Observational Study
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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Nov 27, 2021; 13(11): 1463-1483
Published online Nov 27, 2021. doi: 10.4240/wjgs.v13.i11.1463
Table 1 Sample characteristics, n (%)
Characteristic n (%) Year of diagnosis 2004-2006 3142 (27) 2007-2009 3028 (26) 2010-2012 2850 (25) 2013-2015 2587 (22) Age at diagnosis (yr) Median (range) 69 (12-99) Sex Male 6697 (58) Female 4910 (42) Race White 7045 (61) Black 2076 (18) Asian/Pacific 2486 (21) Marital status Single/divorced 2539 (22) Married 6805 (58) Widowed 1837 (16) NA 426 (4) Insurance status Insured 8033 (69) Uninsured 432 (4) NA 3142 (27) Site of tumor Fundus/body 1866 (16) Antrum/pylorus 4626 (40) Overlapping lesion 1299 (11) Stomach, NOS 3816 (33) Tumor size (cm) ≤ 5 5431 (47) 5.1-10 4203 (36) ≥ 10.1 1135 (10) NA 838 (7) Histology ADC, NOS 4481 (39) Signet ring cell carcinoma 2726 (23) ADC, instestinal type 1943 (17) Carcinoma, diffuse type 958 (8) ADC with mixed subtypes 424 (4) Other 1075 (9) Grade Well/moderately differentiated 2674 (23) Poorly/undifferentiated 8524 (73) NA 409 (4) T stage, 8th ed. T1 290 (2) T2 943 (8) T3 5569 (48) T4a 3551 (31) T4b 1254 (11) N stage, 8th ed. N0 2863 (25) N1 2422 (21) N2 2757 (24) N3a 2498 (21) N3b 1067 (9) Stage, 8th ed. IIA 2585 (22) IIB 2129 (18) IIIA 3049 (26) IIIB 2511 (22) IIIC 1333 (12) Chemotherapy Yes 6473 (56) No 5134 (44) Neoadjuvant chemotherapy Yes 1255 (11) No 10352 (89) Radiotherapy Yes 4285 (37) No 7322 (63) Type of surgery Partial gastrectomy 8320 (72) Total gastrectomy 3287 (28) Number of retrieved lymphnodes < 16 LNs (ILA) 5806 (50) 16-29 LNs (ALA) 4085 (35) ≥ 30 LNs (OLA) 1716 (15)
Table 2 Sample characteristics by the number of retrieved lymph nodes, n (%)
Characteristic ILA ALA OLA P value n = 5806 n = 4085 n = 1716 Year of diagnosis < 0.001 2004-2006 1861 (32) 947 (23) 334 (20) 2007-2009 1563 (27) 1071 (26) 394 (23) 2010-2012 1299 (22) 1080 (27) 471 (27) 2013-2015 1083 (19) 987 (19) 517 (30) Age at diagnosis (yr) < 0.001 Median (range) 71 (12-99) 68 (14-98) 65 (18-93) Sex 0.218 Male 3365 (58) 2318 857) 1014 (59) Female 2441 (42) 1767 (43) 702 (41) Race < 0.001 White 3695 (64) 2377 (58) 973 (57) Black 1061 (18) 747 (18) 268 (15) Asian/Pacific 1050 (18) 961 (24) 475 (28) Marital status < 0.001 Single/divorced 1261 (22) 900 (22) 378 (22) Married 3282 (57) 2439 (60) 1084 (63) Widowed 1059 (18) 595 (15) 183 (11) NA 204 (3) 151 (4) 71 (4) Insurance