CA Cancer J Clin ; Keywords: American Joint Committee on Cancer AJCC ; TNM staging; application programing interface; cancer stage; component content management system; electronic health record; precision medicine; prognostic factors; risk assessment models. Abstract 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.
Publication types Introductory Journal Article. If there is pathologic confirmation of distant metastatic cancer, categorization is pM1, not cM1, in contrast to cT and cN 1 , No single test is sufficient, and thus these investigations are complementary. The order in which they are used is variable and depends on availability, cost, scheduling, and patient and physician preference. There are two common strategies. The endoscopic procedures can be performed at one sitting, ensuring that data for all staging categories are complete.
This strategy is efficient, but costly. For cM0 cancers, clinical staging addresses the other categories necessary to prescribe therapy. This sequential strategy is cost effective but inefficient and does not ensure that all clinical staging categories are determined missing cTNM data. Clinical staging facilitates decision-making and has the potential to provide precision cancer care.
However, as described above, clinical stage may not reflect pathologic stage. Therefore, every effort must be made to add complementary information to increase accuracy of clinical staging categories. Patients with cN1 and cM1 cancers will benefit from histologic confirmation of advanced cancer. The future of decision-making relies on new clinical staging modalities and cancer-specific therapy. Thus, prognostication using clinical stage groups is coarse and may be inaccurate. However, inaccuracies of clinical staging and pathologic assessment after esophagectomy led to the use of pathologic stage after esophagectomy as the sole basis for all cancer staging.
Data analysis in the 8th edition demonstrated that simple sharing of stage groups among classifications was not possible, due to marked survival differences and unique pathologic stage groups after resection esophagectomy or endoscopic resection Table 3 5 - 7. Today, pathologic staging is losing its clinical relevance for advanced-stage cancer as neoadjuvant therapy replaces esophagectomy alone. However, it remains relevant for early-stage cancers, as the most accurate reflection of cancer facts and as a survival reference point.
Before resection, the surgeon or endoscopist must confirm the epicenter of the cancer pL. Complete resection of the primary cancer cannot be overstated. Adequate resection requires obtaining satisfactory margins and preserving all margins, particularly the radial margin.
The definition of a positive radial margin depends on the pathologic reporting system used. The Royal College of Pathologists defines an R1 microscopically positive margin as cancer within 1 mm of the margin 43 ; the College of American Pathologists defines R1 as microscopic involvement of the margin Increasing cT was associated with a positive margin.
Survival is markedly diminished in incompletely resected patients, and although adjuvant radiation is reported to improve survival, it has minimal clinical relevance. To avoid false-positive resection margins, separation of periesophageal soft tissue in the area of the primary cancer should be avoided.
Any clinical or intraoperative finding suggestive of a positive margin should prompt an intraoperative pathology consultation, with frozen section study of the resection margin in question If the margin is positive, resection should be extended to obtain a negative margin if possible.
Lymphadenectomy should be based on the new AJCC 8th edition regional lymph node map 1. Lymphadenectomy sufficient to determine pN is different from that necessary for optimal survival; at surgery, a balance of these goals is necessary More lymph nodes are required to identify the uncommon early-stage cancer with regional lymph node metastases.
Increasing pN is associated with increasing pT, increasing cancer length, increasing G, and more lymph nodes resected. However, a different lymphadenectomy strategy is required to provide a possible therapeutic survival benefit for advanced cancers An accurate count of resected lymph nodes is important to assess quality of resection and for prognostication.
If lymph nodes are fragmented at resection, the surgeon must provide the number of regional lymph nodes in the fragmented specimen.
Accurate pathologic staging requires careful examination of the gross specimen for cancer size, shape, configuration, location, distance from margins proximal, distal, and radial , and nodal dissection. Inking the adventitial aspect of the specimen facilitates microscopic assessment of pT and R.
Lymph node dissection is a major component of pathologic staging. Optimal lymph node staging depends on the amount of nodal tissue resected and the dissecting skills of the pathology staff. The periesophageal soft tissue adventitia should be thoroughly dissected. Lymph node retrieval should be performed only after full-thickness sections of the cancer and deepest extent of invasion into the adventitia have been obtained.
Lack of adherence to this practice leads to false-positive radial margins. In cases where lymph node tissue is submitted as separate specimens, the number of lymph nodes, including presence of matted lymph nodes, should be documented in the pathology report. In specimens received in multiple fragments, accurate lymph node count is not possible if the surgeon has not documented the count, and this fact should be recorded.
The American College of Gastroenterology has endorsed EMR as a modality both for diagnosis and treatment of mucosal nodularity in patients with Barrett esophagus EMR specimens provide larger, intact specimens containing submucosal tissue for accurate pathologic assessment of pG, pT, and lymphovascular invasion in patients with superficial esophageal adenocarcinoma.
To facilitate accurate staging, specimens should be oriented and fixed by pinning to a corkboard and serially sectioned after inking the lateral and deep margins of the specimen. Assessing EMR specimens is challenging because specimen edges often exhibit thermal artifacts and tend to curl.
This precludes accurate assessment of lateral mucosal margins. Duplication of muscularis mucosae, often seen in Barrett-related adenocarcinomas, can result in misinterpreting invasion into the space between duplicated muscularis mucosae as submucosal invasion Cancers should be categorized as pT1b only when neoplastic glands infiltrate beyond the duplicated muscularis mucosal layer, involve the plane containing submucosal glands, or are located adjacent to large-caliber arterial branches not normally found in the mucosa.
