Prognostic nutritional index in predicting survival of patients with gastric or gastroesophageal junction adenocarcinoma: A systematic review

Table 1 Inclusion and exclusion criteria

Inclusion criteria	Exclusion criteria
Cohort studies	Metastatic or recurrent disease
Studies in English language	Patients receiving palliative care
Studies published over the past 10 yr (2013 to 2023)	Cancer other than adenocarcinoma
Adult patients (over 18 years old)	Case-control studies
Patients with histologically confirmed esophagogastric or gastric adenocarcinoma	Commentaries or letters to the editor
Open or laparoscopic gastrectomy
Effect of preoperative PNI on OS as primary outcome

PNI: Prognostic nutritional index; OS: Overall survival.

Table 2 Newcastle-Ottawa scale scores for the included studies

Ref.	Selection				Comparability	Outcomes			Total
	Representativeness of the exposed cohort	Selection of the non exposed cohort	Ascertainment of exposure	Outcome of interest not present at the start of the study		Assessment of outcome	Length of follow-up	Adequacy of follow-up
Hashimoto et al[21]	*	*	*	*	*	*			6/8
Hirahara et al[31]	*	*	*	*	*	*	*	*	8/8
Hirahara et al[22]	*	*	*	*	*	*			6/8
Ishiguro et al[23]	*	*	*	*	*	*		*	7/8
Kudou et al[12]	*	*	*	*	*	*	*	*	8/8
Lee et al[13]	*	*	*	*	*	*	*	*	8/8
Lin et al[15]	*	*	*	*	*	*	*	*	8/8
Liu et al[24]	*	*	*	*	*	*		*	7/8
Murakami et al[1]	*	*	*	*	*	*		*	7/8
Saito et al[25]	*	*	*	*	*	*		*	7/8
Shen et al[26]	*	*	*	*	*	*	*	*	8/8
Takechi et al[17]	*	*	*	*	*	*			6/8
Toyokawa et al[27]	*	*	*	*	*	*	*	*	8/8
Toyokawa et al[28]	*	*	*	*	*	*	*	*	8/8
Wu et al[29]	*	*	*	*	*	*		*	7/8
Xu et al[30]	*	*	*	*	*	*	*	*	8/8

Table 3 Institute, period, and patient demographics

Ref.	Institute	Period	Patients number	Sex	Age (yr)
Hashimoto et al[21]	Sasebo City General Hospital, Japan	2013-2020	109	68 M, 41 F	83 (80-94)
Hirahara et al[31]	Department of Digestive and General Surgery, Shimane University, Japan	2009-2016	218	145 M, 77 F	Low PNI group (n = 109): 78 (46-91). High PNI group (n = 259): 69 (36-89)
Hirahara et al[22]	Department of Digestive and General Surgery, Shimane University, Japan	2010-2016	368	254 M, 114 F	Absent postoperative complications group (n = 265): 70 (36-91). Present postoperative complications group (n = 103): 73 (41-90)
Ishiguro et al[23]	Department of Surgery in Yokohama City, Japan	2015-2021	258	183 M, 75 F	31-88
Kudou et al[12]	Department of Surgery and Science, Kyushu University; Department of Gastroenterological Surgery, National Kyushu Medical Center, Japan	2005-2016; 2010-2019 (respectively to the 2 institutes)	206	151 M, 55 F	66.3 (35-92)
Lee et al[13]	Severance Hospital, South Korea	2001-2010	7781	5150 M, 2631 F	57.1 ± 11.9
Lin et al[15]	Fujian Medical University Union Hospital, China	2009-2014	2182	1643 M, 539 F	60.8 (54-68.3)
Liu et al[24]	Sun Yat-sen University Cancer Center, China	2000-2012	1330	905 M, 425 F	59 (19-89)
Murakami et al[1]	Tottori University Faculty of Medicine, Japan	2001-2013	254	186 M, 68 F	> 70, n = 128; < 70, n = 126
Saito et al[25]	Division of Surgical Oncology, Department of Surgery, School of Medicine, Tottori University Faculty of Medicine, Japan	2005-2013	453	331 M, 122 F	Low PNI group (n = 188): 73.5. High PNI group (n = 265): 63.5
Shen et al[26]	General Surgery Department of the Jinling Hospital, China	2010-2018	525	387 M, 138 F	Training set (n = 369): 58.53 ± 10.14. Validation set (n = 156): 57.87 ± 10.28
Takechi et al[17]	Onomichi General Hospital, Hiroshima, Japan	2011-2014	182	130 M, 52 F	70 (38-91)
Toyokawa et al[27]	Osaka City University Hospital, Japan	1997-2012	240	168 M, 72 F	64.5 (58-71.3)
Toyokawa et al[28]	Osaka City University Hospital, Japan	1997-2012	225	147 M, 78 F	68 (60-75)
Wu et al[29]	Affiliated Hospital of Jiangnan University, Jiangsu Province, China	2015-2017	77	59 M, 18 F	62.58 ± 8.97
Xu et al[30]	Shantou University Medical College’s cancer hospital, China	2016-2020	236	171 M, 65 F	43.68 ± 4.62

PNI: Prognostic nutritional index; M: Male; F: Female.

