The new (Version 9) American Joint Committee on Cancer tumor, node, metastasis staging for cervical cancer.

The American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging for all cancer sites has been periodically updated as a published manual for many years. The last update, the eighth edition AJCC Cancer Staging Manual went into use on January 1, 2018. The AJCC has since restructured and updated its processes, and all AJCC staging-related data are now housed on its new application programming interface. Consequently, the next AJCC TNM staging update, AJCC version 9 TNM staging, will be published electronically and will be released chapter by chapter. The first chapter of version 9 AJCC TNM staging is the updated cervical cancer staging, which is now published. This article highlights the changes to the AJCC TNM cervical cancer staging; these changes align with the International Federation of Gynecology and Obstetrics staging. The most important of the changes are: 1) the incorporation of imaging and surgical findings, 2) the elimination of lateral spread from T1a, 3) the addition of a subcategory to T1b (T1b3), and 4) histopathology is updated to reflect human papillomavirus-associated and human papillomavirus-independent carcinomas.

The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging.

The American Joint Committee on Cancer (AJCC) staging manual has become the benchmark for classifying patients with cancer, defining prognosis, and determining the best treatment approaches. Many view the primary role of the tumor, lymph node, metastasis (TNM) system as that of a standardized classification system for evaluating cancer at a population level in terms of the extent of disease, both at initial presentation and after surgical treatment, and the overall impact of improvements in cancer treatment. The rapid evolution of knowledge in cancer biology and the discovery and validation of biologic factors that predict cancer outcome and response to treatment with better accuracy have led some cancer experts to question the utility of a TNM-based approach in clinical care at an individualized patient level. In the Eighth Edition of the AJCC Cancer Staging Manual, the goal of including relevant, nonanatomic (including molecular) factors has been foremost, although changes are made only when there is strong evidence for inclusion. The editorial board viewed this iteration as a proactive effort to continue to build the important bridge from a "population-based" to a more "personalized" approach to patient classification, one that forms the conceptual framework and foundation of cancer staging in the era of precision molecular oncology. The AJCC promulgates best staging practices through each new edition in an effort to provide cancer care providers with a powerful, knowledge-based resource for the battle against cancer. In this commentary, the authors highlight the overall organizational and structural changes as well as "what's new" in the Eighth Edition. It is hoped that this information will provide the reader with a better understanding of the rationale behind the aggregate proposed changes and the exciting developments in the upcoming edition. CA Cancer J Clin 2017;67:93-99. © 2017 American Cancer Society.

Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual.

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.

External Validation of the New 2023 International Federation of Gynecology and Obstetrics Staging System in Endometrial Cancer Patients: 12-Year Experience from an European Society of Gynecological Oncology-Accredited Center.

Background and Objectives: The new molecular classification of endometrial cancer continuously changes the management of the disease in everyday clinical practice. Recently, FIGO released a new staging system for endometrial cancer, which incorporates molecular substages and subdivides further early-stage disease. The aim of this study was to investigate the differences between the two FIGO staging systems and evaluate the prognostic precision of the new one. Materials and Methods: We retrospectively analyzed the records of patients with endometrial cancer that were fully treated in the 1st Department of Obstetrics & Gynecology, in 2012-2023. Patient characteristics, oncological outcome, and follow-up information were collected. The primary outcomes were the stage shifts and the survival data. Results: Sixty-seven (15.5%) patients had a stage shift and the majority of them concerned early-stage disease and specifically an upshift from 2009 stages IA and IB to 2023 stage IIC. Concerning survival, a better median and 5-year PFS was present in stage II disease, and when comparing the prognostic precision of the two FIGO staging systems no significant difference was present. Conclusions: The new 2023 FIGO staging system better distinguishes early-stage endometrial cancer into its prognostic groups and seems to be as precise as the old 2009 FIGO staging system.

Liver Metastases of Intrahepatic Cholangiocarcinoma: Implications for an Updated Staging System.

