Refining esophageal cancer staging

OBJECTIVE: Cancer staging is dynamic, reflecting accrual of knowledge and experience in treatment. The objectives of this study were to assess current esophageal cancer staging and to determine whether refinements of classification and stage grouping are necessary. METHODS: From 1983 through November 2000, 480 patients underwent esophagectomy without induction therapy. Depth of tumor invasion (T), regional lymph node status (N), distant status (M), number of metastatic regional lymph nodes, and histopathologic type and grade were subjected to survival-tree analysis, multivariable Cox and hazard function analysis, and residual misclassification risk analysis. RESULTS: Inhomogenity of survival was found within and lack of distinction was found between current American Joint Committee on Cancer staging groups, supporting the need for refinement. T1 and N1 were redefined on the basis of survival differences. T1a is intramucosal cancer, T1b is submucosal cancer (P =.008), N1 is 1 or 2 metastatic regional lymph nodes, and N2 is 3 or more metastatic regional lymph nodes (P =.01). Current subclassification of M1 is not warranted (P =.9). Histopathologic type (P =.17) and grade (P =.3) minimally refined staging. Reassignment of staging groups constrained by American Joint Committee on Cancer definitions of stages 0 and IV produced less monotonic, distinctive, and homogeneous survival than free assignment of staging groups. CONCLUSIONS: Current American Joint Committee on Cancer staging of esophageal cancer is inadequate. Refinement requires redefinition of T1, N1, and M1 classifications. Stage grouping within the constraints of American Joint Committee on Cancer definitions produces less accurate prognosis than free assignment based on survival data.     

Surgical staging of esophageal cancer

The rising incidence of adenocarcinoma of the esophagus and the poor overall 5-year survival using current treatment regimens make it essential that clinical trials continue to search for more effective regimens for specific stages of esophageal cancer. It is clear from work in non-small cell lung cancer that clinical efficacy for platinum-based chemotherapeutic regimens has shown promise only in specific subsets of patients, such as those with stage IIIa tumors, but no benefit at all for earlier stages. In lung cancer, mediastinoscopy has been shown to be the most accurate method to stage locoregional lymph nodes and is considered to be the gold standard for clinical trials. In esophageal cancer, accurate surgical staging of all locoregional lymph nodes is more complex and may involve abdominal, thoracic, and cervical areas. Molecular evidence of lymph node involvement in esophageal cancer suggests that even histologically negative nodes may harbor micrometastases in a significant number of cases. Laparoscopy and thoracoscopy now offer a more accurate alternative to conventional staging of esophageal cancer. For distal esophageal cancers near the gastroesophageal junction, laparoscopic staging alone may suffice in most cases. Associated costs and the requirement for a surgical procedure should encourage the continued evaluation of new noninvasive modalities and the further evolution of endoscopic ultrasound. Currently, we recommend the application of minimally invasive surgical staging to assess new noninvasive technologies, such as PET scanning, and for use in clinical trials until the definitive approach to staging esophageal cancer is established. We are currently participating in an ongoing multicenter study of thoracoscopic and laparoscopic staging for esophageal cancer.     

Proposed staging system for gastrointestinal carcinoid tumors

Gastrointestinal carcinoid tumors are rare neuroendocrine tumors with no staging system in existence. The goal of this study was to establish a staging system consistent with the American Joint Commission on Cancer Staging Systems using the TNM strategy. A retrospective review of our prospective database of 990 hepatopancreaticobiliary patients and our tumor registry identified 108 patients with gastrointestinal carcinoid tumors from June 1990 to September 2006. Tumors were classified into our staging system by depth of penetration, size of primary tumor, nodal status, and the presence/absence of distant metastasis. Patients were staged as Stage 1, 22 per cent; Stage II, 29 per cent; Stage 3, 12 per cent; and Stage 4, 35 per cent. There were 41 men and 57 women with a median age of 58.5 years (range, 19-86 years). Primary tumors included 52 small bowel, 12 colon, 19 rectum, nine stomach, and seven of unknown primary origin. The use of our initial staging system demonstrated a trend in differences in survival across all four stages. The use of our initial staging proposal delineates the biology of the disease with accurate overall survival estimates. The addition of a dedicated American Joint Commission on Cancer staging system is needed for gastrointestinal carcinoids. Widespread use of this staging system may contribute to the future management and treatment of gastrointestinal carcinoid tumors.     

