American Joint Committee On Cancer Manual Research Articles

Assessment of the Novel, Practical, and Prognosis-Relevant TNM Staging System for Stage I-III Cutaneous Melanoma

BackgroundThe clinical TNM staging system does not differ between the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging manual. A more practical TNM staging system for patients with stage I-III cutaneous melanoma are needed.MethodsData were accessed from the Surveillance, Epidemiology, and End Results (SEER) open database. We divided the patients into 32 groups based on the T and N categories. The Kaplan-Meier survival curves and treatment guidelines were used to proposed a new TNM staging system. Cox proportional hazards model and 1000-person-years were used to verify accuracy.ResultsThis retrospective study included 68 861 patients from 2010 to 2015. The new proposed staging system was as follows: stage IA, T1aN0M0; stage IB, T1b/T2aN0M0; stage IIA, T3-4aN0M0 and T2bN0M0; stage IIB, T1-4aN1-2M0 and T3-4bN0M0; and stage III, T1-4aN3M0 and T1-4bN1-3M0. Hazard ratios for the new stages IB, IIA, IIB, and III, with stage IA as reference, were 4.311 (95% confidence interval [CI]: 3.217-5.778), 8.993 (95% CI: 6.637-12.186), 13.179 (95% CI: 9.435-18.407), and 20.693 (95% CI: 13.655-31.356), respectively (all p-values < 0.001). Cancer-specific mortality rates per 1000-person-years were 0.812 (95% CI: 0.674-0.978), 6.612 (95% CI: 5.936-7.364), 22.228 (95% CI: 20.128-24.547), 50.863 (95% CI: 47.472-54.496) and 120.318 (95% CI: 112.596-128.570) for stages IA, IB, IIA, IIB and III, respectively.ConclusionWe developed a more practical and prognosis-relevant staging system than that of the 8th edition AJCC manual for patients with stage I-III cutaneous melanoma. Treatments using this new model would improve the quality of life and survival rates of patients with melanoma.

Need to restage Korean melanoma patients following publication of the 8th edition of the American Joint Committee on Cancer staging manual.

The tumor, nodes and metastasis (TNM) classification and stage grouping have been updated in the 8th edition of the American Joint Committee on Cancer (AJCC) melanoma staging manual. However, restaging all the previous cases are not recommended. The aims of the study were to investigate the necessity of restaging Korean melanoma patients staged by the previous edition of the AJCC manual. Differences in the staging criteria of the 7th and 8th editions of the AJCC manual were identified. The staging of 276 primary melanomas from January 2011 to December 2018 was classified by both 7th and 8th editions of the manual and their differences were compared. Staging by 7th and 8th edition of the AJCC manual differed in 64 cases (23.2%). The pathological prognostic staging changed in 35 (12.7%), and 29 (10.5%) had changes in only TNM classification but not the pathological staging. None of the patients needed additional sentinel lymph node biopsy or systemic treatment as a result of restaging. Additional counseling was needed for the patients, because melanoma-specific survival was increased in the 8th edition. This is a retrospective study with relatively small number of patients at a single tertiary center in Korea. Assessment of the need for additional sentinel lymph node biopsy or systemic treatment is recommended because of the latest changes in the AJCC melanoma staging manual. Although the restaging of previously staged melanomas is not significantly needed in our patients, still the differences in TNM classification and/or pathological prognostic staging suggest the need to separately recognize the patients previously staged by 7th edition and recently staged by 8th edition. Careful counseling about melanoma-specific survival is needed for Asian patients.

