Cancer Melanoma Staging System Research Articles

PA02 A teenager with a bleeding neck nodule

Abstract A 14-year-old boy was referred to dermatology with a new bleeding lesion on his right neck that had grown rapidly. There was no preceding history of trauma. Physical examination revealed a discrete eroded pink nodule measuring 10 × 9 mm on his right neck. Dermoscopic examination showed a central area of ulceration, with polymorphous vessels, white lines and multiple shades of pink and milky-white areas. This was excised. Histology confirmed the diagnosis of ulcerated superficial spreading malignant melanoma with a Breslow thickness of 4.8 mm (pT4b). BRAF v600e mutation was present. Initial staging with sentinel lymph node biopsy and whole-body positron emission tomography/­computed tomography were clear, but 6 months after presentation, he developed right-sided cervical lymphadenopathy and a parotid mass that was confirmed to be metastatic disease. Following a right parotidectomy and neck dissection, he was commenced on adjuvant treatment with dabrafenib and trametinib. He remains under close follow-up. Less than 1% of all melanomas are diagnosed in patients younger than 20 years of age. Most paediatric cases occur in adolescence (between 15 and 19 years of age). The majority arise sporadically. Risk factors for melanoma in childhood include giant congenital melanocytic naevi, personal history of malignancy, family history of melanoma, multiple (> 50) melanocytic naevi, history of sunburn or tanning-bed use, immunosuppression or genodermatoses (e.g. xeroderma pigmentosum). Most clinicians are familiar with the ‘ABCDE’ tool (asymmetry, border irregularity, colour variegation, diameter > 6 mm, evolution) used to help with the recognition of melanomas; however, melanoma in children often presents in an atypical fashion. Paediatric melanomas often lack pigment (amelanotic) and are nodular, and so may be misdiagnosed. Because of this, diagnosis may be delayed and patients often present with thicker tumours and lymph node involvement. To facilitate earlier diagnosis, modified ABCD detection criteria have been proposed for paediatric melanoma (amelanosis, bleeding/bump, colour uniformity, de novo development) that can be used in conjunction with the established ABCDE approach. The CUP criteria have also been described (colour that is pink/red/changing, ulceration/upward thickness, pyogenic granuloma-like lesions/pop-up of new lesions). Evolution remains an important point to consider when suspecting melanoma in patients of any age. Management and staging of paediatric melanoma is adopted from the American Joint Committee on Cancer melanoma staging system guidelines for adult melanoma. Currently, there are no specific guidelines for the management of melanoma in children. The mainstay of treatment is surgical resection. Sentinel lymph node biopsy should be considered with ulceration or a Breslow thickness of > 0.75 mm. Patients with stage III and IV melanoma should be considered for adjuvant immunotherapy. All patients with melanoma should be followed-up with regular skin examinations.

Prognostic value of ulceration varies across Breslow thicknesses and clinical stages in acral melanoma: a retrospective study.

