American Joint Committee On Cancer Staging Criteria Research Articles

Survival outcomes used to validate version 9 of the American Joint Committee on Cancer staging system for appendiceal cancer.

The standard for cancer staging in the United States for all cancer sites, including primary carcinomas of the appendix, is the American Joint Committee on Cancer (AJCC) staging system. AJCC staging criteria undergo periodic revisions, led by a panel of site-specific experts, to maintain contemporary staging definitions through the evaluation of new evidence. Since its last revision, the AJCC has restructured its processes to include prospectively collected data because large data sets have become increasingly robust and available over time. Thus survival analyses using AJCC eighth edition staging criteria were used to inform stage group revisions in the version 9 AJCC staging system, including appendiceal cancer. Although the current AJCC staging definitions were maintained for appendiceal cancer, incorporating survival analysis into the version 9 staging system provided unique insight into the clinical challenges in staging rare malignancies. This article highlights the critical clinical components of the now published version 9 AJCC staging system for appendix cancer, which (1) justified the separation of three different histologies (non-mucinous, mucinous, signet-ring cell) in terms of prognostic variance, (2) demonstrated the clinical implications and challenges in staging heterogeneous and rare tumors, and (3) emphasized the influence of data limitations on survival analysis for low-grade appendiceal mucinous neoplasms.

Survival outcomes used to generate version 9 American Joint Committee on Cancer staging system for anal cancer.

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including anal cancer, is the standard for cancer staging in the United States. The AJCC staging criteria are dynamic, and periodic updates are conducted to optimize AJCC staging definitions through a panel of experts charged with evaluating new evidence to implement changes. With greater availability of large data sets, the AJCC has since restructured and updated its processes, incorporating prospectively collected data to validate stage group revisions in the version 9 AJCC staging system, including anal cancer. Survival analysis using AJCC eighth edition staging guidelines revealed a lack of hierarchical order in which stage IIIA anal cancer was associated with a better prognosis than stage IIB disease, suggesting that, for anal cancer, tumor (T) category has a greater effect on survival than lymph node (N) category. Accordingly, version 9 stage groups have been appropriately adjusted to reflect contemporary long-term outcomes. This article highlights the changes to the now published AJCC staging system for anal cancer, which: (1) redefined stage IIB as T1-T2N1M0 disease, (2) redefined stage IIIA as T3N0-N1M0 disease, and (3) eliminated stage 0 disease from its guidelines altogether.

Optimization of an automated tumor-infiltrating lymphocyte algorithm for improved prognostication in primary melanoma.

Tumor-infiltrating lymphocytes (TIL) have potential prognostic value in melanoma and have been considered for inclusion in the American Joint Committee on Cancer (AJCC) staging criteria. However, inter-observer discordance continues to prevent the adoption of TIL into clinical practice. Computational image analysis offers a solution to this obstacle, representing a methodological approach for reproducibly counting TIL. We sought to evaluate the ability of a TIL-quantifying machine learning algorithm to predict survival in primary melanoma. Digitized hematoxylin and eosin (H&E) slides from prospectively-enrolled patients in the NYU melanoma database were scored for % TIL using machine learning and manually graded by pathologists using Clark’s model. We evaluated the association of % TIL with recurrence-free survival (RFS) and overall survival (OS) using Cox proportional hazards modeling and concordance indices. Discordance between algorithmic and manual TIL quantification was assessed with McNemar’s test and visually by an attending dermatopathologist. 453 primary melanoma patients were scored using machine learning. Automated % TIL scoring significantly differentiated survival using an estimated cutoff of 16.6% TIL (Log Rank P<0.001 for RFS; P=0.002 for OS). % TIL was associated with significantly longer RFS (adjusted HR = 0.92 [0.84–1.00] per 10% increase in % TIL) and OS (adjusted HR = 0.90 [0.83–0.99] per 10% increase in % TIL). In comparison, a subset of the cohort (n=240) was graded for TIL by melanoma pathologists. However, TIL did not associate with RFS between groups (P>0.05) when categorized as brisk, non-brisk, or absent. A standardized and automated % TIL scoring algorithm can improve the prognostic impact of TIL. Incorporation of quantitative TIL scoring into the AJCC staging criteria should be considered.