Table 4 Patient clinical characteristics

Ref.	Tumor location	TNM stage	Operation	Chemotherapy
Hashimoto et al[21]	NS	I, n = 53 (48.6%). II, n = 31 (28.4%). III, n = 25 (22.9%)	Open surgery 54 (49.5%), laparoscopic 55 (50.5%). Distal/total/proximal gastrectomy: 70/37/2. D2 lymphadenectomy, n = 38 (34.9%)	Adjuvant 13 (11.9%). Neoadjuvant NS
Hirahara et al[31]	EGJ, n = 6. Upper, n = 41. Middle, n = 91. Lower, n = 80	Ia-Ib, n = 92, IIa-IIb, n = 51, IIIa-IIIc, n = 75. T1/2/3/4: 80/27/45/66. N0/1/2/3: 120/30/33/35	Laparoscopic total/laparoscopic partial/laparoscopy assisted distal gastrectomy: 60/14/144	Adjuvant: Yes n = 79, no n = 139. Neoadjuvant chemotherapy in the exclusion criteria
Hirahara et al[22]	EGJ, n = 11. U, n = 70. M, n = 162. L, n = 125	IA-IB, n = 217. IIA-IIB, n = 65. IIIC-IIIC, n = 86. T1/2/3/4: 192/48/54/74. N0/1/2/3: 244/40/42/42	Laparoscopic total/laparoscopic partial/laparoscopy assisted distal gastrectomy: 82/37/249	Adjuvant: Yes n = 100, no n = 268
Ishiguro et al[23]	Upper, n = 63 (24.4%). Middle, n = 113 (43.8%). Lower, n = 82 (31.8%)	T1, n = 138 (53.5%). T2 or T3, n = 120 (46.5%). Lymphatic invasion positive/negative: 90 (34.9%)/168 (65.1%)	Total/distal/partial gastrectomy: 66/180/11. D1+/D2 lymphadenectomy: 139/112	77% of the patients in the high PNI group and 47% in the low PNI group (amongst stages II and III patients)
Kudou et al[12]	EGJ = 96, UGC = 110	T1 97 (47.1%), T2 25 (12.1%), T3 55 (26.7%), T4 29 (14.1%). N0 136 (66.0%), N1 33 (16.0%), N2 13 (6.3%), N3 24 (11.7%). I/II/III: 113 (54.9%)/52 (25.2%)/41 (19.9%)	Total/proximal gastrectomy: 161/45. D1 lymphadenectomy (for T1 tumors), n = 97. D2 lymphadenectomy (for T2-4 tumors), n = 64	Adjuvant: Yes, n = 51 (24.8%), no, n = 155 (75.2%). Neoadjuvant chemotherapy in the exclusion criteria
Lee et al[13]	NS	T1 4182 (53.8%), T2 944 (12.1%), T3 913 (11.7%), T4a 1700 (21.9%), T4b 42 (0.5%). N0 4967 (63.8%), N1 941 (12.1%), N2 798 (10.3%), N3 1075 (13.8%). Stage I 4608 (59.2%), II 1286 (16.5%), III 1887 (24.3%)	Subtotal gastrectomy 5895 (75.8%). Total gastrectomy 1886 (24.2%)	Patients with stage II or higher disease were recommended for adjuvant chemotherapy (numbers not mentioned). Neoadjuvant chemotherapy in the exclusion criteria
Lin et al[15]	Upper 521 (23.9%). Middle 465 (21.3%). Lower 923 (42.3%). Mixed 273 (12.5%)	TNM stage: I 632 (29.0), II 526 (24.1), III 1024 (46.9)	Total gastrectomy 1134 (52.0%). Distal gastrectomy 998 (45.7%). Proximal gastrectomy 50 (2.3%)	1223 patients (56%): Adjuvant chemotherapy n = 1223 (56%). Neoadjuvant chemotherapy NS