SummaryBackgroundUlceration is regarded as an adverse prognostic factor and is used together with tumour thickness to subcategorize patients with cutaneous melanoma. However, the prognostic impact of ulceration in acral melanoma (AM) is controversial.ObjectivesTo assess the prognostic impact of ulceration in AM and the variability across different Breslow thicknesses and clinical stages.MethodsA multicentre retrospective study of patients diagnosed with AM between January 2000 and December 2017. Differences in melanoma‐specific survival (MSS) between patients with and without ulceration were assessed using the multivariable Cox proportional hazards model and log‐rank test.ResultsAmong 1053 enrolled patients, 62.6% had ulceration. After a median follow‐up of 61 months, patients with ulceration had a lower median MSS than those without: 66.1 months, 95% confidence interval (CI) 60.0–86.0 vs. not reached; hazard ratio 1.41, 95% CI 1.09–1.82; P = 0.012. Among patients with thin (≤ 1 mm) melanoma, the survival curves of patients with vs. without ulceration clearly separated over time (P < 0.001). No association between ulceration and MSS was observed for melanomas of thickness > 1 mm (subgroups of T2, T3 and T4; all P‐values > 0.05) or patients with stage III disease (hazard ratio 1.09, 95% CI 0.71–1.68, P = 0.39).ConclusionsUlceration is an independent negative prognostic factor for patients with AM, but the impact varies across Breslow thicknesses and clinical stages. Ulceration has a significant effect on prognosis for patients with thin (≤ 1 mm) melanoma, but there was no association between ulceration and survival in intermediate/thick AM or stage III AM. What is already known about this topic? Ulceration status is used together with Breslow tumour thickness to subcategorize patients into different stages according to the America Joint Committee on Cancer melanoma staging system.As one distinctive subtype of cutaneous melanoma, acral melanoma (AM) is characterized by poor survival outcomes due to delayed diagnosis and a high prevalence of negative prognostic and genetic features.The prognostic impact of ulceration in AM is still controversial. What does this study add? This was the first large‐scale study to assess the prognostic and staging values of ulceration in patients with AM.Ulceration has a significant effect on prognosis for patients with thin (≤1 mm) melanoma, but no association between ulceration and survival was found in intermediate/thick or stage III AM.These findings should be considered when using ulceration‐based staging systems.

External validation of the American Joint Committee on Cancer melanoma staging system eighth edition using the surveillance, epidemiology, and end results program.

The American Joint Committee on Cancer (AJCC) melanoma staging system eighth edition (AJCC-8) was recently released to provide accurate staging reflecting advances in the treatment of melanoma. Using population registry data, this study independently validates and compares the prognostic performance of AJCC-8 to the seventh edition (AJCC-7). We extracted patient-, tumor-related, and survival data from the SEER-18 registry between 2010 and 2015. To assess overall survival (OS) and cancer-specific survival (CSS) for AJCC-7 and AJCC-8, we performed Kaplan-Meier analysis and computed cumulative hazard functions using Nelson-Aalen function. Of 126,408 individuals, 59,989 (47%) and 60,411 (48%) had available data for pathological and clinical-stage OS analysis, respectively. The 3-year OS for AJCC-7 among pathologically staged patients was: stage IA 97%, stage IB 95%, stage IIA 87%, stage IIB 76%, stage IIC 57%, stage IIIA 86%, stage IIIB 69%, stage IIIC 50%, and stage IV 24%. The 3-year OS for AJCC-8 patients was similar but was 56% for stage IIIC and 30% for stage IIID. Stage IV individuals with an elevated LDH had worse OS and CSS at all measured time-points up to 60 months compared to those with a normal LDH. The discriminatory ability of AJCC-8 and AJCC-7 appear comparable. Changes in AJCC-8 identified stage IIID as a poor prognostic subgroup among stage III patients and elevated LDH in stage IV. However, patients with advanced T-stage, node-negative tumors experienced worse survival compared to those with earlier T-stage, node-positive tumors, and the results of ongoing trials should inform adjuvant therapy in this subset of patients.

How does the mitotic index impact patients with T1 melanoma? Comparison between the 7th and 8th edition of the American Joint Committee on Cancer melanoma staging system

BackgroundThe mitotic index is no longer used to classify T1 melanoma patients into T1a and T1b, so it should not be used to indicate sentinel node biopsy in these patients. ObjectivesTo evaluate patients with T1 melanoma who underwent sentinel lymph node biopsy and to compare those who were classified as T1a with those classified T1b, according to the 7th and 8th Edition of the melanoma staging system, regarding a positive biopsy result. The authors also aimed to assess whether there is any difference in the results in both staging systems. Material and methodsThis was a retrospective analysis of 1213 patients who underwent sentinel lymph node biopsy for melanoma, from 2000 to 2015, in a single institution. ResultsOf 399 patients with thin melanomas, 27 (6.7%) presented positive sentinel lymph nodes; there was no difference in positivity for sentinel node biopsy when comparing T1a vs. T1b in both staging systems. Furthermore, the clinical results were also similar between the two groups. However, in the complete cohort analysis, the mitotic index was associated with positivity for sentinel lymph node biopsy (p < 0.0001), positivity for non-sentinel lymph node (p < 0.0001), recurrence-free survival (p < 0.0001), and specific melanoma survival (p = 0.023). Study limitationUnicentric study. ConclusionThe mitotic index was shown to be a very important prognostic factor in the present study, but it was not observed in patients classified as T1. The mitotic index should no longer be used as the only reason to refer sentinel lymph node biopsy in patients with thin melanoma.