How Should We Assign Large Infiltrative Hepatocellular Carcinomas for Staging?

Simple SummaryThe outcome of hepatocellular carcinoma (HCC) patient varies depending on tumor burden and liver function. The BCLC staging system is based on these two factors while AJCC staging system is based on tumor burden only. However, the outcome of HCC does not solely depend on these two factors, but also the aggressiveness of tumor behavior represented by tumor morphology. The morphology of HCC can be divided into three types; nodular, multinodular confluent and infiltrative type. The infiltrative type is known to be associated with poor prognosis and should be staged differently from other tumors. This study revealed that large infiltrative type HCC (≥4 cm) was associated with worse survival especially in early AJCC T-stages (T1b/2) and BCLC stages (A/B). In addition, reassignment of large infiltrative tumor to T3 and T4 and to BCLC B and C increased the discriminatory ability of each staging system.Infiltrative gross morphology of hepatocellular carcinoma (HCC) is known to be associated with poor prognosis, but this is not considered for staging. A total of 774 HCC patients who underwent curative liver resection were retrospectively reviewed and the prognostic significance of infiltrative type HCC was assessed using the American Joint Committee on Cancer (AJCC) and Barcelona Clinic Liver Cancer (BCLC) staging systems. Seventy-four patients (9.6%) had infiltrative HCCs with a higher proportion of multifocal tumors, larger tumors, vessel invasion, increased tumor marker levels, and advanced T-stages than those with nodular HCC (all, p < 0.01). Infiltrative morphology was independently associated with lower overall survival (OS), but its impact was significant when the tumor size was ≥ 4 cm (p < 0.001). Under current AJCC and BCLC staging criteria, these large infiltrative HCCs were associated with significantly worse OS in early AJCC T-stages (T1b/T2, p < 0.001) and BCLC stage A/B (both, p < 0.01) but not in late AJCC (T3/T4) and BCLC C. The reassignment of this subtype to T3 and T4 increased the discriminatory ability of AJCC T-staging with lower AIC values (3090 and 3088 vs. 3109) and higher c-index (0.69 and 0.69 vs. 0.67), respectively (both, p < 0.001). Similarly, the reassignment of large infiltrative HCC to BCLC stages B and C also improved the prognostic performance. Large infiltrative HCCs should be assigned to more advanced stages in current staging systems for their prognostic impact.

Interobserver Variability of Quantitative and Qualitative Assessment Using MRI in Malignant Pleural Mesothelioma

To evaluate the interobserver variability associated with quantitative and qualitative MRI assessments of malignant pleural mesothelioma (MPM). Patients with MPM who underwent uniform-protocol preoperative MRI between 2009 and 2014 were included. The MRI-derived tumor volume was estimated. Unidimensional measurements of maximal pleural thickness (P max) and average pleural thickness (P avg) on axial MR images; maximal fissural thickness (F max); maximal diaphragmatic thickness (D max); and average diaphragmatic thickness (D avg) on sagittal reconstructed images were acquired. Interobserver agreement regarding the American Joint Committee on Cancer (AJCC) tumor stage at each criterion level was assessed by using Cohen κ statistics. Agreement between quantitative measurements was assessed by using Bland-Altman plots and intraclass correlation coefficients (ICCs). The study cohort included 349 patients (median age, 68 years [age range, 30-90 years), 273 (78%) of whom were men and 203 (58%) of whom had epithelioid-subtype tumors. Qualitative assessment performed by using the AJCC staging criteria (eighth edition) was concordant in 31% of cases and yielded considerable disagreement (κ = 0.177). Inspection of the Bland-Altman plots led to decisive agreement between the two reviewers regarding MRI-derived tumor volume (ICC, 0.979). There was also a good degree of agreement between the two reviewers regarding unidimensional measurements of D max (ICC, 0.807), D avg (ICC, 0.823), P max (ICC, 0.787), P avg (ICC, 0.787), and F max (ICC, 0.659). Quantitative assessment can enhance the clinical staging of MPM. Compared with qualitative assessment, quantitative assessment has low interobserver variability and could yield a tumor size criterion that is currently lacking in the AJCC clinical staging of MPM.Supplemental material is available for this article.© RSNA, 2020.

