Lymph node metastases predict survival after esophagogastric cancer treatment
Lymph node status served as the only independent OS predictor after surgery and chemotherapy for patients with esophagogastric cancer, according to a secondary analysis of a phase 3 trial.
Pathologic response did not independently predict survival outcomes in this patient population, results showed.
The multicenter Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial established perioperative epirubicin, cisplatin and fluorouracil chemotherapy as a standard of care for surgery-eligible patients with esophagogastric cancer.
“Despite multimodal treatment, up to half of the patients who undergo surgery will subsequently relapse and die of their cancer,” Nicola Valeri, MD, PhD, team leader of gastrointestinal cancer biology and genomics at the Centre for Molecular Pathology at The Institute of Cancer Research, London, and colleagues wrote. “Identification of patients requiring additional therapy to prevent relapse remains challenging.”
Valeri and colleagues analyzed resection samples from patients enrolled in the MAGIC trial to determine whether pathologic response and lymph node metastases after neoadjuvant chemotherapy could serve as prognostic markers for survival and need for additional treatment.
The MAGIC trial included 503 patients, 94% (n = 473) of whom underwent surgery. Valenti and colleagues had access to 330 resection samples from surgically treated patients (surgery only, n = 171; chemotherapy plus surgery, n = 159).
Two independent pathologists reviewed the available samples and graded them based on the Mandard tumor regression grading (TRG) system, which includes:
- TRG 1, complete regression or fibrosis with no evidence of tumor cells (surgery alone, 0%; chemotherapy plus surgery, 5%);
- TRG 2, fibrosis with scattered tumor cells (surgery alone, 2%; chemotherapy plus surgery, 18%);
- TRG 3, fibrosis and tumor cells with a dominance of fibrosis (surgery alone, 8%; chemotherapy plus surgery, 34%);
- TRG 4, fibrosis and tumor cells with a dominance of tumor cells (surgery alone, 24%; chemotherapy plus surgery, 29%); and
- TRG 5, tumor without evidence of regression (surgery alone, 66%; chemotherapy plus surgery, 14%).
Median OS for patients treated with chemotherapy did not significantly differ between patients with or without available tissue (23.1 months vs. 21.6 months). However, patients treated with neoadjuvant chemotherapy were significantly more likely to experience tumor regression (P < .001).
Median OS for chemotherapy-treated patients with TRG 1-2 had not been reached, whereas median OS for patients with TRG 3-5 was 20.47 months (HR = 1.94; 95% CI, 1.11-3.39; 5-year OS. Five-year OS was 58.8% (95% CI, 40.3-73.3) for patients with TRG 1-2 and 28.9% for patients with TRG 3-5 (95% CI, 19.5-38.9).
The researchers had access to lymph node dissection data from 272 patients. Patients had fewer than 15 lymph nodes dissected (51%, n = 138), 15 to 20 lymph nodes dissected (22%; n = 60), 21 to 25 lymph nodes dissected (10%; n = 28) or more than 25 lymph nodes dissected (17%; n = 46).
The number of lymph nodes dissected was similar in the chemotherapy-plus-surgery arm and the surgery-alone arm (median, 13 vs. 16).
Univariate analyses showed a negative relation between OS and high TRG (score 3-5; P = .0209) and lymph node metastases (HR = 3.63; 95% CI, 1.88-7).
However, a multivariate analysis found that only lymph node status independently predicted OS (HR = 3.36; 95% CI, 1.7-6.63).
The researchers analyzed several biomarkers — including KRAS, BRAF, PIK3CA, TP53, PTEN and HER-2 — and found no statistically significant associations between mutation status and lymph node involvement.
Study limitations included the researchers’ inability to include all patients from the MAGIC trial, as well as that fewer than half of the patients from MAGIC completed all protocol chemotherapy treatments.
“Because the median survival for patients with resectable Western gastroesophageal cancer undergoing potentially curative surgery is fewer than 3 years, further work is required to identify more effective therapies and improve outcomes,” Valeri and colleagues wrote. – by Cameron Kelsall
Disclosure: Valeri reports holding patents and pending patent applications for intellectual property related to microRNA technology. Please see the full study for a list of the other researchers’ relevant financial disclosures.