status < 0.001 Insured 3721 (64) 2998 (73) 68 (4) Uninsured 224 (4) 140 (4) 1314 (77) NA 1861 (32) 924 (23) 334 (20) Primary site < 0.001 Fundus/body 835 (14) 696 (17) 335 (19) Antrum/pylorus 2562 (44) 1511 (37) 553 (32) Overlapping lesion 549 (10) 515 (13) 235 (14) Stomach, NOS 1860 (32) 1363 (33) 593 (35) Tumor size (cm) < 0.001 ≤ 5 2977 (51) 1808 (44) 646 (38) 5.1-10 1906 (33) 1573 (39) 724 (42) ≥ 10.1 438 (8) 448 (11) 249 (15) NA 485 (8) 256 (6) 97 (6) Hystology < 0.001 ADC, NOS 2426 (42) 1517 (37) 538 (31) Signet ring cell carcinoma 1248 (22) 997 (24) 481 (28) ADC, instestinal type 928 (16) 702 (17) 313 (18) Carcinoma, diffuse type 422 (7) 360 (9) 176 (10) ADC with mixed subtypes 170 (3) 166 (4) 88 (5) Other 612 (10) 343 (9) 120 (7) Grade < 0.001 Well/moderately differentiated 1493 (26) 862 (21) 319 (19) Poorly/undifferentiated 4072 (70) 3106 (76) 1346 (78) NA 241 (4) 117 (3) 51 (3) T stage, 8th ed. < 0.001 T1 111 (2) 131 (3) 48 (3) T2 490 (8) 321 (8) 132 (8) T3 2877 (50) 1897 (47) 795 (46) T4a 1658 (29) 1321 (32) 572 (33) T4b 670 (11) 415 (10) 169 (10) N stage, 8th ed. < 0.001 N0 1810 (31) 794 (19) 259 (15) N1 1528 (26) 671 (16) 223 (13) N2 1517 (26) 900 (22) 340 (20) N3a 951 (16) 1167 (29) 380 (22) N3b 0 553 (14) 514 (30) Stage, 8th ed. < 0.001 IIA 1557 (27) 775 (19) 253 (15) IIB 1293 (22) 621 (15) 215 (13) IIIA 1754 (30) 942 (23) 353 (20) IIIB 1055 (18) 1091 (27) 365 (21) IIIC 147 (3) 656 (16) 530 (31) Chemotherapy < 0.001 Yes 2814 (48) 2490 (61) 1169 (68) No 2992 (52) 1595 (39) 547 (32) Neoadjuvant chemotherapy < 0.001 Yes 408 (7) 536 (13) 311 (18) No 5398 (93) 3549 (87) 1405 (82) Radiotherapy < 0.001 Yes 1993 (34) 1630 (40) 662 (39) No 3813 (66) 2455 (60) 1054 (61) Type of surgery < 0.001 Partial gastrectomy 4623 (80) 2742 (67) 955 (56) Total gastrectomy 1183 (20) 1343 (33) 761 (44)
Table 3 Cox regression analysis of overall survival and cancer-specific survival
Overall survival Cancer-specific survival Variable Univariable Multivariable1 Univariable Multivariable1 HR (95%CI) P value HR (95%CI) P value HR (95%CI) P value HR (95%CI) P value Sex Male Reference Reference Female 1.03 (0.99-1.08) 0.171 1.07 (1.02-1.13) 0.006 Age, yr < 70 Reference Reference Reference Reference ≥ 70 1.57 (1.50-1.64) < 0.001 1.51 (1.43-1.59) < 0.001 1.32 (1.26-1.39) < 0.001 1.33 (1.26-1.41) < 0.001 Race White Reference Reference Reference Black 0.97 (0.91-1.03) 0.283 1.11 (1.05-1.18) 0.001 0.97 (0.90-1.03) 0.317 1.10 (1.03-1.18) 0.005 