CORRELATION OF GENE EXPRESSION PROFILE STATUS AND AMERICAN JOINT COMMISSION ON CANCER STAGE IN UVEAL MELANOMA.

To study the relationship between gene expression profile (GEP) subclass and American Joint Committee on Cancer (AJCC) stage in patients with uveal melanoma (UM). A retrospective, multicenter study was undertaken with patients entered from nine major ocular oncology centers from across the United States. Three hundred sixty eligible patients had UM and underwent I-125 plaque brachytherapy with concurrent tumor biopsy with GEP testing between January 1, 2010, and October 28, 2014. Patient demographics and UM features were analyzed by both GEP and AJCC status. Gene expression profile class divided the cohort into three groups: Class 1a (n = 186), Class 1b (n = 77), and Class 2 (n = 113). When classified using AJCC staging criteria, we found the following: Stage I in 91 cases (25.3%), Stage IIA in 143 cases (39.7%), Stage IIB in 89 cases (24.7%), Stage IIIA in 36 cases (10%), and Stage IIIB in 1 case (0.3%). There were no Stage IV cases, as lymph node and metastatic data were not collected as a part of this study. Among Stage I tumors, both high tumor height and high largest basal diameter were associated with a higher frequency of Class 2 status (P < 0.05). As UMs progress to a larger AJCC tumor group (T1-T4), the odds ratio of having a worse prognosis based on GEP class was 1.75 (95% CI, 1.36-2.25; P < 0.001). Similarly, as UMs progress to a higher AJCC stage, the odds ratio of having a worse prognosis based on GEP class was 1.69 (95% CI, 1.36-2.10; P < 0.001). This report details the differences in clinical features between GEP subclasses and how they are distributed among the AJCC stages. When the tumors were grouped by AJCC staging criteria, both larger AJCC tumor (T) group and worsening AJCC stage were associated with worsening predicted prognosis, based on GEP subclass.

Integration the biologic factors into the staging of breast cancer patients with ipsilateral supraclavicular lymph node metastasis.

Purpose: To investigate the accuracy and the discriminatory performance in the prognostic prediction in breast cancer (BC) patients with ipsilateral supraclavicular lymph node (ISLN) metastasis using the between the American Joint Committee on Cancer (AJCC) 7th and 8th edition staging system.Methods: Female patients diagnosed as BC were retrieved from the Surveillance, Epidemiology, and End Results database between 2010 and 2014. Chi-squared test, Kaplan-Meier method, Cox proportional hazard analysis, and the receiver operating characteristics were used to conduct statistical analysis.Results: We included 1097 BC patients with ISLN metastasis (N3c disease), including 29.4% (n=322) and 70.6% (n=775) of patients with non-metastatic and metastatic stage at diagnosis, respectively. In non-metastatic stage patients, 64.9% of the patients categorized as having stage IIIC disease in the 7th edition AJCC staging system were downstaged to stage IIIA or IIIB according to the 8th AJCC staging criteria. The AJCC 8th edition staging system had better discriminatory prognostic value than the 7th AJCC staging (area under the curve: 0.586 vs. 0.577, P=0.0006), with a 5-year breast cancer-specific survival (BCSS) rate of 71.3%, 62.2%, 45.2% and 39.1% in stage IIIA, IIIB, IIIC, and IV cohorts, respectively (P<0.0001). The multivariate prognostic analysis revealed that the AJCC 8th edition staging system was an independent prognostic factor for BCSS, while no statistical difference in BCSS was found between the 8th AJCC stage IIIC and IV patients (P=0.188).Conclusion: The AJCC 8th edition pathological prognostic staging showed a better discriminatory prognostic value in ISLN-metastasized breast cancer patients. An additional clarification strategy in stage IIIC disease based on the 8th AJCC staging should be developed to differentiate patients who are curable with multimodality therapy and patients who have less benefit from curative treatment.

