Minimally invasive lymphadenectomy for gastric cancer: Could the robotic approach provide any benefits than laparoscopy?

Table 1 Summarized characteristics of Eastern published randomized control trials

Trial	Ref.	Country	Study period	Patients	Patients/center per year	Study design	Approach (n)			Surgery (n)		Neo adjuvant (%)	Pathological T (n)					D2 (%)2	Primary outcomes	Main results
							Open	Laparoscopic	Robotic	Distal	Total1		1	2	3	4	x
KLASS trial	Kim et al[77], 2010	South Korea	2006 to 2007	3424	24	cT1N0-1, cT2N0	161	179	0	342	0	0	/	/	/	/	/	68.7	30-day morbidity and mortality	No significant difference in postoperative complication rates (10.5% in the laparoscopic vs 14.7% in the open group; P = 0.137) and in mortality (1.1% vs 0; P = 0.497)
JLSSG0901	Inaki et al[78], 2015	Japan	2009 to 2013	1744	2	cT2-4a N0-2	89 (not analyzed)	86	0	174	0	0	32	18	19	17	0	86	Anastomotic leakage or pancreatic fistula in laparoscopic group	Single-arm: 4.7% patients underwent laparoscopic gastrectomy had anastomotic leakage or pancreatic fistula (4/86; 95%CI: 1.3-11.5; 1-sided P = 0.00024)
	Etoh et al[17], 2023		2009 to 2016	46	2	cT2-4a N0-2	233	227	0	460	0	0	128	122	123	87	0	100	5-year relapse-free survival	Relapse-free survival did not differ between groups: 73.9% in the open and 75.7% in the laparoscopic group (HR = 0.96; 95%CI: 0.72-1.26; P = 0.03)
Cui	Cui et al[79], 2015	Japan	2010 to 2012	2704	141	cT1-4a N0-3	142	128	0	148	122	0	/	/	/	/	/	100	Short-term surgical outcome	Laparoscopic group had similar number of harvested lymph nodes (29.3 vs 30.1; P = 0.574), less blood loss, longer operation time and faster recovery (P < 0.05) than open
KLASS-01	Kim et al[80], 2016	South Korea	2006 to 2010	13834	24	cT1N0-1, cT2N0	657	726	0	1360	23	0	11027	224	41	1	10	60	30-day morbidity and mortality	The overall complication rate was significantly lower in the laparoscopic (13%) than open group (19.9%); P = 0.001. Mortality was similar (0.6% vs 0.3%; P = 0.687)
	Kim et al[14], 2019		2006 to 2010	13584	24	cT1N0-1, cT2N0	645	714	0	1345	13	0	1097	/	/	/	/	60	5-year overall survival	Overall survival rates were 94.2% in the laparoscopic and 93.3% in the open group; P = 0.64
CLASS-01	Hu et al[81], 2016	China	2012 to 2014	10394	33	cT1-4a N0-3	520	519	0	1015	24	39.4	248	/	/	/	/	99.7	30-day morbidity and mortality	Postoperative morbidity was 15.2% vs 12.9% (95%CI: -1.9 to 6.6; P = 0.285) and mortality rate was 0.4% vs zero (95%CI: -0.4 to 1.4; P = 0.249) in the laparoscopic and open group, respectively
	Yu et al[82], 2019		2012 to 2014	10394	33	cT2-4a N0-3	520	519	0	1015	24	39.4	248	/	/	/	/	99.7	3-year disease-free survival	Disease-free survival did not differ between groups: 76.5% in the laparoscopic and 77.8% in the open group (log-rank P = 0.59; HR = 1.10; 95%CI: 0.84-1.43; P = 0.49)
	Huang et al[16], 2022		2012 to 2014	10394	33	cT2-4a N0-3	520	519	0	1015	24	39.4	248	/	/	/	/	99.7	5-year overall survival	Overall survival did not differ between groups with each tumor stage: 72.6% in the laparoscopic and 76.3% in the open group (log-rank P = 0.19; HR = 1.17; 95%CI: 0.93-1.48; P = 0.19)
JCOG 0912	Katai et al[13], 2017	Japan	2010 to 2013	9124	7.5	cT1N0-1, cT2N0	471	441	0	675	14	0	788	83	31	9	1	24.9	Short-term surgical outcome	Operative time was longer in laparoscopic than in open group (278 vs 194 minutes; P < 0.001), while blood loss was smaller (38 vs 115 mL, P < 0.001)
	Katai et al[18], 2019		2010 to 2013	9124	7.5	cT1N0-1, cT2N0	471	441	0	675	1	0	823	69	19	1	0	24.9	5-year relapse-free survival	5-year relapse-free survival was 94.0% in the open and 95.1% in the laparoscopic group (HR = 0.84; 90%CI: 0.56-1.27; P = 0.0075)
	Hikage et al[83], 2023		2010 to 2013	8814	7	cT1N0-1, cT2N0	447	434	0	653	05	0	/	/	/	/	/	/	Associations between surgery-related factors and the development of late complications	The surgical approach was not a risk factor for any late complications
	Akiyama et al[84], 2023		2010 to 2013	8154	7	cT1N0-1, cT2N0	/	/	0	578	16	0	738	51	20	5	1	17.3	Frequency and location of lymph node metastases	10.9% had positive lymph node metastases. For cancer located in middle third of the stomach, metastases were widely located in each lymph node sites; for cancer located in lower third sites No. 4sb and 9 showed no metastasis