Liu et al[24]	Upper third 511 (38.4%). Middle third 278 (20.9%). Lower third 541 (40.7%)	I 220 (16.5%). II 334 (25.1%). III 776 (58.3%)	D2 gastrectomy with R0 resection	Adjuvant chemotherapy n = 817. Neoadjuvant chemotherapy in the exclusion criteria
Murakami et al[1]	NS	T1 n = 147, T2/3/4 n = 107. N0 n = 181, N1/2/3 n = 73. Stage I n = 161, II/III n = 93	Distal/proximal gastrectomy n = 181, total gastrectomy n = 73. D0/1/1+ lymphadenectomy n = 171, D2 lymphadenectomy n = 83	NS
Saito et al[25]	NS	T1 n = 284, T2/3/4 n = 169. Lymph node metastasis absent/present: 343/110	Curative gastrectomy (R0 resection) with regional dissection of lymph nodes. Partial/proximal/total gastrectomy: 311/42/100	Adjuvant chemotherapy n = 64, neoadjuvant chemotherapy n = 5, perioperative chemotherapy n = 10
Shen et al[26]	Upper 158. Middle 202. Lower 165	Training/validation set: I 138 (37.40%)/64 (41.03%), II 84 (22.76%)/39 (25.00%), III 147 (39.84%)/53 (33.97%)	Robotic gastrectomy proximal/distal/total: 110/272/143	Neoadjuvant chemotherapy n = 116, adjuvant n = 267
Takechi et al[17]	NS	Stage: I n = 114 (62.6%), II n = 38 (20.9%), III n = 30 (16.5%)	Distal/total/proximal gastrectomy: 124 (68.1%)/51 (28%)/7 (3.8%). D1/D1+/D2 lymphadenectomy: 32 (17.6%)/74 (40.7%)/76 (41.8%)	Postoperative patients with stages II and III GC n = 33 (18.1%). Neoadjuvant NS
Toyokawa et al[27]	Upper n = 57 (23.8%). Middle n = 98 (40.8%). Lower n = 83 (34.6%). Whole n = 2 (0.8%)	Only stage II patients: IIA n = 111 (46.3%), IIB n = 129 (53.7%)	Total/proximal/distal gastrectomy: 72/1/167	Adjuvant chemotherapy: Yes 62/no 178. Neoadjuvant in the exclusion criteria
Toyokawa et al[28]	Upper/middle/lower n = 209 (92.9%). Whole 16 (7.1%)	IIIA 80 (35.6%), IIIB 72 (32.0%), IIIC 73 (32.4%)	Total/distal gastrectomy: 108 (48%)/117 (52%)	Adjuvant chemotherapy: Yes 41 (18.2%)/no 184 (81.8%)
Wu et al[29]	NS	Only stage III: n = 77 (100%)	Partial gastrectomy (n = 15), total gastrectomy (n = 62)	The average number of chemotherapy cycles was 6.77 ± 4.14, and all patients completed > 2 chemotherapy cycles. Neoadjuvant chemotherapy in the exclusion criteria
Xu et al[30]	EGJ	I 48 (20.3%), II 53 (22.4%), III 135 (57.2%)	Curative gastro-esophageal resection with R0 resection	NS

