Eighth Edition Staging System Research Articles

Validation of American Joint Committee on Cancer eighth staging system for gallbladder cancer and its lymphadenectomy guidelines

BackgroundFor gallbladder cancer (GBC), the American Joint Committee on Cancer eighth edition (AJCC 8) staging system classifies lymph node (LN) stage by the number of positive LN and recommends sampling of ≥6 LNs. We evaluated the prognostic capability of the AJCC 8 for patients undergoing resection and the current national trends in LN staging in the context of these new recommendations for nodal (N) sampling. MethodsUtilizing the National Cancer Data Base, we identified all gallbladder adenocarcinoma patients treated with surgical resection in 2004-2014. Cox regression modeling was used to calculate the concordance index of AJCC 8 in predicting overall survival. N sampling and positivity rates were analyzed over the study period. ResultsIn our cohort, predicted 5-year overall survival by AJCC 8 was: stage I, 62.5%; II, 50.2%; IIIA, 25.7%; IIIB, 22.1%; IVA, 15.7%; IVB, 6.7% (P < 0.01). The concordance index for the staging system was 0.832. Only 50.7% of the patients had any LN sampling to determine the N stage. LN sampling rates improved from 45.6% in 2004 to 55.1% in 2013 (P < 0.001). However, only 24.5% of patients with any LN sampling had ≥6 LNs resected (12.4% of eligible cohort), with a median LN sample of two. ConclusionsAJCC 8 offers adequate discrimination for GBC staging, especially for node-positive patients. With actual GBC LN sampling rates at 50.7%, and far short of the ≥6 LN threshold, quality improvement measures may need to focus on requiring any LN sampling before raising the minimum to six LNs.

Impact of paranasal sinus invasion on advanced nasopharyngeal carcinoma treated with intensity-modulated radiation therapy: the validity of advanced T stage of AJCC/UICC eighth edition staging system.

The aim of this study was to clarify the prognostic role of paranasal sinus invasion in advanced NPC patients. Data of patients (n = 295) with advanced NPC (T3/T4N0‐3 M0) treated with intensity‐modulated radiation therapy were retrospectively analyzed. Staging was according to the AJCC/UICC eighth edition staging system. Overall survival (OS), local recurrence‐free survival (LRFS), distant metastasis‐free survival (DMFS), and disease‐free survival (DFS) were calculated, and differences were compared between patients with and without paranasal sinus invasion. Multivariate analysis was used to identify the independent predictors of different survival parameters. Paranasal sinus invasion was present in 126 of 295 (42.7%) patients. Sphenoid, ethmoid, maxillary, and frontal sinus involvements were present in 123 of 295 (41.7%), 95 of 295 (32.2%), 45 of 295 (15.3%), and 0 of 295 (0%), respectively. All survival parameters were significantly better in patients without paranasal sinus invasion. When paranasal sinus invasion was reclassified as T4 instead of T3, all survival rates, other than LRFS (P = 0.156), were significantly better in the new T3 patients, and differences in all survival parameters remained nonsignificant between T3 with paranasal sinus invasion and T4 without paranasal sinus invasion patients (all P > 0.05). In multivariate analysis, paranasal sinus invasion was found to be an independent negative prognostic factor for OS, DFS, and DMFS (P = 0.016, P = 0.004, and P = 0.006, respectively), but not for LRFS (P = 0.068). Paranasal sinus invasion has prognostic value in advanced NPC. It may be reasonable to classify paranasal sinus invasion as T4 stage.

Incorporating Biology Into Breast Cancer Staging: American Joint Committee on Cancer, Eighth Edition, Revisions and Beyond.