Shi	Shi et al[85], 2018	China	2010 to 2012	3223	133	cT2-4a N0-3	156	166	0	196	126	0	0	65	257	0	0	100	Short-term surgical outcomes	Laparoscopic group had longer operation time (P < 0.001), less estimated blood loss (P < 0.001), and less intraoperative transfusion (P = 0.048) than open. The average number of retrieved lymph nodes was 32 in both groups (P = 0.377)
	Shi et al[86], 2019		2010 to 2012	3223	133	cT2-4a N0-3	156	166	0	196	126	0	0	65	257	0	0	100	5-year overall survival	Overall survival rate was 49.0% in the laparoscopic and 50.7% in the open group; log-rank P = 0.59. No differences in each tumor stages
COACT 1001	Park et al[87], 2018	South Korea	2010 to 2011	195	21	cT2-4a N0-3	95	100	0	190	5	0	/	/	/	/	/	45.6	Noncompliance rate of the lymph node dissection	No significant differences between laparoscopic (47%) and open groups (43.2%); P = 0.648. For clinical stage III disease, the noncompliance rate was 52% vs 25%; P = 0.043
Wang	Wang et al[88], 2019	China	2014 to 2017	4424	26	cT2-4a N0-3	234	208	0	418	24	0	110	80	136	116	0	99.6	30-day morbidity and mortality	No significant differences between laparoscopic (13.1%) and open groups (17.7%); P = 0.174. Independent risk factors were age (OR ≥ 60) and BMI (OR ≥ 25). No operation-related death occurred in both arms
Li	Li et al[89], 2019	China	2015 to 2017	954	37	cT2-4a N0-3	47	48	0	92	3	100	187	16	36	18	0	84.2	3-year recurrence-free survival (ongoing); short-term clinical outcomes	Laparoscopic group had lower postoperative complication rate (20% vs 46%; P = 0.007) after neoadjuvant, and better adjuvant chemotherapy completion (OR = 4.39; 95%CI: 1.63-11.80; P = 0.003)
KLASS-02	Lee et al[15], 2019	South Korea	2011 to 2015	10114	23	cT2-4a N0-1	498	513	0	985	26	0	267	218	274	252	0	99.4	30-day morbidity and 90-day mortality	Morbidity was significantly lower after laparoscopic (16.6%) than after open gastrectomy (24.1%); P = 0.003. 90-day mortality was similar in both groups (laparoscopic 0.4% vs open 0.6%; P = 0.682)
	Son et al[90], 2022		2011 to 2015	9744,5	22	cT2-4a N0-1	482	492	0	947	27	0	262	217	267	228	0	99.7	5-year overall survival and relapse-free survival	No significant difference in the 5-year overall survival (88.9% vs 88.7%; P = 0.30) and relapse-free survival (79.5% vs 81.1%; P = 0.658) between laparoscopic and open groups. Most common types of recurrence were peritoneal carcinomatosis (42.1%)
	Hyung et al[91], 2020		2011 to 2015	9744,5	22	cT2-4a N0-1	482	492	0	947	27	0	262	217	267	228	0	99.7	3-year relapse-free survival	Relapse-free survival did not differ between groups: 81.3% in the laparoscopic and 80.3% in the open group (log-rank P = 0.827; HR = 1.035; 95%CI: 0.762-1.406; P = 0.039)
CLASS-02	Liu et al[92], 2020	China	2017 to 2018	214	10	cT1N0-1, cT2N0	109	105	0	0	214	0	1447	39	19	5	0	83.2	30-day morbidity and mortality	No significant difference in the overall postoperative complication rate (18.1% vs 17.4%) and in mortality (1% vs 0)
Lu	Lu et al[50], 2021	China	2017 to 2020	2953	121	cT1-4a N0-3	0	142	141	283	12	0	92	42	104	45	0	67.5	30-day postoperative outcomes, quality of lymphadenectomy	Surgical morbidity was comparable in the robotic and laparoscopic groups (3.5% vs 6.3%; P = 0.279). Higher extraperigastric lymph nodes were retrieved in the robotic group (17.6 vs 15.8; P = 0.018)
	Lu et al[93], 2024		2017 to 2020	2833	118	cT1-4a N0-3	0	142	141	283	0	0	92	42	104	45	0	67.5	3-year disease-free survival	3-year disease-free survival was 85.8% and 73.2% in the RDG and LDG groups (P = 0.011). Difference in local recurrence rate (2.1% vs 7.7%), while no difference in peritoneal and liver metastasis
Ojima	Ojima et al[54], 2021	Japan	2018 to 2020	2364	47	cT1-4a N0-3	0	119	113	160	76	0	131	24	51	30	0	47	Postoperative intra-abdominal infectious complications of C-D grade > 2	No significant difference in the incidence of intra-abdominal infectious complications (8.4% in the laparoscopic vs 6% in the robotic group; P = 0.47)

