American Joint Committee On Cancer/International Union Against Cancer Research Articles

A novel staging system for adrenocortical carcinoma better predicts survival in patients with stage I/II disease

Current American Joint Committee on Cancer/International Union against Cancer (AJCC/UICC) and European Network for the Study of Adrenal Tumors staging for adrenocortical carcinoma (ACC) have not shown a survival difference between patients with stage I/II disease. This study evaluates current staging systems for survival prediction using a larger cohort and assesses whether incorporating age into ACC staging improves survival predictions. Patients in the National Cancer Data Base (1985-2006) with a diagnosis of ACC were identified and staged using a novel TNM-A staging system: Stage I (T1/T2N0M0, age ≤ 55), stage II (T1/T2N0M0, age >55), stage III (T1/T2N1M0 or T3/T4N0-N1M0, any age), or stage IV (any T any NM1, any age). Differences in overall survival (OS) by stage were compared using a Cox proportional hazards model. Staging was derived for 1,579 of 3,262 patients. Median age was 54 years; mean tumor size was 11.6 cm. Using current staging, differences in 5-year OS was observed only between patients with stages II/III and III/IV ACC. With TNM-A staging, differences in 5-year OS between all stages was significant (I/II [P < .003], II/III [P < .0001], III/IV [P < .0001]). A staging system that incorporates patient age better predicts 5-year OS among patients with stages I/II ACC. Consideration should be given to including age in staging for ACC, because it may better inform providers about treatment and prognosis.

Hormone profiling, WHO 2010 grading, and AJCC/UICC staging in pancreatic neuroendocrine tumor behavior

Pancreatic neuroendocrine tumors (pNETs) are the second most common pancreatic neoplasms, exhibiting a complex spectrum of clinical behaviors. To examine the clinico-pathological characteristics associated with long-term prognosis we reviewed 119 patients with pNETs treated in a tertiary referral center using the WHO 2010 grading and the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging systems, with a median follow-up of 38 months. Tumor size, immunohistochemistry (IHC) profiling and patient characteristics-determining stage were analyzed. Primary clinical outcomes were disease progression or death. The mean age at presentation was 52 years; 55% were female patients, 11% were associated with MEN1 (multiple endocrine neoplasia 1) or VHL (Von Hippel–Lindau); mean tumor diameter was 3.3 cm (standard deviation, SD) (2.92). The clinical presentation was incidental in 39% with endocrine hypersecretion syndromes in only 24% of cases. Nevertheless, endocrine hormone tissue immunoreactivity was identified in 67 (56.3%) cases. According to WHO 2010 grading, 50 (42%), 38 (31.9%), and 3 (2.5%) of tumors were low grade (G1), intermediate grade (G2), and high grade (G3), respectively. Disease progression occurred more frequently in higher WHO grades (G1: 6%, G2: 10.5%, G3: 67%, P = 0.026) and in more advanced AJCC stages (I: 2%, IV: 63%, P = 0.033). Shorter progression free survival (PFS) was noted in higher grades (G3 vs. G2; 21 vs. 144 months; P = 0.015) and in more advanced AJCC stages (stage I: 218 months, IV: 24 months, P < 0.001). Liver involvement (20 vs. 173 months, P < 0.001) or histologically positive lymph nodes (33 vs. 208 months, P < 0.001) were independently associated with shorter PFS. Conversely, tissue endocrine hormone immunoreactivity, independent of circulating levels was significantly associated with less aggressive disease. Age, gender, number of primary tumors, and heredity were not significantly associated with prognosis. Although the AJCC staging and WHO 2010 grading systems are useful in predicting disease progression, tissue endocrine hormone profiling provides additional information of potentially important prognostic value.Although the AJCC staging and WHO 2010 grading systems are useful in predicting disease progression, tissue endocrine hormone profiling provides additional information of potentially important prognostic value.

Prognostic Implications of the Seventh Edition of the International Union Against Cancer Classification for Patients With Gastric Cancer: The Western Experience of Patients Treated in a Single-Center European Institution