Proposed revision of the esophageal cancer staging system to accommodate pathologic response (pP) following preoperative chemoradiation (CRT)

OBJECTIVE: To determine the impact of pathologic response following preoperative chemoradiation (CRT) on the AJCC esophageal cancer staging system. SUMMARY BACKGROUND DATA: Increasing numbers of locoregionally advanced esophageal cancer patients are treated with preoperative CRT prior to surgical resection. METHODS: Five hundred ninety-three pts from 1985 to 2003 with esophageal cancer who underwent surgery with (n = 239) or without CRT (n = 354) were reviewed. Resected esophageal tumors were assessed for pathologic response by determining extent of residual tumor following CRT (P0, 0% residual; P1, 1%-50% residual; P2, >50% residual). RESULTS: After CRT down-staging, pTNM specific survival was similar, irrespective of treatment group (P = 0.98). The pTNM stage distribution was more favorable in the CRT group (P < 0.001) despite a more advanced initial cTNM stage distribution (P < 0.001). Following CRT, the pathologic response (pP) at the primary tumor as defined by extent of residual tumor predicted overall survival (3 years: P0, 0% residual = 74%; P1, 1%-50% residual = 54%; P2, >50% residual = 24%, P < 0.001) and stage specific survival with greater accuracy than pTNM stage alone. CONCLUSIONS: Our analyses demonstrate that following CRT, pTNM continues to predict survival. The extent of pathologic response following CRT is an independent risk factor for survival (pP) and should be incorporated in the pTNM esophageal cancer staging system to better predict patient outcome in esophageal cancer.     

Evolving insights into penile cancer pathology and the eighth edition of the AJCC TNM staging system

The majority of penile malignant tumors are squamous cell carcinomas. They are pathologically defined as epithelial neoplasms originating in the squamous cells of the inner mucosal lining of the glans, coronal sulcus or foreskin. Tumor location and site of origin is preferentially in glans (70%) followed by foreskin (25%) and coronal sulcus (5%). Despite the variable geographic distribution, pathological features of penile carcinomas in areas of high- and low-risk are similar. Penile tumors are morphologically heterogeneous. A major advance, based on biological, etiological and prognostic factors, is the 2016 WHO classification separating epithelial penile neoplasia, precancerous and invasive, in non-HPV and HPV-related.     

Iris metastasis of esophageal cancer

Ocular metastasis in patients with esophageal cancer is quite rare. Several cases have been reported in the literature, but no successful treatments for such metastases have ever been described. We herein report a case of esophageal cancer in which the ocular metastasis was controlled by systemic chemotherapy.     

New techniques for staging esophageal cancer

Correct staging is essential for treatment selection, discussion of prognosis, and scientific communication. The CT scan has long been the essential tool for staging esophageal cancer and still remains valuable for initial screening for distant metastases. The development of endoscopic ultrasonography (EUS), with EUS fine-needle aspiration, positron emission tomography, and minimally invasive surgical staging via thoracoscopy and laparoscopy has resulted in more precise staging. These new tools will allow better definition of patient subsets that may benefit from selected therapies and clinical investigations.     