¹Proximal gastrectomies are included.

²D2 lymphadenectomy according to Japanese gastric cancer treatment guidelines.

³A fraction (< 10%) of patients underwent Billroth 1 reconstruction.

⁴A fraction (10%-70%) of patients underwent Billroth 1 reconstruction.

⁵Thirty-seven patients, including those who underwent R1/R2 resection, were lost to follow-up, or experienced operative mortality, were excluded to evaluate survival outcomes.

⁶Remnant patients underwent pylorus-preserving gastrectomy and gastro-gastro reconstruction.

⁷Remnant patients resulted ypT0 or ypTis.

C-D: Clavien-Dindo grade; CI: Confidence interval; CLASS: Chinese Laparoscopic Gastrointestinal Surgery Study Group; HR: Hazard ratio; JCOG: Japan Clinical Oncology Group; JLSSG: Japanese Laparoscopic Surgery Study Group; KLASS: Korean Laparo-endoscopic Gastrointestinal Surgery Study Group; LDG: Laparoscopic distal gastrectomy; OR: Odds ratio; RDG: Robotic distal gastrectomy.

Table 2 Summarized characteristics of Western published randomized control trials

Trial	Ref.	Country	Study period	Patients	Patients/center per year	Study design	Approach (n)			Surgery (n)		Neo adjuvant (%)	Pathological T (n)					D2 (%)1	Primary outcomes	Main results
							Open	Laparoscopic	Robotic	Distal	Total		1	2	3	4	x
Huscher	Huscher et al[94], 2005	Italy	1998 to 2001	59	24.5	cT1-4 N0-2	29	30	0	59	0	0	13	15	21	10	0	69.5	Short-term surgical outcome, 5-year overall and disease-free survival	Laparoscopic group had similar mean number of harvested lymph nodes (33.4 vs 30; P > 0.05) and operative mortality (27.6% vs 26.7%; P > 0.05) than open. Five-year overall and disease-free survival rates were similar between groups; P > 0.05
STOMACH	van der Wielen et al[23], 2021	European Union	2015 to 2018	96	2	cT1-4a N0-3	49	47	0	0	96	100	142	9	36	27	0	42.7	Oncological safety, measured as the number of resected lymph nodes and radicality	Mean number of resected lymph nodes was 43.4 ± 17.3 in open and 41.7 ± 16.1 in minimally invasive group (P = 0.612) after neoadjuvant. No significant differences in R0 resection between laparoscopic (98%) and open groups (93.6%); P = 0.617
LOGICA	van der Veen et al[22], 2021	Netherland	2015 to 2018	215	6.5	cT1-4a N0-3	105	110	0	123	92	72.2	292	26	89	55	0	99.5	Hospital stay	Median hospital stay was 7 days (interquartile range, 5-9) in both groups; P = 5.34
Ribeiro	Ribeiro et al[72], 2022	Brazil	2015 to 2020	60	12.5	cT1-4a N0-1	31	0	29	51	9	0	26	12	11	11	0	100	Short-term surgical outcome	Robotic group had similar mean number of harvested lymph nodes (41.3 vs 42.4; P = 0.805), longer surgical time (354 vs 215 minutes; P < 0.001), and less bleeding (124 vs 276 mL; P < 0.001) compared to open

¹D2 lymphadenectomy according to Japanese gastric cancer treatment guidelines.

²Remnant patients resulted ypT0 or ypTis.