Purpose To identify baseline prognostic factors and assess whether pretreatment quality of life (QoL) predicts survival in patients with locally advanced or metastatic esophago-gastric cancer. Patients and Methods Between 1992 and 2001, 1,080 patients were enrolled into three randomized, controlled trials assessing fluorouracil-based combination chemotherapy. All patients were required to complete the European Organization for Research and Treatment of Cancer core QoL questionnaire before random assignment. Results Of the 1,080 patients randomly assigned, 979 (91%) died. Four independent poor prognostic factors were identified by multivariate analysis: performance status ≥ 2 (hazard ratio [HR], 1.58; 99% CI, 1.25 to 1.98), liver metastases (HR, 1.41; 99%CI, 1.14 to 1.74), peritoneal metastases (HR, 1.33; 99%CI, 1.01 to 1.74) and alkaline phosphatase ≥ 100 U/L (HR, 1.41; 99% CI, 1.14 to 1.76). A prognostic index was constructed dividing patients into good (no risk factor), moderate (one or two risk factors...

Multivariate Prognostic Factor Analysis in Locally Advanced and Metastatic Esophago-Gastric Cancer—Pooled Analysis From Three Multicenter, Randomized, Controlled Trials Using Individual Patient Data

Objective:To investigate whether the number of lymph nodes metastasis (LNMs) and the ratio between metastatic and examined lymph nodes (LNs) are better prognostic factors when compared with traditional staging systems in patients with esophageal carcinoma.Summary Background Data:The accuracy of the

The number of metastatic lymph nodes and the ratio between metastatic and examined lymph nodes are independent prognostic factors in esophageal cancer regardless of neoadjuvant chemoradiation or lymphadenectomy extent.

The aim of this study was to evaluate the prognostic value of metabolic tumor volume (MTV) measured by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in patients with esophageal carcinoma. We retrospectively reviewed 151 patients with pathologically proven esophageal carcinoma (146 squamous cell carcinomas and 5 adenocarcinomas) who underwent pretreatment 18F-FDG PET. MTV and maximum standardized uptake value (SUVmax) for the primary tumors were measured by 18F-FDG PET. The prognostic significance of MTV, SUVmax, and other clinicopathological variables was assessed by Cox proportional hazards regression analysis. To further evaluate and compare the predictive performance of PET parameters, MTV and SUVmax, time-dependent receiver operating characteristic curve (ROC) analysis was used. In the univariate analysis, age, American Joint Committee on Cancer (AJCC) stage, tumor–node–metastasis (TNM) factors, MTV, and SUVmax of primary tumor were significant predictors of survival. On multivariate analysis adjusted for age, sex, and treatment modality, independent predictive factors associated with decreased overall survival were T stage [hazard ratio (HR) 4.325, P = 0.006], M stage (HR 2.009, P = 0.007), and MTV (HR 1.013, P = 0.021). SUVmax was not a significant factor (HR 0.97, P = 0.061). On time-dependent ROC analysis, MTV showed good predictive performance for overall survival consistently better than SUVmax. MTV, a volumetric parameter of 18F-FDG PET, is an important independent prognostic factor for survival and a better predictor of survival than SUVmax for the primary tumor in patients with esophageal carcinoma.

Prognostic Value of Metabolic Tumor Volume Measured by 18F-Fluorodeoxyglucose Positron Emission Tomography in Patients with Esophageal Carcinoma

Superficially invasive esophageal adenocarcinomas are a heterogeneous group of tumors, including tumors invading into mucosa and submucosa. The prognostic significance of the depth of tumor invasion and lymph node status in this group of patients remain unclear. We evaluated 90 consecutive patients with resected T1 adenocarcinoma of esophagus or esophagogastric junction. The T1 tumors were classified into four groups based on the depth of invasion: T1a, invading into lamina propria; T1b, into muscularis mucosae; T1c, into superficial submucosa; and T1d, into deep submucosa. The depth of tumor invasion was compared with clinicopathologic features. The depth of tumor invasion was significantly associated with the presence of lymph node metastasis (36% in T1d, 8% in T1c, 12% in T1b, and 0% in T1a; P 1.2 cm in T1d, 75% in T1c, 35% in T1b, and 25% in T1a; P < 0.001). The 5-year recurrence-free and overall survivals were significantly better in patients with tumors confined to mucosa (100% and 91%, respectively) than invasive into submucosa (60% and 58%; P = 0.0005 and P = 0.02, respectively). Lymph node metastasis was associated with tumor recurrence (P = 0.01) but not overall survival. Lymphovascular invasion was associated with both tumor recurrence (P = 0.001) and overall survival (P < 0.001) and was an independent prognostic factor in multivariate analysis (P = 0.04). Our study indicated evaluation of depth of tumor invasion, status of lymph nodes, and lymphovascular invasion is important in resected superficially invasive esophageal adenocarcinoma and may provide supportive information for the decision about postoperative adjuvant therapy.

