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Evaluation of the Eighth Edition of the American Joint Committee on Cancer TNM Staging System for Gastric Cancer: An Analysis of 7371 Patients in the SEER Database.

ABSTRACT: Objective:To investigate the validity of the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system for gastric cancer. Methods:The clinicopathologic data of 7371 patients who were diagnosed with gastric cancer and had 16 or more involved lymph nodes (LNs) were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and retrospectively reviewed. Results:Stage migration occurred primarily during stage III between the 7th and 8th edition TNM staging systems. Stages IIIB and IIIC in the 7th edition staging system were divided in the 8th edition and had obvious differences in survival rates (both P < 0.001). The 8th edition TNM stages IIIC and IV showed similar survival rates (P = 0.101). The prognosis of patients with T4aN3bM0 was not different from that of patients with TxNxM1 (P = 0.433), while the prognosis of patients with T4bN3bM0 was significantly poorer than that of patients with TxNxM1 (P = 0.008). A revised TNM system with both T4aN3bM0 and T4bN3bM0 incorporated into stage IV was proposed. Multivariable regression analysis showed that the revised TNM system, but not the 7th and 8th editions, was an independent factor for disease-specific survival (DSS) in the third step of the analysis. Further analyses revealed that the revised TNM system had superior discriminatory ability to the 8th edition staging system, which was also an improvement over the 7th edition staging system. Conclusion:The 8th edition of the AJCC TNM staging system is superior to the 7th edition for predicting the DSS rates of gastric cancer patients. However, for better prognostic stratification, it might be more suitable for T4aN3bM0/T4bN3bM0 to be incorporated into stage IV in the 8th edition TNM staging system.

SUBMITTER: Cao LL

PROVIDER: S-EPMC6487090 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Evaluation of the Eighth Edition of the American Joint Committee on Cancer TNM Staging System for Gastric Cancer: An Analysis of 7371 Patients in the SEER Database.

Cao Long-Long LL Lu Jun J Li Ping P Xie Jian-Wei JW Wang Jia-Bin JB Lin Jian-Xian JX Chen Qi-Yue QY Lin Mi M Tu Ru-Hong RH Zheng Chao-Hui CH Huang Chang-Ming CM

Gastroenterology research and practice 20190414

<h4>Objective</h4>To investigate the validity of the 8<sup>th</sup> edition of the American Joint Committee on Cancer (AJCC) TNM staging system for gastric cancer.<h4>Methods</h4>The clinicopathologic data of 7371 patients who were diagnosed with gastric cancer and had 16 or more involved lymph nodes (LNs) were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and retrospectively reviewed.<h4>Results</h4>Stage migration occurred primarily during stage III between the ...[more]

PMID: 31097961

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Project description:BackgroundThe American Joint Committee on Cancer (AJCC) maintains that the eighth edition of its Staging Manual (AJCC8) has improved accuracy compared with the seventh (AJCC7). However, there are concerns that implementation may disrupt analysis of active clinical trials for stage III patients. We used an independent cohort of melanoma patients to test the extent to which AJCC8 has improved prognostic accuracy compared with AJCC7.MethodsWe analyzed a cohort of 1315 prospectively enrolled patients. We assessed primary tumor and nodal classification of stage I-III patients using AJCC7 and AJCC8 to assign disease stages at diagnosis. We compared recurrence-free (RFS) and overall survival (OS) using Kaplan-Meier curves and log-rank tests. We then compared concordance indices of discriminatory prognostic ability and area under the curve of 5-year survival to predict RFS and OS. All statistical tests were two-sided.ResultsStage IIC patients continued to have worse outcomes than stage IIIA patients, with a 5-year RFS of 26.5% (95% confidence interval [CI] = 12.8% to 55.1%) vs 56.0% (95% CI = 37.0% to 84.7%) by AJCC8 (P = .002). For stage I, removing mitotic index as a T classification factor decreased its prognostic value, although not statistically significantly (RFS concordance index [C-index] = 0.63, 95% CI = 0.56 to 0.69; to 0.56, 95% CI = 0.49 to 0.63, P = .07; OS C-index = 0.48, 95% CI = 0.38 to 0.58; to 0.48, 95% CI = 0.41 to 0.56, P = .90). For stage II, prognostication remained constant (RFS C-index = 0.65, 95% CI = 0.57 to 0.72; OS C-index = 0.61, 95% CI = 0.50 to 0.72), and for stage III, AJCC8 yielded statistically significantly enhanced prognostication for RFS (C-index = 0.65, 95% CI = 0.60 to 0.70; to 0.70, 95% CI = 0.66 to 0.75, P = .01).ConclusionsCompared with AJCC7, we demonstrate that AJCC8 enables more accurate prognosis for patients with stage III melanoma. Restaging a large cohort of patients can enhance the analysis of active clinical trials.

