Neoadjuvant chemoradiotherapy improves survival in locally advanced esophageal squamous cell carcinoma

COPENHAGEN, Denmark — The addition of neoadjuvant chemoradiotherapy to surgery extended OS in patients with locally advanced esophageal squamous cell carcinoma, according to phase 3 study results presented at the European Society for Medical Oncology Congress.

Perspective from Florian Lordick, MD, PhD

“Surgery is the main treatment of esophageal squamous cell carcinoma, but the prognosis of patients with locally advanced disease is unsatisfactory,” Hong Yang, MD, associate professor in the department of thoracic surgery at Sun Yet-sen University Cancer Center in Guangzhou, China, said during his presentation. “Based on previous studies, preoperative chemoradiotherapy followed by surgery seems to hopefully improve the survival of these patients. Nevertheless, the results of different studies were inconsistent.”

Yang and colleagues evaluated whether neoadjuvant chemoradiotherapy prolonged OS in 451 patients aged 18 to 70 years with stage IIB to stage III squamous cell carcinoma of the thoracic esophagus from eight cooperative cancer centers.

Two hundred twenty-seven patients underwent surgery alone. The other 224 patients first received two cycles of 25 mg/m² vinorelbine (day 1, 8, 22 and 29) and 75 mg/m² cisplatin (day 1 and 22) concurrently with 40 Gy radiotherapy delivered in 20 daily fractions of 2 Gy each for 4 weeks.

Three- and 5-year OS served as the study’s primary endpoints. Secondary endpoints included DFS, safety, rate of R0 resection and rate of pathologic complete response after induction chemoradiotherapy.

Median follow-up for surviving patients was 30.6 months.

A total of 184 patients in the chemoradiotherapy arm proceeded to surgery 4 to 6 weeks after completion of neoadjuvant therapy.

More patients who received chemoradiotherapy achieved R0 resection (98.4% vs. 91.2%; P = .002) and pathologic complete response (43.2% vs. 0%).

“This suggested that neoadjuvant chemoradiotherapy would significantly increase the R0 resection rate, which a positive prognostic factor,” Yang said. “Pathologic complete response is another positive independent prognostic factor. It has been reported that the 5-year OS can be higher than 60%, so can this transfer into a survival benefit?”

At 3 years, OS was 69.6% in the chemoradiotherapy arm and 62.4% in the surgery-alone arm (HR = 0.71; 95% CI, 0.52-0.98).

Common adverse events associated with chemoradiotherapy included low hemoglobin (grade 3, 3.6%; grade 4, 0.4%), leukopenia (grade 3, 31.8%; grade 4, 17%), neutropenia (grade 3, 23.3%; grade 4, 22.4%), thrombocytopenia (grade 3, 4.5%; grade 4, 2.7%) and hepatic dysfunction (grade 1, 10.3%). There was no significant difference in the incidence or surgery-related complications, with the exception of arrhythmia in the chemoradiotherapy arm (13% vs. 4%; P = .001).

“Neoadjuvant chemoradiotherapy followed by surgery can increase the R0 resection rate, downstage the patient significantly and achieve a [higher] pathologic complete response rate, with satisfactory safety and toxicity,” Yang said. “It can significantly prolong OS compared with surgery alone.” – by Alexandra Todak

Reference:

Yang H, et al. Abstract 611O. Presented at: European Society for Medical Oncology Congress; Oct. 7-11, 2016; Copenhagen, Denmark.

Disclosure: The researchers report no relevant financial disclosures.

Perspective

Florian Lordick, MD, PhD

Overall, this study is a confirmation of some studies we have seen in Europe. But, some criticisms should be made. The follow-up is a bit short, at 30.6 months, and we should see survival data with longer follow-up. There was a high dropout rate of 17% in the chemoradiotherapy followed by surgery arm, whereas there was a 0% dropout rate in the surgery-alone arm.

Seventeen percent of the patients [in the chemoradiotherapy arm] did not undergo surgery — maybe for good reasons, maybe for bad reasons, but they did not undergo surgery. If you report on rate of R0 resections on an intention-to-treat basis, and not only in the operated patients, then the numbers would be a bit different.

There was a 91% R0 resection rate, which is exceptionally good. In this regard, this study is really an outlier compared with what has been shown in other studies.

There was a 0.4% postoperative death rate in both arms, which also is exceptionally low and another outlier.

So, it will be interesting to see this study fully published, with longer follow-up and clearness about some of the questions that remain after this presentation.

Florian Lordick, MD, PhD

University Hospital Leipzig

Disclosures: Lordick reports no relevant financial disclosures.