Significance of the depth of tumor invasion and lymph node metastasis in superficially invasive (T1) esophageal adenocarcinoma.

Between 1943 and 1952, the Frenchman Pierre Denoix developed the TNM system for the classification of malignant tumors.1 Soon thereafter, in 1958, the first recommendations for the clinical stage classification of cancers were published by the UICC committee on Clinical Stage Classification and Applied Statistics.2 In the year 2002, the 6th edition with the latest recommendations for classification of cancers was released by the International Union Against Cancer (UICC). This included the staging classification for esophageal cancer.3

One important objective of TNM staging is to give an as accurate possible indication of prognosis.4 For the classification of esophageal cancer, however, there is an ongoing debate about revision of the current guidelines, driven by surgeons who think that it does not stratify patients appropriately for prognosis.5–8 For example, a strong plea has been made to redefine the T1 stage into pT1a (intramucosal) and pT1b (submucosal) tumors and to use the number of tumor-positive nodes for staging, since both indicators have been shown to refine the TNM staging system.6,9–11 Furthermore, the subdivision of distant metastatic disease into nonregional lymph node metastases (M1b) and other metastases (M1a) seems, at least from a clinical perspective, not appropriate.12 Also, several pathologic characteristics of the primary tumor, including tumor length, perineural invasion, and vaso-invasive growth, have been shown to correlate with outcome after treatment of esophageal cancer13–15 In this study, we tried to address these issues by evaluating outcome in relation to several prognostic factors and different staging classifications in a well-defined homogeneous cohort of patients who underwent esophagectomy for cancer.

An evaluation of prognostic factors and tumor staging of resected carcinoma of the esophagus

BACKGROUND

The current TNM classification system does not consider tumor length or the number of lymph nodes in the staging and classification scheme for patients with esophageal carcinoma. Using data from the National Cancer Institute SEER Program, the authors explored the effect of tumor length and number of positive lymph nodes on survival in patients with esophageal carcinoma.



METHODS

Patients with esophageal adenocarcinoma or squamous cell carcinoma were subgrouped according to historic stage with localized, regional, or distant disease. Demographic factors (age at diagnosis, race, and gender) and tumor characteristics (morphology, histologic grade, tumor length, primary site, depth of invasion, number of positive lymph nodes, proportion of positive lymph nodes dissected, and distant metastatic sites) were examined.



RESULTS

Overall factors that were associated with an increased mortality risk included increasing age at diagnosis, black race versus white race, histologic grade, primary tumor site in the lower esophagus and abdomen versus upper regions, and increasing depth of invasion. Among patients with regional disease, the number of positive lymph nodes (≥ 5 vs. < 5) was related to an increasing risk (hazard ratio [HR], 1.29; 95% confidence interval [95%CI], 1.06–1.56). The proportion of positive lymph nodes compared with the number of lymph nodes dissected conferred an increased risk (HR, 1.63; 95%CI, 1.26–2.11). Among patients with distant disease, sites other than distant lymph nodes implied an increased mortality risk (HR, 1.37; 95%CI, 1.37–1.65). Tumor length was an independent predictor of mortality when controlling for depth of invasion in patients with localized disease (HR, 1.15; 95%CI, 1.08–1.21).



CONCLUSIONS

Tumor length, the number of involved lymph nodes, and the ratio of positive lymph nodes are important prognostic factors for survival in patients with esophageal carcinoma. A revised TNM classification system for patients with esophageal carcinoma might consider adding tumor length and number of positive lymph nodes as two important prognostic factors. Cancer 2002;95:1434–43. © 2002 American Cancer Society.



DOI 10.1002/cncr.10868

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.10868

Carolyn E. Reed

Papers

Prognostic factors for the survival of patients with esophageal carcinoma in the U.S.: the importance of tumor length and lymph node status.