American Joint Committee On Cancer 8th Edition Staging System Research Articles

Traversing the Terrain: Potential Pitfalls within the AJCC 8th Edition Staging System for Lip and Oral Cavity Cancers.

In 1977, the American Joint Committee on Cancer (AJCC) introduced the inaugural Cancer Staging Manual, which implemented the T (tumor extent), N (regional lymph node status), and M (presence or absence of distant metastasis) staging system. This systematic approach aimed to convey the extent of disease across various cancer types, providing clinicians with a practical framework to plan treatment strategies, predict prognosis, and assess outcomes. The AJCC 8th edition, effective from January 1, 2018, continues this tradition. However, certain shortcomings persist in the AJCC 8th edition, as identified through clinical experience. Specifically, challenges arise in accurately assessing depth of invasion in unique histological variants of oral squamous cell carcinoma (e.g., Oral verrucous carcinoma, Carcinoma cuniculatum, and Papillary squamous cell carcinoma) and minor salivary gland tumors. Additionally, discrepancies exist in the perception of bone invasion patterns and in reporting practices. There is also a need for staging guidelines for malignant odontogenic tumors and multifocal tumors of the oral cavity, supplemented by diagrammatic representations. Lastly, there is a call for comprehensive staging criteria for carcinomas of the ear, external auditory canal, and temporal bone. We advocate for the inclusion of these considerations in future editions of the AJCC Cancer Staging Manual.

Abstract PO5-27-01: Comparison between the 7th and the 8th edition of TNM Staging System of American joint committee on Cancer(AJCC) for Breast Cancer Patients, diagnosed and treated at King Abdulaziz Medical City

Abstract Breast cancer is a heterogeneous disease with different biological and molecular characteristics that affect local recurrence, metastases, prognoses, and response to available therapies. The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for breast cancer has incorporated the biological and molecular characteristics, tumor grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor status(Her-2)and tumor grade, into the traditional anatomical 7th edition that only considers tumor size, lymph nodes status, and distant metastases. The aim of this study is to compare the 7th to 8th editions of the AJCC staging system for prognostic impact, assess the effect of the new edition on the treatment and treatment outcome Method A retrospective cohort study was performed for all breast cancer patients, diagnosed between (2013 -2019) and underwent upfront surgery at King Abdulaziz Medical City (KAMC).Patients’ clinicopathological, immunohistochemical, surgical, therapeutic, and follow-up data were retrieved. Overall survival (OS) and breast cancer-specific survival (BCSS) were estimated using the Kaplan–Meier method. Univariate analysis using Fisher's exact test was used to compare staging systems' prognostic accuracy. Multivariable analysis using Cox proportional hazards regression analysis was performed to identify factors independently associated with disease outcome Results A total of 169 female patients were included, the 8th AJCC staging system resulted in a reallocation of 108 (63.9%) of the patients to a different stage group. The majority were downstaged(60.9%) while only 3% were upstaged, most of the upstaged patients had a triple-negative subtype (80%). The change in overall stage for the 8th edition was most significant in stage I (an increase by 140.3%), followed by stage II (downstaged by 74.3%) and stage III (downstaged by 49.7%) compared to the 7th edition. Critically 42.8% of all downstaged patients treated with adjuvant chemotherapy were found to have received unnecessary chemotherapy after applying the 8th AJCC staging system as per National Comprehensive Cancer Network (NCCN) clinical practice guidelines recommendations. The 8th AJCC staging system was a better prognostic predictor of disease survival, patients in 8th AJCC stage 3 had a higher tendency to develop metastases and die because of their disease (P-value 0.03, 0.051, respectively). Conclusions: Our comparison revealed that the AJCC 8th edition staging system is superior and more comprehensive than the 7th, in term of prognostic value, and in defining the precise adjuvant therapy Figure 1 Comparison of the 7th AJCC and the 8th AJCC staging system Citation Format: Nafisa Abdelhafiez, Abdulmohsen Alkushi, Lolwah Alriyees, Mohammad Arabi, Faris Alsalamah, Emad Masuadi, Ahmad Omair, Mohammad Alkaiyat, Hussam Shehata. Comparison between the 7th and the 8th edition of TNM Staging System of American joint committee on Cancer(AJCC) for Breast Cancer Patients, diagnosed and treated at King Abdulaziz Medical City [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-27-01.

Preoperative MRI features predicting very early recurrence of intrahepatic mass-forming cholangiocarcinoma after R0 resection: a comparison with the AJCC 8th edition staging system.

This study aimed to establish a nomogram based on preoperative magnetic resonance imaging (MRI) features to predict the very early recurrence (VER, less than 6months) of intrahepatic mass-forming cholangiocarcinoma (IMCC) after R0 resection. This study enrolled a group of 193 IMCC patients from our institution between March 2010 and January 2022. Patients were allocated into the development cohort (n=137) and the validation cohort (n=56), randomly, and the preoperative clinical and MRI features were collected. Univariate and multivariate stepwise logistic regression assessments were adopted to assess predictors of VER. Nomogram was constructed and certificated in the validation cohort. The performance of the prediction nomogram was evaluated by its discrimination, calibration, and clinical utility. The performance of the nomogram was compared with the T stage of the American Joint Committee on Cancer (AJCC) 8th edition staging system. Fifty-three patients (27.5%) experienced VER of the tumor and 140 patients (72.5%) with non-VER, during the follow-up period. After multivariate stepwise logistic regression, number of lesions, diffuse hypoenhancement on arterial phase, necorsis and suspicious lymph nodes were independently associated with VER. The nomogram demonstrated significantly higher area under the curve (AUC) of 0.813 than T stage (AUC=0.666, P=0.006) in the development cohort, whereas in the validation cohort, the nomogram showed better discrimination performance, with an AUC of 0.808 than T stage (0.705) with no significantly difference (P=0.230). Decision curve analysis reflected the clinical net benefit of the nomogram. The nomogram based on preoperative MRI features is a reliable tool to predict VER for patients with IMCC after R0 resection. This nomogram will be helpful to improve survival prediction and individualized treatment.