Higher-quality imaging, refined surgical procedures, enhanced pathologic evaluation, and improved understanding of the impact of tumor biology on treatment and prognosis have necessitated revisions of the AJCC breast cancer staging system. The eighth edition includes clinical and pathologic prognostic stages that incorporate biologic variables-grade, estrogen and progesterone receptor status, HER2 status, and multigene panels-with the anatomic extent of disease defined by tumor, node, and metastasis categories. The prognostic staging systems facilitate more refined stratification with respect to survival than anatomic stage alone. Because the prognostic staging systems are dependent on biologic factors, accuracy is dependent on rigorous pathologic evaluation of tumors and on administration of treatment dictated by tumor biology. It is anticipated that technological advances will facilitate even more refined determination of underlying biology within tumors and in the peripheral blood, which increasingly is being evaluated as a compartment that reflects the primary tumor and sites of distant metastases. Diseases should be staged according to the eighth edition staging system to accurately reflect prognosis and to allow standardized data collection. Such standardization will facilitate assessment of the impact of advances in diagnosis and treatment of patients with breast cancer.

Major prognostic factors for recurrence and survival independent of the American Joint Committee on Cancer eighth edition staging system in patients with cutaneous squamous cell carcinoma treated with multimodality therapy

The purpose of this study was to assess changes resulting from the American Joint Committee on Cancer (AJCC) eighth edition for cutaneous squamous cell carcinoma (SCC) and evaluate pertinent excluded factors. In 101 patients receiving surgery and postoperative radiation, recurrence and survival were estimated by cumulative incidence and Kaplan-Meier method. Time-to-event analysis was performed using Cox proportional hazards and Fine-Gray competing risks regression models. The 2-year locoregional recurrence, overall survival (OS), and cause-specific mortality rates were 25%, 72%, and 13%, respectively. The AJCC eighth edition upstaged T classification in 50% of patients and overall stage in 39%. In multivariate analysis, immunosuppression and in-transit metastasis were associated with locoregional recurrence. Older age and in-transit metastasis were associated with worse OS. In univariate analysis (limited by number of events), cause-specific mortality was associated with positive margin, in-transit metastasis, and the seventh edition dichotomized T classification and overall stage. In-transit metastasis was significantly associated with locoregional recurrence, OS, and cause-specific mortality. Efforts should be made to define in-transit metastasis in the staging system.

Validation of the American Joint Committee on Cancer eighth edition staging system in patients undergoing hepatectomy for hepatocellular carcinoma: a US population-based study

BackgroundThe American Joint Committee on Cancer (AJCC) eighth edition staging system for hepatocellular carcinoma (HCC) has incorporated several significant changes. This study aims to evaluate the newly proposed staging system and assess its strengths and weaknesses. Materials and methodsUsing the Surveillance, Epidemiology, and End Results database, we identified patients with pathologically confirmed stage I-III HCC diagnosed between 2004 and 2014. ResultsAfter all exclusion criteria were applied, AJCC seventh and eighth edition staging was possible in 4931 patients. According to the AJCC eighth edition staging system, stages IB and II did not differ significantly in terms of overall survival (OS) and cause-specific survival (CSS) (P = 0.928 and 0.872, respectively). On the basis of the above results, we reclassified T1a, T1b, and T2 into several subgroups. According to the modified AJCC eighth edition staging system, OS and CSS among the five groups of patients differed significantly. For OS predication, the Akaike information criterion values for the AJCC seventh, eighth, and modified eighth edition staging systems were 29,288.24, 29,282.85, and 27,182.21, respectively, and the c-indices for the AJCC seventh, eighth, and modified eighth edition staging systems were 0.5716, 0.5805, and 0.6082, respectively. Regarding CSS, the Akaike information criterion values for the AJCC seventh, eighth, and modified eighth edition staging systems were 21,701.11, 21,682.12, and 20,313.26, respectively, and the c-indices for the AJCC seventh, eighth, and modified eighth edition staging systems were 0.5983, 0.6117, and 0.6436, respectively. ConclusionsThis is the first large-scale validation of the AJCC eighth edition staging system for patients undergoing hepatectomy. Our study revealed that there was a lack of discrepancy in the outcomes for stage IB and II tumors for AJCC eighth edition staging system of HCC. Our modified AJCC eighth edition staging system allows for finer stratification of patients undergoing hepatectomy according to more detailed tumor size and vascular invasion classifications.