NS: Not stated; TNM: Tumor-node-metastasis; EGJ: Esophagogastric junction; U: Upper; M: Middle; L: Lower; UGC: Upper gastric cancer; GC: Gastric cancer.

Table 5 Prognostic nutritional index cut-off value calculation method, threshold value and range, follow-up, and survival of the patients

Ref.	PNI calculation	PNI cut-off value and groups	PNI range	Follow up (months)	Outcome
Hashimoto et al[21]	ROC curve analysis	44.2. PNI > 44.2 (n = 72), PNI < 44.2 (n = 37)	NS	23.9 (0.4-81.9)	The 30-d, 180-d, 1-yr, and 3-yr cumulative OS rates were 100%, 97.0%, 91.6%, and 74.7%, respectively
Hirahara et al[31]	ROC curve analysis	44.3. PNI < 44.3 (n = 109), PNI > 44.3, n = 109	NS	Observation period from date of surgery till day of death	5-yr OS: Low PNI, 50.9%; high PNI, 73.6% (P < 0.001). In elderly patients (age > 70) 5-yr OS: Low PNI 52.5%, high PNI 82.5%. Non elderly patients (age < 70), 5-yr OS: Low PNI 46.6%, high PNI 54.7%
Hirahara et al[22]	ROC curve analysis	44.5. PNI < 44.5 n = 114, PNI > 44.5, n = 254	NS	NS	NS
Ishiguro et al[23]	Set according to previous reports	47. PNI < 47 (n = 75), PNI > 47 (n = 183)	NS	NS	5-yr OS: A: 44.7%; B: 77.2% (P < 0.001)
Kudou et al[12]	ROC curve analysis	44.7. PNI < 44.7 (n = 167, 81.1%), PNI > 44.7 (n = 39, 18.9%)	NS	60	Worse 5-year OS rates were associated with PNI < 44.7 (vs > 44.7) (OS: 41.7% vs 84.5%, HR = 5.460, P < 0.0001). In subgroup analysis PNI < 44.7 (vs > 44.7) was significantly associated with poor prognosis in patients with stages II and III disease
Lee et al[13]	ROC curve analysis	46.7. PNI < 46,7 (n = 779), PNI > 46,7, n = 7002	54.2 ± 5.9	60	The low PNI group had a poor prognosis for all stages of disease (for all stages and stages I, II, and III: P < 0.001)
Lin et al[15]	Set according to previous reports	46. PNI ≤ 46 (n = 1348, (61.8%), PNI > 46 (n = 834, 38.2%)	NS	52 (1-118)	Low PNI 5-yr OS = 55.5%, high PNI 5-yr OS = 75.4%
Liu et al[24]	Set according to previous reports	45. Low PNI group PNI < 45. Number of patients NS		35 (range 1-179). Final follow-up June 2015, 806 patients were alive by then	NS
Murakami et al[1]	ROC curve analysis	Preoperative PNI of ≥ 52 (pre-PNIhigh) n = 82, preoperative PNI < 52 (pre-PNIlow) n = 172, postoperative PNI ≥ 49 (post-PNIhigh) n = 95, postoperative PNI < 49 (pre-PNIlow) n = 159. Group A, patients with pre-PNIhigh and post-PNIhigh; group B, patients with either pre-PNIhigh and post-PNIlow or pre-PNIlow and post-PNIhigh; group C, patients with pre-PNIlow and post-PNIlow	Preoperative PNI range 30.6-63.6. Postoperative range 24.2-61.7	NS	5-yr OS prePNIhigh 95.8%, prePNIlow 70% (P < 0.0001). 5-yr OS postPNIhigh 91.4%, postPNIlow 70.1% (P < 0.0001). 5-yr OS prePNIlow and postPNIhigh 80.1%, prePNIlow and postPNIlow 67.1% (P = 0.031). 5-yr OS prePNIhigh and postPNIhigh 100%, prePNIhigh and postPNIlow 83.4% (P = 0.0021)
Saito et al[25]	ROC curve analysis	46.7. PNI ≥ 46.7 (n = 265, 58.5%) and PNI < 46.7 (PNIlow, n = 188, 41.5%)	Range 27.7-63.6	NS	5-yr OS PNIlow 59.5%, PNIhigh 88.2% (P < 0.0001)
Shen et al[26]	X-tile 3.6.1 software1 (Yale University, New Haven, CT, United States)	45.39. Training set low PNI n = 48 (13.01%), high PNI 321 (86.99%), validation set low PNI n = 29 (18.59%), high PNI n = 127 (81.41%). Patients were randomly divided into the training set and the validation set at a 7:3 ratio	NS	41 (range 2-102) training set and 38 (range 1-101) validation set	3-yr and 5-yr OS rates were 80.9% and 74.8% in the training set, and 81.6% and 73.5% in the validation set
Takechi et al[17]	Set according to previous reports	45. PNI < 45 (n = 97), PNI ≥ 45 (n = 85)	NS	39 (range, 1-72)	NS
Toyokawa et al[27]	ROC curve analysis	49.2. PNI ≤ 49.2 (n = 136), PNI > 49.2) (n = 104)	NS	100.5 (70.0-136.8)	The 5-yr OS rate for the entire study population was 78.8%
Toyokawa et al[28]	ROC curve analysis	45.6. PNI ≤ 45.6 (n = 90, 40%), PNI > 45.6 (n = 135, 60%)	46.8 (IQR: 42.5-49.9)	Median 80 (69-124)	The 5-yr OS rate for the entire study population was 48.7%.
Wu et al[29]	ROC curve analysis	42.3. Low PNI group PNI < 42.3. Number of patients NS	NS	Shortest 30, longest 64	3-yr OS low PNI group < 40%, high PNI group > 60%. Exact number NS (only survival curves available)
Xu et al[30]	ROC curve analysis	45.6. Propensity matching patients. PNI < 45.6 (n = 58), PNI > 45.6 (n = 85)	NS	Every 3 months first 2 yr, every 12 months for 3rd-5th yr, once per year after that. Final follow-up December 2022	Low PNI group had a 5-yr OS rate of 46.9%, high PNI group had a 5-yr OS rate of 71.30%

¹A bioinformatics tool for biomarker assessment and outcome-based cut-point optimization designed by Yale University.