Quantitative associations between health insurance and stage of melanoma at diagnosis among nonelderly adults in the United States.

Health insurance plays a critical role in the accessibility to and quality of health care for patients with melanoma in the United States. Current knowledge regarding the association between insurance status and stage of melanoma is limited because few studies to date have simultaneously controlled for factors known to influence the risk of diagnosis of late-stage melanoma. The current study was conducted to examine the association between health insurance status and stage of melanoma at the time of diagnosis in nonelderly adults, accounting for known risk factors for late-stage diagnosis. In this cross-sectional study, the authors analyzed the National Cancer Data Base for cases of invasive melanoma diagnosed between 2004 and 2015 among individuals aged 26 to 64years. Using the American Joint Committee on Cancer melanoma staging system, early-stage melanoma was defined as stage I or stage II whereas late-stage melanoma was defined as stage III or stage IV. Late-stage diagnosis was the primary outcome compared across 4 insurance types (private, Medicaid, none, and unknown). Adjusted covariates were age, sex, race/ethnicity, educational level, income, year of diagnosis, number of comorbidities, and facility location. Logistic regression was used for univariable and multivariable analyses. Among 177,247 cases, individuals with Medicaid or no health insurance were found to have 3.12 (95% CI, 2.97-3.28) and 2.21 (95% CI, 2.10-2.33) times greater odds, respectively, of being diagnosed with late-stage melanoma compared with individuals with private insurance after adjusting for risk factors in late-stage diagnosis. Future investigation into insurance disparities in the diagnosis of late-stage melanoma may help to prioritize melanoma screening in populations with nonprivate insurance.

Should Sentinel Lymph Node Biopsy Be Performed for All T1b Melanomas in the New 8th Edition American Joint Committee on Cancer Staging System?

In the 8th edition of the American Joint Committee on Cancer melanoma staging system, the T1b category has been redefined based solely on thickness and ulceration. National Comprehensive Cancer Network guidelines recommend consideration of sentinel lymph node biopsy (SLNB) for all patients with T1b melanomas (0.8 to 1.0 mm thick). We hypothesized that the new staging system would lead to excessive use of SLNB in patients with non-ulcerated T1b melanomas with a low risk of positive sentinel lymph nodes. The National Cancer Database 2015 Melanoma Public Use File was used to select patients undergoing SLNB for thin T1 cutaneous melanoma from 2010 to 2015. Clinicopathologic risk factors for having a positive SLNB were evaluated. Univariable and multivariable logistic regression models and classification and regression tree analysis were performed to identify groups with high and low risk of positive SLNB. We selected patients undergoing SLNB without ulceration with thickness 0.75 to 1.04 mm, staged T1b in the new 8th edition American Joint Committee on Cancer by thickness criteria alone (6,894 patients). Independent risk factors for a positive sentinel lymph node were age 56 years or younger (odds ratio [OR] 1.74; 95% CI 1.38 to 2.17), thickness 1.0 vs 0.8 to 0.9 mm (OR 1.36; 95% CI 1.09 to 1.70), female sex (OR 1.36; 95% CI 1.09 to 1.69), and mitotic rate ≥1/mm2 (OR 2.01; 95% CI 1.54 to 2.64). Classification and regression tree analysis identified 2 groups based on age, mitotic rate, and thickness with a risk of positive SLNB <5%. These 2 groups made up 55% of T1b, nonulcerated melanoma patients who underwent SLNB. The new 8th edition American Joint Committee on Cancer melanoma staging system T1b category should not be used to determine use of SLNB in thin melanoma, as more than one half of T1b lesions without ulceration have a low risk of positive sentinel lymph nodes.