A Lymph Node Ratio-Based Staging Model Is Superior to the Current Staging System for Pancreatic Neuroendocrine Tumors.

The incidence of pancreatic neuroendocrine tumors (PNETs) is increasing. Current staging systems include nodal positivity, but the association of lymph node status and worse survival is controversial. The study aim was to determine the prognostic significance of lymph node ratio (LNR) and compare it with nodal positivity for PNET. A retrospective analysis of the Surveillance, Epidemiology, and End Results database between 2004 and 2011 was performed in patients who underwent a pancreatectomy with lymphadenectomy. The primary outcome was disease-specific survival (DSS). Of the 896 patients analyzed, T stage, N stage, distant metastasis, grade, extent of resection, sex, and age ≥57 years were significantly associated with worse DSS on univariate analysis. On multivariate analysis, age ≥57 [hazard ratio (HR) 1.75, 95% confidence interval (CI), 1.12 to 2.74, P = 0.015], male sex (HR 1.58; 95% CI, 1.01 to 2.48; P = 0.046), grade (poorly differentiated/undifferentiated: HR 7.59; 95% CI, 4.71 to 12.23; P < 0.001), distant metastases (HR 2.45; 95% CI, 1.58 to 3.79; P < 0.001), and partial pancreatectomy (HR 2.55; 95% CI, 1.2 to 5.4; P = 0.015) were associated with worse DSS. Comparison between staging models constructed based on LNR cutoffs and the American Joint Committee on Cancer (AJCC) eighth edition staging system revealed that a model based on LNR ≥0.5 was superior. LNR ≥0.5 is independently associated with worse DSS. A staging system with LNR ≥0.5 was superior to the current AJCC eighth edition staging system.

Interpretation and evaluation of the American Joint committee on Cancer (AJCC) 8th Edition Staging System for patients with gastroenteropancreatic neuroendocrine tumors

American Joint Committeeon Cancer (AJCC) released the eighth edition staging system manual in October 2016. Based on the shortcomings in the seventh edition of AJCC staging system, staging classifications for gastroenteropancreatic neuroendocrine tumor (GEP-NET) were updated. The changes are as follow: small intestinal NET was divided into two groups, duodenal and jejunoileal NET and lymphatic metastasis was redefined into N1 and N2 in jejunoileal NET; stages were condensed except colorectal NET; the staging classification for pancreatic NET proposed by European Neuroendocrine Tumor Society(ENETS) was adopted. However, problems still exist in the eighth edition AJCC staging classifications for GEP-NET. For instance, whether the definitions of N1 and N2 in jejunoileal NET are accurate in clinical management is still less understood. Thus, further clinical validations of the AJCC eighth edition staging system for GEP-NET are needed. Meanwhile, the eighth edition AJCC staging classifications for GEP-NET still did not step towards precision medicine and risks assessment models with high quality are still absent.

Assessment of the Lymph Node Status in Patients Undergoing Liver Resection for Intrahepatic Cholangiocarcinoma: the New Eighth Edition AJCC Staging System

IntroductionThe role of routine lymphadenectomy for intrahepatic cholangiocarcinoma (ICC) is still controversial. The AJCC eighth edition recommends a minimum of six harvested lymph nodes (HLNs) for adequate nodal staging. We sought to define outcome and risk of death among patients who were staged with ≥6 HLNs versus <6 HLNs. Materials and MethodsPatients undergoing hepatectomy for ICC between 1990 and 2015 at 1 of the 14 major hepatobiliary centers were identified. ResultsAmong 1154 patients undergoing hepatectomy for ICC, 515 (44.6%) had lymphadenectomy. On final pathology, 200 (17.3%) patients had metastatic lymph node (MLN), while 315 (27.3%) had negative lymph node (NLN). Among NLN patients, HLN was associated with 5-year OS (p = 0.098). While HLN did not impact 5-year OS among MLN patients (p = 0.71), the number of MLN was associated with 5-year OS (p = 0.02). Among the 317 (27.5%) patients staged according the AJCC eighth edition staging system, N1 patients had a 3-fold increased risk of death compared with N0 patients (hazard ratio 3.03; p < 0.001). ConclusionOnly one fourth of patients undergoing hepatectomy for ICC had adequate nodal staging according to the AJCC eighth edition. While the six HLN cutoff value impacted prognosis of N0 patients, the number of MLN rather than HLN was associated with long-term survival of N1 patients.