BACKGROUND AND AIMS: Intrahepatic cholangiocarcinoma (iCCA) with liver metastases is perceived to have a poor prognosis, but the American Joint Committee on Cancer (AJCC) classifies them as early stage in the absence of lymph nodes or extrahepatic spread. APPROACH AND RESULTS: Patients with iCCA from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) and Surveillance, Epidemiology, and End Results (SEER) registries with survival/staging (AJCC v.7) data were eligible. Modified staging was used (mAJCC v.7): group A: stages I-III (excluding T2bN0); group B: stage IVa (excluding T2bN1M0); group C: liver metastases (T2bN0/1); and group D: stage IVb (extrahepatic metastases). Survival analysis (Kaplan-Meier and Cox regression) was performed in an ENS-CCA training cohort (TC) and findings internally (ENS-CCA iVC) and externally (SEER) validated. The aim was to assess whether liver metastases (group C) had a shorter survival compared to other early stages (group A) to propose a modified version of AJCC v.8 (mAJCC v.8). A total of 574 and 4,171 patients from the ENS-CCA and SEER registries were included. Following the new classification, 19.86% and 17.31% of patients from the ENS-CCA and SEER registries were reclassified into group C, respectively. In the ENS-CCA TC, multivariable Cox regression was adjusted for obesity (p = 0.026) and performance status (P < 0.001); patients in group C (HR, 2.53; 95% CI, 1.18-5.42; P = 0.017) had a higher risk of death (vs. group A). Findings were validated in the ENS-CCA iVC (HR, 2.93; 95% CI, 2.04-4.19; P < 0.001) and in the SEER registry (HR, 1.88; 95% CI, 1.68-2.09; P < 0.001). CONCLUSIONS: iCCA with liver metastases has a worse outcome than other early stages of iCCA. Given that AJCC v.8 does not take this into consideration, a modification of AJCC v.8 (mAJCC v.8), including "liver metastases: multiple liver lesions, with or without vascular invasion" as an "M1a stage," is suggested.

Validation of the revised 8th AJCC breast cancer clinical prognostic staging system: analysis of 5321 cases from a single institution.

The anatomic stage groups (ASG) have been arguably the most powerful in predicting breast cancer (BC) outcomes. Recognizing the prognostic influence of histologic grade and receptor status, the 8th AJCC mandates their incorporation into the newly established prognostic stage groups (PSG). This staging scheme was subsequently revised to provide pathological and clinical prognostic stage tables (PPSG/CPSG) due to its incapability to categorize a significant subset of BCs, with the former only used for patients having surgical resection as the initial treatment, and the latter for all patients. Given the increasingly used neoadjuvant therapy, PPSG cannot be assigned in a significant proportion of higher staged BCs. In this study, we validated the CPSG in a cohort of 5321 BCs. Compared to ASG, the application of CPSG resulted in assigning 16.1% and 27.2% of cases to a higher or a lower stage group in non-stage IV BCs, respectively. The changes were seen mostly frequently in ASG IB, followed by IIIC, IIB, IIA, IIIA, IIIB, and IA. In 7.9% of cases, the assigned CPSG changed more than one stage group from the ASG. CPSG provided an improved overall discriminating power in predicting BC-specific survival when compared to ASG. Pairwise comparison using the Cox proportional hazard model demonstrated further advantages for CPSG as the latter showed a significant difference in all categories when compared to their proximate groups, except IIA vs. IB and IIIA vs. IIIB. In contrast, a significantly different hazard was only seen when comparing IIB vs. IIA, IIIA vs. IIB, and IV vs. IIIC for ASG. Thus, the revised 8th AJCC CPSG provided a superior overall staging scheme for predicting prognostic outcomes in BC patients receiving standard of care treatment. Further validation using the available data with larger populations and longer follow-up may be needed to refine and improve this table.

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.

Proposing the 3-tier staging system for improving prognostication in Stage I uterine leiomyosarcoma.