Accuracy of computed tomography in nodal staging of colon cancer patients

AIM: To predict node-positive disease in colon cancer using computed tomography(CT).METHODS: American Joint Committee on Cancer stage Ⅰ-Ⅲ colon cancer patients who underwent curavtiveintent colectomy between 2007-2010 were identified at a single comprehensive cancer center. All patients had preoperative CT scans with original radiology reports from referring institutions. CT images underwent blinded secondary review by a surgeon and a dedicated abdominal radiologist at our institution to identify pericolonic lymph nodes(LNs). Comparison of outside CT reports to our independent imaging review was performed in order to highlight differences in detection in actual clinical practice. CT reviews were compared with final pathology. Results of the outside radiologist review, secondary radiologist review, and surgeon review were compared with the final pathologic exam to determine sensitivity, specificity, positive and negative predictive values, false positive and negative rates, and accuracy of each review. Exclusion criteria included evidenceof metastatic disease on CT, rectal or appendiceal involvement, or absence of accompanying imaging from referring institutions.RESULTS: From 2007 to 2010, 64 stageⅠ-Ⅲ colon cancer patients met the eligibility criteria of our study. The mean age of the cohort was 68 years, and 26(41%) patients were male and 38(59%) patients were female. On final pathology, 26 of 64(40.6%) patients had nodepositive(LN+) disease and 38 of 64(59.4%) patients had node-negative(LN-) disease. Outside radiologic review demonstrated sensitivity of 54%(14 of 26 patients) and specificity of 66%(25 of 38 patients) in predicting LN+ disease, whereas secondary radiologist review demonstrated 88%(23 of 26) sensitivity and 58%(22 of 38) specificity. On surgeon review, sensitivity was 69%(18 of 26) with 66% specificity(25 of 38). Secondary radiology review demonstrated the highest accuracy(70%) and the lowest false negative rate(12%), compared to the surgeon review at 67% accuracy and 31% false negative rate and the outside radiology review at 61% accuracy and 46% false negative rate.CONCLUSION: CT LN staging of colon cancer has moderate accuracy, with administration of NCT based on CT potentially resulting in overtreatment. Active search for LN+ may improve sensitivity at the cost of specificity.     

The assessment of 8th edition AJCC prognostic staging system and a simplified staging system for breast cancer: The analytic results from the SEER database

The prognostic value of the prognostic staging system that incorporated estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor‐2 (Her‐2), and histological grade has been validated in breast cancer (BC) patients, but the staging system seems to be somewhat complex. Recently, an updated bioscore system based on these tumor biological factors was proposed. The purpose of this study was to compare the prognostic stratification between prognostic staging system of American Joint Commission on Cancer (AJCC) and a simplified staging system based on the bioscore system and anatomic TNM staging for BC patients. A total of 44 593 patients with invasive ductal carcinoma who underwent radical resection between 2010 and 2011 were reviewed using the SEER database. The patients were reclassified into different groups according to the anatomic staging system, prognostic staging system, risk bioscore system, and simplified staging system, respectively. The prognostic differences between different groups were compared and clinicopathologic features were analyzed. The anatomic TNM staging failed to clearly distinguish the prognostic difference between stage IIIB and stage IIIC. Therefore, we proposed an adjusted anatomic staging, in which T1N3 and T2N3 were downstaged from stage IIIC to stage IIIB, and T4N2 was upstaged from stage IIIB to stage IIIC. Histological grade III, ER(?), PR(?), and Her‐2(?) were identified as independent prognostic factors in the multivariate analysis, and these factors were separately marked as 1 point. There were significant survival differences among different risk points except for the comparison between 0 and 1 point. The higher the risk points, the poorer the prognosis of BC patients. In addition, the curve distance between stage IIA and stage IIB was not significantly broaden according to the prognostic staging system. However, the prognostic stratification for BC patients could be significantly improved by the simplified staging system incorporated the bioscore system and adjusted anatomic staging. Several drawbacks may still exist in the prognostic staging system of AJCC. A simplified staging system that incorporated risk score system and the anatomic staging could provide more accurate prognostic information for BC patients.     

Molecular staging of lung and esophageal cancer

In both esophageal and NSCLC, the TNM stage at diagnosis remains the most important determinant of survival. Significant research to investigate the biology of NSCLC and esophageal carcinoma is ongoing, and the roles of proto-oncogenes, tumor suppressor genes, angiogenic factors, extracellular matrix proteases, and adhesion molecules are being elucidated. While evidence is accumulating that various markers are involved in NSCLC and esophageal tumor virulence, the current studies are compromised by small sample sizes, heterogeneous populations, and variations in techniques. Large prospective studies with homogenous groups designed to evaluate the role of these various markers should clarify their potential involvement in NSCLC and esophageal cancer. Identification of occult micrometastases in lymph nodes and bone marrow using immunohistochemical techniques and rt-PCR is intriguing. These techniques are promising as a method to more accurately stage patients, and therefore to predict outcomes and to determine therapies. Perhaps the most promising area of research is the development of novel drugs whose mechanism of action targets the pathways of various molecular markers. Molecular biologic substaging offers an opportunity to individualize a chemotherapeutic regimen based on the molecular profile of the tumor, thus providing the potential for improved outcomes with less morbidity in patients with both NSCLC and esophageal cancer.