PNI: Prognostic nutritional index; OS: Overall survival; ROC: Receiver operating characteristic; NS: Not stated; IQR: Interquartile range; HR: Hazard ratio.

Table 6 Univariate and multivariate analysis results

Ref.	Univariate analysis	Multivariate analysis
Hashimoto et al[21]	Low PNI associated with poor OS (P = 0.049)	Low PNI was an independent prognostic factor for poor OS (P = 0.044)
Hirahara et al[31]	Low PNI value was a significant risk factor for shorter OS (P < 0.001)	PNI was confirmed as an independent prognostic factor for OS (P < 0.001)
Hirahara et al[22]	PNI was significantly associated with OS (HR = 3.316, 95%CI: 2.133-5.196, P < 0.001)	In patients with high PNI, only CEA was was independently associated with OS (P = 0.002)
Ishiguro et al[23]	PNI was significantly associated with OS (P < 0.001)	PNI was an independent predictor of OS (HR = 3.452, 95%CI: 2.042-5.836, P = 0.007)
Kudou et al[12]	PNI < 44.7 (vs > 44.7) was associated with worse OS (P < 0.0001)	PNI (P < 0.0001, HR = 8.946) was independently associated with OS
Lee et al[13]	Low PNI was significantly associated with worse OS (HR = 2.864, 95%CI: 2.544-3.223, P < 0.001)	Low PNI was independently associated with OS (HR = 1.383, 95%CI: 1.221-1.568, P < 0.001)
Lin et al[15]	PNI was significantly associated with OS (P < 0.001)	PNI was independently associated with OS (P = 0.004) and the 5-yr OS rate in the low PNI group was significantly lower than that in the normal PNI group (55.5% vs 75.4%, P < 0.05)
Liu et al[24]	PNI was associated with OS (HR = 1.627, 95%CI: 1.274-2.078, P < 0.001)	PNI (HR = 1.356, 95%CI: 1.051-1.748, P = 0.019) was independently associated with OS. In stage stratified analysis PNI was not significantly associated with OS
Murakami et al[1]	5-yr survival rates were 100.0, 83.0, and 67.1% for groups A, B, and C, respectively	5-yr OS 100%, 92.4%, and 78.3% for groups A, B, and C, respectively, in non-elderly patients (age < 70) (P = 0.017). 5-yr OS 100%, 75.1%, and 59% for groups A, B, and C, respectively, for elderly patients (age > 70) (P = 0.0029). Group stratification mentioned in Table 4
Saito et al[25]	NS	5-yr OS PNI low group 59.5%, PNI high group 88.2% (P < 0.0001). Median age of the PNI high group (63.5 yr) was significantly younger than of the PNI low group (73.5 yr)
Shen et al[26]	PNI was an independent prognostic factor for OS. PNI (≤ 45.39 vs > 45.39) (HR = 0.439, 95%CI: 0.236-0.734, P = 0.002)	PNI was an independent prognostic factor for OS. PNI (≤ 45.39 vs > 45.39) (HR = 0.553, 95%CI: 0.306-0.993, P = 0.048)
Takechi et al[17]	Low PNI was significantly associated with worse OS (HR = 4.261, 95%CI: 1.734-10.47, P = 0.002). Stage I GC patients in the high PNI group showed significantly better OS than patients in the low PNI group (P < 0.001). No significant difference in OS between PNI groups in stage II and III GC patients	Only PNI score was an independent prognostic factor for OS (HR = 2.889, 95%CI: 1.104-7.563, P = 0.031)
Toyokawa et al[27]	PNI was significantly associated with OS (HR = 0.381, 95%CI: 0.219-0.662, P = 0.001)	PNI was an independent prognostic factor for OS (HR = 0.415, 95%CI: 0.234-0.736, P = 0.003)
Toyokawa et al[28]	PNI was not significantly associated with OS (P = 0.073)	PNI was not significantly associated with OS (P = 0.676)
Wu et al[29]	-	The group with high pre-chemotherapy PNI values had significantly better overall survival than the group with low pre-chemotherapy PNI values (HR = 0.485, 95%CI: 0.255-0.920; P = 0.027)
Xu et al[30]	Lower PNI was a significant predictor of shorter OS (P = 0.004)	In comparison to the high PNI group, the hazard of endpoint mortality was 2.442 times greater in the low PNI group (P = 0.003)

PNI: Prognostic nutritional index; OS: Overall survival; HR: Hazard ratio; CI: Confidence interval; GC: Gastric cancer; CEA: Carcinoembryonic antigen.