Abstract PS6-23: Comparison between the American joint committee on cancer (AJCC) anatomic and prognostic stages for breast cancer

Abstract Introduction: The knowledge regarding the tumor biology of breast cancer has grown substantially and resulted in the identification of different breast cancer subtypes based on their molecular profile, which led to an important change in treatment, it went from standardized therapy for personalized therapy. A panel of experts and representatives from AJCC were responsible for preparing the newest Cancer Staging Manual. The panel recognized the clinical usefulness of biological factors such as histological grade, expression of hormone receptors - HR (estrogen and progesterone) and overexpression and / or amplification of the human epidermal growth factor 2 (HER2) receptor in predicting patient survival and incorporated data regarding these biomarkers in the new staging system. In addition, for eligible cases, the ‘Recurrence score’ was also incorporated, a score generated by the analysis of OncotypeDx (genomic test). The new manual, therefore, started to use 3 stays. Anatomical staging - based on the classic TNM; the clinical prognostic staging and pathological prognosis staging - TNM association with the prognostic biomarkers (using clinical data in the first and data after surgical treatment in the second). Objective: To verify the concordance between anatomical staging from the 7th edition of the AJCC manual and the prognosis from its 8th edition in a cohort of patients with breast cancer at the Hospital do Servidor Público Estadual de São Paulo. Methodology: Observational and cross-sectional study, which evaluated patients undergoing surgical treatment at Hospital do Servidor Público Estadual from March 2014 to March 2019. Information was collected regarding age, menopausal status, tumor characteristics, anatomical and clinical staging, neoadjuvant chemotherapy, adjuvant chemotherapy and radiotherapy and type of surgery performed. The patients were staged using the digital platform “TNM8 Breast Cancer Calculator”. Results: 805 patients were included in the analysis. All patients were female, aged between 29 and 97 years, mostly in the post-menopausal period (78.88%). 74.04% of the cases were positive for ER, 66.21% positive PR and 88.07% HER2 negative. Prognostic staging downgraded a total of 285 out of 805 patients (35.4%). Almost all of the cases that decreased in staging were ER and / or PR + (283 of 285). Most of those who went up were Triple Negatives (100 out of 111). Conclusion: Prognostic Staging changes staging in almost half of the cases and there was a greater number of staging decreases in total and an association of increased staging with tumors considered to have a worse prognosis, which is in agreement with several studies already carried out since the launch of the new manual. Table 1. Changes in the staging groups. Anatomical Staging vs. Prognostic StagingAnatomical Staging (%)StageIAIBIIAIIBIIIAIIIBIIICIVPrognostic Staging (%)IA2486972Total that decreased staging285 (35,4%)IB21472619IIA602727IIB22294IIIA34297IIIB17122014IIIC14226IV4Total staging that increased 111(13,8%)Total unchanged 409 (50,8%) Table 2. Relationship of the immunohistochemical profile and change of stagingBiomarkersTotal (%)DifferenceTotalHR + / HER2 -575 (71,42%)-196 (16,70%)-2140 (24,34%)-321 (3,65%)0308 (53,57%)+110 (1,74%)HR + / HER2 +49 (6,09%)-19 (18,37%)-217 (34,69%)022 (44,90%)+11 (2,04%)HR - / HER2 +47 (5,84%)-12 (4,3%)045 (95,7%)HR - / HER2 -134 (16,65%)034 (25,4%)+169 (51,5%)+231 (23,1%)805 (100%) Citation Format: Mariana Soares Cardoso, Marcelo Antonini, Odair Ferraro, Matheus de Paula Solino, Samira Marcondes Cabral, Raissa Naiara Alves de Barros Vasconcelos. Comparison between the American joint committee on cancer (AJCC) anatomic and prognostic stages for breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-23.

Clinical Calculator Based on Molecular and Clinicopathologic Characteristics Predicts Recurrence Following Resection of Stage I-III Colon Cancer.