Positive margin and advanced depth of invasion as the indicators for assessing the necessity of adjuvant chemoradiotherapy in early-stage oral cavity squamous cell carcinoma.

e18052 Background: Adjuvant therapy was indicated for patients with a high risk of disease progression after curative therapy, and RTOC 9501/EORTC 22931 were the landmark studies for assessing the necessity of adjuvant therapy in oral cavity squamous cell carcinoma (OCSCC). However, the role of adjuvant therapy in early-staging OCSCC, which was redefined by the 8th edition American Joint Committee on Cancer (AJCC) staging system, was unknown. Methods: A total of 485 early-staging OCSCC patients (pT1-2N0) diagnosed between Jan 2010 and Dec 2019 were retrospectively enrolled. All of them were newly diagnosed and reevaluated to meet the criteria of the 8th edition AJCC staging system. Adjuvant therapy was discussed and concluded in the combined conference of the head and neck multidisciplinary team at Chung Shan Medical University Hospital. And the enrolled patients were divided into the groups with or without adjuvant therapy. The effectiveness of adjuvant therapy and prognostic factor for locoregional recurrence-free survival (LRFS) were analyzed. Results: Nearly one-sixth (16.1%, 78/485) of the enrolled patients received adjuvant therapy. The patients with adjuvant therapy were worse in pathologic T staging ( P < 0.001), histologic grade ( P < 0.001), and pathologic features (depth of invasion [DOI] > 4mm, P < 0.001; perineural invasion, P < 0.001) than those without. Positive margin and advanced DOI ( > 4mm) were the independent factors for LRFS. Adjuvant therapy did not improve LRFS that the 3-year LRFS of the patients with or without adjuvant therapy were 79.7% and 81.5%, respectively ( P = 0.718)(hazard ratio [HR], 95% confidence interval [CI]: 1.10 [0.67-1.80]). However, adjuvant chemoradiotherapy (CRT) indeed prolonged LRFS in some subgroups, such as those with positive margin or advanced DOI (the subgroup with positive margin, 3-year LRFS of those with or without adjuvant therapy, 100% and 58.8%, HR[95% CI]: 0.04[0.00-267.330]; the subgroup with advanced DOI, 3-year LRFS, 83.3% and 73.1%, HR[95% CI]: 0.48[0.16-2.01]). In addition to positive margin, advanced DOI was the most critical correlation coefficient factor among the pathologic features, including pathologic T staging, perineural invasion, lymphovascular invasion, poorly differentiated, and close margin. For the patients eligible for evaluation, forty percent (40.1%, 180/439) of the patients were diagnosed with positive margins or advanced DOI and these patients might be considered to receive adjuvant CRT in the future. Conclusions: Positive margin and DOI were the most important indicators to evaluate the necessity of adjuvant CRT in early-staging OCSCC. Future warranted studies were needed.

Evaluation of the 8th Edition AJCC Staging System for the Clinical Staging of Pancreatic Cancer.

Simple SummaryThe 8th edition of the AJCC staging system for pancreatic cancer has been validated for pathological staging; however, its suitability for clinical staging is still uncertain. Clinical staging is important for pancreatic cancer because surgical resection is not suitable for most patients. We validated the prognostic performance and suitability of the current staging system for clinical staging. In our analysis using a prospectively collected pancreatic cancer cohort database, survival difference was not shown between stage IB and IIA, which were divided by the new size-based T3 criterion. Among the patients who received surgery, the pathological stage was more advanced than the clinical stage in 57.3%, mostly due to a false-negative lymph node in clinical staging. These findings suggest that the 8th edition AJCC staging system is not validated for clinical staging and separate criteria more suitable for clinical staging should be established.The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic cancer (PC) has been validated for pathological staging; however, its significance for clinical staging remains uncertain. We validated the prognostic performance and suitability of the current staging system for the clinical staging of PC. We identified 1043 patients from our PC registry who were staged by imaging according to the 8th edition staging system and conducted analysis, including overall survival (OS) comparison. Gradual prognostic stratification according to stage hierarchy yielded significant OS differences between stage groups, except between stage I and II (p = 0.193). A substage comparison revealed no survival differences between IB (T2N0) and IIA (T3N0), which were divided by the T3 criterion only (p = 0.278). A higher N stage had significantly shorter OS than a lower N stage (all pairwise p < 0.05). However, among the 150 patients who received upfront surgery, the pathological stage was more advanced than the clinical stage in 86 (57.3%), mostly due to a false-negative cN0 (70.9%). Our results suggest that the new definition of T3 and the number-based N criteria in the 8th edition AJCC staging system may be not adequate for clinical staging. Establishing separate criteria more suitable for clinical staging should be considered.

