the follow-up of patients with melanoma. CXR does not detect recurrence at levels sufficient to justify its routine use and, therefore, cannot be recommended as part of the standard surveillance regimen for these patients., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Objective: This analysis was performed to investigate the hypothesis that ulceration predicts improved response to adjuvant interferon (IFN) therapy., Summary Background Data: Several studies have demonstrated that adjuvant therapy for high-risk melanoma patients with IFN alfa-2b improves disease-free survival (DFS), although the impact on overall survival (OS) is controversial. Recent data have suggested that IFN therapy may preferentially benefit patients with ulcerated primary melanomas., Methods: Post hoc analysis was performed by a prospective multi-institutional randomized study of observation versus adjuvant IFN therapy for melanoma. All patients underwent sentinel lymph node biopsy; completion lymphadenectomy was performed for patients with sentinel lymph node metastasis. Patients were stratified by Breslow thickness, ulceration, and nodal status. Kaplan-Meier analysis of DFS and OS was performed and included univariate and multivariate analyses., Results: A total of 1769 patients were analyzed (1311 without ulceration, 458 with ulceration) with a median follow-up of 71 months. Ulceration was associated with significantly worse DFS and OS in both node-negative and node-positive patients. Kaplan-Meier analysis of node-negative and node-positive patients by ulceration status revealed that the only significant impact of interferon was improved DFS in the ulcerated node-positive patients (P = 0.0169). IFN therapy had no significant impact on OS regardless of ulceration status, however. On multivariate analysis, IFN treatment was a significant independent predictor of DFS among ulcerated patients (odds ratio, 0.51; 95% confidence interval, 0.30-0.83; P = 0.0053), but not among patients without ulceration., Conclusions: These data support the conclusion that ulceration is a predictive marker for response to adjuvant IFN therapy. Future studies to evaluate specifically the differential effect of IFN on patients with ulcerated melanomas may allow us to focus this therapy on patients most likely to benefit from it.

The objective of this study was to determine the incidence of multiple primary melanomas (MPM) and other cancers types among patients with melanoma. Factors associated with development of MPM were assessed in a post hoc analysis of the database from a multi-institutional prospective randomized trial of patients with melanoma aged 18 to 70 years with Breslow thickness 1 mm or greater. Disease-free survival (DFS) and overall survival (OS) were evaluated by Kaplan-Meier analysis. Forty-eight (1.9%) of 2506 patients with melanoma developed additional primary melanomas. Median follow-up was 66 months. Except in one patient, the subsequent melanomas were thinner (median, 0.32 mm vs. 1.50 mm; P < 0.0001). Compared with patients without MPM, patients with MPM were more likely to be older (median age, 54.5 vs. 51.0 years; P = 0.048), to have superficially spreading melanomas (SSM) (P = 0.025), to have negative sentinel lymph nodes (P = 0.021), or to lack lymphovascular invasion (LVI) (P = 0.008) with the initial tumor. On multivariate analysis, age (P = 0.028), LVI (P = 0.010), and SSM subtype of the original melanoma (P = 0.024) were associated with MPM. Patients with MPM and patients with single primary melanoma had similar DFS (5-year DFS 88.7 vs. 81.3%, P = 0.380), but patients with MPM had better OS (5-year OS 95.3 vs. 80.0%, P = 0.005). Nonmelanoma malignancies occurred in 152 patients (6.1%). Ongoing surveillance of patients with melanoma is important given that a significant number will develop additional melanoma and nonmelanoma tumors. With close follow-up, second primary melanomas are usually detected at an early stage.

Hypothesis: Sentinel lymph node (SLN) biopsy provides valuable prognostic information for patients with thick (T4) melanoma., Design: Post hoc analysis of data from a prospective, randomized trial., Setting: Academic and private hospitals., Patients: Data of 240 patients with melanoma thicker than 4 mm were analyzed. Patients with tumor-positive SLNs underwent completion lymphadenectomy. Disease-free and overall survival were evaluated by Kaplan-Meier analysis. Univariate and multivariate analyses were performed to evaluate factors predictive of tumor-positive SLNs and disease-free and overall survival., Results: Median thickness of melanoma was 5.6 mm, and patients were followed up for a median of 50 months. The SLNs were tumor positive in 100 patients (41.7%); 18% of these had additional positive nodes on completion lymphadenectomy. Extremity tumor location (risk ratio, 1.66; 95% confidence interval, 1.24-2.24; P = .001), Clark level (1.95; 1.33-2.87; P = .02), and lymphovascular invasion (1.57; 1.13-2.17; P = .01) were associated with a greater risk of tumor-positive SLNs. The patients with tumor-negative SLNs had significantly better median disease-free survival (46.5 vs 31.0 months; P = .04) and overall survival (55.5 vs 43.0 months; P = .004) compared with patients with tumor-positive SLNs. On multivariate analysis, male sex (risk ratio, 1.59; 95% confidence interval, 1.05-2.50; P = .02), increasing Breslow thickness (1.58; 1.10- 2.30; P = .03), ulceration (1.73; 1.18-2.59; P = .02), and tumor-positive SLNs (1.68; 1.17-2.43; P = .009) were associated with worse overall survival., Conclusion: The SLN biopsy provides useful prognostic information for patients with T4 melanoma.

