Risk of peritoneal recurrence following laparoscopic versus open surgery for stage II or III colorectal cancer (JCOG2310A): An integrated analysis of three phase III randomized controlled trials.
Authors: Hanaoka Marie , Ouchi Akira , Mizusawa Junki , Kataoka Kozo , Shimada Yasuhiro , Inomata Masafumi , Hamaguchi Tetsuya , Takii Yasumasa , Takayama Yuichi , Ito Masaaki , Fujita Shin , Suwa Yusuke , Ikenaga Masakazu , Souda Hiroaki , Tanaka Chihiro , Sano Yusuke , Tsukamoto Shunsuke , Takashima Atsuo , Kanemitsu Yukihide 
Published: January 2025

161

Background:
Peritoneal recurrence in colorectal cancer (CRC) has long been a concern. Although studies have examined the higher risk of peritoneal recurrence following laparoscopic (LAP) compared with open (OP) surgery, the issue remains unresolved, largely due to the heterogeneity of existing data and the limited number of observed peritoneal recurrence events, preventing any definitive conclusions. This study aimed to evaluate whether LAP for pStage II/III CRC presents a potential risk factor for peritoneal recurrence compared with OP.
Methods:
Data from three phase III trials (JCOG0404, JCOG0910, JCOG1006) were extracted from an ancillary research database (JCOG2310A). From this cohort, patients with pStage II or III CRC who underwent curative surgery were included, and the incidence of peritoneal recurrence was compared between LAP and OP. A multivariate analysis was conducted to adjust covariates between the two groups. The primary outcome was the cumulative incidence of peritoneal recurrence, and the secondary outcome was recurrence in specific high-risk subgroups identified through a univariate analysis.
Results:
From 3061 patients (OP: 1734; LAP: 1327), pT4 (25% vs. 17%), pStage III (65% vs. 83%), and right-sided tumor (63% vs. 70%) were different between OP and LAP, respectively. With a median follow-up for peritoneal recurrence of 6.2 years, the 5-year cumulative incidence of peritoneal recurrence was 2.8% in the OP group and 2.9% in the LAP group (hazard ratio (HR): 0.940, 95% confidence interval (CI): 0.621-1.425 in the univariate analysis, and HR: 1.086, 95% CI: 0.683-1.727 in the multivariate analysis. The univariate analysis identified pT4, pN2, pStage III, right-sided tumor, poorly differentiated (por/sig/muc), and ECOG-PS 1 as risk factors for peritoneal recurrence. No significant difference was observed in the subgroups (see table). An exploratory propensity score matching analysis with 1066 patients in each group also showed no difference between the groups (the 5-year cumulative incidence of peritoneal recurrence was 2.8% in the OP group and 3.0% in the LAP group [HR: 1.002, 95% CI: 0.625-1.607]).
Conclusions:
This study revealed that LAP was not a risk factor regarding peritoneal recurrence following curative surgery for Stage II/III CRC.

Subgroup analysis of cumulative incidence of peritoneal recurrence.

OutcomeMeasures
Subgroups

pT4
pN2
pStage III
Right-sided
Poorly differentiated
ECOG PS 1

N(OP vs. LAP)
428 vs. 229
274 vs. 184
1133 vs. 1105
635 vs. 403
122 vs. 66
56 vs. 25

Event(OP vs. LAP)
31 vs. 23
13 vs. 10
45 vs. 32
28 vs. 18
10 vs. 2
7 vs. 2

5-year peritoneal recurrence rate (OP vs. LAP)(%)
6.8 vs. 10.1
4.8 vs. 5.4
3.6 vs. 2.9
4.1 vs. 4.5
7.5 vs. 3.0
9.1 vs. 8.0

HR (95% CI)
1.403(0.819-2.402)
1.144(0.503-2.603)
0.725(0.461-1.139)
1.014(0.562-1.829)
0.372(0.081-1.699)
0.609(0.130-2.862)