Validation and modification of AJCC 8th edition staging system for hepatocellular carcinoma--analysis based on SEER database

Objective: To assess the accuracy of the American Joint Committee on Cancer (AJCC) 8th edition staging system for hepatocellular carcinoma (HCC) and to make an appropriate modification. Methods: Data of patients diagnosed with HCC who underwent surgery were extracted from 2004 to 2015 within the SEER database. Overall survival (OS) and disease-specific survival (DSS) of patients were analyzed. Results: A total of 7 911 patients were included and there were 2 117 females and 5 794 males. The male-to-female ratio was 1.00: 0.36. There were 4 050 patients older than 60 years old. Tumor size ranged from 24 to 65 mm. Tumors with single lobes (80.8%) or single lesions (62.8%) were more common. There were 230 cases and 2 052 cases received radiotherapy and chemotherapy, accounting for 2.9% and 25.9%, respectively. The median follow-up was 42 months. Analysis of the 8th edition of AJCC staging system showed that the survival curves of ⅣA stage and ⅢA stage intersected in both OS and DSS, and the differences were not statistically significant between them (both P>0.05). Analysis of patients in subgroup of ⅣA stage showed that there was no statistically significant difference in the four groups of T1N1M0/T2N0M0, T2N1M0/T3N0M0, T3N1M0/T4N0-1M0 and T3N1M0/T1-4N0-1M1 (all P>0.05). Therefore, the modified 8th edition of the AJCC staging system was proposed after retaining the definition of T/N/M in the old edition: ⅠA and ⅠB stages were retained; ⅣA stage was split: T1N1M0 was included in Ⅱ stage, T2N1M0 in Ⅲ stage, and Ⅳ stage included T3N1M0, T4N0-1M0 and T1-4N0-1M1. Cox proportional risk regression analysis of the modified 8th edition of the AJCC staging showed that significant differences were observed among the four groups, with ⅠB/ⅠA (HR=1.462, 95%CI:1.294-1.651), Ⅱ/ⅠB (HR=1.091, 95%CI:1.003-1.186), Ⅲ/Ⅱ (HR=2.034, 95%CI: 1.793-2.307) and Ⅲ/Ⅳ (HR=1.374, 95%CI: 1.192-1.583) for OS, respectively. The similar findings were seen in DSS, with ⅠB/ⅠA (HR=2.007, 95%CI:1.671-2.411), Ⅱ/ⅠB (HR=1.140, 95%CI:1.023-1.271), Ⅲ/Ⅱ (HR=2.344, 95%CI: 2.018-2.724) and Ⅲ/Ⅳ (HR=1.391, 95%CI:1.180-1.639), respectively. Conclusion: The modified AJCC 8th edition staging system could predict the survival outcome of HCC more accurately.

Development of a predictive nomogram for early recurrence of hepatocellular carcinoma in patients undergoing liver transplantation.

BackgroundAn individual prognostic model that includes inflammation caused by the delayed recovery of liver function after surgery for the early recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) has not been well determined. Our aim was to develop a nomogram model for predicting individual survival and early recurrence following LT for patients.MethodsRetrospective data, including clinical pathology and follow-up data, on HCC patients were collected between October 2016 and October 2019 at Huashan Hospital Affiliated to Fudan University. A nomogram estimating recurrence post-transplantation was constructed using multivariate Cox regression analysis.ResultsA total of 210 patients were included in the present study. The multivariate estimators of recurrence consisted of age, maximum tumor diameter, tumor thrombus, microvascular invasion (MVI), alanine aminotransferase and alpha-fetoprotein on postoperative day 7. Nomogram of recurrence-free survival was developed. The calibration and discrimination of the novel model were assessed with the calibration curves and concordance index (C-index). Its reliability and advantages were evaluated by comparing it with the conventional American Joint Committee on Cancer (AJCC) 8th edition staging system using integrated discrimination improvement (IDI) and net reclassification improvement (NRI). In comparison to the AJCC 8th edition staging system, the C-index (development set: 0.796 vs. 0.643, validation set: 0.741 vs. 0.563), the area under the receiver operating characteristic curve (AUC) of the validation set (1-year AUC: 0.732 vs. 0.586, 2-year AUC: 0.705 vs. 0.504), the development set (1-year AUC: 0.799 vs. 0.551, 2-year AUC: 0.801 vs. 0.512), and this model’s calibration plots all showed improved performance. In addition, NRI and IDI verified that the nomogram is an accurate prognostic tool. Subsequently, a web calculator was generated to assess the risk of tumor recurrence post-LT.ConclusionsThe nomogram, based on clinical and pathological factors, showed good accuracy in estimating prognostic recurrence and can be used to guide individual patient follow-up and treatment.

Prognostic Relevance of the Eighth Edition of TNM Classification for Resected Perihilar Cholangiocarcinoma.