Comparison of the Seventh and Eighth Editions of the American Joint Committee on Cancer pT and pN Classifications as Predictors of Survival in Patients With Oral Squamous Cell Carcinoma.

We retrospectively compared the seventh and eighth editions of American Joint Committee on Cancer (AJCC) TNM frameworks as disease-free survival (DFS) and overall survival (OS) predictors in oral squamous carcinomas (OSCCs). We restaged the 342 patients with the revised pT and pN criteria and performed survival analyses. The 3-year DFS (mean follow-up, 364 days; recurrences, 99) was 50%, and the 5-year OS (mean follow-up, 615 days; deaths, 69) was 42%. The eight edition pN classification was an independent multivariate survival predictor. The revised TNM criteria upstaged pT, pN, and stage groupings in 99 (38.8%), 58 (37.3%), and 101 (29.5%) patients. The latter two groups revealed significantly worse DFS and OS compared with those whose categorizations had remained unaltered. In addition, their classification/staging criteria demonstrated superior discrimination, monotonicity, and accuracy for survival estimations. Of the competing AJCC staging criteria, the revised pN classification was the most powerful system to predict OSCC survivals.

Is mitotic rate still useful in the management of patients with thin melanoma?

T1 melanoma substaging was recently modified by the American Joint Committee on Cancer (AJCC). Although sentinel lymph node (SLN) positivity is the most important prognostic factor in melanoma, there is a lack of consensus on whether SLN biopsy should be performed in patients with thin melanoma (≤1 mm). The main aim of this study was to investigate predictors of SLN positivity in patients with thin melanoma, with a special emphasis on mitotic rate. A secondary aim was to evaluate survival in this group of patients. Retrospective multicenter observational study with analysis of age, sex, tumour location, thickness, mitotic rate, regression and microscopic satellites. Predictive factors were identified using a classification and regression tree (CART) approach. Melanoma-specific survival according to SLN status was estimated using Kaplan-Meier curves. We analysed 203 patients with a melanoma ≤1 mm. Using the new AJCC staging criteria, the CART algorithm identified a 7.5% likelihood of SLN positivity in T1a patients. In the case of T1b melanoma, there was a 14.3% likelihood of SLN positivity in patients with a mitotic rate >1 mitosis/mm2 and a 3.2% likelihood in those with ≤1 mitoses/mm2 . None of the patients with T1b disease who had ≤1 mitoses/mm2 and regression had SLN positivity. In T1b patients, 5-year melanoma-specific survival was 98.7% in the SLN-negative group and 75% in the SLN-positive group (P = 0.05). When stratified by mitotic rate, survival was 100% for patients with a mitotic rate of ≤1 mitoses/mm2 and 91.4% for those with >1 mitosis/mm2 (P = 0.022). There were no deaths in the T1a subgroup. Sentinel lymph node metastasis was less common in patients with T1b melanoma who had a mitotic rate of ≤1 mitoses/mm2 . Performance of SLN biopsy should be carefully considered in this subgroup of patients, particularly considering the good prognosis.

Staging for Cutaneous Squamous Cell Carcinoma as a Predictor of Sentinel Lymph Node Biopsy Results

The appropriate clinical setting for the application of sentinel lymph node biopsy (SLNB) in the management of cutaneous squamous cell carcinoma (cSCC) is not well characterized. Numerous case reports and case series examine SLNB findings in patients who were considered to have high-risk cSCC, but no randomized clinical trials have been performed. To analyze which stages in the American Joint Committee on Cancer (AJCC) criteria and a recently proposed alternative staging system are most closely associated with positive SLNB findings in nonanogenital cSCC. Medical literature review and case data extraction from private and institutional practices to identify patients with nonanogenital cSCC who underwent SLNB. Patients were eligible if sufficient tumor characteristics were available to classify tumors according to AJCC staging criteria and a proposed alternative staging system. One hundred thirty patients had sufficient data for AJCC staging, whereas 117 had sufficient data for the alternative system. Nonanogenital cSCC and SLNB. Positive SLNB findings by cSCC stage, quantified as the number and percentage of positive nodes. A positive SLN was identified in 12.3% of all patients. All cSCCs with positive SLNs were greater than 2 cm in diameter. The AJCC criteria identifed positive SLNB findings in 0 of 9 T1 lesions (0%), 13 of 116 T2 lesions (11.2%), and 3 of 5 T4 lesions (60.0%). No T3 lesions were identified. The alternative staging system identified positive SNLB findings in 0 of 9 T1 lesions (0%), 6 of 85 T2a lesions (7.1%), 5 of 17 T2b lesions (29.4%), and 3 of 6 T3 lesions (50.0%). Rates of positive SLNB findings in patients with T2b lesions were statistically higher than those with T2a lesions (P = .02, Fisher exact test) in the alternative staging system. Our findings suggest that most cSCCs associated with positive SLNB findings occur in T2 lesions (in both staging systems) that are greater than 2 cm in diameter. The alternative staging system appears to more precisely delineate high-risk lesions in the T2b category that may warrant consideration of SLNB. Future prospective studies are necessary to validate the relationship between tumor stage and positive SLNB findings and to identify the optimal staging system.

