In patients with esophageal cancer, hybrid minimally invasive esophagectomy (HMIE) in patients with esophageal cancer is associated with improved long-term oncological results — but not improved overall survival (OS) — compared with open esophagectomy due to the decreased incidence of postoperative complications, according to a recent analysis published in JAMA Surgery.
And, according to researchers Frederiek Nuytens, MD, of the Centre Hospitalier Universitaire (CHU) de Lille, Lille, France, and colleagues, major postoperative and pulmonary complications in patients undergoing HMIE were independently associated with impaired OS and disease-free survival (DFS).
In an accompanying editorial, however, Katherine D. Gray, MD, and Daniela Molena, MD, both of Memorial Sloan Kettering Cancer Center, New York City, took issue with these conclusions and stressed that while this analysis was sufficiently designed to assess perioperative morbidity and establish the efficacy of HMIE as a viable surgical option in patients with esophageal cancer, results for the survival analyses were not.
“We commend the authors on a prospective randomized trial that was well designed to capture perioperative morbidity and establish HMIE as an acceptable surgical approach for esophageal cancer. However, the survival analysis presented is confounded and underpowered, and while it is true that perioperative morbidity may affect long-term outcomes of esophagectomy, the results of this trial do not show a relationship between lower complication rates and survival benefit in the HMIE group,” they wrote.
The increasing incidence of esophageal cancer worldwide is worrisome, as it carries incredibly high mortality rates, despite therapeutic advances and improvements, the study authors explained.
“Esophageal cancer is an important and increasing global health problem. In 2012, more than 456,000 new cases of esophageal cancer were diagnosed worldwide, and the incidence of this disease, especially esophageal adenocarcinoma, is expected to increase further. Although substantial improvements in multimodal therapy have been achieved, the all-stage mortality rate of esophageal cancer is still among the highest, with a reported five-year survival between 10% and 25%. Radical resection is the mainstay of curative treatment for esophageal cancer but is associated with a high rate of postoperative complications, especially pulmonary,” they wrote.
In this post-hoc study of results from the open-label Multicentre Randomized Controlled Phase Trial (MIRO), Nuytens and colleagues assessed the five-year outcomes of HMIE compared with open esophagectomy in patients with resectable squamous cell carcinoma or adenocarcinoma of the middle or lower third of the esophagus or a junctional tumor.
For the open-label, phase III, prospective, randomized MIRO study, 207 patients (mean age: 61 years; 85% male) were randomized to either HMIE or open esophagectomy. The primary end point of the study was the rate of major intraoperative or postoperative complications within 30 days of surgery. In contrast, the primary endpoints of the post-hoc analysis of the study conducted by Nuytens and colleagues were OS and disease-free survival (DFS).
Five-year OS in the HMIE group was 59% (95% CI 48%-68%), compared with 47% (95% CI 37%-57%) in the open esophagectomy group (HR: 0.71; 95% CI 0.48-1.06). Upon multivariate analysis, the following risk factors were associated with decreased OS: major intraoperative and postoperative complications (HR: 2.21; 95% CI 1.41-3.45; P ˂ 0.001) and major pulmonary complications (HR: 1.94; 95% CI 1.21-3.10; P=0.005).
In the HMIE group, five-year DFS was 52% (95% CI 42%-61%) versus 44% (95% CI 34%-53%) in the open esophagectomy group (HR: 0.81; 95% CI 0.55-1.17). Multivariate analysis of DFS revealed that risk factors included major intraoperative and postoperative complications (HR: 1.93; 95% CI 1.28-2.90; P=0.002) and major pulmonary complications (HR: 1.85; 95% CI 1.19-2.86; P=0.006).
In all, 42% of patients had disease recurrence, and there were no significant between-group differences in recurrence rate or location. In the HMIE group, 40% of patients had recurrent disease (12 locoregional, 23 distant metastases, 6 mixed), compared with 44% in the open esophagectomy group (12 locoregional, 24 distant metastases, 10 mixed).
Data from 205 patients were evaluable for complications. Among the 50% who experienced a major complication, 58% died during follow-up. In addition, 24% of patients had pulmonary complications, of whom 59% died during follow-up.
In DFS comparisons in patients with and without major complications, 58% of patients with major complications also experienced recurrent disease or died, compared with 40% of those without major complications (χ2P=0.006).
In patients with major complications, five-year DFS was 39% (95% CI 29%-48%) compared with 58% (95% CI 47%-67%) in those without. The hazard ratio for recurrent disease or death was 1.88 (95% CI 1.28-2.74; log-rank P=0.001).
In the 111 patients experiencing recurrent disease or death, 29% experienced major postoperative pulmonary complications. Forty-nine patients had major postoperative pulmonary complications, of whom 65% had recurrent disease or death, compared with 18% who were disease free (χ2P=0.05). Twenty-eight percent of patients with major pulmonary complications had recurrent disease, while 72% of those with recurrent disease had no major pulmonary complications.
In patients with major pulmonary complications, the 5-year DFS was 36% (95% CI 23%-50%) compared with 52% (95% CI 44%-60%) in those without. In these patients, the HR for recurrent disease or death was 1.73 (95% CI 1.15-2.62; log-rank P=0.008).
Editorialists Gray and Molena took particular issue with the associations between survival and complications.
“This study’s misstep comes with the assertion that HMIE itself is associated with improved survival because of decreased complications, despite its own multivariable analysis showing that surgical approach was not an independent risk factor for overall or disease-free survival. Although the authors do report an improvement in median overall and disease-free survival between HMIE and open esophagectomy, these differences do not reach statistical significance. The study was not powered to detect differences in survival, and competing risks analysis for recurrence were not used,” they concluded.
The limitation of this analysis is that the original MIRO study protocol was not designed for the analysis of long-term results or the factors associated with OS and DFS.
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Hybrid minimally invasive esophagectomy (HMIE) was associated with improved long-term oncological results compared with open esophagectomy, primarily due to decreased postoperative complications.
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In an accompanying editorial, authors took issue with the study’s methodology, refuting the conclusion that HMIE is associated with improved survival due to decreased complications.
Liz Meszaros, Contributing Writer, BreakingMED™
This study was funded by the French clinical research projects funding program (PHRC) from the French National Cancer Institute.
Nuytens reported no disclosures.
Molena reported consulting fees from Intuitive, Urogen, Johnson & Johnson, and Boston Scientific as well as being a member of the steering committee for AstraZeneca.
Cat ID: 935
Topic ID: 78,935,730,935,192,925,159,256