Asian/Pacific 0.80 (0.75-0.85) < 0.001 0.82 (0.77-0.87) < 0.001 0.82 (0.77-0.87) < 0.001 0.83 (0.78-0.89) < 0.001 Insurance status NA Reference Reference Insured 0.92 (0.88-0.97) 0.001 1.05 (0.91-1.21) 0.550 Uninsured 0.96 (0.84-1.09) 0.501 0.95 (0.83-1.09) 0.459 Site of tumor Fundus-body Reference Reference Antrum-pylorus 1.08 (1.01-1.15) 0.030 1.08 (0.99-1.16) 0.055 Overlapping lesion of the stomach 1.30 (1.19-1.42) < 0.001 1.35 (1.23-1.49) < 0.001 Stomach, NOS 1.05 (0.98-1.13) 0.167 1.04 (0.96-1.12) 0.373 Histology ADC, NOS Reference Reference Reference Reference Signet ring cell carcinoma 1.16 (1.09-1.23) < 0.001 1.14 (1.07-1.21) < 0.001 1.28 (1.20-1.37) < 0.001 1.16 (1.09-1.25) < 0.001 ADC, instestinal type 0.87 (0.81-0.93) < 0.001 0.98 (0.91-1.05) 0.547 0.79 (0.73-0.86) < 0.001 0.93 (0.86-1.01) 0.086 Carcinoma, diffuse type 1.15 (1.06-1.26) 0.001 1.12 (1.03-1.23) 0.011 1.22 (1.11-1.34) < 0.001 1.11 (1.00-1.22) 0.045 ADC with mixed subtypes 1.06 (0.94-1.20) 0.349 1.09 (0.96-1.24) 0.169 1.12 (0.98-1.28) 0.103 1.08 (0.94-1.24) 0.281 Other 0.92 (0.85-1.00) 0.062 0.97 (0.89-1.06) 0.543 0.95 (0.86-1.04) < 0.001 1.01 (0.92-1.11) 0.862 T stage, 8th ed. T1 Reference Reference Reference Reference T2 1.13 (0.93-1.36) 0.217 1.08 (0.88-1.32) 0.455 1.12 (0.89-1.41) 0.322 1.01 (0.79-1.28) 0.963 T3 1.52 (1.28-1.80) < 0.001 1.37 (1.09-1.73) 0.008 1.69 (1.37-2.07) < 0.001 1.34 (1.02-1.76) 0.033 T4a 2.34 (1.98-2.78) < 0.001 1.72 (1.33-2.22) < 0.001 2.89 (2.35-3.55) < 0.001 1.70 (1.27-2.28) < 0.001 T4b 2.83 (2.37-3.38) < 0.001 2.08 (1.48-2.93) < 0.001 3.54 (2.86-4.39) < 0.001 2.06 (1.40-3.01) < 0.001 N stage, 8th ed. N0 Reference Reference Reference Reference N1 1.22 (1.14-1.31) < 0.001 1.30 (1.16-1.46) < 0.001 1.31 (1.21-1.43) < 0.001 1.26 (1.10-1.43) 0.001 N2 1.49 (1.39-1.59) < 0.001 1.49 (1.28-1.73) < 0.001 1.70 (1.57-1.84) < 0.001 1.44 (1.22-1.70) < 0.001 N3a 2.05 (1.92-2.19) < 0.001 2.10 (1.61-2.74) < 0.001 2.51 (2.32-2.71) < 0.001 2.06 (1.55-2.76) < 0.001 N3b 2.90 (2.66-3.15) < 0.001 3.22 (2.17-4.80) < 0.001 3.68 (3.36-4.03) < 0.001 3.29 (2.14-5.05) < 0.001 Stage, 8th ed. IIA Reference Reference Reference Reference IIB 1.34 (1.24-1.45) < 0.001 1.17 (1.05-1.31) 0.005 1.62 (1.47-1.78) < 0.001 1.38 (1.22-1.57) < 0.001 IIIA 1.96 (1.83-2.10) < 0.001 1.43 (1.21-1.70) < 0.001 2.53 (2.33-2.75) < 0.001 1.78 (1.48-2.15) < 0.001 IIIB 2.47 (2.30-2.66) < 0.001 1.44 (1.08-1.92) 0.012 3.38 (3.11-3.68) < 0.001 1.87 (1.37-2.55) < 0.001 IIIC 3.68 (3.39-3.99) < 0.001 1.59 (1.04-2.44) 0.034 5.19 (4.73-5.70) < 0.001 2.05 (1.29-3.26) 0.003 Grade Well/moderately differentiated Reference Reference Reference Poorly/undifferentiated 1.35 (1.28-1.43) < 0.001 1.19 (1.12-1.26) < 0.001 1.59 (1.49-1.70) < 0.001 Type of surgery Partial gastrectomy Reference Reference Reference Reference Total gastrectomy 1.25 (1.19-1.32) < 0.001 1.23 (1.17-1.30) < 0.001 1.32 (1.25-1.40) < 0.001 1.22 (1.15-1.29) < 0.001 Chemotherapy No Reference Reference Reference Reference Yes 0.62 (0.59-0.64) < 0.001 0.68 (0.64-0.72) < 0.001 0.71 (0.67-0.74) < 0.001 0.73 (0.68-0.78) < 0.001 Neoadjuvant chemotherapy No Reference Reference Yes 0.76 (0.71-0.83) < 0.001 0.82 (0.75-0.89) < 0.001 Radiotherapy No Reference Reference Reference Reference Yes 0.65 (0.62-0.68) < 0.001 0.77 (0.73-0.82) < 0.001 0.70 (0.66-0.73) < 0.001 0.75 (0.71-0.80) < 0.001 Number of retrieved lymph nodes ILA Reference Reference Reference Reference ALA 0.84 (0.79-0.88) < 0.001 0.68 (0.64-0.71) < 0.001 0.85 (0.81-0.90) < 0.001 0.64 (0.60-0.68) < 0.001 OLA 0.73 (0.68-0.79) < 0.001 0.48 (0.44-0.52) < 0.001 0.80 (0.74-0.86) < 0.001 0.47 (0.43-0.51) < 0.001
Table 4 Propensity score matching subgroups
Characteristic ALA, n = 1714 OLA, n = 1714 P value Year of diagnosis 0.978 2004-2006 339 (20) 334 (19) 2007-2009 385 (23) 394 (23) 2010-2012 468 (27) 471 (28) 2013-2015 522 (30) 515 (30) Age at diagnosis (yr) 0.861 Median (range) 66 (14-98) 66 (18-93) Sex 0.945 Male 1011 (59) 1013 (59) Female 703 (41) 701 (41) Race 0.181 White 972 (57) 973 (57) Black 303 (18) 268 (16) Asian/Pacific 439 (25) 473 (28) Marital status 0.234 Single/divorced 389 (23) 378 (22) Married 1035 (60) 1082 (63) Widowed 218 (13) 183 (71) NA 72 (4) 71 (4) Insurance status 0.958 Insured 1305 (76) 1312 (77) Uninsured 339 (20) 334 (19) NA 70 (4) 68 (4) Primary site 0.926 Fundus/body 327 (19) 333 (19) Antrum/pylorus 571 (33) 553 (32) Overlapping lesion 235 (14) 235 (14) Stomach, NOS 581 (34) 593 (35) Tumor size (cm) 0.016 ≤ 5 737 (43) 645 (38) 5.1-10 663 (39) 724 (42) ≥ 10.1 222 (13) 248 (15) NA 92 (5) 97 (6) Hystology 0.046 ADC, NOS 557 (32) 538 (31) Signet ring cell carcinoma 492 (29) 480 (28) ADC, Instestinal type 289 (17) 313 (18) Carcinoma, diffuse type 177 (10) 175 (10) ADC with mixed subtypes 69 (4) 88 (5) Other 130 (8) 110 (7) Grade 0.892 Well/moderately differentiated 310 (18) 319 (19) Poorly/undifferentiated 1351 (79) 1345 (79) NA 53 (3) 50 (3) T stage, 8th ed. 0.553 T1 59 (3) 48 (3) T2 137 (8) 132 (8) T3 769 (45) 793 (46) T4a 597 (35) 572 (33) T4b 152 (9) 169 (10) N stage, 8th ed. 0.659 N0 250 (15) 259 (15) N1 252 (15) 223 (13) N2 342 (20) 340 (20) N3a 380 (22) 380 (22) N3b 490 (29) 512 (30) Stage, 8th ed. 0.808 IIA 263 (15) 253 (15) IIB 226 (13) 215 (13) IIIA 351 (21) 353 (21) IIIB 377 (22) 365 (21) IIIC 497 (29) 528 (30) Chemotherapy 0.025 Yes 1105 (65) 1167 (32) No 609 (35) 1167 (68) Neoadjuvant chemotherapy < 0.001 Yes 225 (13) 310 (18) No 1499 (87) 1404 (82) Radiotherapy 0.051 Yes 718 (42) 662 (39) No 996 (58) 1052 (61) Type of surgery < 0.001 Partial gastrectomy 1099 (64) 955 (56) Total gastrectomy 615 (36) 759 (44)
Table 5 Kaplan-Meier estimates in propensity score matching subgroups
Median OS, mo(95%CI) P value Median CSS, mo(95%CI) P value ALA 26 (23.5-28.4) < 0.001 31 (27.3-34.7) < 0.001 OLA 34 (30.0-38.0) 42 (35.9-48.1)
Table 6 Overall survival Cox regression results for overall survival and cancer-specific survival after propensity score matching
Overall survival Cancer-specific survival Variable Univariable Multivariable1 Univariable Multivariable1 HR (95%CI) P value HR (95%CI) P value HR (95%CI) P value HR (95%CI) P value Sex Male Reference Reference Female 0.98 (0.90-1.07) 0.662 1.03 (0.94-1.14) 0.517 Age < 70 Reference Reference ≥ 70 1.56 (1.43-1.71) < 0.001 1.35 (1.23-1.49) < 0.001 Race White Reference Reference Reference Black 0.96 (0.85-1.08) 0.528 1.10 (0.97-1.24) 0.147 0.94 (0.83-1.08) 0.383 1.08 (0.94-1.23) 0.274 Asian/pacific 0.80 (0.72-0.89) < 0.001 0.84 (0.75-0.93) 0.001 0.81 (0.72-0.90) < 0.001 0.87 (0.77-0.97) 0.014 Insurance status NA Reference Reference Insured 0.87 (0.79-0.97) 0.009 0.87 (0.78-0.97) 0.013 Uninsured 0.99 (0.78-1.27) 0.972 0.96 (0.74-1.25) 0.754 Site of tumor Fundus-body Reference Reference Antrum-pylorus 1.07 (0.95-1.22) 0.275 1.11 (0.97-1.27) 0.140 Overlapping lesion of the stomach 1.33 (1.15-1.55) < 0.001 1.39 (1.18-1.64) < 0.001 Stomach, NOS 1.04 (0.92-1.18) 0.516 1.03 (0.90-1.19) 0.631 Histology ADC, NOS Reference Reference Reference Signet ring cell carcinoma 1.26 (1.13-1.41) < 0.001 1.37 (1.22-1.54) < 0.001 1.22 (1.08-1.38) 0.001 ADC, instestinal type 0.89 (0.79-1.03) 0.114 0.81 (0.70-0.95) 0.008 0.91 (0.78-1.06) 0.238 Carcinoma, diffuse type 1.23(1.06-1.44) 0.008 1.29 (1.09-1.52) 0.003 1.18 (0.99-1.40) 0.054 ADC with mixed subtypes 1.15 (0.93-1.43) 0.193 1.28 (1.02-1.60) 0.032 1.13 (0.89-1.42) 0.318 Other 0.93 (0.77-1.13) 0.472 0.99 (0.81-1.21) 0.913 