Treatment patterns and survival outcomes in pancreatic ductal adenocarcinoma: a large-scale population-based retrospective cohort study

Pancreatic cancer (PC) is increasingly threatening human life and health and imposes a serious socioeconomic burden[1]. Previous studies have reported the clinical features and outcomes of histological subtypes of PC separately[2]. However, there is a dearth of comprehensive assessments among these histological subtypes. Therefore, it is necessary to analyze the treatment patterns and survival outcomes of these histological subtypes using a large-scale population. In this study, the demographics and characteristics of patients diagnosed with PC from 2010 to 2016 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The detailed process of patient selection and statistical analysis can be found in Supplemental Digital Content available at: https://links.lww.com/JS9/G777 and Supplemental Digital Content Table S1 available at: https://links.lww.com/JS9/G776[3,4]. This study has been strictly reported in line with the STROCSS and TITAN guidelines[5,6]. Among 8427 patients with PC, 6390 had pancreatic ductal adenocarcinoma (PDAC), accounting for 75.82%, followed by pancreatic neuroendocrine tumor (pNET, 1554, 18.44%), invasive intraductal papillary mucinous neoplasm (IPMN, 305, 3.62%), and other histological subtypes are less common (178, 2.12%) (Supplemental Digital Content Table S2, available at: https://links.lww.com/JS9/G776). PDAC patients had a significantly older age of disease onset than did those with others (P < 0.001). Meanwhile, the majority of PDAC patients have Grade II and AJCC staging IIB disease. For treatment patterns, surgical intervention was the most preferred treatment option for all histological subtypes of PC (Supplemental Digital Content Table S3, available at: https://links.lww.com/JS9/G776), and surgical intervention has been significantly associated with improved overall survival (OS) in patients with PDAC (P < 0.001, Supplemental Digital Content Table S4, available at: https://links.lww.com/JS9/G776). For survival outcomes, PDAC patients had poorer OS than pNET and IPMN (pNET, HR 0.091, 95% CI: 0.077–0.108; IPMN, HR 0.627, 95% CI: 0.533–0.738, P < 0.001). The survival rates of each histological subtype of PC are shown in Supplemental Digital Content Table S5, available at: https://links.lww.com/JS9/G776. Notably, as shown in Table 1, compared to the surgery alone group, the surgery combined with adjuvant treatment group had a longer OS (P < 0.001) a higher prevalence of pancreatic head (82.06% vs. 79.12%, P = 0.012), a higher proportion of AJCC staging IIB and III (69.06% vs. 59.73%, P < 0.001), more lymph node metastases (70.80% vs. 63.91%, P < 0.001), and less distant metastasis (2.12% vs. 3.10%, P = 0.030). The propensity scores for both groups exhibited significant overlap. Before PSM, the median OS for PDAC patients was 23 (23–24) months in the surgery combined with adjuvant treatment group and 12 (11–13) months in the surgery alone group (P < 0.001, Figure 1A). While after PSM, the median OS for PDAC patients was 24 (22–26) months in the surgery combined with