Project description:Answer questions and earn CME/CNE To update the melanoma staging system of the American Joint Committee on Cancer (AJCC) a large database was assembled comprising >46,000 patients from 10 centers worldwide with stages I, II, and III melanoma diagnosed since 1998. Based on analyses of this new database, the existing seventh edition AJCC stage IV database, and contemporary clinical trial data, the AJCC Melanoma Expert Panel introduced several important changes to the Tumor, Nodes, Metastasis (TNM) classification and stage grouping criteria. Key changes in the eighth edition AJCC Cancer Staging Manual include: 1) tumor thickness measurements to be recorded to the nearest 0.1 mm, not 0.01 mm; 2) definitions of T1a and T1b are revised (T1a, <0.8 mm without ulceration; T1b, 0.8-1.0 mm with or without ulceration or <0.8 mm with ulceration), with mitotic rate no longer a T category criterion; 3) pathological (but not clinical) stage IA is revised to include T1b N0 M0 (formerly pathologic stage IB); 4) the N category descriptors "microscopic" and "macroscopic" for regional node metastasis are redefined as "clinically occult" and "clinically apparent"; 5) prognostic stage III groupings are based on N category criteria and T category criteria (ie, primary tumor thickness and ulceration) and increased from 3 to 4 subgroups (stages IIIA-IIID); 6) definitions of N subcategories are revised, with the presence of microsatellites, satellites, or in-transit metastases now categorized as N1c, N2c, or N3c based on the number of tumor-involved regional lymph nodes, if any; 7) descriptors are added to each M1 subcategory designation for lactate dehydrogenase (LDH) level (LDH elevation no longer upstages to M1c); and 8) a new M1d designation is added for central nervous system metastases. This evidence-based revision of the AJCC melanoma staging system will guide patient treatment, provide better prognostic estimates, and refine stratification of patients entering clinical trials. CA Cancer J Clin 2017;67:472-492. © 2017 American Cancer Society.

Project description:ImportanceThe recently released eighth edition of the American Joint Committee on Cancer TNM staging system for pancreatic cancer seeks to improve prognostic accuracy but lacks international validation.ObjectiveTo validate the eighth edition of the American Joint Committee on Cancer TNM staging system in an international cohort of patients with resected pancreatic ductal adenocarcinoma.Design, setting, and participantsThis international multicenter cohort study took place in 5 tertiary centers in Europe and the United States from 2000 to 2015. Patients who underwent pancreatoduodenectomy for nonmetastatic pancreatic ductal adenocarcinoma were eligible. Data analysis took place from December 2017 to April 2018.ExposuresPatients were retrospectively staged according to the seventh and eighth editions of the TNM staging system.Main outcomes and measuresPrognostic accuracy on survival rates, assessed by Kaplan-Meier and multivariate Cox proportional hazards analyses and concordance statistics.ResultsA total of 1525 consecutive patients were included (median [IQR] age, 66 (58-72) years; 802 (52.6%) male). Distribution among stages via the seventh edition was stage IA in 41 patients (2.7%), stage IB in 42 (2.8%), stage IIA in 200 (13.1%), stage IIB in 1229 (80.6%), and stage III in 12 (0.8%); this changed with use of the eighth edition to stage IA in 118 patients (7.7%), stage IB in 144 (9.4%), stage IIA in 22 (1.4%), stage IIB in 643 (42.2%), and stage III in 598 (39.2%). With the eighth edition, 774 patients (50.8%) migrated to a different stage; 183 (12.0%) were reclassified to a lower stage and 591 (38.8%) to a higher stage. Median overall survival for the entire cohort was 24.4 months (95% CI, 23.4-26.2 months). On Kaplan-Meier analysis, 5-year survival rates changed from 38.2% for patients in stage IA, 34.7% in IB, 35.3% in IIA, 16.5% in IIB, and 0% in stage III (log-rank P < .001) via classification with the seventh edition to 39.2% for patients in stage IA, 33.9% in IB, 27.6% in IIA, 21.0% in IIB, and 10.8% in stage III (log-rank P < .001) with the eighth edition. For patients who were node negative, the T stage was not associated with prognostication of survival in either edition. In the eighth edition, the N stage was associated with 5-year survival rates of 35.6% in N0, 20.8% in N1, and 10.9% in N2 (log-rank P < .001). The C statistic improved from 0.55 (95% CI, 0.53-0.57) for the seventh edition to 0.57 (95% CI, 0.55-0.60) for the eighth edition.Conclusions and relevanceThe eighth edition of the TNM staging system demonstrated a more equal distribution among stages and a modestly increased prognostic accuracy in patients with resected pancreatic ductal adenocarcinoma compared with the seventh edition. The revised T stage remains poorly associated with survival, whereas the revised N stage is highly prognostic.