BACKGROUND AND OBJECTIVES: To examine the utility of a 3-tier schema (≤5 cm, 5.1-10 cm, and > 10 cm) in determining characteristics and survival in Stage I uterine leiomyosarcoma. METHODS: This retrospective observational study queried the National Cancer Institute's Surveillance, Epidemiology, and End Result Program from 1988 to 2016. Surgically treated stage I uterine leiomyosarcomas with known tumor size were examined (N = 2217). Trends, characteristics, and survival were assessed based on tumor size. RESULTS: The most common tumor size was 5.1-10 cm (45.7%) followed by >10 cm (35.0%) and ≤5 cm (19.4%). Tumor size-shift occurred during the study period; the percentage of tumor size >10 cm increased from 12.9% to 44.5% and the groups with smaller tumor sizes decreased (p < .001). In weighted models, 5-year overall survival rates ranged from 49.9% to 71.6% in the 3-tier system and 55.2%-70.6% in the 2-tier system: the absolute difference was larger in the 3-tier system (21.7% vs. 15.4%). In the 3-tier system, all-cause mortality risk of tumor size >10 cm versus ≤5 cm nearly doubled (hazard ratio 1.96, 95% confidence interval 1.78-2.16). CONCLUSION: In the past decades, tumors of stage I uterine leiomyosarcoma have become larger. Our study suggests that a tumor size-based 3-tier staging system may be useful to differentiate survival in stage I uterine leiomyosarcoma.

The prognostic value of tumor deposits and the impact on the TNM classification system in esophageal cancer patients.

OBJECTIVE: To explore the prognostic significance of tumor deposits (TDs), isolated tumor foci lacking residual lymph nodes, in esophageal cancer (EC). METHODS: A retrospective review of patients with EC undergoing esophagectomy between 2005 and 2017 was conducted. The prognostic value of TD was evaluated using a Cox regression model. Patients from different sources and periods were split into discovery and validation sets. A propensity score matching model was used in the validation set to reduce the confounding bias. The impact of TD on the TNM classification system was evaluated. RESULTS: The discovery and validation sets included 179 and 2875 patients, respectively. Propensity-matched patients with and without TDs were constructed in the validation set with 132 patients in each group. Overall survival (p < .001 and p = .004, respectively) and disease-free survival (p < .001 and p = .019, respectively) were both decreased in TD positive patients in the discovery set and propensity-matched groups of validation set. Classifying patients with TDs into pN3 stage improved the discriminative power of the current TNM staging system. CONCLUSIONS: TD is an independent prognostic factor for EC. The inclusion of TD in the TNM staging system may upstage appropriate patients to help guide therapy, and future studies are warranted.

Clinical benefit of baseline imaging in Merkel cell carcinoma: Analysis of 584 patients.

BACKGROUND: Merkel cell carcinoma (MCC) guidelines derive from melanoma and do not recommend baseline cross-sectional imaging for most patients. However, MCC is more likely to have metastasized at diagnosis than melanoma. OBJECTIVE: To determine how often baseline imaging identifies clinically occult MCC in patients with newly diagnosed disease with and without palpable nodal involvement. METHODS: Analysis of 584 patients with MCC with a cutaneous primary tumor, baseline imaging, no evident distant metastases, and sufficient staging data. RESULTS: Among 492 patients with clinically uninvolved regional nodes, 13.2% had disease upstaged by imaging (8.9% in regional nodes, 4.3% in distant sites). Among 92 patients with clinically involved regional nodes, 10.8% had disease upstaged to distant metastatic disease. Large (>4 cm) and small (<1 cm) primary tumors were both frequently upstaged (29.4% and 7.8%, respectively). Patients who underwent positron emission tomography-computed tomography more often had disease upstaged (16.8% of 352), than those with computed tomography alone (6.9% of 231; P = .0006). LIMITATIONS: This was a retrospective study. CONCLUSIONS: In patients with clinically node-negative disease, baseline imaging showed occult metastatic MCC at a higher rate than reported for melanoma (13.2% vs <1%). Although imaging is already recommended for patients with clinically node-positive MCC, these data suggest that baseline imaging is also indicated for patients with clinically node-negative MCC because upstaging is frequent and markedly alters management and prognosis.

Integrating the melanoma 31-gene expression profile test with surgical oncology practice within national guideline and staging recommendations.

Aim: Define changes in clinical management resulting from the use of the prognostic 31-gene expression profile (31-GEP) test for cutaneous melanoma in a surgical oncology practice. Patients & methods: Management plans for 112 consecutively tested patients with stage I-III melanoma were evaluated for duration and number of clinical visits, blood work and imaging. Results: 31-GEP high-risk (class 2; n = 46) patients received increased management compared with low-risk (class 1; n = 66) patients. Test results were most closely associated with follow-up and imaging. Of class 1 patients, 65% received surveillance intensity within guidelines for stage I-IIA patients; 98% of class 2 patients received surveillance intensity equal to stage IIB-IV patients. Conclusion: We suggest clinical follow-up and metastatic screening be adjusted according to 31-GEP test results.