Clinical calculators and nomograms have been endorsed by the American Joint Committee on Cancer (AJCC), as they provide the most individualized and accurate estimate of patient outcome. Using molecular and clinicopathologic variables, a third-generation clinical calculator was built to predict recurrence following resection of stage I-III colon cancer. Prospectively collected data from 1,095 patients who underwent colectomy between 2007 and 2014 at Memorial Sloan Kettering Cancer Center were used to develop a clinical calculator. Discrimination was measured with concordance index, and variability in individual predictions was assessed with calibration curves. The clinical calculator was externally validated with a patient cohort from Washington University's Siteman Cancer Center in St Louis. The clinical calculator incorporated six variables: microsatellite genomic phenotype; AJCC T category; number of tumor-involved lymph nodes; presence of high-risk pathologic features such as venous, lymphatic, or perineural invasion; presence of tumor-infiltrating lymphocytes; and use of adjuvant chemotherapy. The concordance index was 0.792 (95% CI, 0.749 to 0.837) for the clinical calculator, compared with 0.708 (95% CI, 0.671 to 0.745) and 0.757 (0.715 to 0.799) for the staging schemes of the AJCC manual's 5th and 8th editions, respectively. External validation confirmed robust performance, with a concordance index of 0.738 (95% CI, 0.703 to 0.811) and calibration plots of predicted probability and observed events approaching a 45° diagonal. This third-generation clinical calculator for predicting cancer recurrence following curative colectomy successfully incorporates microsatellite genomic phenotype and the presence of tumor-infiltrating lymphocytes, resulting in improved discrimination and predictive accuracy. This exemplifies an evolution of a clinical calculator to maintain relevance by incorporating emerging variables as they become validated and accepted in the oncologic community.

Differences in cutaneous melanoma survival between the 7th and 8th edition of the American Joint Committee on Cancer (AJCC). A multicentric population-based study.

The 8th edition of the AJCC manual for melanoma includes many changes leading to major substage migrations, which could lead to important clinical reassessments. To evaluate the differences and prognostic value of the 8th AJCC classification in comparison with the 7th edition. Clinical and histopathological data were retrieved from five melanoma referral centers including 7815 melanoma patients diagnosed between January 1998 and December 2018. All patients were reclassified and compared using the 7th and 8th classifications of the AJCC. Sankey plots were used to evaluate the migration of patients between the different versions. The primary outcome was overall survival (OS), and curves based on the Kaplan-Meier method were used to investigate survival differences between the 7th and 8th editions. The number of patients classified as stages IB, IIIA, and IIIB decreased while the patients classified as stages IA and IIIC increased notably. Migration analysis showed that many patients in group I were understaged whereas a significant percentage of patients in group III were upstaged. Indirect OS analysis showed a loss in the linearity in the AJCC 8th edition and the groups tended to overlap. Direct OS analysis between groups and versions of the AJCC showed a better prognosis within the new stage III patients, with no effect on those in stages I and II. The 8th AJCC edition represents an important change in the classification of patients. We observe that the main migratory changes occur in stage I and III, that severity linearity is lost and groups overlap, and that a more advanced stage does not mean a worse prognosis.

Benefits of the 8th American Joint Committee on Cancer System for Hepatocellular Carcinoma Staging

We aimed to emphasize the prognostic impact of differences included in the 8th versus the previous 7th edition of AJCC (American Joint Committee on Cancer) Cancer Staging manual for hepatocellular carcinoma (HCC). A number of 87 consecutive HCCs were retrospectively evaluated and staged, using the 7th and 8th edition of AJCC staging systems. The clinicopathological parameters were correlated with the overall survival rate. No preoperative chemotherapy was received by any of the patients. According to the 7th edition of AJCC manual, 52 of the 87 cases were staged as pT2 and 35 as pT1. After restaging, according to the 8th edition, 23 of the 52 pT2 cases were understaged as pT1b, and the rest of the 29 remained as pT2. Regarding the 35 HCCs classified as pT1, using 7th edition, all of them were restaged as pT1a. Compared to the 7th staging system, using the 8th edition of AJCC manual, the percentage of pT2 tumors significantly decreased, from 59.77 to 33.33%. The patient's gender, age, tumor focality, and grade of differentiation did not prove to have any prognostic value. Regarding pT stage, it does not influence the overall survival rate, independently from the used staging system. The staging criteria, in the most recent edition of AJCC, are simplified and allowed tumor understaging. These changes do not have independent prognostic value. The prognostic impact of pT understaging should be evaluated in larger cohorts.