Validity of the seventh edition of the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging systems for gastric cancer has been evaluated in several studies, mostly in Asian patient populations. Only few data are available on the prognostic implications of the new classification system on a Western population. Therefore, we investigated its prognostic ability based on a German patient cohort. Data from a single-center cohort of 1,767 consecutive patients surgically treated for gastric cancer were classified according to the seventh edition and were compared using the previous TNM/UICC classification. Kaplan-Meier analyses were performed for all TNM stages and UICC stages in a comparative manner. Additional survival receiver operating characteristic analyses and bootstrap-based goodness-of-fit comparisons via Bayesian information criterion (BIC) were performed to assess and compare prognostic performance of the competing classification systems. We identified the UICC pT/pN stages according to the seventh edition of the AJCC/UICC guidelines as well as resection status, age, Lauren histotype, lymph-node ratio, and tumor grade as independent prognostic factors in gastric cancer, which is consistent with data from previous Asian studies. Overall survival rates according to the new edition were significantly different for each individual's pT, pN, and UICC stage. However, BIC analysis revealed that, owing to higher complexity, the new staging system might not significantly alter predictability for overall survival compared with the old system within the analyzed cohort from a statistical point of view. The seventh edition of the AJCC/UICC classification was found to be valid with distinctive prognosis for each stage. However, the AJCC/UICC classification has become more complex without improving predictability for overall survival in a Western population. Therefore, simplification with better predictability of overall survival of patients with gastric cancer should be considered when revising the seventh edition.

Intramural and extramural vascular invasion in colorectal cancer

Blood vessel invasion has been associated with poor outcome in colorectal cancer (CRC), whereas the prognostic impact of lymphatic invasion is less clear. The authors of this report evaluated venous and lymphatic invasion as potential prognostic indicators in patients with CRC focusing on lymph node-negative patients and compared routine and review pathology diagnoses. In total, 381 tumors from randomly selected patients were retrospectively reviewed. The presence of vascular invasion was related to disease-free and cancer-specific survival using the Kaplan-Meier method. For multivariable analysis, Cox proportional hazards regression models were performed. Lymphatic invasion and venous invasion were observed in 126 patients (33%) and 87 patients (23%), respectively, and were associated significantly with tumor classification, lymph node status, American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) disease stage, tumor differentiation, pattern of invasion, and extent of tumor budding. The detection of vascular invasion was related to the number of examined tissue blocks. Venous and lymphatic invasion proved to be significant prognostic variables in univariable and multivariable analyses. Extramural vascular involvement was of particular significance. When the analysis was restricted to patients with (AJCC/UICC) stage II disease, venous invasion, but not lymphatic invasion, was identified as an independent prognostic variable. Review pathology diagnoses differed significantly from routine diagnoses with respect to prognostic impact. Venous and lymphatic invasion proved to be significant prognostic variables in patients with CRC. The detection of vascular invasion and, consequently, risk stratification of affected patients were related to the quality of pathology workup, ie, the number of examined tissue blocks. Observed differences between review and routine pathology diagnoses illustrated the need for high-quality pathology reporting and also for standardized quality control.

Prognosis of 980 patients with gastric cancer after surgical resection

Although surgery is the only possible means to cure gastric cancer, the prognosis is often discrepant. The American Joint Committee on Cancer / International Union against Cancer (AJCC/UICC) published the TNM classification of Malignant Tumors (seventh edition) for gastric cancer recently. This study aimed to use this new edition staging system to investigate the prognostic factors for gastric cancer. The clinicopathologic data of 980 patients with gastric cancer treated by surgical resection in our hospital between January 2000 and December 2006 were analyzed retrospectively. The overall survival rate was determined by using Kaplan-Meier method and log-rank test was used to determine significance. The prognosis was analyzed using univariate analysis and multivariate analysis with the Cox proportional hazards model. The 6th and 7th edition AJCC/UICC TNM staging systems were used to compare the survival outcomes for the cohort of patients. The overall 1-, 3-, 5-year survival rates for the whole group were 82.5%, 58.7%, and 52.6%. The 5-year survival rates for patients with pTNM stage I, II, III, and IV disease classified by the 7th edition staging system were 93.2%, 72.4%, 39.1%, and 5.2%, respectively. In both univariate analysis and Cox multivariate analysis, age, tumor site, tumor size, histological type, resection type, radical resection, lymphatic/venous invasion, depth of invasion, nodal status, metastasis, retrieved lymph nodes, metastatic lymph node ratio, and adjuvant chemotherapy were prognostic factors with these patients. Compared with the 6th edition system, the new edition of TNM staging system for gastric cancer can accurately predict the survival after operation.