Clinical implications of the eighth edition of the American Joint Committee on Cancer melanoma staging.

The new edition of the American Joint Committee on Cancer staging system for melanoma builds on the foundation of prior editions but has several important improvements. The availability of regional nodal staging using sentinel lymph node biopsy (with subsequent follow-up) has resulted in more accurate prognostication for patients and clinicians. This facilitates identification of those at higher risk for recurrence, and allows for the appropriate selection of patients for new adjuvant therapy and clinical trials. Although more complex than previous editions, the eighth edition will provide granularity to outcome analysis based on more precise risk stratification.

Primary Dermal Melanoma: A Case Report and a Review of the Literature

Patients with cutaneous metastatic melanoma of unknown primary origin (stage IV M1a disease according to the American Joint Committee on Cancer melanoma staging system) have an estimated 5-year survival rate of between 5% and 17.9% and a median survival of 6 months. However, certain patients with stage IV M1a disease have much higher survival rates. The existence of this subpopulation has given rise to the term primary dermal melanoma to describe such cases.We report a case of melanoma with characteristics consistent with primary dermal melanoma and review the relevant literature. A diagnosis of primary dermal melanoma requires careful clinical and pathologic correlation and should be considered in all patients with a solitary melanoma confined to the dermis and subcutaneous tissue when there is no evidence of a primary tumor or disease at other sites following appropriate staging studies. We believe that familiarity with this subtype of melanoma is essential in order to provide patients with optimal care and better prognostic information.

Assessment of mitotic rate reporting in melanoma

BackgroundIn 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 mm2, with a conversion factor of 1 mm2 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. MethodsA 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 mm2 group versus the mitoses per 10-hpf group. ResultsA total of 1,148 patients were identified; of these, 759 were reported as per mm2 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 mm2 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. ConclusionsAlthough the American Joint Committee on Cancer staging system reports a conversion factor for MR of 1 mm2 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 mm2 equaling 10 hpf was used. Therefore, for practical purposes, MR reported per 10 hpf approximates MR per mm2.

Melanoma dérmico primario: presentación de un caso y revisión de la literatura

Patients with cutaneous metastatic melanoma of unknown primary origin (stage IV M1a disease according to the American Joint Committee on Cancer melanoma staging system) have an estimated 5-year survival rate of between 5% and 17.9% and a median survival of 6 months. However, certain patients with stage IV M1a disease have much higher survival rates. The existence of this subpopulation has given rise to the term primary dermal melanoma to describe such cases.We report a case of melanoma with characteristics consistent with primary dermal melanoma and review the relevant literature. A diagnosis of primary dermal melanoma requires careful clinical and pathologic correlation and should be considered in all patients with a solitary melanoma confined to the dermis and subcutaneous tissue when there is no evidence of a primary tumor or disease at other sites following appropriate staging studies. We believe that familiarity with this subtype of melanoma is essential in order to provide patients with optimal care and better prognostic information.

Quality of histopathological reporting on melanoma and influence of use of a synoptic template

To evaluate the quality of histopathological reporting for melanoma in a whole population, to assess the influence on quality of the use of a synoptic template and thus to provide an evidence base to guide improvement in reporting melanoma pathology. Histopathology reports of all primary invasive melanomas notified to the New South Wales Central Cancer Registry between October 2006 and October 2007 (n = 3784) were reviewed. A detailed audit of histopathology reports for consecutively diagnosed primary invasive melanoma over 6 months (n = 2082) was performed to assess the quality of each report based on compliance with the 2008 Clinical Practice Guidelines for the Management of Melanoma in Australia and New Zealand. Only half of the initial excision specimen reports included the essential components necessary to stage a melanoma patient according to the 2002 American Joint Committee on Cancer/International Union Against Cancer melanoma staging system. Report format was strongly correlated with completeness and validity of reporting: reports in a synoptic format, with or without a descriptive component, achieved the highest quality levels. Even in a population with a high incidence of melanoma, concordance of pathology reports with current guidelines was comparatively low. Wider adoption of synoptic reporting is likely to increase report quality.

