Abstract
Background: An overview of promising prognostic variables and predictive subgroups concerning the curative treatment of esophageal and gastric cancer from randomized controlled trials (RCTs) is lacking. Therefore, we conducted a systematic review and meta-analysis. Methods: PubMed, EMBASE, CENTRAL, and ASCO/ESMO conferences were searched up to March 2019 for RCTs on the curative treatment of esophageal or gastric cancer with data on prognostic and/or predictive factors for overall survival. Prognostic factors were deemed potentially clinically relevant according to the following criteria; (1) statistically significant (p < 0.05) in a multivariate analysis, (2) reported in at least 250 patients, and (3) p < 0.05, in ≥33% of the total number of patients in RCTs reporting this factor. Predictive factors were potentially clinically-relevant if (1) the p-value for interaction between subgroups was <0.20 and (2) the hazard ratio in one of the subgroups was significant (p < 0.05). Results: For gastric cancer, 39 RCTs were identified (n = 13,530 patients) and, for esophageal cancer, 33 RCTs were identified (n = 8618 patients). In total, we identified 23 potentially clinically relevant prognostic factors for gastric cancer and 16 for esophageal cancer. There were 15 potentially clinically relevant predictive factors for gastric cancer and 10 for esophageal cancer. Conclusion: The identified prognostic and predictive factors can be included and analyzed in future RCTs and be of guidance for nomograms. Further validation should be performed in large patient cohorts.
Highlights
Gastric and esophageal cancer treated with curative intent both have a poor prognosis with five-year survival rate varying between 30% and 40% [1]
This could be related to the total number of patients in which each factor was investigated, as a systematic review with over 60,000 patients found that diffuse type tumors had a worse survival compared to intestinal subtype tumors [116]
We found in one randomized controlled trials (RCTs) (CROSS trial) that squamous cell cancer (SCC) patients experience more survival benefit from neoadjuvant chemoradiotherapy than adenocarcinoma (AC) patients (p interaction: 0.11) [8]
Summary
Gastric and esophageal cancer treated with curative intent both have a poor prognosis with five-year survival rate varying between 30% and 40% [1]. For the curative treatment of esophageal cancer neoadjuvant chemoradiotherapy, i.e., the European CROSS regimen (carboplatin or paclitaxel with radiotherapy) or the American CALGB 9781 regimen (5-fluorouracil or cisplatin with radiotherapy), [8,9] or neoadjuvant chemotherapy (5-fluorouracil with cisplatin) [10,11] are commonly used strategies. Methods: PubMed, EMBASE, CENTRAL, and ASCO/ESMO conferences were searched up to March 2019 for RCTs on the curative treatment of esophageal or gastric cancer with data on prognostic and/or predictive factors for overall survival. Prognostic factors were deemed potentially clinically relevant according to the following criteria; (1) statistically significant (p < 0.05) in a multivariate analysis, (2) reported in at least 250 patients, and (3) p < 0.05, in ≥33% of the total number of patients in RCTs reporting this factor. Predictive factors were potentially clinically-relevant if (1) the p-value for interaction between subgroups was
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