Validation of the Updated 7th Edition AJCC TNM Staging Criteria for Gastric Adenocarcinoma

IntroductionThe recently published 7th edition of the American Joint Committee on Cancer (AJCC) TNM staging criteria for gastric adenocarcinoma contains important revisions to T and N classifications, as well as overall stage grouping. Our goal was to validate the new staging system using a cancer registry. MethodsRetrospective review of gastric cancer patients from Surveillance, Epidemiology, and End Results (SEER) registry data (2004–2007). Patients were staged according to both 6th and 7th edition criteria, and 3-year disease-specific survival was compared. ResultsThirteen thousand five hundred forty-seven patients with gastric adenocarcinoma were identified with complete staging information. When using 7th edition criteria, there was an increase in the number of patients classified as stage III (23% vs. 13%), and a decrease in patients classified as stage IV (47% vs. 53%). Statistically significant differences in 3-year disease-specific survival were observed for all T and N categories and re-staging the same population according to the 7th edition criteria improved survival discrimination. Multivariate analysis revealed statistically significant differences in survival and linear progression of hazard ratios for each stage grouping. ConclusionsThe 7th edition AJCC staging criteria for gastric adenocarcinoma demonstrate better survival discrimination and risk stratification than previous criteria.

Malignant melanoma of the vulva: An extension of cutaneous melanoma?

Objective To determine the prognostic significance of the 2002 revisions of the American Joint Committee on Cancer (AJCC) Staging System for cutaneous melanoma in melanoma of the vulva and review the current surgical utilized for treatment of this neoplasm. Methods Demographic, surgical and outcomes data were obtained from the records of vulvar melanoma patients treated from 1990 to 2006 at five academic medical centers. The 2002 modifications of the AJCC staging system for cutaneous melanoma, Breslow thickness and Clark level, were applied to all subjects. Kaplan–Meier Modeling and Linear Regression analysis were utilized for data analysis. Statistics were performed with SAS v 9.1. Results Seventy-seven patients were identified with a median age of 62 years. 73% had Stage I/II disease. Surgical radicality did not impact recurrence rates or survival. Breslow thickness was associated with recurrence (p = 0.002) but not survival. Only the 2002 modified AJCC staging criteria were predictive of overall survival (p = 0.006) in patients with malignant melanoma of the vulva. Conclusions In the largest multi-site series of vulvar melanoma, the AJCC-2002 staging system for cutaneous malignant melanoma appears to be applicable to primary vulvar melanoma. Moreover, surgical radicality was associated with significant morbidity but not with improvement in survival. Utilization of standard operative staging and resection principles in cutaneous melanoma should be used for all vulvar melanoma patients. Moreover, these patients should also be considered for enrollment in cutaneous melanoma clinical trials.

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.

