By Mary Ellen Schneider
Adding docetaxel or radiotherapy to cisplatin plus 5-fluorouracil as preoperative therapy does not appear to increase the risk of perioperative complications or mortality in patients with locally advanced, potentially resectable thoracic esophageal cancer, according to findings reported at the American Society of Clinical Oncology’s 2021 Gastrointestinal Cancers Symposium.
But the combination of cisplatin plus 5-fluorouracil with radiotherapy (CF-RT) did increase the risk of Grade 2 chylothorax after esophagectomy.
“Intense preoperative treatment didn’t influence the surgical safety and didn’t increase the perioperative complications,” said Kazuo Koyanagi, MD, PhD, of the National Cancer Center in Tokyo, Japan, who presented the study findings.
The phase 3 trial had three arms comparing cisplatin plus 5-fluorouracil (CF), which is the current standard of care in Japan, to CF plus docetaxel (DCF) and CF-RT. The study, JCOG 1109, is in the follow-up phase with a primary analysis planned for 2023 (Abstract 162).
Patients were eligible for the trial if they had histologically proven squamous cell carcinoma, adenosquamous carcinoma, or basaloid carcinoma with lesions located in the thoracic esophagus. Patients also needed to be either clinical Stage IB, II, or III (excluding T4) with an ECOG Performance Status of 0 or 1. Trial participants could not have any prior therapy for esophageal cancer except complete resection by endoscopic mucosal resection or endoscopic mucosal dissection. No prior chemotherapy, radiotherapy, or hormonal therapy for any cancer was allowed.
Researchers randomized 601 patients to the three preoperative arms. Ultimately, 185 patients in the CF arm, 183 patients in the DCF arm, and 178 patients in the CF-RT arm underwent surgery. Total or subtotal thoracic esophagectomy and regional lymphadenectomy were recommended.
“Patients who underwent surgery were well balanced among the three arms,” Dr. Koyanagi said.
Operative details such as operation time, blood loss, and thoracic and abdominal approach were not different between arms. The extent of lymph node dissection and residual tumor were also not different between the arms. However, the median number of lymph nodes harvested was significantly lower in the CF-RT arm than in the CF arm (49 versus 58, P<0.0001).
Researchers found no increase in intraoperative complications in the DCF and CF-RT groups, compared with CF. In contrast, the incidence of any postoperative complication was significantly decreased after preoperative DCF, compared with preoperative CF (43.7% versus 56.2%, P=0.02). Pneumonia, anastomotic leakage, and recurrent laryngeal nerve paralysis were not different between the groups. However, the incidence of grade 2 chylothorax was higher in patients in the CF-RT arm than in patients in the CF arm (5.1% versus 1.1%, P=0.03).
“The reason for the decrease in harvested lymph nodes and increase in chylothorax in the CF-RT group is unclear, but tissue fibrosis due to radiation therapy might be one of the possible factors,” Dr. Koyanagi said.
There was no difference in the incidence of reoperation and intra-hospital death in any of the preoperative arms.
In a multivariate analysis, the researchers found that preoperative therapy with DCF significantly decreased the risk for grade 2 or greater postoperative complications, compared with preoperative CF. “From these results, we could at least say preoperative DCF or CF-RT didn’t increase the risk of postoperative complications,” Dr. Koyanagi said. “Whether the decrease in the risk in the DCF group will be reflected in the improvement of prognosis should be examined in the future.”