Risk of preoperative understaging of duodenal neuroendocrine neoplasms: a plea for caution in the treatment strategy.

PURPOSE: Pretreatment staging is the milestone for planning either surgical or endoscopic treatment in duodenal neuroendocrine neoplasms (dNENs). Herein, a series of surgically treated dNEN patients was evaluated to assess the concordance between the pre- and postsurgical staging. METHODS: Retrospective analysis of patients with a histologically confirmed diagnosis of dNENs, who underwent surgical resection observed at eight Italian tertiary referral centers. The presurgical TNM stage, based on the radiological and functional imaging, was compared with the pathological TNM stage, after surgery. RESULTS: From 2000 to 2019, 109 patients were included. Sixty-six patients had G1, 26 a G2, 7 a G3 dNEN (Ki-67 not available in 10 patients). In 46/109 patients (42%) there was disagreement between the pre- and postsurgical staging, being it understaged in 42 patients (38%), overstaged in 4 (3%). As regards understaging, in 25 patients (22.9%), metastatic loco-regional nodes (N) resulted undetected at both radiological and functional imaging. Understaging due to the presence of distal micrometastases (M) was observed in 2 cases (1.8%). Underestimation of tumor extent (T) was observed in 12 patients (11%); in three cases the tumor was understaged both in T and N extent. CONCLUSIONS: Conventional imaging has a poor detection rate for loco-regional nodes and micrometastases in the presurgical setting of the dNENs. These results represent important advice when local conservative approaches, such as endoscopy or local surgical excision are considered and it represents a strong recommendation to include endoscopic ultrasound in the preoperative tools for a more accurate local staging.

A Prognostic Model of Gastrointestinal Diffuse Large B Cell Lymphoma.

BACKGROUND The digestive tract is the most common site of extranodal involvement in diffuse large B cell lymphoma (DLBCL) and its prognostic evaluation is different from that of ordinary DLBCL. Currently, for gastrointestinal lymphoma, in addition to the Ann Arbor staging system, the Lugano and the TNM staging systems are commonly used. However, there is no effective prognostic model to identify poor prognosis in patients with localized gastrointestinal diffuse large B cell lymphoma (GI-DLBCL). MATERIAL AND METHODS This study included 82 patients with GI-DLBCL that had a median follow-up of 75 months, and developed a model (HLAMA) with 5 variables: hemoglobin, age, lactate dehydrogenase (LDH), serum albumin, and the maximum intra-abdominal lesion diameter (MIALD). The specific indicators are: HGB <105 g/L (2 points); LDH ≥300 U/L; age ≥75 years, ALB <38 g/L, MIALD ≥4 cm (each scoring 1 point). We also developed a simplified model, which includes only 3 variables (HGB, LDH, and age). RESULTS HLAMA model and the simplified model both demonstrated good ability to predict prognosis of patients with GI-DLBCL (P<0.001), performing better than the IPI score as it could distinguish low-risk groups in relatively elderly patients (60-75 years old). CONCLUSIONS This study established a prognostic model for diffuse large B cell lymphoma of the gastrointestinal tract. Both the HLAMA model and its simplified version are similar to the IPI score, but could be considered better as they can provide a simpler and more accurate prognostic assessment in patients with GI-DLBCL. For patients with localized GI-DLBCL, our model could distinguish high-risk patients.

Merkel cell carcinoma.

Merkel cell carcinoma (MCC) of the skin is a rare, aggressive form of skin cancer that metastasizes to other parts of the body. This cutaneous neuroendocrine tumour mainly affects older people, with most cases generally occurring over the age of 50 years. Merkel cell polyomavirus has been shown to induce gene mutations resulting in this skin cancer, with immunosuppression and ultraviolet radiation being other key risk factors in its pathogenesis. MCC is clinically seen as a rapidly enlarging, isolated, irregular erythematous nodule typically found on sun-exposed sites. Diagnosis is through clinical examination followed by tissue biopsy, which demonstrates characteristic histopathological neuroendocrine features. Immunohistochemistry plays a crucial role in diagnosis with the characteristic perinuclear staining with cytokeratin-20 helping to differentiate it from other morphologically similar tumours. Sentinel lymph node biopsy and imaging is essential for staging and determining prognosis. Surgical excision is the mainstay of treatment for localized disease although adjuvant radiotherapy is often required. Metastatic disease involves a very poor prognosis, and immune checkpoint inhibitors have recently shown promise in the treatment of metastatic disease. Avelumab, a monoclonal antibody that binds to the programmed death-1 receptor, has been approved by the National Institute for Health and Care Excellence and shown encouraging survival outcomes. It provides an option for treating metastatic carcinoma in adults after they have failed ≥ 1 line of chemotherapy for metastatic disease.