The IASLC Mesothelioma Staging Project: Proposals for Revisions of the N Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Pleural Mesothelioma

IntroductionNodal categories for malignant pleural mesothelioma are derived from the lung cancer staging system and have not been adequately validated. The International Association for the Study of Lung Cancer developed a multinational database to generate evidence-based recommendations to inform the eighth edition of the TNM classification of malignant pleural mesothelioma. MethodsData from 29 centers were entered prospectively (n = 1566) or by transfer of retrospective data (n = 1953). Survival according to the seventh edition N categories was evaluated using Kaplan-Meier survival curves and Cox proportional hazards regression analysis. Survival was measured from the date of diagnosis. ResultsThere were 2432 analyzable cases: 1603 had clinical (c) staging, 1614 had pathologic (p) staging, and 785 had both. For clinically staged tumors there was no separation in Kaplan-Meier curves between cN0, cN1 or cN2 (cN1 versus cN0 hazard ratio [HR] = 1.06, p = 0.77 and cN2 versus cN1 HR = 1.04, p = 0.85). For pathologically staged tumors, patients with pN1 or pN2 tumors had worse survival than those with pN0 tumors (HR = 1.51, p < 0.0001) but no survival difference was noted between those with pN1 and pN2 tumors (HR = 0.99, p = 0.99). Patients with both pN1 and pN2 nodal involvement had poorer survival than those with pN2 tumors only (HR = 1.60, p = 0.007) or pN0 tumors (HR = 1.62, p < 0.0001). ConclusionsA recommendation to collapse both clinical and pN1 and pN2 categories into a single N category comprising ipsilateral, intrathoracic nodal metastases (N1) will be made for the eighth edition staging system. Nodes previously categorized as N3 will be reclassified as N2.

The IASLC Mesothelioma Staging Project: Proposals for Revisions of the T Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Pleural Mesothelioma

IntroductionThe current T component for malignant pleural mesothelioma (MPM) has been predominantly informed by surgical data sets and consensus. The International Association for the Study of Lung Cancer undertook revision of the seventh edition of the staging system for MPM with the goal of developing recommendations for the eighth edition. MethodsData elements including detailed T descriptors were developed by consensus. Tumor thickness at three pleural levels was also recorded. An electronic data capture system was established to facilitate data submission. ResultsA total of 3519 cases were submitted to the database. Of those eligible for T-component analysis, 509 cases had only clinical staging, 836 cases had only surgical staging, and 642 cases had both available. Survival was examined for T categories according to the current seventh edition staging system. There was clear separation between all clinically staged categories except T1a versus T1b (hazard ratio = 0.99, p = 0.95) and T3 versus T4 (hazard ratio = 1.22, p = 0.09), although the numbers of T4 cases were small. Pathological staging failed to demonstrate a survival difference between adjacent categories with the exception of T3 versus T4. Performance improved with collapse of T1a and T1b into a single T1 category; no current descriptors were shifted or eliminated. Tumor thickness and nodular or rindlike morphology were significantly associated with survival. ConclusionsA recommendation to collapse both clinical and pathological T1a and T1b into a T1 classification will be made for the eighth edition staging system. Simple measurement of pleural thickness has prognostic significance and should be examined further with a view to incorporation into future staging.