Project description:ImportanceImmune checkpoint inhibitors (ICIs) have transformed the survival of patients with metastatic melanoma. Patient prognosis is reflected by the American Joint Committee on Cancer (AJCC) staging system; however, it is unknown whether the metastatic (M) stage categories for cutaneous melanoma remain informative of prognosis in patients who have received ICIs.ObjectivesTo evaluate the outcomes of patients with metastatic cutaneous melanoma based on the M stage category from the AJCC eighth edition and to determine whether these designations continue to inform the prognosis of patients who have received ICIs.Design, setting, and participantsThis cohort study included patients with metastatic cutaneous melanoma who were treated between August 2006 and August 2019 at the University of Michigan. The estimated median follow-up time was 35.5 months. Patient data were collected via the electronic medical record system. Critical findings were externally validated in a multicenter nationwide cohort of patients treated within the Veterans Affairs health care system. Data analysis was conducted from February 2020 to January 2021.ExposuresAll patients were treated with dual-agent concurrent ipilimumab and nivolumab followed by maintenance nivolumab or single-agent ipilimumab, nivolumab, or pembrolizumab therapy. Patients were staged using the AJCC eighth edition.Main outcomes and measuresUnivariable and multivariable analyses were used to assess the prognostic value of predefined clinicopathologic baseline factors on survival.ResultsIn a discovery cohort of 357 patients (mean [SD] age, 62.6 [14.2] years; 254 [71.1%] men) with metastatic cutaneous melanoma treated with ICIs, the M category in the AJCC eighth edition showed limited prognostic stratification by both univariable and multivariable analyses. The presence of liver metastases and elevated levels of serum lactate dehydrogenase (LDH) offered superior prognostic separation compared with the M category (liver metastases: hazard ratio, 2.22; 95% CI, 1.48-3.33; P < .001; elevated serum LDH: hazard ratio, 1.73; 95% CI, 1.16-2.58; P = .007). An updated staging system based on these factors was externally validated in a cohort of 652 patients (mean [SD] age, 67.9 [11.6] years; 630 [96.6%] men), with patients without liver metastases or elevated LDH levels having the longest survival (median overall survival, 30.7 months).Conclusions and relevanceThis study found that the AJCC eighth edition M category was poorly reflective of prognosis in patients receiving ICIs. Future staging systems could consider emphasizing the presence of liver metastases and elevated LDH levels. Additional studies are needed to confirm the importance of these and other prognostic biomarkers.