ESD is emerging as an endoscopic technique for en bloc resection of cancers. Theoretically, pathologic staging could facilitate decision-making and has the potential to provide precision cancer care in the post-esophagectomy period. However, use of this information to direct postoperative adjuvant therapy awaits more effective treatment.
Survival according to pTNM stage group was the best distributed of all classifications, with monotonically decreasing survival with increasing subgroup and group, except for stage group 0, which by AJCC definition was limited to pTis.
Subgrouping maximized distinctiveness of survival between groups and subgroups. Homogeneity of survival within groups was excellent in all but the advanced groups, which would be remedied by additional higher pN subcategories, but is clinically irrelevant because survival is poor in patients with more than seven regional lymph node metastases N3.
Thus, prognostication using pathologic stage groups is the most refined of all classifications. Personalized prognostication is afforded with additional cancer and patient variables in the prediction model. New to the 8th edition is stage grouping of patients who have undergone neoadjuvant therapy and pathologic review of the resection specimen. Drivers of this addition include absence of equivalent pathologic pTNM categories for the peculiar postneoadjuvant categories ypT0NM0 and ypTisNM0, dissimilar stage group compositions, and markedly different survival profiles.
The groupings are identical for both cell types Table 4. Just as for pTNM, adequate resection with preservation of margins and adequate lymphadenectomy are essential. That lymphadenectomy has not been demonstrated to affect survival in patients undergoing resection after preoperative therapy 4 , 50 should not influence extent of lymphadenectomy. Gross appearance of a cancer may vary depending on response to neoadjuvant therapy.
With minimal response, the cancer is readily visualized and is sampled similarly to a non-treated cancer or cancer treated by esophagectomy alone.
With a good response, the cancer may show only ulceration or mucosal irregularity. The cancer bed should be completely submitted for histologic evaluation. Obliteration of anatomic landmarks poses diagnostic challenges in assigning ypT, especially for EGJ cancers In some institutions, for EGJ cancers, the esophageal adventitial surface and gastric serosa are inked with different colors to determine the exact anatomic location and ypT This practice will be obviated with genetic signature determination of cancer cell of origin.
Neoadjuvant therapy induces several histologic changes, including ulceration, mural fibrosis, acellular mucin pools, and dystrophic calcification. Cancer cells must be distinguished from reactive stromal cells and macrophages. Regardless of the cell type, residual cancer cells usually demonstrate enlarged, irregular, and hyperchromatic nuclei with a dense homogeneous nuclear chromatin pattern and abundant cytoplasm.
Occasionally, residual cancer cells show neuroendocrine phenotype or squamous features. These foci should be considered when determining ypT Neoadjuvant histopathologic changes may preclude accurate grading of cancer, especially in cases with minimal residual cancer.
This underscores the importance of grading cancers on preoperative biopsy. Acellular mucin pools should not be used to determine pT or R Cancer regression grading as described by Mandard et al. The three-tiered cancer regression grading system outlined by Ryan et al. In patients receiving neoadjuvant therapy, lymph nodes can atrophy and be difficult to recognize macroscopically. In these cases, histologic assessment of most of the periesophageal soft tissue is helpful to retrieve grossly impalpable lymph nodes.
After treatment, lymph node parenchyma shows fibrosis, lymphoid depletion, and acellular mucin lakes. Lymph nodes with these changes, and without any viable cancer cells, should be considered negative for metastasis ypN0.
However, because false-positive results may occur, they should be interpreted in conjunction with morphologic findings. The role of ypTNM in additional treatment planning is currently limited. To realize precision cancer care, advances are necessary in both targeted neoadjuvant and adjuvant therapies.
With the introduction of 8th edition ypTNM cancer staging, prognostication is specific for patients undergoing neoadjuvant therapy and is not shared with any other classification. Conflicts of Interest: The authors have no conflicts of interest to declare. National Center for Biotechnology Information , U. Journal List Ann Cardiothorac Surg v. Ann Cardiothorac Surg.
Thomas W. Rice , 1 Deepa T. Patil , 2 and Eugene H. Blackstone 1, 3. Deepa T. Eugene H. Author information Article notes Copyright and License information Disclaimer. Corresponding author. Correspondence to: Thomas W. Rice, MD.
Email: gro. Received Dec 8; Accepted Mar 7. Copyright Annals of Cardiothoracic Surgery. All rights reserved. This article has been cited by other articles in PMC. Keywords: Clinical stage, pathologic stage, postneoadjuvant stage, decision-making, prognostication, precision cancer care.
Table 1 Cancer staging categories for cancer of the esophagus and esophagogastric junction. Prominent keratinization with pearl formation and a minor component of nonkeratinizing basal-like cells. Tumor cells are arranged in sheets, and mitotic counts are low G2 Moderately differentiated. Variable histologic features, ranging from parakeratotic to poorly keratinizing lesions.
Consists predominantly of basal-like cells forming large and small nests with frequent central necrosis. CiteScore measures average citations received per document published.
Read more. The outcomes are generally very good: disease recurrence rates are low Durante et al. Evidence-based management is crucial to avoid overtreatment of these low-risk tumors, which can reduce quality of life and yet identify accurately those requiring more aggressive therapy. Several staging systems have been generated to inform DTC management. Revision of the system was undertaken to address several specific limitations identified in the 7th edition AJCC-7 , which has been in use since Tuttle et al.
It is a classification system of the anatomical extent of tumor cancers. It has gained wide international acceptance for many solid tumor cancers, but is not applicable to leukaemia and tumors of the central nervous system. Most common tumors have their own TNM classification. Sometimes also described as the AJCC system. Skip to content. File Name: tnm 8th edition. It is available for purchase now on Amazon and is the most current version of the manual September
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