Background: Sentinel lymph node (SLN) biopsy generally is recommended for patients who have melanoma with a Breslow thickness > or = 1 mm. Most patients with melanoma between 1 mm and 2 mm thick have tumor-negative SLNs and an excellent long-term prognosis. The objective of the current study was to evaluate prognostic factors in this subset of patients and determine whether all such patients require SLN biopsy., Methods: Patients with melanoma between 1 mm and 2 mm in Breslow thickness were evaluated from a prospective multi-institutional study of SLN biopsy for melanoma. Disease-free survival (DFS) and overall survival (OS) were evaluated by Kaplan-Meier analysis to compare patients with melanoma that measured from 1.0 mm to 1.59 mm (Group A) versus patients with melanoma that measured from > or = 1.6 mm to 2.0 mm thick (Group B). Univariate and multivariate analyses were performed to evaluate factors predictive of tumor-positive SLN status, DFS, and OS., Results: The current analysis included 1110 patients with a median follow-up of 69 months. SLN status was tumor-positive in 133 of 1110 patients (12%) including 66 of 762 patients (8.7%) in Group A and 67 of 348 patients (19.3%) in Group B (P < .0001). On multivariate analysis, age, Breslow thickness, and lymphovascular invasion were independently predictive of a tumor-positive SLN (P < .05). DFS (P < .0001) and OS (P = .0001) were significantly better for Group A than for Group B. When tumor thickness was treated as either a continuous variable (P < 0.0001) or a categorical variable (P < .0001), it was significantly predictive of DFS and OS. On multivariate analysis, Breslow thickness, age, ulceration, histologic subtype, regression, Clark level, and SLN status were significant factors predicting DFS; and Breslow thickness, age, primary tumor location, sex, ulceration, and SLN status were significant factors predicting OS (P < .05). A subgroup of patients who had tumors <1.6 mm in Breslow thickness, had no lymphovascular invasion, and were aged > or = 59 years had a low risk (5%) of tumor-positive SLN., Conclusions: The current findings indicated that there is significant diversity in the biologic behavior of melanoma between 1 mm and 2 mm in Breslow thickness. SLN biopsy is recommended for all such patients to identify those with lymph node metastasis who are at the greatest risk of recurrence and mortality.

Introduction: Some melanoma patients who undergo sentinel lymph node (SLN) biopsy will have false-negative (FN) results. We sought to determine the factors and outcomes associated with FN SLN biopsy., Methods: Analysis was performed of a prospective multi-institutional study that included patients with melanoma of thickness > 1.0 mm who underwent SLN biopsy. FN results were defined as the proportion of node-positive patients who had a tumor-negative sentinel node biopsy. Kaplan-Meier survival analysis and univariate and multivariate analyses were performed., Results: This analysis included 2,451 patients with median follow-up of 61 months. FN, true-positive (TP), and true-negative (TN) SLN results were found in 59 (10.8%), 486 (19.8%), and 1,906 (77.8%) patients, respectively. On univariate analysis comparing the FN with TP groups, respectively, the following factors were significantly different: age (52.6 vs. 47.6 years, p = 0.004), thickness (mean 2.1 vs. 3.1 mm, p = 0.003), lymphovascular invasion (LVI; 3.7 vs. 13.7%, p = 0.037), and local/in-transit recurrence (LITR; 32.2 vs. 12.4%, p < 0.0001); these factors remained significant on multivariate analysis. Overall 5-year survival was greater in the TN group (86.7%) compared with the TP (62.3%) and FN (51.3%) groups (p < 0.0001); however, there was no significant difference in overall survival comparing the TP and FN groups (p = 0.32)., Conclusions: This is the largest study to evaluate FN SLN results in melanoma, with a FN rate of 10.8%. FN results are associated with greater patient age, lower mean thickness, less frequent LVI, and greater risk of LITR. However, survival of patients with FN SLN is not statistically worse than that of patients with TP SLN.

Sun exposure is known to cause melanoma; what is not known is whether patients from the Southern United States have a different profile of clinicopathologic factors and outcomes than those from the Northern United States. Data from a prospective, randomized trial on surgery for cutaneous melanoma were analyzed. All patients underwent wide excision and sentinel lymph node biopsy. Patients were categorized into two groups: Northern or Southern according to their state of residence. Clinicopathologic factors and outcomes were compared between groups. A total of 2025 patients were included in the analysis; 1214 (60%) were from Southern states. The median follow-up was 52 months. Despite significant differences in clinicopathologic features between groups on both univariate and multivariate analysis, two important factors, namely primary tumor thickness and ulceration were not different, nor was the rate of lymph node metastasis. Additionally, there were no differences in disease-free survival or overall survival between the two groups. Significant differences exist between primary melanomas based on geographic regions; however there are no differences in survival. Cumulative versus episodic sun exposure may play some role in these differences.