Fourier Transform Infrared Spectroscopy in Oral Cancer Diagnosis.

Oral cancer is one of the most common cancers worldwide. Despite easy access to the oral cavity and significant advances in treatment, the morbidity and mortality rates for oral cancer patients are still very high, mainly due to late-stage diagnosis when treatment is less successful. Oral cancer has also been found to be the most expensive cancer to treat in the United States. Early diagnosis of oral cancer can significantly improve patient survival rate and reduce medical costs. There is an urgent unmet need for an accurate and sensitive molecular-based diagnostic tool for early oral cancer detection. Fourier transform infrared spectroscopy has gained increasing attention in cancer research due to its ability to elucidate qualitative and quantitative information of biochemical content and molecular-level structural changes in complex biological systems. The diagnosis of a disease is based on biochemical changes underlying the disease pathology rather than morphological changes of the tissue. It is a versatile method that can work with tissues, cells, or body fluids. In this review article, we aim to summarize the studies of infrared spectroscopy in oral cancer research and detection. It provides early evidence to support the potential application of infrared spectroscopy as a diagnostic tool for oral potentially malignant and malignant lesions. The challenges and opportunities in clinical translation are also discussed.

Challenges with colorectal cancer staging: results of an international study.

Challenges exist with standardized colorectal cancer reporting despite adoption of the American Joint Committee on Cancer-Staging Manual 8th edition. We performed this study to gauge current practice patterns among a diverse group of surgical pathologists. A web-based questionnaire depicting problematic issues and images related to colorectal carcinoma staging was circulated among 118 surgical pathologists and their responses were correlated with their geographic location (North America vs. Europe vs. others), nature of practice (academic vs. community), the sign-out model (gastrointestinal subspecialty vs. general surgical pathology), and years of professional experience. We found that a substantial number of practicing pathologists ignore recommended-staging criteria in specific settings, particularly with respect to assessment of advanced T stage. Tumors that communicated with the serosa through inflammatory foci were staged as pT3 (49%) or pT4a (51%) by nearly equal numbers of pathologists regardless of level of experience, the sign-out model, or geographic location. Only 65% assigned T stage and margin status based on extent of viable tumor in the neoadjuvant setting. One-third of pathologists, particularly those in Europe (p = 0.015), classified acellular mucin deposits as N1 disease when detected in treatment-naive cases. Nearly 50% of pathologists classified isolated tumor cells (i.e., deposits <0.2 mm) in lymph nodes as metastatic disease (i.e., pN1, p = 0.02). Our results suggest that pathologists ignore recommendations that are based on insufficient data and apply individualized criteria when faced with situations that are not addressed in the American Joint Committee on Cancer Staging Manual 8th edition. These variations in practice limit the ability to compare outcome data across different institutions and draw attention to areas that require further study.

Prognostic Performance of Preoperative Staging: Assessed by Using Multidetector Computed Tomography-Between the New Clinical Classification and the Pathological Classification in the Eighth American Joint Committee on Cancer Classification for Gastric Carcinoma.