Objectives: In our study, we evaluated and compared the prognostic value and performance of the 6th, 7th, and 8th editions of the American Joint Committee on Cancer (AJCC) staging system in patients undergoing surgery for perihilar cholangiocarcinoma (PHC). Methods: Patients undergoing liver surgery with curative intention for PHC between 2002 and 2019 were identified from a prospective database. Histopathological parameters and stage of the PHC were assessed according to the 6th, 7th, and 8th editions of the tumor node metastasis (TNM) classification. The prognostic accuracy between staging systems was compared using the area under the receiver operating characteristic curve (AUC) model. Results: Data for a total of 95 patients undergoing liver resection for PHC were analyzed. The median overall survival time was 21 months (95% CI 8.1–33.9), and the three- and five-year survival rates were 46.1% and 36.2%, respectively. Staging according to the 8th edition vs. the 7th edition resulted in the reclassification of 25 patients (26.3%). The log-rank p-values for the 7th and 8th editions were highly statistically significant (p ≤ 0.01) compared to the 6th edition (p = 0.035). The AJCC 8th edition staging system showed a trend to better discrimination, with an AUC of 0.69 (95% CI: 0.52–0.84) compared to 0.61 (95% CI: 0.51–0.73) for the 7th edition. Multivariate survival analysis revealed male gender, age >65 years, positive resection margins, presence of distant metastases, poorly tumor differentiation, and lymph node involvement, such as no caudate lobe resection, as independent predictors of poor survival (p < 0.05). Conclusions: In the current study, the newly released 8th edition of AJCC staging system showed no significant benefit compared to the previous 7th edition in predicting the prognosis of patients undergoing liver resection for perihilar cholangiocarcinoma. Further research may help to improve the prognostic value of the AJCC staging system for PHC—for instance, by identifying new prognostic markers or staging criteria, which may improve that individual patient’s outcome.

Addition of the tumour-stroma ratio to the 8th edition American Joint Committee on Cancer staging system improves survival prediction for patients with oral tongue squamous cell carcinoma.

One of the objectives of current research is to customise the treatment of cancer patients. The achievement of this objective requires stratification of patients based on the most significant prognostic factors. The aims of this study were to evaluate the prognostic value of the tumour-stroma ratio (TSR), defined as the proportion of tumour cells relative to surrounding stroma, in patients with oral tongue squamous cell carcinoma (OTSCC), and to develop a prognostic nomogram based on the most significant clinicopathological features. Clinicopathological data of 211 patients treated at 'Ospedali Riuniti' General Hospital (Ancona, Italy) for OTSCC were collected. One hundred and thirty-nine patients were restaged according to the 8th edition American Joint Committee on Cancer (AJCC) staging system. Evaluation of the TSR was performed on haematoxylin and eosin-stained slides, and correlation with survival outcomes was evaluated. In addition, with the aim of integrating the independent value of the TSR with the 8th edition AJCC staging system, a prognostic nomogram for OTSCC has been developed. OTSCC with a low TSR (i.e. a high proportion of stroma and a low proportion of tumour cells) was shown to have negative prognostic value in terms of disease-specific survival, with a hazard ratio (HR) of 1.883 and a 95% confidence interval (CI) of 1.033-3.432 (P=0.039), and overall survival (HR=1.747, 95% CI 0.967-3.154; P=0.044), independently of other histological and clinical parameters. For the cohort of 139 patients restaged according to the 8th edition AJCC staging system, variables correlating with a poor prognosis were: the TSR, perineural invasion, and sex. The nomogram built on these parameters showed good predictive capacity, outperforming the 8th edition AJCC staging system in stratifying disease-specific survival in OTSCC patients. Including the TSR in the predictive model could improve risk stratification of OTSCC patients and aid in making treatment decisions.

Validation of Stage N3 of the Eighth Edition AJCC Staging System for Nasopharyngeal Carcinoma.

To validate stage nodal (N)3 of the 8th edition American Joint Committee on Cancer (AJCC) staging system for nasopharyngeal carcinoma (NPC). This retrospective cohort study extracted NPC patients from the Surveillance, Epidemiology, and End Results database between 2004 and 2016. Pathologically confirmed patients with complete data of level IV, N3a, and N3b lymph node metastasis were investigated. The included patients were divided into level IV, N3a, and N3b groups. Five-year overall survival (OS) and cancer-specific survival (CSS) were compared among the three groups. A total of 693 patients were included: 285 (41.13%) patients in the level IV group, 124 (17.89%) patients in the N3a group, and 284 (40.98%) patients in the N3b group. The 5-year OS (57.1%, 55.0%, and 55.2%) and CSS (64.4%, 63.5%, and 64.4%) were not different among the level IV, N3a, and N3b groups. Multivariate regression analysis revealed that N stage was not an independent prognostic factor for OS (hazard ratio [HR] = 1.03, 95% confidence interval [CI]: 0.91-1.17; P = .65) or CSS (HR = 1.03, 95% CI: 0.89-1.19; P = .70). Stage N3 of the 8th edition AJCC staging system for NPC is reasonable. III Laryngoscope, 131:535-540, 2021.

A prognostic nomogram for pancreatic ductal adenocarcinoma patients' all-cause survival in a Surveillance, Epidemiology, and End Results analysis.

