Testing a new staging system for cutaneous melanoma proposed by the American Joint Committee on Cancer

The American Joint Committee on Cancer (AJCC) recently proposed a new staging system for cutaneous melanoma. We tested its practicability and its prognostic value was compared with the currently used TNM classification. The data of 1976 melanoma patients were used for the testing. 1218 patients (61.6%) could be assigned to the proposed pT classification, 136 patients (90.1%) with lymph node metastases and/or in-transit metastases to the proposed pN classification and all 14 patients with distant metastases to the proposed pM classification. Proposed pathological staging was possible for 971 patients (49%). The number of pT1 patients (399 versus 230) and stage I patients (544 versus 393) was distinctly higher in the proposed classification. In proposed stage II and III groups, subgroups with different prognosis could be identified. The new staging system includes more detailed information on clinical and pathohistological findings. Nevertheless, it is practicable and enables more patients with excellent prognosis to be identified.     

Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma.

PURPOSE: To revise the staging system for cutaneous melanoma under the auspices of the American Joint Committee on Cancer (AJCC). MATERIALS AND METHODS: The prognostic factors analysis described in the companion publication (this issue), as well as evidence from the published literature, was used to assemble the tumor-node-metastasis criteria and stage grouping for the melanoma staging system. RESULTS: Major changes include (1) melanoma thickness and ulceration but not level of invasion to 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 to be used in the N category; (3) the site of distant metastases and the presence of elevated serum lactic dehydrogenase to be used in the M category; (4) an upstaging of all patients with stage I, II, and III disease when a primary melanoma is ulcerated; (5) a merging of satellite metastases around a primary melanoma and in-transit metastases into a single staging entity that is grouped into stage III disease; and (6) a new convention for defining clinical and pathologic staging so as to take into account the staging information gained from intraoperative lymphatic mapping and sentinel node biopsy. CONCLUSION: This revision will become official with publication of the sixth edition of the AJCC Cancer Staging Manual in the year 2002.     

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.     

A population-based validation of the American Joint Committee on Cancer melanoma staging system.

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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 eighth edition American Joint Committee on Cancer (AJCC) melanoma staging system: implications for melanoma treatment and care

Introduction: The eighth edition of the American Joint Committee on Cancer (AJCC) melanoma staging system was implemented in the United States on 1 January 2018.

Areas covered: This article provides an overview of important changes in the eighth edition AJCC staging system from the seventh edition based on analyses of a large international melanoma database. The clinical implications of these changes for melanoma treatment are also discussed.

Expert commentary: A standardized and contemporary cancer staging system that facilitates accurate risk stratification is essential to guide patient treatment. The eighth edition of the AJCC staging system is currently the most widely accepted approach to melanoma staging and classification at initial diagnosis.     

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

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: The results of this evidence-based methodology were incorporated into the AJCC melanoma staging as described in the companion publication.     

Revision of the American Joint Committee on Cancer staging system for breast cancer.

PURPOSE: To revise the American Joint Committee on Cancer staging system for breast carcinoma. MATERIALS AND METHODS: A Breast Task Force submitted recommended changes and additions to the existing staging system that were (1) evidence-based and/or consistent with widespread clinical consensus about appropriate diagnostic and treatment standards and (2) useful for the uniform accrual of outcome information in national databases. RESULTS: Major changes included the following: size-based discrimination between micrometastases and isolated tumor cells; identifiers to indicate usage of innovative technical approaches; classification of lymph node status by number of involved axillary lymph nodes; and new classifications for metastasis to the infraclavicular, internal mammary, and supraclavicular lymph nodes. CONCLUSION: This revised staging system will be officially adopted for use in tumor registries in January 2003.     