Interobserver Variation in the Histopathologic Reporting of Key Prognostic Parameters, Particularly Clark Level, Affects Pathologic Staging of Primary Cutaneous Melanoma

Accurate reporting of prognostically important histopathologic parameters is critical for optimal management of melanoma patients. Previous studies have shown that assessment of Breslow thickness and ulceration is more reproducible between pathologists than estimation of Clark level. However, detailed quantification of the magnitude of variation between observers and its effect on melanoma staging has not been reported. Nine hundred twelve melanoma patients referred to the Sydney Melanoma Unit (SMU) with pathology reports from referring pathology services and reports following histopathologic review by SMU pathologists were studied. Breslow thickness, Clark level, ulceration, and pathologic staging (American Joint Committee on Cancer, 2002) data were extracted from each matched pair of SMU and non-SMU reports. The degree of concordance for these parameters was assessed. There was excellent agreement between SMU and non-SMU pathologists in the assessment of Breslow thickness (kappa = 0.883; intraclass correlation coefficient = 0.968) and ulceration (kappa = 0.832), while that for Clark level was only moderate (kappa = 0.627). The degree of concordance in the assessment of overall pathologic stage was excellent (96.2%), but there was poor agreement for the evaluation of substages IB (77.3%) and IIB (72.4%), due largely to poor Clark level concordance. Although there was a high level of agreement between pathologists in the assessment of overall pathologic stage, the significant level of discordance in pathologic substaging suggests that accurate and reliable substage-based prognostic prediction may not be possible in all cases. It will be important to consider these issues in future revisions of the American Joint Committee on Cancer melanoma staging system.

Management of primary melanoma of the female urogenital tract

Primary melanoma of the urogenital tract in women is rare, but biologically aggressive. They usually affect elderly women and account for less than 10% of all cancer of the urogenital tract in women and less than 10% of all melanoma diagnosed in women. Tumours originate from melanocytes that are present in the urogenital mucosal epithelium of about 3% of women. Tumour staging can be challenging; however, the American Joint Committee on Cancer melanoma staging system has been recommended for use in vulvar and vaginal melanoma. Surgery is the treatment of choice; less-extensive surgery can be a sensible approach because satisfactory locoregional control might be obtained from wide local excision and radiotherapy, without the morbidity and disfigurement associated with radical surgery. Complete regional lymphadenectomy does not seem necessary if a sentinel lymph-node biopsy sample is negative; however, this decision should be made with caution. Various chemotherapy and biotherapy (ie, immunotherapy and biological-response modifiers) regimens have been used in advanced or metastatic melanoma. However, the role of chemotherapy for women with urogenital-tract melanoma has not been established, and biotherapy methods presented to date have been anecdotal.

Reflecting on the 2001 American Joint Committee on Cancer Staging System for Melanoma

The Melanoma Staging Committee of the American Joint Committee on Cancer (AJCC) promulgated in 2001 major revisions of the melanoma tumor-node-metastasis (TNM) categories and stage grouping criteria, for a new staging system of cutaneous melanoma. The Committee invited data analyses relevant to the proposed new melanoma staging for validation of the system. Validation studies that were published subsequently confirmed most of the parameters of the new staging system, identified new prognostic factors that had not been included in the revised AJCC staging, whereas the prognostic power of some parameters could not be confirmed in the data of other institutions. This article provides an in-depth analysis of the current AJCC staging for melanoma, addresses areas of controversy, and offers proposals for consideration at the next revision of the system.