BackgroundThe American Joint Committee on Cancer (AJCC) staging system is not adequate for predicting the all-cause survival of patients with pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to establish a comprehensive nomogram for PDAC and compare its prognostic ability with that of the AJCC 8th edition staging system.MethodsThis study identified 5,097 patients with PDAC in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016, and R software was used to divide them into training (n=3,567) and validation (n=1,530) cohorts. Multivariate Cox regression was used to select predictive variables. The concordance index (C-index), the area under the time-dependent receiver operating characteristics curve (AUC), the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), calibration plotting, and decision-curve analysis (DCA) were used to compare the new survival model with the AJCC 8th edition prognosis model.ResultsAfter performing a multivariate Cox regression analysis, data on the age at diagnosis, marital status, primary site, pathology grade, regional nodes examined, AJCC stage, surgery status, adjuvant radiotherapy status, and adjuvant chemotherapy status were entered into the model and used to establish the nomogram. The C-index for the nomogram (0.668 for the training cohort and 0.670 for the validation cohort) was higher than those for the AJCC staging system (0.590 and 0.578, respectively). The AUC, NRI, IDI, calibration plotting, and DCA showed that the nomogram performed better than the AJCC staging system.ConclusionsWe have developed and validated a prognosis nomogram as a predictive model for PDAC patients provides significantly improved predictive performance and is superior to the latest AJCC 8th edition staging system.

Prognostic value of the AJCC 8th edition staging system for Japanese patients treated with surgery followed by radiotherapy for breast cancer.

American Joint Committee on Cancer (AJCC) 8th Edition Breast Cancer Staging System, biological information in addition to anatomical information was added as a basis for prognosis evaluation, but its prognostic impact in Japanese patients treated with postoperative radiotherapy has not been discussed. To determine the applicability of the updated prognostic staging system, we evaluated the prognostic value and confirmed the effectiveness of this system in patients in whom postoperative radiotherapy was performed. Patients who were treated with postoperative radiotherapy for breast cancer in our institution between January 2011 and December 2015 were restaged by the AJCC 8th pathological prognosis staging system, and then overall survival (OS), disease-free survival (DFS) rates and hazard ratios (HR) were analyzed to compare the predictive fit of the two staging systems. Five hundred and seven patients who in whom postoperative radiotherapy was performed for breast cancer were enrolled in this study. 36.1% patients were downstaged and 5.3% patients were upstaged from the 7th to 8th editions staging system classification. Kaplan-Meier curves and HRs showed differences in OS and DFS rates between the 7th edition and 8th edition staging systems. The AJCC 8th edition prognostic stage system has a better prognostic prediction of OS and DFS than does the 7th edition anatomic stage system. Compared with the 7th edition in breast cancer, AJCC 8th edition prognostic stage system has more precise stratification and superior prognostic value, providing a more accurate reference for the choice of radiotherapy for patients with breast cancer.

Abstract P5-06-19: AJCC 8th edition prognostic staging system provide no better discriminatory ability in prognosis than anatomical staging system in triple negative breast cancer: A cohort from two institutions and a large population based study

