Safety and efficacy of perioperative chemotherapy combined with PD-1 inhibitor versus chemotherapy with D2 gastrectomy plus PAND in gastric cancer with PALD metastasis: A single-center retrospective cohort study.
Authors: Du Yian , Ye Zeyao 
Published: January 2025

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Background:
Gastric cancer with para-aortic lymph node (PALD) metastasis is associated with a poor prognosis. When the metastasis is limited to the PALD, preoperative systemic therapy combined with D2 gastrectomy plus para-aortic lymph node dissection (PAND) may enhance survival. The benefit of perioperative chemotherapy combined with immune checkpoint inhibitors for these patients is unknown.
Methods:
A total of 133 patients with gastric cancer and limited No.16a2/b1 lymph node metastasis underwent perioperative systemic therapy combined with D2 gastrectomy plus PAND. Patients receiving chemotherapy combined with a PD-1 inhibitor were assigned to Group A (n=62), while those receiving chemotherapy alone were assigned to Group B (n=71). Pathological response, safety, efficacy, and survival outcomes were compared between the two groups.
Results:
Adverse events occurred at comparable rates between the two groups. No treatment-related deaths occurred in either group. In Group A, all patients (100%) achieved R0 resection, compared to 70 patients (98.6%) in Group B. Group A showed significantly better pathological outcomes than Group B, with higher rates of pathological complete response (pCR) (37.1% vs. 4.2%, P < 0.001), and major pathological response (MPR) (58.1% vs. 22.5%, P < 0.001). Group A showed a higher 2-year overall survival (OS) rate compared to Group B (90.3% vs. 62.9%, P = 0.011). The median overall survival (mOS) in Group B was 35.0 months, while follow-up data for Group A are currently insufficient to assess mOS.
Conclusions:
The addition of a PD-1 inhibitor to chemotherapy significantly improves the pathological response rate and prognosis in gastric cancer patients with PALD. Notably, the combination did not increase adverse events. These findings suggest that combining PD-1 inhibitor with chemotherapy could be a promising strategy for improving outcomes in this patient population, though further prospective studies are necessary to confirm long-term survival benefits.

Postoperative outcomes and pathological response.

Variable
Group A (n=62)
%
Group A (n=71)
%
P Value

Vascular tumor embolus

0.005

Negative
43
69.4%
32
45.1%

Positive
19
30.6%
39
54.9%

Nerve infiltration

0.004

Negative
44
71.0%
33
46.5%

Positive
18
29.0%
38
53.5%

No.16a2/b1

0.057

Negative
53
85.5%
51
71.8%

Positive
9
14.5%
20
28.2%

Tumor resection

0.970

Distal
26
41.9%
30
42.3%

Total
36
58.1%
41
57.7%

Serum CEA (U/mL）

0.805

Normal
56
90.3%
65
91.5%

>5
6
9.7%
6
8.5%

Serum CA125 (U/mL)

0.280

Normal
30
48.4%
41
57.7%

>35
32
51.6%
30
42.3%

Serum CA199 (U/mL)

0.783

Normal
56
90.3%
65
91.5%

>37
6
9.7%
6
8.5%

pT-stage

<0.001

≤T2
37
59.7%
19
26.8%

＞T2
25
40.3%
52
73.2%

pN-stage

0.001

N0/1
42
67.7%
27
38.0%

N2/3
20
32.3%
44
62.0%

TRG

＜0.001

0
23
37.1%
3
4.2%

1
13
21.0%
13
18.3%

2
22
35.5%
47
66.2%

3
4
6.5%
8
11.3%

pCR
23
37.1%
3
4.2%
＜0.001

MPR
36
58.1%
16
22.5%
＜0.001