For people with stomach or esophageal cancer, a major goal of treatment before surgery is to shrink or even eliminate the tumor—what doctors call a 'pathologic complete response' or pCR. It's a hopeful sign, and for years, clinical trials have used it as a shortcut to predict whether a new treatment will help patients live longer. But a new, large review of 26 randomized trials involving over 7,400 patients suggests we should be very careful with that hope. The analysis found that, overall, whether a patient achieved a pCR had almost no meaningful connection to how long they ultimately lived. At the trial level, when a treatment improved pCR rates, that improvement explained very little about whether it also improved overall survival. The story gets more complicated when you look at specific cancers. For cancers starting in the esophagus, a complete response was a very strong predictor of longer life. For stomach cancers, the link was moderate. But for cancers at the junction of the stomach and esophagus, there was no link at all. The type of treatment also mattered: trials that included radiation showed a strong link, while chemotherapy-only trials did not. The bottom line: a tumor disappearing before surgery is a positive event, but it's not a reliable guarantee of survival for most patients with these cancers, and doctors need to interpret trial results with caution.
When a cancer disappears before surgery, does it mean patients live longer? Not always, a major review finds.
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What this means for you:
A tumor disappearing before surgery is a hopeful sign, but it's not a reliable guarantee of longer life for most stomach and esophageal cancers. What this means for you:
A tumor disappearing before surgery is a hopeful sign, but it's not a reliable guarantee of longer life for most stomach and esophageal cancers. View Original Abstract ↓
BACKGROUND: Pathologic complete response (pCR) is frequently used as a surrogate endpoint in neoadjuvant gastroesophageal adenocarcinoma (GEA) trials, yet its validity in predicting overall survival (OS) remains uncertain.
METHODS: This systematic review and meta-analysis, follows PRISMA and ReSEEM guidelines, and evaluates pCR as a surrogate for OS in randomized controlled trials (RCTs) of neoadjuvant therapy for GEA. Randomized trials enrolling patients with resectable distal esophageal, gastroesophageal junction (GEJ), or gastric adenocarcinoma were included if both pCR and OS were reported. Individual-level surrogacy was assessed by correlating pCR rates with median OS across trial arms; trial-level surrogacy was evaluated by correlating treatment effects on pCR (odds ratios) with treatment effects on OS (hazard ratios) using weighted linear regression and calculating the coefficient of determination (R²).
RESULTS: Twenty-six RCTs including 7452 patients were analyzed. Overall, pCR showed no meaningful correlation with OS at the individual-level (R² = 0.006; p = 0.210), and treatment effects on pCR explained little of the variability in OS effects at the trial level (R² = 0.060; p = 0.206). Most trials evaluated cytotoxic chemotherapy or chemoradiotherapy. Surrogacy varied by subgroup, being strong for esophageal adenocarcinoma (R² = 0.886; p < 0.001), moderate for gastric cancer (R² = 0.386; p = 0.041), and absent for GEJ trials. Trials incorporating radiotherapy demonstrated strong surrogacy, whereas chemotherapy-only trials did not.
CONCLUSIONS: The interpretation of pCR results in gastroesophageal adenocarcinoma trials requires caution. Surrogacy might need to be reassessed in the upcoming immunotherapy trials.