Abstract Background The American Joint Committee on Cancer (AJCC) eighth edition cancer staging manual has updated with a prognostic stage group for breast cancer by incorporating traditional TNM anatomic parameters and biomarkers (ER, PR, Her-2 status and tumor grade, etc.). In this study, we retrospectively compared the prognostic value between the AJCC 8th Edition anatomic and prognostic staging system for triple negative breast cancer(TNBC) in a cohort from two involved institutions and a large population database. Design Clinicopathological data of patients who underwent breast surgery as the initial intervention and with TNBC were identified in Sun Yat-sen University Cancer Center(SYSUCC) during 2005-2013 and Prince of Wales Hospital (PWH) during 2002-2008. Data from surveillance, epidemiology, and end results (SEER) database during 2010-2015 was also accessed. We restaged all cases into anatomic stage (AS) and prognostic stage (PS) group according to the AJCC 8th Edition staging system. The Kaplan-Meier analysis with log-rank test was used to compare differences in disease-specific survival (DSS), overall survival (OS) and progression-free survival (PFS) between groups. The Harrell concordance index (C index) was calculated to measure predictive performance for the AS and PS models. The relationshipof AS and PS with DSS, PFS or OS was examined using a Cox proportional hazards regression model. Results A total of 611 patients with stage I to IIIC TNBC were identified in the SYSUCC-PWH cohort with a median follow-up of 53.5 months. Compared with the AS, PS upstaged 46.1% of patients. No patient was downstaged by PS in this cohort. No significant difference was observed in C index between AS and PS models for either DSS (0.84 vs. 0.83, p=0.943) or PFS (0.82 vs. 0.80, p=0.887), demonstrating that PS do not reflect a more accurate predictive model than AS. A total of 31941 patients with stage I to IIIC TNBC were identified in the SEER cohort with a median follow-up of 27 months. PS upstaged 62.4% of patients and downstaged eight patients (from IIIC to IIIB) in this cohort. Similarly, PS model do not performed better than the AS in either DSS (C index, 0.85 vs. 0.86, p=0.95) or OS (C index, 0.90 vs. 0.90, p=0.98). Compared those with stage changed to other without, in SYSUCC-PWH cohort, patients with IIIC unchanged stage showed worse PFS compared to patients with AS IIIA or IIIB upstaged to PS IIIC (p=0.049). Similarly, in SEER cohort, patients with IIIC unchanged stage showed worse OS and DSS compared to patients with AS IIIA or IIIB upstaged to PS IIIC (p&amp;lt;0.001). Conclusion Our findings demonstrated that PS did not provide better discriminatory ability in predicting TNBCs prognosis than AS. Further update with additional morphological and genomic information regarding the prognostic significance should be incorporated into prognosis staging model for TNBCs. Table 1. 5-year PFS and DSS by AS and PS of TNBCs included in SYSUCC-PWH cohort (N=611)StageNo. at risk5-year PFS (95% CI)p-value5-year DSS (95% CI)p-valueASI(A*)10086.5(76.2,92.5)&amp;lt;0.001**92.9(83.4,97.0)0.001**II37182.0(77.0,86.0)0.001#90.6(86.3,93.6)0.080#IIA24087.9(82.4,91.9)92.7(87.7,95.7)IIB13171.0(60.9,79.0)86.2(76.8,92.0)III14050.9(41.1,59.8)0.045Δ74.1(64.2,81.7)0.099ΔIIIA7856.6(43.7,67.6)80.4(67.8,88.5)IIIB2955.2(28.6,75.4)51.4(23.1,73.9)IIIC3334.9(18.3,52.2)70.4(46.9,85.0)PSI10086.5(76.2,92.5)&amp;lt;0.001**92.9(83.4,97.0)&amp;lt;0.001**IA3NANAIB9786.0(75.4,92.3)92.7(88.5,97.0)II29183.9(78.3,88.2)0.002#91.9(87.2,94.9)0.209#IIA24087.9(82.4,91.9)92.7(89.7,95.7)IIB5164.1(46.1,77.5)87.3(79.4,95.1)III22060.1(52.3,66.9)&amp;lt;0.001Δ78.2(70.7,83.9)0.023ΔIIIA8374.7(62.2,83.6)85.5(78.7,92.3)IIIB2673.7(50.4,87.3)83.5(72.5,94.5)IIIC11144.9(34.0,55.1)70.7(61.8,79.7) Table 2. 5-year OS and DSS by AS and PS of TNBCs included in SEER cohort (N=31941)StageNo. at risk5-year OS (95% CI)p-value5-year DSS (95% CI)p-valueASI1270087.2(86.2,88.0)&amp;lt;0.001**93.5(82.8,94.2)&amp;lt;0.001**IA1229387.4(86.5,88.3)0.004*93.8(93.1,94.4)0.001*IB40780.4(73.9,85.5)86.2(80.6,90.2)II1429275.3(74.2,76.4)&amp;lt;0.001#82.7(81.8,83.7)&amp;lt;0.001#IIA971378.5(77.2,79.7)86.0(84.9,87.0)IIB457968.3(66.1,70.4)75.5(73.5,77.4)III494946.8(44.8,48.7)&amp;lt;0.001Δ54.0(52.0,56.0)&amp;lt;0.001ΔIIIA251557.1(54.3,59.7)63.6(60.8,66.2)IIIB116438.5(34.5,42.5)47.0(42.6,51.2)IIIC127034.3(30.5,38.2)41.4(37.3,45.2)PSI1229387.4(86.5,88.3)&amp;lt;0.001**93.8(93.1,94.4)&amp;lt;0.001**IA40789.4(83.6,93.2)0.212*94.6(89.2,97.3)0.259*IB1188687.4(86.5,88.3)93.8(93.1,94.4)II1072677.9(76.7,79.1)&amp;lt;0.001#85.5(84.4,86.5)&amp;lt;0.001#IIA1012078.6(77.3,79.8)86.0(85.0,87.0)IIB60667.4(61.2,72.9)75.4(69.3,80.4)III892256.3(54.8,57.8)&amp;lt;0.001Δ63.5(62.0,65.0)&amp;lt;0.001ΔIIIA398668.7(66.4,70.8)75.6(73.4,77.6)IIIB36556.3(47.8,64.0)62.1(53.0,70.0)IIIC457145.9(43.9,48.0)53.3(51.2,55.4) Citation Format: Peng Sun, JYS Tsang, Xiaodan Xu, Jibin Li, Mei Li, Xue Chao, Rongzhen Luo, Gary Tse, Jiehua He. AJCC 8th edition prognostic staging system provide no better discriminatory ability in prognosis than anatomical staging system in triple negative breast cancer: A cohort from two institutions and a large population based study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-06-19.

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.

The 8th edition of the American Joint Committee on Cancer staging system provide improved prognostic accuracy in T1-2N1M0 postmastectomy breast cancer patients

Objective: To validate whether the prognostic stage groups by the 8th edition of the American Joint Committee on Cancer (AJCC) staging system provides improved prognostic accuracy in T1-2N1M0 postmastectomy breast cancer patients compared to 7th edition. Methods: a total of 1 823 female patients with T1-2N1M0 breast cancer who underwent mastectomy and axillary lymph node dissection without neoadjuvant chemotherapy were analyzed and restaged according to 8th edition. Univariate analysis of prognostic factors was evaluated by using log-rank test. Multivariate analysis was estimated by using the Cox proportional hazards model. The prognostic accuracy of the two staging systems was compared using receiver operating characteristic (ROC) analyses and the concordance index (C-index). Results: 5-year locoregional recurrence rate (LRR) for the whole group was 6.0%, 5-year distant metastasis (DM) rate was 11.5%, 5-year disease-free survival (DFS) was 85.0%, and 5-year overall survival (OS) was 93.1%. Cox analysis showed that 7th edition of the AJCC staging system and progesterone receptor status were independent risk factors for LRR, DM, DFS and OS (P<0.05). Compared with stage by 7th edition, 1 278(70.1%) were assigned to a different prognostic stage group: 1 088 (85.1%) to a lower stage and 190 (14.9%) to a higher stage. LRR, DM, DFS and OS were significantly different between prognostic stage ⅠA, ⅠB, ⅡA, ⅡB and ⅢA according to 8th edition of the AJCC staging system(P<0.001). Prognostic stage had significantly higher C-indexes and provided better estimation of prognosis compared to stage by 7th edition of the AJCC staging system (P<0.001). Conclusion: The prognostic stage groups of 8th edition AJCC staging system has superior prognostic accuracy compared to 7th edition in T1-2N1M0 breast cancer, and has better clinical therapeutic guidance value.