Early-Stage Melanoma: Staging Criteria and Prognostic Modeling

Accurate risk assessment is central to the process of making rational surgical and systemic treatment recommendations for melanoma patients and in establishing appropriate clinical trial stratification criteria. The current American Joint Commission on Cancer melanoma staging system incorporated relevant prognostic variables to provide a framework for the estimation of risk for recurrence; however, significant prognostic heterogeneity exists within the stage groupings. In the stage I/II group, survival rates range from 40% to 95% as defined by the combination of tumor thickness and ulceration. The use of novel prognostic factors, such as mitotic rate, sentinel node biopsy, and prognostic modeling using a variety of factors, can minimize this prognostic heterogeneity and provide a more accurate and individualized prognostic profile. Recent modifications in the stage III criteria include the number of positive nodes, whether the nodal disease is microscopic or clinically apparent, and the presence of an ulcerated primary. Through these factors, survival estimates can be provided, but like the stage I/II group, wide ranges in prognosis exist. The complexion of the stage III population is in evolution as a result of increasing numbers of patients being diagnosed as having microscopic sentinel node disease. Contemporary efforts are focused on defining the prognosis and natural history of this group. Through prognostic modeling using the number of nodes involved, ulceration status, and a measure of disease burden--disease in the sentinel node--relatively homogeneous subgroups can be identified. Long-term follow-up of patients staged with PCR molecular techniques on sentinel nodes shows conflicting value in assessing prognosis and therefore cannot be routinely used outside a clinical trial. The combination of genomic profiling using microarray analyses and the development of targeted therapy holds the future promise of individualizing prognosis and therapy.

Estimates of Stage-Specific Survival Are Altered by Changes in the 2002 American Joint Committee on Cancer Staging System for Melanoma

Estimates of Stage-Specific Survival Are Altered by Changes in the 2002 American Joint Committee on Cancer Staging System for Melanoma

Estimates of stage‐specific survival are altered by changes in the 2002 American Joint Committee on Cancer staging system for melanoma

The objectives of the current study were to examine how the estimated stage-specific survival is altered in the 2002 American Joint Committee on Cancer (AJCC) melanoma staging system compared with the 1997 AJCC staging system and to contrast the predictive accuracy of the 2 staging systems. There were 5847 consecutive melanoma patients who presented to Memorial Sloan-Kettering Cancer Center from 1996 to 2004 and who were entered prospectively into a data base. These patients were staged according to both the 1997 and 2002 AJCC staging criteria. Overall survival estimates were determined using the Kaplan-Meier method. The overall predictive accuracy of the two staging systems was compared using concordance estimation. In total, 1035 patients were shifted to a lower stage in the 2002 staging system, whereas only 15 patients were upstaged. The number of patients with Stage I melanoma increased by 697 under the 2002 system (n = 2166 patients) compared with the 1997 system (n = 1463 patients). Because of the changes in 2002, the estimated 5-year overall survival for patients with Stage II melanoma decreased considerably, from 79% (1997) to 64% (2002). With the initiation of subgroups in 2002, it became apparent that patients with Stage III melanoma were very heterogeneous in terms of their survival probabilities (5-yr overall survival ranged from 70% in patients with Stage IIIA disease to 24% in patients with Stage IIIC disease). Furthermore, in the 2002 system, there was substantial prognostic overlap between Stage II and Stage III. Despite the increased complexity of the 2002 system, the 2 staging systems had similar concordance estimates: 58% for the 1997 staging system compared with 58% (ignoring the subgroups) and 59% (with subgroups) for the 2002 system. Estimates of stage-specific survival were altered substantially by the changes made in the 2002 AJCC staging system for melanoma, particularly for Stage II. Stage subgroups that were added in the 2002 system resulted in a large diversity of risk within Stage III. This must be taken into account to stratify patients properly for clinical trials. The increased complexity of the 2002 system did not improve its predictive ability over the simpler 1997 system, highlighting the importance of developing individualized risk-prediction models.