Project description:ImportanceControversy exists around the American Joint Committee on Cancer (AJCC) TNM staging system for medullary thyroid cancer (MTC). Because of the rarity of the disease and limited available data, the staging system for MTC has been largely extrapolated from staging for differentiated thyroid cancer.ObjectivesTo evaluate how well the current (seventh and eighth editions) AJCC TNM staging system correlates with survival for patients with MTC and to suggest a possible revision.Design, setting, and participantsThis population-based retrospective cohort analysis used the National Cancer Database to select patients aged 18 years or older diagnosed with MTC in the United States between 1998 and 2012. Patient demographic and tumor characteristics were assessed, and pathologic tumor stages were provided as T, N, and M categories. Recursive partitioning with bootstrapping was used to divide patients by TNM stages into groups with similar survival. The newly identified groupings were validated in a Surveillance, Epidemiology, and End Results (SEER) cohort. Data analysis was conducted between July 17, 2016, and November 11, 2016.Main outcomes and measuresOverall survival and disease-specific survival.ResultsOf the 3315 patients with MTC included in the analysis, 1941 (58.6%) were women. The median (interquartile range) age was 54 (42-65) years, and 2839 (85.6%) self-reported their race/ethnicity as white. The current AJCC TNM staging system classified 941 of these patients (28.4%) as stage I, 907 (27.4%) as stage II, 424 (12.9%) as stage III, and 1043 (31.5%) as stage IV. Recursive partitioning analysis yielded 4 TNM groups: stage I (T1N0-1aM0, T2N0M0), stage II (T1N1bM0, T2N1a-bM0, and T3N0M0), stage III (T3N1a-bM0, T4N0-1bM0), and stage IV (T1-4N0-1bM1). Based on these proposed TNM groupings, 1797 of the 3315 patients (54.2%) were classified as stage I, 684 (20.6%) as stage II, 669 (20.2%) as stage III, and 165 (5.0%) as stage IV. Under the proposed TNM groupings, survival differences across TNM groups were more distinct than under the current AJCC TNM staging system. With stage I as the reference, the hazard ratios of the proposed TNM groupings and the current AJCC TNM staging system were 2.19 (95% CI, 1.37-3.12) vs 1.45 (95% CI, 1.09-1.92) for stage II, 4.20 (95% CI, 2.75-5.75) vs 2.17 (95% CI, 1.59-2.89) for stage III, and 10.97 (95% CI, 5.52-18.57) vs 5.33 (95% CI, 4.13-6.86) for stage IV. In a SEER cohort, the proposed TNM groupings were better at discriminating survival than was the current AJCC TNM staging system.Conclusions and relevanceThe current AJCC TNM staging system for MTC appears to be less than optimal in distinguishing risk of mortality among stage groups, upstaging a significant number of patients to stage IV. The current AJCC TNM staging system could be improved with the new TNM groupings proposed here for more accurate risk stratification and potential treatment selection.

Project description:Importance:The American Joint Committee on Cancer (AJCC) eighth edition staging manual introduced a new prognostic stage for breast cancer incorporating biologic factors in addition to traditional anatomic factors. Objective:To perform a validation study of the AJCC eighth edition prognostic stage in a single-institution cohort and a large population database. Design, Setting, and Participants:Patients with breast cancer treated with surgery as an initial intervention were identified in a prospective institutional database from The University of Texas MD Anderson Cancer Center and the California Cancer Registry. Vital status data were complete through December 31, 2016, in The University of Texas MD Anderson cohort and through December 31, 2014, in the California Cancer Registry cohort. Patients receiving neoadjuvant systemic therapy, those with inflammatory or rare breast cancers, and those with unknown clinicopathologic factors were excluded. Factors evaluated included T, N, and M categories and tumor grade, as well as estrogen receptor, progesterone receptor, and HER2 status. Main Outcomes and Measures:Disease-specific survival was calculated by the Kaplan-Meier method. The Harrell concordance index (C index) was used to quantify models' predictive performance, and the Akaike information criterion (AIC) was used to compare model fits. Results:A total of 3327 patients with stage I to IIIC breast cancer treated between 2007 and 2013 at The University of Texas MD Anderson Cancer Center (median follow-up of 5 years) with complete clinicopathologic data were identified. Compared with the AJCC anatomic stage, the prognostic stage upstaged 29.5% of patients and downstaged 28.1%. The prognostic stage (C index, 0.8357 and AIC, 816.8) provided more accurate stratification with respect to disease-specific survival than the anatomic stage (C index, 0.737 and AIC, 1039.8) (P?<?.001 for the C index). A total of 54?727 patients with stage I to IV breast cancer treated between 2005 and 2009 were identified in the California Cancer Registry (median follow-up of 7 years). The prognostic stage upstaged 31.0% of patients and downstaged 20.6%. The prognostic stage (C index, 0.8426 and AIC, 80?661.68) performed better than the anatomic stage (C index, 0.8097 and AIC, 81?577.89) (P?<?.001 for the C index). Conclusions and Relevance:The prognostic stage provided more accurate prognostic information than the anatomic stage alone in both a single-institution cohort and a large population database, thereby supporting its use in breast cancer staging.

Dataset Information

Evaluation of the Eighth Edition of the American Joint Committee on Cancer TNM Staging System for Gastric Cancer: An Analysis of 7371 Patients in the SEER Database.

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Evaluation of the Eighth Edition of the American Joint Committee on Cancer TNM Staging System for Gastric Cancer: An Analysis of 7371 Patients in the SEER Database.

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