Evaluation of the Seventh American Joint Committee on Cancer/International Union Against Cancer Classification of gastric adenocarcinoma in comparison with the sixth classification

The seventh TNM staging system for gastric cancer of the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) had a more detailed classification than the sixth TNM staging system for both the tumor (T) and lymph nodes (N). The authors compared survival rates assessed by the seventh staging system with those by the sixth system. The authors analyzed the prospectively collected database on patients with gastric cancer who underwent surgery at Seoul National University Hospital between 1986 and 2006, and calculated the survival rates of 9998 cases with primary cancer, R0 resection, and >14 retrieved lymph nodes. The 5-year cumulative survival rates (5YSR) according to the seventh edition T or N classifications were significantly different. The 5YSR according to seventh edition of the TNM staging system were 95.1% (stage IA), 88.4% (stage IB), 84.0% (stage IIA), 71.7% (stage IIB), 58.4% (stage IIIA), 41.3% (stage IIIB), and 26.1% (stage IIIC), which were significantly different from each other. The 5YSR of the seventh edition T2 and T3 classifications had significant differences in patients with every N classification, and the 5YSR of seventh edition N1 and N2 classifications had significant differences in T2 patients, T3 patients, and T4 patients. Each stage in the sixth edition was divided into the seventh edition stage with different survival rates. In addition, the number of homogenous groupings in seventh edition TNM stages was increased from 1 to 2. The seventh system provided a more detailed classification of prognosis than the sixth system, especially between T2 and T3 tumors and N1 and N2 tumors, although further studies were found to be needed for the N3a and N3b classification.

Cancer of the esophagus and esophagogastric junction

Previous American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) stage groupings for esophageal cancer have not been data driven or harmonized with stomach cancer. At the request of the AJCC, worldwide data from 3 continents were assembled to develop data-driven, harmonized esophageal staging for the seventh edition of the AJCC/UICC cancer staging manuals. All-cause mortality among 4627 patients with esophageal and esophagogastric junction cancer who underwent surgery alone (no preoperative or postoperative adjuvant therapy) was analyzed by using novel random forest methodology to produce stage groups for which survival was monotonically decreasing, distinctive, and homogeneous. For lymph node-negative pN0M0 cancers, risk-adjusted 5-year survival was dominated by pathologic tumor classification (pT) but was modulated by histopathologic cell type, histologic grade, and location. For lymph node-positive, pN+M0 cancers, the number of cancer-positive lymph nodes (a new pN classification) dominated survival. Resulting stage groupings departed from a simple, logical arrangement of TNM. Stage groupings for stage I and II adenocarcinoma were based on pT, pN, and histologic grade; and groupings for squamous cell carcinoma were based on pT, pN, histologic grade, and location. Stage III was similar for histopathologic cell types and was based only on pT and pN. Stage 0 and stage IV, by definition, were categorized as tumor in situ (Tis) (high-grade dysplasia) and pM1, respectively. The prognosis for patients with esophageal and esophagogastric junction cancer depends on the complex interplay of TNM classifications as well as nonanatomic factors, including histopathologic cell type, histologic grade, and cancer location. These features were incorporated into a data-driven staging of these cancers for the seventh edition of the AJCC/UICC cancer staging manuals.

Comparative performances of staging systems for early hepatocellular carcinoma

BackgroundSeveral staging systems for patients with hepatocellular carcinoma (HCC) have been proposed, but studies of their prognostic accuracy have yielded conflicting conclusions. Stratifying patients with early HCC is of particular interest because these patients may derive the greatest benefit from intervention, yet no studies have evaluated the comparative performances of staging systems in patients with early HCC. MethodsA retrospective cohort study was performed using data on 379 patients who underwent liver resection or liver transplantation for HCC at six major hepatobiliary centres in the USA and Europe. The staging systems evaluated were: the Okuda staging system, the International Hepato-Pancreato-Biliary Association (IHPBA) staging system, the Cancer of the Liver Italian Programme (CLIP) score, the Barcelona Clinic Liver Cancer (BCLC) staging system, the Japanese Integrated Staging (JIS) score and the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging system, 6th edition. A recently proposed early HCC prognostic score was also evaluated. The discriminative abilities of the staging systems were evaluated using Cox proportional hazards models and the bootstrap-corrected concordance index (c). ResultsOverall survival of the cohort was 74% at 3 years and 52% at 5 years, with a median survival of 62 months. Most systems demonstrated poor discriminatory ability (P > 0.05 on Cox proportional hazards analysis, c≈ 0.5). However, the AJCC/UICC system clearly stratified patients (P < 0.001, c= 0.59), albeit only into two groups. The early HCC prognostic score also clearly stratified patients (P < 0.001, c= 0.60) and identified three distinct prognostic groups. DiscussionThe early HCC prognostic score is superior to the AJCC/UICC staging system (6th edition) for predicting the survival of patients with early HCC after liver resection or liver transplantation. Other major HCC staging systems perform poorly in patients with early HCC.