A Population-Based Validation of the American Joint Committee on Cancer Melanoma Staging System

A major revision of the American Joint Committee on Cancer (AJCC) stages for melanoma was implemented in 2002 after its validation in multinational cohorts including patients from cancer centers and cooperative groups. This staging system has not been validated in a US population-based cohort. We used 41,417 patients with primary invasive cutaneous melanoma diagnosed between 1988 and 2001 from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) cancer registry to validate the revised AJCC staging system. Survival rates computed from stage-specific Kaplan-Meier curves (time to melanoma-specific death) were compared with the survival rates from 17,600 patients in the original AJCC validation study. In the SEER cohort, 65% of reported melanomas were < or = 1.00 mm in thickness and 8.7% were more than 4.00 mm compared with 39% and 10% in the AJCC cohort (P < .001), respectively. AJCC stages were able to discriminate among SEER patient groups with different prognosis. However, SEER survival rates were significantly higher than those in the AJCC study and notably so in patients with T1a lesions (< or = 1 mm without ulceration). This population-specific effect remained significant after controlling for lesion thickness in all substages except stage IIA. Although this national population-based study validates the most recent revision of AJCC stages for melanoma, it emphasizes that survival rates are population specific and found them to be generally higher for SEER compared with AJCC patients. Population-specific survival rates should be used in study designs and decisions about patient-specific interventions.

The revised American Joint Committee on Cancer staging system for melanoma

Substantial progress has been made in identifying the most significant clinical and pathologic characteristics of melanoma that predict for metastasis and survival. The American Joint Committee on Cancer (AJCC) staging system for cutaneous melanoma was recently revised to include these prognostic variables. Major changes in the staging include: (1) melanoma thickness and ulceration but not level of invasion will be used in the T category (except for T1 melanomas); (2) the number of metastatic lymph nodes rather than their gross dimensions and the delineation of clinically occult (ie, “microscopic”) versus clinically apparent (ie, “macroscopic”) nodal metastases will be used in the N category; (3) the site of distant metastases and the presence of elevated serum lactate dehydrogenase (LDH) will be used in the M category; (4) all patients with stage I, II, or III disease will be upstaged when a primary melanoma is ulcerated; (5) satellite metastases around a primary melanoma and in-transit metastases will be merged into a single staging entity that is grouped into stage III disease; and (6) distinct definitions for clinical and pathologic staging will take into account the new staging information gained from intraoperative lymphatic mapping and sentinel node biopsy. Semin Oncol 29:361-369. Copyright 2002, Elsevier Science (USA). All rights reserved.

Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system.

The American Joint Committee on Cancer (AJCC) recently proposed major revisions of the tumor-node-metastases (TNM) categories and stage groupings for cutaneous melanoma. Thirteen cancer centers and cancer cooperative groups contributed staging and survival data from a total of 30,450 melanoma patients from their databases in order to validate this staging proposal. There were 17,600 melanoma patients with complete clinical, pathologic, and follow-up information. Factors predicting melanoma-specific survival rates were analyzed using the Cox proportional hazards regression model. Follow-up survival data for 5 years or longer were available for 73% of the patients. This analysis demonstrated that (1) in the T category, tumor thickness and ulceration were the most powerful predictors of survival, and the level of invasion had a significant impact only within the subgroup of thin (< or = 1 mm) melanomas; (2) in the N category, the following three independent factors were identified: the number of metastatic nodes, whether nodal metastases were clinically occult or clinically apparent, and the presence or absence of primary tumor ulceration; and (3) in the M category, nonvisceral metastases was associated with a better survival compared with visceral metastases. A marked diversity in the natural history of pathologic stage III melanoma was demonstrated by five-fold differences in 5-year survival rates for defined subgroups. This analysis also demonstrated that large and complex data sets could be used effectively to examine prognosis and survival outcome in melanoma patients. The results of this evidence-based methodology were incorporated into the AJCC melanoma staging as described in the companion publication.