Which Staging System Is More Suitable for Gastric Neuroendocrine Cancer and Mixed Adenoneuroendocrine Carcinomas? A Multicenter Cohort Study

Purpose: To evaluate whether the European Neuroendocrine Tumor Society (ENETS) system or the 8th American Joint Committee on Cancer (AJCC) staging manual are suitable for gastric neuroendocrine carcinomas and/or mixed adenoneuroendocrine carcinomas (G-NECs/MANECs). Methods: Patients in a multicentric series with G-NEC/MANEC who underwent curative-intent surgical resection for a primary tumor were included. An optimal staging system was proposed base on analysis of the T and N status and validated by the SEER database. Results: Compared with the ENETS system, the survival curves of the T category and N category in the 8th AJCC system were better separated and distributed in a more balanced way, but the survival curves of T2 vs. T3, N0 vs. N1, and N3a vs. N3b overlapped. For the T category, the 8th AJCC T category was modified by combining T2 and T3, which was consistent with the T category in the 6th AJCC manual for GC. For the N category, the optimal cut-off values of metastatic lymph nodes using X-tile were also similar to those of the N category in the 6th AJCC system. The Kaplan-Meier plots of the 6th AJCC system showed statistically significant differences between individual substages. Compared with the other 2 classifications, the 6th AJCC system also showed superior prognostic stratification. Similar results were obtained in both multicentric and SEER validation sets. Conclusions: Compared to the 8th AJCC and ENETS systems, the 6th AJCC staging system for GC is more suitable for G-NEC/MANEC and can be adopted in clinical practice.

Assessment of the Prognostic Staging System of American Joint Committee on Cancer 8th Edition for Breast Cancer: Comparisons with the Conventional Anatomic Staging System.

PurposeThe 8th edition of the American Joint Committee on Cancer (AJCC) staging manual introduced a new prognostic staging system for breast cancer. This study aimed to evaluate the changes in staging distribution and predictive power of the new staging system.MethodsOf the 12,275 patients with breast cancer identified from the Severance Breast Cancer Registry who underwent surgery between 1978 and 2016, 12,125 patients met the inclusion criteria.ResultsIn both the 7th and 8th staging systems, stage I patients constituted the largest proportion (38.2% and 48.4%). Migration from the 7th to 8th edition of the AJCC manual resulted in a decrease in stage II population and an increase in stage I and III populations. A total of 1,293 (15.4%) patients were upstaged, and 1,201 (14.3%) were downstaged. Downstaged patients had better recurrence-free and overall survival (p < 0.001). Pathologic complete response after neoadjuvant therapy showed good prognosis as p stage 0, and yp stages I and III showed poorer outcomes than the same p stage (p < 0.001).ConclusionsStaging migrations are common in early breast cancer under the prognostic staging system. The prognostic staging system of the 8th edition of the AJCC manual discriminates survival outcomes better than the anatomical staging system of the 7th edition of the AJCC manual.

Validation of the pathological prognostic staging system proposed in the revised eighth edition of the AJCC staging manual in different molecular subtypes of breast cancer.

The authors investigated the clinical utility of the revised prognostic staging system proposed in the eighth edition of the American Joint Committee on Cancer (AJCC) staging manual in breast cancer (BC) patients. We retrospectively reviewed the data of 714 BC patients that received surgical treatment and standard adjuvant therapy from January 2005 to December 2007. All patients were restaged for anatomic TNM stage and pathological prognostic (PP) stage as defined in the revised eighth edition of the AJCC manual. Compared with anatomic stage, PP stage was different from anatomic stage in 325 (45.5%) patients, 254 were down-staged and 71 were upstaged. There were significant differences in overall survival (OS) and disease-free survival (DFS) according to different anatomic stages or PP stages (all, p < 0.001). In anatomic stage I patients, OS was significantly different between PP stages IA and IB (p < 0.001), but no significant difference was observed between anatomic stages IA and IB (p = 0.413). PP stages exhibited significant OS differences in anatomic stage IIB (p = 0.011), but survival differences according to PP stages were not observed in anatomic stage IIA, IIIA, or IIIC. PP stages were found to have prognostic value with respect to OS and DFS for luminal (p < 0.001 and p < 0.001), HER2-positive (p = 0.001 and p = 0.013), and triple-negative (p = 0.008 and p = 0.03) subtypes. The prognostic staging system proposed in the eighth edition of the AJCC more accurately predicts the clinical outcomes of BC patients than the traditional anatomic staging system.