Staging and reporting of urothelial carcinoma of the urinary bladder

Significant progress has been made in the standardization of bladder neoplasm classification and reporting. Accurate staging using the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) TNM system is essential for patient management, and has been reinforced by clinical evidence in recent years. It is now recognized that ‘superficial’ bladder carcinomas are a heterogenous group of tumors with diverse biological and clinical manifestations. The term ‘superficial,‘ therefore, is no longer used for bladder tumor nomenclature. Recognition of diagnostic pitfalls associated with lamina propria invasion is critical for the evaluation of bladder tumor specimens. Neither the 1973 nor the 2004 WHO grading system appears to be useful for predicting the clinical outcome of invasive urothelial carcinoma. This review will discuss recent progress and controversial issues on the staging and substaging of bladder carcinomas. Essential elements for handling and reporting of bladder tumor specimens will also be discussed.

Diode laser microsurgery for treatment of Tis and T1 glottic carcinomas

Purpose The aim of the study was to demonstrate the oncologic safety of diode laser surgery in the treatment of early glottic carcinoma. Materials and methods The study included 45 patients affected by Tis and T1 glottic squamous cell carcinomas and treated endoscopically by diode laser (60 W, 810 nm). The endoscopic resections were graded according to the European Laryngological Society Classification including 5 types of cordectomy. These cases were classified according to the 2002 American Joint Committee on Cancer-International Union Against Cancer (AJCC-UICC) TNM system and included 9 Tis (20%), 31 T1a (68.9%), and 5 T1b (11.1%) glottic carcinomas. The length of follow-up ranged from 24 to 86 months, with an average follow-up period of 36 months. The case study included 39 males (86.7%) and 6 females (13.3%), aged 35 to 81 years, with a mean age of 51 years. Results There were 5 recurrences (11.1%): 4 local (8.9%), in which 3 were salvaged, and 1 (2.2%) regional. Three patients (6.7%) developed second primary cancers on the controlateral cord after a mean of 18 months. All local recurrences occurred in patients with T1b lesions. Forty patients (88.9%) were alive and disease-free at a median follow-up of 36 months. The overall larynx preservation was 97.6%. The actuarial recurrence-free survival analysis by the Kaplan-Meier method showed a survival of 92.3% at 2 years, 89.2 at 5 years, and 85.6 at 7 years. Conclusions Diode laser microsurgery is an oncologically safe, function-preserving modality for the treatment of Tis and T1 glottic carcinomas. This surgical technique provides excellent local control of disease and laryngeal preservation.

Accuracy of nasopharyngeal carcinoma staging by magnetic resonance imaging.

To audit the accuracy of magnetic resonance (MR) staging of nasopharyngeal carcinoma (NPC) in daily reporting, the MR images of 101 adult patients with newly diagnosed NPC reported between December 1996 and February 2002 were reviewed retrospectively. Based on the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) TNM staging criteria (1997), the tumour staging obtained from the MR reports and the MR films was compared by two experienced head and neck radiologists. The number of patients being upstaged, downstaged or unchanged was noted. In all stages, the NPC staging obtained from the MR reports revealed 18 (17.8%) understaged, eight (7.9%) overstaged and 75 (74.2%) the same stage when compared to the staging obtained from the MR films based on the AJCC/UICC criteria. The percentage of patients being understaged or overstaged, in decreasing order of frequency, were stages II, III, IV and I. Magnetic resonance of NPC should be reported by radiologists who are not only familiar with the pathology of this condition and its pattern of spread but who should also base their reports on the AICC/UICC staging criteria. The necessity to improve our MR staging accuracy is largely because it determines the type of therapy to be given and this has to be appropriate and adequate for a successful treatment.

Prognosis of node-positive colon cancer

The most recent American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging system subgroups patients into one to three and four or more positive nodes. However, the Gastrointestinal Study Group and the National Surgical Adjuvant Breast and Bowel Project divides node-positive patients into one to four and five or greater. A Cox multi-variate retrospective analysis was done of the overall survival of node-positive colon cancer patients with the specific objective of determining the most appropriate subcategorization. Data on 306 patients with node-positive colon cancer who underwent potentially curative surgery from 1970 to 1984 were analyzed retrospectively. No patient received adjuvant chemotherapy. Also excluded were patients with synchronous resected metastatic disease or those with rectal primaries. The median follow-up was 6 years, and the median survival for the entire group was 8.6 years. By univariate analysis, the following were significant prognostic features: number of positive nodes (P less than 0.0001), degree of differentiation (P less than 0.0001), colon primary site (P = 0.009), tumor stage (P = 0.001), and tumor size (P less than 0.0001). Lymphatic/blood vessel invasion and a mucinous histology were not significant. By Cox multivariate analysis the number of positive lymph nodes remained the best discriminant of survival (P = 0.0001). The number of positive nodes was related inversely to prognosis with the optimal dichotomization between one to three (66% 5-year survival) and four or greater nodes (37% 5-year survival).