Laparoscopic distal gastrectomy with D2 lymphadenectomy demonstrated comparable rates of 3-year relapse-free survival vs open distal gastrectomy in patients with locally advanced gastric cancer.
Laparoscopic distal gastrectomy with D2 lymphadenectomy demonstrated comparable rates of 3-year relapse-free survival (RFS) vs open distal gastrectomy in patients with locally advanced gastric cancer, according to findings from the phase 3 KLASS-02-RCT trial that were published in the Journal of Clinical Oncology.1
Patients who underwent laparoscopy had a 3-year RFS rate of 80.3% (95% CI, 76.0%-85.0%) compared with 81.3% (95% CI, 77.0%-85.0%) in those who underwent open surgery (log-rank P = .726). In the intention-to-treat patient population, the 3-year RFS rates were 77.8% (95% CI, 73.3%-82.3%) vs 80.0% (95% CI, 75.8%-84.1%), respectively (log-rank P = .489).
The hazard ratio (HR) after adjusting for surgeon stratification using a Cox regression model was 1.035 (95% CI, 0.762-1.406; log-rank P = .827; P for noninferiority = .039). Further analysis showed that the HR was 1.020 when stratified by pathologic stage per a Cox regression model (95% CI, 0.751-1.385; log-rank P = .900; P for noninferiority = .030).
Taken collectively, these findings suggest that laparoscopic distal gastrectomy could be a potential standard treatment option for this patient population.
In early-stage gastric cancer, laparoscopic surgery is a widely accepted treatment option. The KLASS-01 trial, among other randomized studies, showed that patients with stage I gastric cancer who underwent laparoscopy derived short-term benefits, including less blood loss, reduced postoperative pain, faster recovery, and shorter hospital stay compared with open surgery.1
However, laparoscopy surgery is controversial for patients with locally advanced disease because of the risk of high wound and trocar site recurrence from carbon dioxide pneumoperitoneum. Additionally, D2 lymphadenectomy is associated with potential technical difficulties regarding adequate cancerous organs or tissue manipulation.
The hypothesis of the investigator-initiated, multicenter, open-label, prospective trial was that laparoscopic surgery was noninferior to open surgery with regard to 3-year RFS. The trial was conducted by 20 qualified surgeons from 13 tertiary hospitals.
In total, 1050 patients were randomized to laparoscopic surgery (n = 524) or open surgery (n = 526). In the laparoscopic arm, 16 patients were excluded: 9 withdrew consent, 2 did not undergo surgery per researcher’s choice, and 2 did not undergo surgery because the researcher closed the patients’ abdomens after opening them (open and closed). In the open surgery group, 23 patients were excluded: 11 withdrew consent, 4 did not undergo surgery per researcher’s choice, 7 were open and closed, and 1 underwent surgery, such as bypass, but not gastrectomy.
Of the patients who underwent laparoscopic gastrectomy, 21 were excluded from the full analysis because they achieved R1 or R2 resection (n = 10), were lost to follow-up (n = 9), or experienced operative mortality (n = 2). In the open surgery group, 16 patients were excluded because they achieved R1 or R2 resection (n = 7), were lost to follow-up (n = 6), or experienced operative mortality (n = 3).
Crossover was permitted on the trial. Eleven patients from the open surgery group crossed over to undergo laparoscopic surgery, and 6 patients from the laparoscopic group crossed over to undergo open surgery.
With both surgical approaches, standard radical distal gastrectomy with D2 lymphadenectomy with total omentectomy was performed, with optional 14v lymph node dissection. Surgeon preference determined the method of reconstruction that was implemented.
Additionally, all patients with pathologic stage II or greater advanced disease were recommended for adjuvant chemotherapy with tegafur/gimeracil/oteracil or oxaliplatin plus capecitabine.
Following surgery, patients received regular follow-ups every 3 months for the first 2 years and every 6 months for the next 3 years.