BACKGROUND: Since the eighth American Joint Committee on Cancer (AJCC) classification recently introduced the clinical classification for preoperative staging of gastric cancer, the new clinical classification has not been extensively validated yet. Therefore, in this study, we compared the prognostic performance of the new clinical classification and the pathologic classification for preoperative staging of gastric cancer. METHODS: We reviewed 3027 patients with gastric cancer who were surgically treated between 2009 and 2013. Patient survival was analyzed according to the preoperative stage by the clinical classification and the pathologic classification in the eighth AJCC classification. The prognostic performance was examined using the Akaike information criterion (AIC) value and Harrell c-index. RESULTS: Patient survival was significantly different across the different stages when both classifications were used. However, individual pairwise comparisons showed that survival differences between each stage were more distinctive and homogeneous in the pathologic classification. In the multivariate model adjusted for the final pathologic stage, preoperative staging by the pathologic classification was an independent prognostic factor, whereas the clinical classification was not. The pathologic classification showed a lower AIC value compared with the clinical classification (5100.64 vs. 5114.14). The Harrell c-index was higher in the pathologic classification than in the clinical classification (0.741 vs. 0.739). CONCLUSIONS: The new clinical classification in the eighth AJCC classification discriminates patient survival well. However, it does not appear to have a better prognostic performance compared with the pathologic classification for preoperative staging of gastric cancer.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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 41.5 months. 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). CONCLUSIONS: 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.

Staging for Breast Cancer Patients Receiving Neoadjuvant Chemotherapy: Utility of Incorporating Biologic Factors.

BACKGROUND: The American Joint Committee on Cancer (AJCC) breast cancer pathological prognostic stage, which incorporates biologic factors, was developed using data from patients undergoing upfront surgery, and its application in patients receiving neoadjuvant chemotherapy (NAC) is unknown. We previously developed the Neo-Bioscore, incorporating clinical and pathological TNM categories with biologic factors, to improve the prognostic stratification of NAC patients. OBJECTIVE: This study was undertaken to evaluate the use of available staging models incorporating biologic factors in NAC patients. METHODS: Patients treated with NAC between 2005 and 2012 at MD Anderson (n = 2363) were staged using the Neo-Bioscore and the AJCC 8th edition: (1) clinical anatomic stage; (2) pathological anatomic stage; (3) clinical prognostic stage; and (4) pathological prognostic stage. Five-year disease-specific survival (DSS) and overall survival (OS) rates, along with Harrell's concordance index (C-index), were estimated. A National Cancer Database (NCDB) cohort (n = 12,887) treated with NAC between 2010 and 2013 was used for validation. RESULTS: In the MD Anderson cohort, staging systems incorporating biologic factors better predicted DSS (bias-corrected C-index: pathological prognostic stage = 0.8026; Neo-Bioscore = 0.7483) and OS (bias-corrected C-index: pathological prognostic stage = 0.7780; Neo-Bioscore = 0.7260) than those using anatomic factors only. Similar results were seen in the NCDB cohort. In pairwise comparisons, the pathological prognostic stage was significantly better (p < 0.0001) than other staging systems in all comparisons except for OS in the NCDB cohort, where it was not significantly different than the Neo-Bioscore (p = 0.2). CONCLUSION: Biologic factors are important for determining prognosis in patients receiving NAC. These data indicate that the 8th edition AJCC pathological prognostic stage is applicable in these patients.

Global and mitosis-specific interobserver variation in mitotic count scoring and implications for malignant melanoma staging.

AIMS: Staging is the gold standard for predicting malignant melanoma outcome but changes in its criteria over time indicate ongoing evolution. One notable recent change from the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual was removal of mitotic count. We explore the extent to which this feature is limited by interobserver error in order to find ways to improve its fitness for use should it be revisited in future staging versions. METHODS AND RESULTS: In a cohort of 476 patients with melanoma ≤1.0 mm, a mitotic count of 0 versus 1 was significant for metastasis-free survival, but not melanoma-specific or overall survival. In 10 melanomas that were 0.9-1.0 mm thick, the mitotic count intraclass correlation coefficient for histopathologists was 0.58 (moderate agreement). Uniquely, we also assessed agreement for specific putative mitotic figures, identifying precise reasons why specific mitotic figures qualified for scoring or elimination. A kappa score was 0.54 (moderate agreement). We also gathered data on other staging features. Breslow thickness had an intraclass correlation coefficient of 0.41 (moderate agreement) and there was a systematic difference between histopathologists among cases (P = 0.04). Every case had a range that crossed the AJCC8 0.8-mm pT1a/pT1b staging boundary. Ulceration was only identified in two of the 10 cases. For ulceration, kappa agreement score was 0.31 (fair). CONCLUSION: This study supports the removal of mitotic count from staging, but shows that its scoring is substantially affected by interobserver variation, suggesting that more prescriptive guidelines might have a beneficial impact on its prognostic value.