1.15 (0.93-1.41) 0.199 T stage, 8th ed T1 Reference Reference T2 1.18 (0.83-1.67) 0.356 1.43 (0.91-2.24) 0.121 T3 1.85 (1.37-2.51) < 0.001 2.60 (1.74-3.87) < 0.001 T4a 2.84 (2.10-3.86) < 0.001 4.28 (2.87-6.39) < 0.001 T4b 3.44 (2.49-4.75) < 0.001 5.13 (3.39-7.77) < 0.001 N stage, 8th ed N0 Reference Reference N1 1.09 (0.89-1.34) 0.380 1.08 (0.86-1.36) 0.518 N2 1.56 (1.31-1.87) < 0.001 1.63 (1.33-1.99) < 0.001 N3a 2.28 (1.93-2.69) < 0.001 2.61 (2.16-3.16) < 0.001 N3b 4.58 (3.91-5.37) < 0.001 5.50 (4.59-6.58) < 0.001 Stage, 8th ed IIA Reference Reference Reference Reference IIB 1.38 (1.12-1.70) 0.003 1.47 (1.18-1.81) < 0.001 1.70 (1.33-2.18) < 0.001 1.77 (1.38-2.29) < 0.001 IIIA 1.96 (1.63-2.35) < 0.001 2.21 (1.83-2.66) < 0.001 2.39 (1.92-2.98) < 0.001 2.66 (2.12-3.32) < 0.001 IIIB 2.85 (2.39-3.40) < 0.001 3.31 (2.76-3.96) < 0.001 3.75 (3.04-6.64) < 0.001 4.22 (3.40-5.23) < 0.001 IIIC 5.73 (4.85-6.77) < 0.001 6.32 (5.31-7.52) < 0.001 8.06 (6.58-9.88) < 0.001 8.58 (6.97-10.57) < 0.001 Grade Well/moderately differentiated Reference Reference Reference Poorly/undifferentiated 1.52 (1.35-1.72) < 0.001 1.19 (1.05-1.35) 0.007 1.70 (1.49-1.96) < 0.001 Type of surgery Partial gastrectomy Reference Reference Reference Reference Total gastrectomy 1.40 (1.29-1.53) < 0.001 1.28 (1.17-1.40) < 0.001 1.43 (1.31-1.58) < 0.001 1.24 (1.13-1.37) < 0.001 Chemotherapy No Reference Reference Reference Reference Yes 0.56 (0.51-0.61) < 0.001 0.63 (0.56-0.70) < 0.001 0.61 (0.55-0.67) < 0.001 0.66 (0.89-0.74) < 0.001 Neoadjuvant chemotherapy No Reference Reference Reference Reference Yes 0.71 (0.62-0.81) < 0.001 1.48 (1.35-1.63) < 0.001 0.76 (0.66-0.87) < 0.001 1.33 (1.20-1.48) < 0.001 Radiotherapy No Reference Reference Reference Reference Yes 0.64 (0.59-0.70) < 0.001 0.77 (0.69-0.86) < 0.001 0.67 (0.61-0.73) < 0.001 0.76 (0.68-0.85) < 0.001 Number of retrieved lymph nodes ALA Reference Reference Reference Reference OLA 0.81 (0.75-0.89) < 0.001 0.71 (0.65-0.78) < 0.001 0.84 (0.76-0.92) < 0.001 0.74 (0.67-0.82) < 0.001
Citation: Desiderio J, Sagnotta A, Terrenato I, Garofoli E, Mosillo C, Trastulli S, Arteritano F, Tozzi F, D'Andrea V, Fong Y, Woo Y, Bracarda S, Parisi A. Long-term survival of patients with stage II and III gastric cancer who underwent gastrectomy with inadequate nodal assessment. World J Gastrointest Surg 2021; 13(11): 1463-1483
URL: https://www.wjgnet.com/1948-9366/full/v13/i11/1463.htm
DOI: https://dx.doi.org/10.4240/wjgs.v13.i11.1463