The Prognostic Value of the AJCC 8th Edition Staging System for Patients Undergoing Neoadjuvant Chemotherapy for Breast Cancer.

The American Joint Committee on Cancer (AJCC) 8th edition staging system for breast cancer has been validated in the upfront surgery setting, but has not been examined for its prognostic impact on patients undergoing neoadjuvant chemotherapy. The National Cancer Data Base was used to identify patients with invasive unilateral breast cancer from 2010 to 2015 who underwent neoadjuvant chemotherapy. AJCC clinical stage classification was compared between the 7th and 8th editions. Receiver operating characteristic analysis of Kaplan-Meier overall survival (OS) was used to determine the predictive fit of the 7th and 8th edition staging in estimating OS. AJCC 7th and 8th clinical staging assignments were applied to 57,466 patients who underwent neoadjuvant chemotherapy for stage I-III breast cancer from 2010 to 2015. Overall, 37.5% of patients were downstaged and 27.8% were upstaged from the 7th to the 8th edition classification. Kaplan-Meier curves comparing 7th and 8th edition staging differed in OS rates, with a mean follow-up time of 41.5months. AJCC 8th edition prognostic staging was a better predictor of OS than 7th edition anatomic staging for both clinical stage [area under the curve (AUC) 0.67 vs. 0.62, p<0.01] and pathological stage (AUC 0.70 vs. 0.66, p<0.01). Sixty-five percent of patients have a shift in clinical stage in the AJCC 8th edition. AJCC 8th edition staging has better predictive value for OS than 7th edition staging. While validation of these findings with an independent dataset is needed, 8th edition staging will help improve prognostic modeling in patients undergoing neoadjuvant chemotherapy.

Modifications of the AJCC 8th edition staging system for intrahepatic cholangiocarcinoma and proposal for a new staging system by incorporating serum tumor markers

BackgroundSeveral studies have noted that the discriminatory ability and stratification performance of the AJCC 8th edition staging system is not entirely satisfactory. We aimed to improve the American Joint Committee on Cancer (AJCC) 8th edition staging system for intrahepatic cholangiocarcinoma (ICC). MethodsA multicentric database from three Chinese mainland centers (n = 1601 patients) was used to modify the 8th edition staging system. This modified TNM (mTNM) staging system was then validated using the SEER database (n = 761 patients). A new TNM staging system, by incorporating serum tumor markers (TNMIS) into the mTNM staging system was then proposed. ResultsThe 8th edition staging system did not provide an adequate stratification of prognosis in the Chinese multicentric cohort. The mTNM staging system offered a better discriminatory capacity in the multicentric cohort than the original 8th edition. External validation in the SEER cohort showed that the mTNM staging system also had a good stratification performance. After further incorporating a serum marker stage into the mTNM staging, the TNMIS staging system was able to stratify prognosis even better. ConclusionThe proposed mTNM staging system resulted in better stratification performance and the TNMIS staging system provided even more accurate prognostic classification than the conventional TNM system.

Validation of the 8th AJCC Cancer Staging System for Pancreas Neuroendocrine Tumors Using Korean Nationwide Surgery Database.

PurposeThe 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic neuroendocrine tumor (PNET) included several significant changes. We aim to evaluate this staging system compared to the 7th edition AJCC staging system and European Neuroendocrine Tumors Society (ENETS) system.Materials and MethodsWe used Korean nationwide surgery database (2000-2014). Of 972 patients who had undergone surgery for PNET, excluding patients diagnosed with ENETS/World Health Organization 2010 grade 3 (G3), only 472 patients with accurate stage were included.ResultsPoor discrimination in overall survival rate (OSR) was noted between AJCC 8th stage III and IV (p=0.180). The disease-free survival (DFS) curves of 8th AJCC classification were well separated between all stages. Compared with stage I, the hazard ratio of II, III, and IV was 3.808, 13.928, and 30.618, respectively (p=0.007, p < 0.001, and p < 0.001). The curves of OSR and DFS of certain prognostic group in AJCC 7th and ENETS overlapped. In ENETS staging system, no significant difference in DFS between stage IIB versus IIIA (p=0.909) and IIIA versus IIIB (p=0.291). In multivariable analysis, lymphovascular invasion (p=0.002), perineural invasion (p=0.003), and grade (p < 0.001) were identified as independent prognostic factors for DFS.ConclusionThis is the first large-scale validation of the AJCC 8th edition staging system for PNET. The revised 8th system provides better discrimination compared to that of the 7th edition and ENETS TNM system. This supports the clinical use of the system.