adjuvant treatment group (P < 0.001, Figure 1B). Finally, the prognostic factors influencing OS of PDAC patients were shown in Supplemental Digital Content Table S6, available at: https://links.lww.com/JS9/G776. Figure 1.: The Kaplan–Meier curves analysis of OS for patients with PDAC in different groups. (A) OS analysis of PDAC patients in the surgery combined with adjuvant treatment and the surgery alone groups before PSM. (B) OS analysis of PDAC patients in the surgery combined with adjuvant treatment and the surgery alone groups after PSM. The P-values < 0.05 indicate a significant difference. OS, overall survival; PSM, propensity score matching; PDAC, pancreatic ductal adenocarcinoma. Table 1 - Baseline characteristics and survival outcomes of patients with PDAC stratified by surgery and adjuvant therapy status before and after propensity score matching Total Surgery alone Surgery combined with adjuvant therapy P-value Total Surgery alone Surgery combined with adjuvant therapy P-value Parameters N = 6252 N = 1485 N = 4767 N = 2970 N = 1485 N = 1485 OS 16 (8, 27) 12 (11, 13) 23 (23, 24) <0.001 14 (7, 26) 12 (11, 13) 24 (22, 26) <0.001 Status <0.001 <0.001 Alive 2310 (36.95) 395 (26.60) 1915 (40.17) 1004 (33.80) 395 (26.60) 609 (4.01) Dead 3942 (63.05) 1090 (73.40) 2852 (59.83) 1966 (66.20) 1090 (73.40) 876 (58.99) Age group, years <0.001 <0.001 ≤24 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) 25–34 18 (0.29) 4 (0.27) 14 (0.29) 8 (0.27) 4 (0.27) 4 (0.27) 35–44 137 (2.19) 18 (1.21) 119 (2.50) 56 (1.89) 18 (1.21) 38 (2.56) 45–54 703 (11.24) 105 (7.07) 598 (12.54) 283 (9.53) 105 (7.07) 178 (11.99) 55–64 1841 (29.45) 304 (20.47) 1537 (32.24) 814 (27.41) 304 (20.47) 510 (34.34) 65–74 2201 (35.21) 501 (33.74) 1700 (35.67) 1012 (34.07) 501 (33.74) 511 (34.41) 75–84 1230 (19.67) 474 (31.92) 756 (15.86) 707 (23.80) 474 (31.92) 233 (15.69) ≥85 122 (1.95) 79 (5.32) 43 (0.90) 90 (3.03) 79 (5.32) 11 (0.74) Race 0.268 0.225 White 5074 (81.15) 1213 (81.69) 3861 (80.10) 2415 (81.32) 1213 (81.69) 1202 (80.95) Black 615 (9.84) 131 (8.82) 484 (10.15) 287 (9.66) 131 (8.82) 156 (10.51) Other 563 (9.01) 141 (9.49) 422 (8.85) 268 (9.02) 141(9.49) 127 (8.55) Sex 0.319 0.399 Female 3087 (49.38) 750 (50.51) 2337 (49.02) 1477 (49.73) 750 (50.51) 727 (48.96) Male 3165 (50.62) 735 (49.49) 2430 (50.98) 1493 (50.27) 735 (49.49) 758 (51.04) Site 0.012 0.128 Head 5087 (81.37) 1175 (79.12) 3912 (82.06) 2383 (80.24) 1175 (79.12) 1208 (81.35) Body and Tail 1165 (18.63) 310 (20.88) 855 (17.94) 587 (19.76) 310 (20.88) 277 (18.65) Diagnosed year 0.104 0.455 2010-2013 3620 (57.90) 887 (59.73) 2733 (57.33) 1754 (59.06) 887 (59.73) 867 (58.38) 2014-2016 2632 (42.10) 598 (40.27) 2034 (42.67) 1216 (40.94) 598 (40.27) 618 (41.62) Grade 0.274 0.972 I 640 (10.24) 161 (10.84) 479 (10.05) 320 (10.77) 161 (10.84) 159 (10.71) II 3263 (52.19) 757 (20.98) 2506 (52.57) 1513 (50.94) 757(20.98) 756 (50.91) III 2296 (36.72) 559 (37.64) 1737 (36.44) 1119 (37.68) 559 (37.64) 560 (37.71) IV 53 (0.85) 8 (0.54) 45 (0.94) 18 (0.61) 8 (0.54) 10 (0.67) AJCC Staging <0.001 <0.001 IA 449 (7.18) 155 (10.44) 294 (6.17) 252 (8.48) 155 (10.44) 97 (6.53) IB 1017 (16.27) 269 (18.11) 