Evaluation of Prostate Cancer Stage Groups Updated in the 8th Edition of the American Joint Committee on Cancer Tumor-Node-Metastasis Staging Manual.

The American Joint Committee on Cancer (AJCC) tumor, node, metastasis classification system (TNM) staging manual has been updated and provides more specified stage grouping for prostate cancer (PCa). We aimed to validate the updated AJCC stage groups for PCa using a radical prostatectomy (RP) cohort. We analyzed the data of 3032 patients previously treated with RP for localized PCa. We stratified patients into stage groups according to the 8th edition of the AJCC manual and compared biochemical recurrence (BCR)-free survival using Kaplan-Meier analyses. There were 217 patients in stage group I, 33 in IIA, 1101 in IIB, 535 in IIC, 129 in IIIA, 781 in IIIB, and 236 in IIIC. There were no significant differences in BCR-free survival between stage groups IIC and IIIA (P= .875). Subsequently, the low-Gleason score (GS) IIIA subgroup (GS≤ 3+ 4, P= .025) showed superior BCR-free survival than the IIC group, and the high-GS IIIA subgroups (GS≥ 4+ 3, P= .004) showed a poorer BCR-free survival than the IIC group. Furthermore, there were no significant differences between groups I and IIA (P= 330) and between groups IIA and IIB (P= .942). Our new staging system provided a better ability to discriminate the prognosis of each group. However, our study has several limitations, such as retrospective design, relatively short follow-up period, and need for further validation. The current AJCC prognostic groups show some contradictory results, particularly concerning prognosis of the IIC and IIIA groups. We suggest that GS be given more weight than serum prostate-specific antigen level in stage group stratification.

Evaluation of appendiceal mucinous neoplasms with a new classification system and literature review

Appendiceal mucinous neoplasms constitute a diagnostic spectrum ranging from adenoma to mucinous adenocarcinoma. To date, many classification systems have been proposed to reflect the histomorphological diversity of neoplasms in this range and their clinical correspondence, and also to form a common terminology between the pathologist and clinicians. The aim of this review is to provide an updated perspective on the pathological features of appendiceal mucinous neoplasms. Using the 2016 Modified Delphi Consensus Protocol (Delphi) and the Eighth Edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 19 cases presented from June 2011 to December 2016 were evaluated and diagnosed with appendiceal mucinous neoplasia. According to the Delphi, non-carcinoid epithelial tumours of the appendix were categorized in eight histomorphological architectural groups. These groups are adenoma, serrated polyp, low-grade appendiceal mucinous neoplasm, high-grade appendiceal mucinous neoplasm, mucinous adenocarcinoma, poorly-differentiated adenocarcinoma with signet-ring, signet-ring cell carcinoma and adenocarcinoma. The most common symptom was right lower quadrant pain. The median age of these cases was 60±15 years. There was a preponderance of females (F/M: 15/4). In our re-evaluation, six cases were diagnosed as serrated polyp. There were 11 cases in the LAMN group and two cases in the mucinous adenocarcinoma group. Using the Delphi and the AJCC manual, there were many changes in the classification, evaluation and treatment of appendiceal mucinous neoplasms. These classification systems have facilitated the compatibility and communication of clinicians and pathologists and have guided clinicians on treatment methods.