Proposed revision of the 8th edition AJCC clinical staging system for esophageal squamous cell cancer treated with definitive chemo-IMRT based on CT imaging

PurposeTo validate and propose revision of the 8th edition American Joint Committee on Cancer (AJCC) clinical staging system for esophageal squamous cell cancer (ESCC) patients treated with definitive intensity-modulated radiation therapy combined with concurrent chemotherapy (Chemo-IMRT) based on computed tomography (CT) imaging.MethodsThe clinical data of patients with ESCC treated with Chemo-IMRT were collected and retrospectively reviewed. All CT images were independently reevaluated and restaged according to the 8th edition AJCC staging system. The overall survival (OS) rates were analyzed statistically. ROC curves of the various parameters of the primary tumor and metastatic lymph nodes were generated in order to identify the cutoff values correlated to patient survival using the area under curve.ResultsThe gross tumor volume of the primary tumor (GTV-prT) and the clinical N stage (cN) were independent factors that influenced OS. The 5-year OS rate of patients with GTV-prT ≤28 cm3, GTV-prT > 28 and ≤ 56 cm3, and GTV-prT > 56 cm3 were 54.6, 31.1 and 18.6%, respectively. The 5-year OS rate of patients with cN0, cN1 SLNM (−), cN2 SLNM (−), cN3 SLNM (−) and SLNM (+) were 62.8 (P < 0.001), 34.0 (P = 0.16), 20.0 (P = 0.785), 0 (P < 0.001) and 26.9%, respectively. After restaging the SLNM as regional MLNs, the 5-year OS rates of the patients with cN0, 1, 2 and 3 were 62.8, 36.3, 23.7 and 7.8%, respectively. Various GTV-prT were combined with the cN to establish a new clinical TNM staging system: I, GTV-prT1 and cN0; II, GTV-prT2 or 3 and cN0, GTV-prT1 and cN1; III, GTV-prT1 and cN2, GTV-prT2 and cN1,2; Iva, GTV-prT3 and cN1,2; IVb, GTV-prTany and cN3; IVc, TanyNanyM1. Subsequently, the OS differed significantly between the adjacent GTV-prT cN categories, except those of stage I vs. II.ConclusionThe SLNM should be dealt with as a regional rather than a distant disease in patients with ESCC when treated with CRT. The proposed nonsurgical staging system based on the GTV-prT and N appears to be a simple and accurate prognosis predictor for patients with ESCC who have undergone definitive Chemo-IMRT.

Abstract P1-03-03: Comparing staging assignments based on the 7th and 8th editions of the American Joint Committee on Cancer staging system for breast cancer

Abstract Background: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for breast cancer has redefined breast cancer staging to better represent the heterogeneity of the disease. The previously established TNM system reflected only tumor size (T), nodal status (N), and distant metastasis (M). The updated staging system introduces new clinical and pathological prognostic staging systems by incorporating tumor grade, tumor markers, and genomic assays. Prospective comparisons of staging assignment between AJCC 7th and 8th edition staging systems have not been performed in the United States. The objective of this study was to compare subjects' assigned stage between the AJCC 7th and 8th edition staging systems. Methods: Data were collected from patients with non-metastatic breast carcinoma who presented to the University of Chicago between January 1, 2018 and May 31, 2018. Upstaging or downstaging was defined as an increase or decrease by one or more letter or number stages (i.e. from IIA to IIB or IB). Descriptive data were generated for all collected data. Analysis was performed in Stata 14.0. Results: Clinical anatomic and prognostic stages were assigned to 246 patients while pathologic anatomic and prognostic stages were assigned to 142 patients. Forty-seven patients underwent neoadjuvant therapy and were not assigned a pathologic prognostic stage, while 57 patients had not undergone surgery at our institution by the end of the study period and were not assigned a pathologic stage. Two patients had lobular carcinomia in situ and were no longer considered to have a malignancy by the 8th edition staging system; anatomic staging was otherwise unchanged from 7th edition to 8th edition staging in this cohort. Of the 246 patients assigned clinical anatomic and prognostic stages, 48 patients were upstaged (19.5%), 37 were downstaged (15.0%), and 161 were not affected (65.5%) by prognostic staging. Of the 142 patients assigned pathologic anatomic and prognostic staging, nine patients were upstaged (6.3%), 32 were downstaged (22.5%), and 101 were not affected (71.1%) by prognostic staging. Four patients were eligible to be downstaged in pathologic prognostic staging by genomic assays such as Oncotype (consisting of Stage 1B or higher patients with T1N0M0 HER2 - ER + PR - Grade 3 disease or T2N0M0 HER2 - ER + disease). Of these patients, three had genomic assays performed by the end of the study period. Results from genomic assays did not affect the staging of these three patients. Stage Changes with the AJCC 8th Edition Upstaged % (n)Downstaged % (n)No Change in Stage % (n)Clinical Stage19.5 (48)15.0 (37)65.5 (161)Pathologic Stage6.3 (9)22.5 (32)71.1 (101) Conclusions: Approximately one third of breast cancer patients were assigned new clinical or pathologic stages with the AJCC 8th edition staging system. These findings confirm that implementation of the new criteria for staging will be important to many patients in discussions of treatment and prognosis. Citation Format: Brian R, Tseng J, Bao J, Jaskowiak N. Comparing staging assignments based on the 7th and 8th editions of the American Joint Committee on Cancer staging system for breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-03-03.