Purpose: To evaluate the prognostic significance of molecular staging using reverse transcriptase polymerase chain reaction (RT-PCR) in detecting occult melanoma cells in sentinel lymph nodes (SLNs) and circulating bloodstream., Patients and Methods: In this multicenter study, eligibility criteria included patient age 18 to 71 years, invasive melanoma > or = 1.0 mm Breslow thickness, and no clinical evidence of metastasis. SLN biopsy and wide excision of the primary tumor were performed. SLNs were examined by serial-section histopathology and S-100 immunohistochemistry. A portion of each SLN was frozen for RT-PCR. In addition, RT-PCR was performed on peripheral-blood mononuclear cells (PBMCs). RT-PCR analysis was performed using four markers: tyrosinase, MART1, MAGE3, and GP-100. Disease-free survival (DFS), distant-DFS (DDFS), and overall survival (OS) were analyzed., Results: A total of 1,446 patients with histologically negative SLNs underwent RT-PCR analysis. At a median follow-up of 30 months, there was no difference in DFS, DDFS, or OS between the RT-PCR-positive (n = 620) and RT-PCR-negative (n = 826) patients. Analysis of PBMC from 820 patients revealed significant differences in DFS and DDFS, but not OS, for patients with detection of more than one RT-PCR marker in peripheral blood., Conclusion: In this large, prospective, multi-institutional study, RT-PCR analysis on SLNs and PBMCs provides no additional prognostic information beyond standard histopathologic analysis of SLNs. Detection of more than one marker in PBMC is associated with a worse prognosis. RT-PCR remains investigational and should not be used to direct adjuvant therapy at this time.

Objective: To better understand the factors associated with the well-established gender difference in survival for patients with melanoma., Summary Background Data: Gender is an important factor in patients with cutaneous melanoma. Male patients have a worse outcome when compared with females. The reasons for this difference are poorly understood., Methods: This prospective multi-institutional study included patients aged 18 to 70 years with melanomas > or =1.0 mm Breslow thickness. Wide excision and sentinel lymph node (SLN) biopsy was performed in all patients. Clinicopathologic factors, including gender, were assessed and correlated with disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS)., Results: A total of 3324 patients were included in the covariate analyses; 1829 patients had follow-up data available and were included in the survival analyses. Median follow-up was 30 months. On univariate analysis, men (n = 1906) were more likely than women to be older than 60 years (P < 0.0001), have thicker melanomas (P < 0.0001), have primary tumor regression (P = 0.0054), ulceration (P < 0.0001), and axial primary tumor location (P < 0.0001). On multivariate analysis, age (P = 0.0002), thickness (P < 0.0001), ulceration (P = 0.015), and location (P < 0.0001) remained significant in the model. There was no difference in the rate of SLN metastasis between men and women (P = 0.37) on multivariate analysis. When factors affecting survival were considered, the prognosis was worse for men as validated by lower DFS (P = 0.0005), DDFS (P < 0.0001), and OS (P < 0.0001)., Conclusions: Male gender is associated with a greater incidence of unfavorable primary tumor characteristics without an increased risk for nodal metastasis. Nonetheless, gender is an independent factor affecting survival.

Background: Age of patients with melanoma varies directly with mortality and inversely with the presence of sentinel lymph node (SLN) metastasis. To gain further insight into this apparent paradox, we analyzed the relationship between age and other major prognostic factors., Methods: The Sunbelt Melanoma Trial is a prospective, randomized study with 79 institutions involving SLN biopsy for melanoma. Eligible patients were 18 to 70 years old with melanoma of > or = 1.0-mm Breslow thickness and clinically N0 regional lymph nodes. SLNs were evaluated by serial histological sections and immunohistochemistry for S-100 protein., Results: A total of 3076 patients were enrolled in the study, with a median follow-up of 19 months. Five age groups were examined: 18 to 30, 31 to 40, 41 to 50, 51 to 60, and 61 to 70 years. Trends between age and several key prognostic factors was identified: as age group increased, so did Breslow thickness (analysis of variance; P <.001), the incidence of ulceration and regression, and the proportion of male patients (each variable: chi2, P <.001). The incidence of SLN metastasis, however, declined with increasing age (chi2; P <.001)., Conclusions: As age increases, so does Breslow thickness, the incidence of ulceration and regression, and the proportion of male patients-all poor prognostic factors. However, the frequency of SLN metastasis declines with increasing age. It is not known whether this represents a decreased sensitivity (higher false-negative rate) of the SLN procedure in older patients or a different biological behavior (hematogenous spread) of melanomas in older patients.