Regardless of follow-up schedule, patients with specific symptoms, such as abdominal mass, weight loss, or obstruction were evaluated because these symptoms can develop concurrently with disease recurrence. Patients without specific symptoms received screening tests, such as abdominopelvic computed tomography, to detect potential recurrence. If the results of these tests were suspicious, patients then underwent a whole-body PET-CT scan, MRI of the liver, or laparoscopic exploration to confirm recurrence.
Baseline patient characteristics were similar between groups. Patients ranged from 20 years old to 80 years old and the majority were men. All patients had an ECOG performance status of 0 or 1, an American Society of Anesthesiologists class of I, II, or III, and primary gastric carcinoma with clinical stage T2, T3, or T4a disease. No patients had nodal metastasis or limited perigastric nodal metastasis in the preoperative studies.
Patients with possible distant metastasis detected in preoperative studies, past history of gastric resection, gastric cancer–related complications, a history of chemotherapy or radiotherapy for gastric cancer, other malignancy diagnosed within the past 5 years, presence of vulnerable conditions, such as cognitive impairment, and ongoing or planned pregnancy, and current or past participation in another clinical trial within the past 6 months were excluded from the study.
Prior to the KLASS-02-RCT trial, a separate study, KLASS-02-QC, was conducted to qualify surgeons with appropriate skills based on standardized protocol for laparoscopic and open gastrectomy. Eligible surgeons had to have performed more than 100 gastrectomies for gastric cancer, including at least 50 laparoscopic and 50 open procedures. Participating hospitals had to have an annual volume of more than 80 gastrectomies.
Although operation details were similar between groups, patients who underwent laparoscopic surgery showed a significantly higher incidence of gastrojejunostomy and longer operation time compared with those who received open surgery (P < .001). Patients in the laparoscopic group experienced bowel function recovery within 3.5 days vs 3.7 days in the open surgery group (P = .0431). Additionally, the mean hospital stay was 8.0 days and 9.1 days, respectively (P = .0047).
Additionally, patients in the laparoscopy group experienced fewer early complications and late complications vs those in the open surgery group. Specifically, 15.7% of patients in the laparoscopic group experienced early postoperative complications, such as intra-abdominal fluid collection and bleeding, compared with 23.4% of patients in the open surgery group (P = .0027). The laparoscopic group also experienced a reduced complication rate during follow-up vs the open surgery group (4.7% vs 9.5%, respectively; P = .0038), with 2.2% and 4.4% of patients experiencing intestinal obstruction, respectively. Although not statistically significant, 8.1% of patients in the laparoscopy group developed Clavien-Dindo grade III or higher complications vs 11.6% in the open surgery group (P = .5812).
Postoperative adjuvant chemotherapy was given in 60.6% of patients who underwent laparoscopic surgery vs 62.0% of those who underwent open surgery. No significant differences were observed with regard to chemotherapy regimen type, completion rate of adjuvant chemotherapy, or time to chemotherapy initiation.
At a median follow-up of 36.3 months, 9.1% of patients in the laparoscopy group (n = 45) and 9.3% of patients in the open surgery group (n = 45) died. The 3-year overall survival rates were 90.6% (95% CI, 88.0%-93.2%) and 90.3% (95% CI, 87.6%-93.0%), respectively (log-rank P = .961).
Additionally, 17.3% of patients in the laparoscopy group (n = 85) vs 16.6% in the open surgery group (n = 80) died or had disease recurrence.
With these findings, Woo Jin Hyung, MD, PhD, of the Department of Surgery at Yonsei University in Seoul, South Korea, and study co-authors concluded, “This study supports use of laparoscopic distal gastrectomy with D2 lymphadenectomy as a potential standard treatment option for clinical locally advanced gastric cancer if the procedure is performed by qualified surgeons.”
An ongoing trial will compare laparoscopic total gastrectomy with open surgery for patients with advanced upper gastric cancer. Additionally, a clinical trial is planned to evaluate laparoscopic surgery after neoadjuvant chemotherapy in patients with gastric cancer.