Stage specific survival is altered by the changes in the 2002 AJCC staging for melanoma

7510 Purpose: To examine how stage specific survival is altered in the 2002 American Joint Committee on Cancer (AJCC) melanoma staging system compared to the 1997 AJCC staging system. Patient and Methods: 5,847 consecutive patients presented with melanoma to Memorial Sloan Kettering Cancer Center (MSKCC) from 1996 to 2004 and were prospectively entered into a database. These patients were staged under both the 1997 and 2002 AJCC staging criteria. Overall survival estimates were determined using the Kaplan-Meier method. Results: 1,035 patients were shifted to a lower stage in the 2002 staging system while only 15 patients were upstaged. The number of stage I patients increased greatly under the 2002 system (n=2,166) as compared to the 1997 system (n=1,463) although stage I survival probability estimates were virtually the same with both classification systems. As a result of the changes in 2002, the stage II survival estimates decreased considerably with a 15% lower 5 year overall survival (79% (1997) versus 64% (2002)). With the initiation of subgroups in 2002, it became apparent that stage III patients were very heterogeneous in terms of their survival probabilities (5 year overall survival ranged from 70% in IIIA to 24% in IIIC). Conclusions: Stage specific survival was substantially altered by the changes made in the 2002 AJCC staging for melanoma, particularly for stage II. It is very important to be aware of this effect so that accurate conclusions can be drawn with regard to treatment efficacy or comparisons across different studies. In addition, stage subgroups were added in 2002 that demonstrated the diversity of risk within stage group and did not improve prediction ability. This highlights the importance of developing individualized risk prediction models. No significant financial relationships to disclose.

Changes in the 2003 American Joint Committee on Cancer staging for breast cancer dramatically affect stage-specific survival.

To evaluate how implementation of the 2003 American Joint Committee on Cancer (AJCC) staging system will affect stage-specific survival of breast cancer patients. Records of 1,350 patients treated on sequential institutional protocols with mastectomy and adjuvant doxorubicin-based chemotherapy were reviewed. Pathologic stage was assigned retrospectively according to the 1988 and the 2003 AJCC staging criteria. Overall stage-specific survival (OS) was calculated using the Kaplan-Meier method, and hypothetical differences were compared by the log-rank test. Six hundred five of 1,087 patients with stage II disease according to the 1988 classification system had stage II disease according to the 2003 system. The 10-year OS for patients with stage II disease was significantly improved using the 2003 system (76% [2003] v 65% [1988]; P <.0001). Two hundred eighty-nine of 633 patients with stage IIb disease using the 1988 system were stage IIb with the 2003 system, and 10-year OS was 58% (1988) versus 70% (2003; P =.003). The number of patients with stage III disease increased from 207 (1988) to 443 (2003), and the 10-year OS changed from 45% (1988) to 50% (2003; P =.077). Most of this difference resulted from changes within stage IIIa: OS, 45% (1988) versus 59% (2003; P <.0001). Stage reclassification using the new AJCC staging system for breast cancer will result in significant changes in reported outcome by stage. It is imperative that careful attention is devoted to this effect so that accurate conclusions regarding the efficacy of new treatment strategies can be drawn.

Revised American Joint Committee on Cancer staging criteria accurately predict sentinel lymph node positivity in clinically node-negative melanoma patients.

The American Joint Committee on Cancer (AJCC) has recently modified staging criteria for primary melanoma patients and recommends sentinel lymph node (SLN) biopsy in many because microscopic nodal metastasis represents the most important factor predicting survival. The purpose of this study was to correlate the incidence of SLN metastasis with revised AJCC staging. The records of 1375 melanoma patients undergoing SLN biopsy were reviewed. Univariate and multivariate analyses were performed to identify predictors of a positive SLN. Patients were stratified by using revised AJCC criteria to determine whether such groups also predicted positive SLNs. A positive SLN was found in 16.9% of patients. By multivariate analysis, tumor thickness (relative risk [RR], 3.4) and ulceration (RR, 2.2) were dominant independent predictors of SLN metastases; age < or =50 years (RR, 1.8) and axial tumor location (RR, 1.5) were also significant. When patients were stratified by AJCC staging criteria, a significant increase in SLN metastases between successive stages was demonstrated. Stratification of patients by using AJCC classification reveals an increasing risk of SLN metastases with successive stage groups. Given the significant association of SLN status and survival, the ability of the revised AJCC staging system to predict survival is likely due to its ability to predict the risk of occult nodal disease.