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Prognostic factors of cutaneous melanoma and a new staging system proposed by the American Joint Committee on Cancer (AJCC): validation in a cohort of 1284 patients

This study, involving a cohort of 1284 evaluable patients, validates the American Joint Committee on Cancer (AJCC) proposal for the introduction of ulceration of primary cutaneous melanoma as an independent prognostic factor of survival. In univariate analyses, ulceration (Hazard Ratio (HR) 1.983; P<0.0001; 95% Confidence Intervals (CI) 1.692-2.325) was a predictor of worse overall survival. In multivariate analyses, ulceration (HR 1.302; P=0.022; (95% CI: 1.039-1.633) retained its prognostic significance for survival independent of tumour thickness (HR 1.101; P<0.0001; 95% CI: 1.055-1.150); mitotic activity (HR 1.039; P=0.005; 95% CI: 1.012-1.067); and age (HR 1.009; P=0.006; 95% CI: 1.003-1.016). Ulceration lost its significance in a subgroup analysis of 256 patients with clinically apparent regional lymph node metastases to the number of lymph nodes involved (HR 1.15; P=0.004; 95% CI:1.047-1.263). Ulceration is prognostically significant in the tumour but not the nodal classification of melanoma, with mitotic activity the second most important prognostic factor after tumour thickness.     

Thin primary cutaneous malignant melanoma: a prognostic tree for 10-year metastasis is more accurate than American Joint Committee on Cancer staging.

PURPOSE: The majority of invasive primary melanomas are thin (< or = 1.00 mm). Since the current staging system imperfectly predicts outcome in patients with such lesions, we sought to develop a more effective classification scheme to better identify both patients at high risk of metastasis who are candidates for further staging and therapy and those with little risk. PATIENTS AND METHODS: This prospective cohort study included 884 patients who had thin invasive melanomas. A tree-structured analysis of 10-year metastasis was used to develop a new classification scheme. RESULTS: The overall 10-year metastasis rate was 6.5% (95% CI, 4.8% to 8.1%). The prognostic tree defined four risk groups: high-risk: men with vertical growth phase (VGP) lesions that had mitotic rates (MRs) greater than 0, and for whom the 10-year metastasis rate was 31% (22% to 42%; n = 90); moderate-risk: women with VGP lesions that had MRs greater than 0 and for whom the rate was 13% (9% to 18%; n = 136); low-risk: patients with VGP lesions that had MR of 0 for whom the rate was 4% (2% to 7%; n = 247); and minimal-risk: patients with invasive lesions without VGP for whom the rate was 0.5% (0% to 1.2%; n = 411). Survival curves differed significantly among the four groups (P <.001). CONCLUSION: Growth phase, mitotic rate, and sex are important prognostic factors for patients with thin melanomas, and they identify subgroups at substantial risk for metastasis. After validation in other populations, the proposed prognostic tree will be useful in the design of clinical trials and clinical management.     

New American Joint Commission on Cancer staging system for melanoma: prognostic impact and future directions

Accurate melanoma staging is critical in establishing management strategies and estimating disease relapse. Combined with assessment of comorbidities and understanding treatment toxicities, risk assessment is central to offering appropriate surgical or systemic therapies. The American Joint Commission on Cancer (AJCC) melanoma staging system provides survival estimates within anatomically defined disease categories. Newer prognostic factors and methods of prognostic analyses can augment predictions for the presence of micro-metastatic disease and further define the risk for relapse. This article highlights relevant changes, evidence supporting future incorporation of more recently defined prognostic variables, novel approaches used as adjuncts to the current staging system, and future directions of the AJCC staging committee.     