748 (15.69) 509 (17.14) 269 (18.11) 240 (16.16) IIA 322 (5.15) 83 (5.59) 239 (5.01) 165 (5.56) 83 (5.59) 82 (5.52) IIB 2344 (37.49) 492 (33.13) 1852 (38.85) 1044 (35.15) 492 (33.13) 552 (37.18) III 1835 (29.35) 395 (26.60) 1440 (30.21) 843 (28.38) 395 (26.60) 448 (30.17) IV 285 (4.56) 91 (6.13) 194 (4.07) 157 (5.29) 91 (6.13) 66 (4.44) T Staging 0.008 0.039 T1 921 (14.73) 255 (17.17) 666 (13.97) 461 (15.52) 255 (17.17) 206 (13.87) T2 3686 (58.96) 840 (56.57) 2846 (59.71) 1712 (57.64) 840 (56.57) 872 (58.72) T3 1373 (21.96) 335 (22.56) 1038 (21.77) 669 (22.53) 335 (22.56) 334 (22.49) T4 272 (4.35) 55 (3.70) 217(4.55) 128 (4.31) 55 (3.70) 73 (4.92) Tumor size 32.00 (25.00, 40.00) 31.00 (24.00, 40.00) 32.00 (25.00, 40.00) 0.841 32.00 (25.00, 40.00) 31.00 (24.00, 40.00) 32.00 (25.00, 40.00) 0.796 N Staging <0.001 0.042 N0 1928 (30.84) 536 (36.09) 1392 (29.20) 1007 (33.91) 536 (36.09) 471 (31.72) N1 2548(40.75) 546 (36.77) 2002 (42.00) 1134 (38.18) 546 (36.77) 588 (39.60) N2 1776 (28.41) 403 (27.14) 1373 (28.80) 829 (27.91) 403 (27.14) 426 (28.68) RLN 16.00 (11.00, 23.00) 15.00(10.00, 21.00) 17.00 (12.00, 24.00) <0.001 16.00 (11.00, 22.00) 15.00 (10.00, 21.00) 17.00 (12.00, 24.00) <0.001 PLN 2.00 (0.00, 4.00) 1.00(0.00, 4.00) 2.00 (0.00, 4.00) 0.004 2.00 (0.00, 4.00) 1.00 (0.00, 4.00) 2.00 (0.00, 4.00) 0.032 M Staging <0.001 0.040 M0 5967(95.44) 1394(93.87) 4573 (95.93) 2813 (94.71) 1394 (93.87) 1419 (95.56) M1 285(4.56) 91(6.13) 194 (4.07) 157 (5.29) 91 (6.13) 66 (4.44) Liver Metastasis 0.030 0.108 No 6105 (97.65) 1439 (96.90) 4666 (97.88) 2892 (97.37) 1439 (96.90) 1453 (97.85) Yes 147 (2.35) 46 (3.10) 101 (2.12) 78 (2.63) 46 (3.10) 32 (2.15) P-values < 0.05 indicate a significant difference between the two groups are given in bold.Abbreviations: PDAC, pancreatic ductal adenocarcinoma; RLN, retrieved lymph nodes; PLN, positive lymph nodes; OS, overall survival. This study provides a comprehensive overview of treatment patterns and survival outcomes for different histological subtypes of PC. Our findings highlight that surgical intervention combined with adjuvant therapy has been associated with improved survival outcomes in patients with PDAC. It offers important insights into treatment decision-making for PDAC in a significant manner. Our findings validate PDAC had worse OS than most other histological subtypes of PC. This finding is consistent with previous literature reports[1,3]. Our study also suggests that patients with older age, higher grade classification, larger tumor size, lymph node metastasis, and liver metastasis had worse survival outcome. This study is mainly limited by inherent defects and missing variables of the retrospective cohort from SEER database. However, to the best of our knowledge, our study is the largest retrospective cohort specifically investigating treatment patterns and survival outcomes in PC patients. Further prospectively designed studies are needed to confirm our findings. In conclusion, surgical intervention is considered a superior treatment option for all histological subtypes of PC. For patients with PDAC, surgery-based multimodal therapy is associated with improved survival outcomes.