Defining the Prevalence and Prognostic Value of Perineural Invasion and Angiolymphatic Invasion in Human Papillomavirus–Positive Oropharyngeal Carcinoma

Importance Recently, the American Joint Committee on Cancer (AJCC) updated its staging system for human papillomavirus (HPV)–positive oropharyngeal squamous cell carcinoma (OPSCC). The prognostic significance of perineural invasion (PNI) and angiolymphatic invasion (ALI) within this staging system is unknown. Objective To examine the prevalence and prognostic significance of PNI and ALI in HPV-positive OPSCC. Design, Setting, and Participants A retrospective review was performed of all patients with HPV-positive OPSCC treated surgically at the University of Pittsburgh Medical Center from January 1, 1980, through December 31, 2015, with at least 1 year of follow-up or death within 1 year. Interventions Surgical treatment of HPV-positive OPSCC. Main Outcomes and Measures The prevalence of PNI and ALI was determined from review of pathologic data, and Kaplan-Meier curves were generated for overall survival and disease-free survival when stratified by the presence of PNI and ALI. Multivariate analysis was performed using a Cox proportional hazards regression model. Results A total of 201 patients met the inclusion criteria (mean [SD] age, 57.4 [9.0] years; 79.6% [3.0%] male, and 20.4% [3.0%] female). Perineural invasion was identified in 32 of 201 primary specimens (15.9%), whereas ALI was identified in 74 of 201 primary specimens (36.8%). Both were significantly associated with increasing T stage. On multivariate analysis, the presence of at least 1 risk factor was significantly associated with overall and disease-free survival (overall hazard ratio, 2.78; 95% CI, 1.15-6.76; disease-free survival hazard ratio, 3.10; 95% CI, 1.17-8.23). Among patients classified as having stage II disease according to the eighth edition of the AJCC manual, the presence of at least 1 risk factor was associated with worse overall survival (hazard ratio, 11.7; 95% CI, 1.2-111.7). Conclusions and Relevance Both PNI and ALI were commonly found in HPV-positive OPSCC, with increasing prevalence as T stage increased. The presence of at least 1 risk factor was associated with worse overall and disease-free survival. Specifically, among patients classified as having stage II disease according to the eighth edition of the AJCC manual, the presence of ALI or PNI may suggest a poorer prognosis.

The newly proposed clinical and post-neoadjuvant treatment staging classifications for gastric adenocarcinoma for the American Joint Committee on Cancer (AJCC) staging.

New stage grouping classifications for clinical (cStage) and post-neoadjuvant treatment (ypStage) stage for gastric adenocarcinoma have been proposed for the eighth edition of the AJCC manual. This article summarizes the analysis for these stages. Gastric adenocarcinoma patients diagnosed in 2004-2009 were identified from the National Cancer Database (NCDB). The cStage cohort included both surgical and nonsurgical cases, and the ypStage cohort included only patients who had chemotherapy or radiation therapy before surgery. Survival differences between the stage groups were determined by the log-rank test and prognostic accuracy was assessed by concordance index. Analysis was performed using SAS 9.4 (SAS, Cary, NC, USA). Five strata for cStage and four strata for ypStage were developed. The 5-year survival rates for cStages were 56.77%, 47.39%, 33.1%, 25.9%, and 5.0% for stages I, IIa, IIb, III, and IV, respectively, and the rates for ypStage were 74.2%, 46.3%, 19.2%, and 11.6% for stages I, II, III, and IV, respectively. The log-rank test showed that survival differences were well stratified and stage groupings were ordered and distinct (p<0.0001). The proposed cStage and ypStage classification was sensitive and specific and had high prognostic accuracy (cStage: c index=0.81, 95% CI, 0.79-0.83; ypStage: c index=0.80, 95% CI, 0.73-0.87). The proposed eighth edition establishes two new staging schemata that provide essential prognostic data for patients before treatment and for patients who have undergone surgery following neoadjuvant therapy. These additions are a significant advance to the AJCC staging manual and will provide critical guidance to clinicians in making informed decisions throughout the treatment course.