基于第六版AJCC分期的乳腺癌临床分析

目的比较1997年第五版和2002年第六版AJCC的病理分期标准对乳腺癌预后预测的不同点。方法1996年～1999年治疗157例早期女性乳腺癌患者,根据我们医院的存档资料,按照第五版和第六版的AJCC分期系统进行重新病理分期并随访;主要观察目标为不同分期下的无复发生存率和生存期,用Kaplan-Meier和log-rank进行统计学检验。结果第五版Ⅱ期例数有93例,在第六版分期则只有64例(68.8%)仍是Ⅱ期,其中Ⅱa期例数无变化,Ⅱb期71例中有42.3%(30/71)产生了分期的变化。第五版Ⅰ期患者无复发,Ⅱ和Ⅲ期的无复发生存率有差别,平均无复发生存期分别为77.1个月和64.8个月,但无显著性差异(Log-RankP=0.069)。第六版Ⅰ期患者无复发,Ⅱ和Ⅲ期的无复发生存率亦有明显差别,平均无复发生存期分别为81.2个月和65.4个月,有显著性差异(Log-RankP=0.029)。结论由于体现了淋巴结侵犯的数目,AJCC第六版TNM病理分期系统定义了更多的Ⅲ期患者,Ⅱ、Ⅲ期患者间的无复发生存率具有更显著的差别,较第五版分期系统有了进一步改进,新的分期系统一样适用于中国乳腺癌患者。     

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.     

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.     

Validation of the American Joint Committee on Cancer 8th edition staging system for the pancreatic ductal adenocarcinoma

Background & aimsThe American Joint Commission on Cancer (AJCC) 8th edition staging system for pancreatic ductal adenocarcinoma (PDA) contains several significant changes. This study aimed to validate the AJCC 8th edition staging system of PDA.MethodsWe analyzed patients with resected PDA between 2001 and 2017 using the Korean Pancreatic Cancer (K-PaC) registry. Overall survival (OS) was estimated using the Kaplan-Meier survival curves and compared via the log-rank test.ResultsIn total, 701 resected PDA patients were identified. During a median follow-up of 24.5 months, the median OS was 21.7 months. Meanwhile, the median OS of each stage according to the AJCC 8th edition was 73.5 months (stage IA), 41.9 months (stage IB), 24.2 months (stage IIA), 18.3 months (stage IIB), and 16.8 months (stage III). However, the new N-category (pN1 vs. pN2) did not subdivide prognosis, although the lymph node ratio (i.e., the ratio of the number of LN involved to the number of examined LN) did. Although pT3 and pN2 belong under stage III, pN2 has a significantly longer median OS than pT3 (16.9 months vs 11.2 months; p < 0.01).ConclusionThe AJCC 8th edition staging system appropriately stratifies the prognosis of PDA patients. However, the cutoff of the N-category is not statistically valid, and the new stage III includes a heterogeneous category (pN2 and pT4). Therefore, we propose that stage III be divided into stage IIIA (Tany N2 M0) and stage IIIB (T4 Nany M0).     

Validation of the seventh edition of the American Joint Committee on Cancer TNM staging system for gastric cancer

BACKGROUND:

The seventh edition of the American Joint Committee on Cancer (AJCC) TNM classification for gastric cancer was published in 2010 and included major revisions. The aim of the current study was to evaluate the validity of the seventh edition TNM classification for gastric cancer based on an Asian population.

METHODS:

A total of 2916 gastric cancer patients who underwent R0 surgical resection from 1989 through 2008 in a single institute were included, and were analyzed according to the seventh edition of the TNM classification for validation.

RESULTS:

When adjusted using the seventh edition of the TNM classification, upstaging was observed in 771 patients (26.4%) and downstaging was observed in 178 patients (6.1%) compared with the sixth edition of the TNM classification. The relative risk (RR) of seventh edition pT classification was found to be increased with regular intensity compared with the sixth edition pT classification. The RR of seventh edition pN classification was found to be increased with irregular intensity compared with the sixth edition pN classification. In survival analysis, there were significant differences noted for each stage of disease, but only a marginal difference was demonstrated between stage IA and stage IB (P = .049). In the hybrid TNM classification, which combines the seventh edition pT classification and the sixth edition pN classification, both pT and pN classifications demonstrated a more ideal distribution of the RR, and 5‐year survival rates also showed a significant difference for each stage (P <.01).

CONCLUSIONS:

The seventh edition of the TNM classification was considered valid based on the results of the current study. However, the hybrid TNM classification, comprised of a combination of the seventh edition pT classification and sixth edition pN classification, should be considered for the next edition. Cancer 2011. © 2011 American Cancer Society.