Supplementary Material

Supplemental Table 1. American Joint Committee on Cancer (AJCC) 8th edition staging system for pancreatic cancer

Primary tumour (T) Regional lymph nodes (N) Distant metastasis (M) T1 Tumour invades lamina propria, muscularis mucosae, or N0 No regional lymph node submucosa metastasis T2 Tumour invades muscularis propria N1 Metastasis in 1-2 regional M0 No distant metastasis lymph nodes T3 Tumour penetrates subserosal connective tissue without N2 Metastasis in 3-6 regional M1 Distant metastasis invasion of visceral peritoneum or adjacent structures lymph nodes T4a Tumour invades serosa (visceral peritoneum) N3a Metastasis in 7-15 regional lymph nodes T4b Tumour invades adjacent structures N3b Metastasis in 16 or more regional lymph nodes

Stage

IA T1N0M0 IB T1N1M0 , T2N0M0 IIA T1N2M0 , T2N1M0 , T3N0M0 IIB T1N3aM0 , T2N2M0 , T3N1M0 , T4aN0M0, IIIA T2N3aM0 , T3N2M0 , T4aN1M0 , T4aN2M0 , T4bN0M0 IIIB T1N3bM0 , T2N3bM0 , T3N3aM0 ,T4aN3aM0 , T4bN1M0 , T4bN2M0 IIIC T3N3bM0 , T4bN3aM0 , T4bN3bM0 , T4aN3bM0 , IV Any T,N, M1

Supplemental Table 2 Multivariate Cox analysis of T, N and stage classification on overall and cancer-specific survival in AJCC 7th edition staging system

AJCC 8th Overall survival Cancer-specific survival Edition HR* (95%CI) P HR* 95%CI P pT T1 Reference Reference T2 1.81 (1.62, 2.02) <0.001 2.24 (1.93, 2.60) <0.001 T3 3.61 (3.31, 3.93) <0.001 5.86 (5.20, 6.60) <0.001 T4a 5.74 (5.24, 6.28) <0.001 9.69 (8.58, 10.94) <0.001 T4b 7.45 (6.72, 8.25) <0.001 12.80 (11.22, 14.60) <0.001 pN N0 Reference Reference N1 2.41 (2.23, 2.60) <0.001 2.97 (2.71, 3.26) <0.001 N2 3.46 (3.21, 3.73) <0.001 4.41 (4.03, 4.82) <0.001 N3 6.10 (5.67, 6.57) <0.001 8.07 (7.40, 8.79) <0.001 pStage IA Reference Reference IB 1.63 (1.43, 1.86) <0.001 2.01 (1.65, 2.45) <0.001 IIA 2.54 (2.26, 2.85) <0.001 3.95 (3.35, 4.66) <0.001 IIB 3.99 (3.56, 4.48) <0.001 7.21 (6.15, 8.46) <0.001 IIIA 5.44 (4.85, 6.09) <0.001 10.11 (8.64, 11.83) <0.001 IIIB 7.35 (6.60, 8.18) <0.001 14.15 (12.16, 16.47) <0.001 IIIC 11.14 (9.95, 12.47) <0.001 21.90 (18.75, 25.58) <0.001 IV 12.90 (11.57, 14.38) <0.001 25.96 (22.31, 30.21) <0.001 Abbreviation: HR, hazard ratio; AJCC, American Joint Committee on Cancer

*Adjusted for age, sex, year, race, marital status, tumour grade, radiation, surgery, chemotherapy, number of examined lymph nodes. Supplemental Table 3. Comparison of stage classification between AJCC 7th and AJCC 8th edition staging system

Variable AJCC 7th Staging groups

IA pT1N0M0 IB pT1N1M0 , pT2N0M0 IIA pT1N2M0 , pT2N1M0 , pT3N0M0 IIB pT1N3M0 , pT2N2M0 , pT3N1M0, pT4aN0M0 IIIA pT2N3M0 , pT3N2M0 , pT4aN1M0 IIIB pT3N3M0 , pT4aN2M0 , pT4bN0M0, pT4bN1M0 IIIC pT4aN3M0, pT4bN2M0 , pT4bN3M0 IV Any pT,pN,pM1 AJCC 8th Staging groups

IA pT1N0M0 IB pT1N1M0 , pT2N0M0 IIA pT1N2M0 , pT2N1M0 , pT3N0M0 IIB pT1N3aM0 , pT2N2M0 , pT3N1M0 , pT4aN0M0 IIIA pT2N3aM0 , pT3N2M0 , pT4aN1M0 , pT4aN2M0 , pT4bN0M0 IIIB pT1N3bM0 , pT2N3bM0, pT3N3aM0 , pT4aN3aM0 , pT4bN1M0 , pT4bN2M0 IIIC pT3N3bM0 , pT4bN3aM0, pT4bN3bM0 , pT4aN3bM0 IV Any pT, pN, pM1 Abbreviation: AJCC, American Joint Committee on Cancer. Difference between AJCC 7th and 8th indicated in yellow. Supplemental Table 4. Distribution of patients according to the 8th and 7th edition AJCC pTNM staging system

AJCC 8th edition IA IB IIA IIB IIIA IIIB III IV Total C A IA 1,778 ------1,778 J IB - 893 ------893 C IIA - - 1,292 - - - - - 1,292 C IIB - - - 1,149 - 7 - - 1,156 7t IIIA - - - - 1,145 16 - - 1,161 h IIIB - - - - 623 741 215 - 1,579 e IIIC - - - - - 693 569 - 1,262 di IV ------1,330 1,330 ti o n Total 1,778 893 1,292 1,149 1,768 1,457 784 1,330 Abbreviation: AJCC, American Joint Committee on Cancer Supplemental Table 5. Stage migration from the AJCC 7th to 8th edition stage system

AJCC 7th edition AJCC 8th edition Up-staged Direction T1N3bM0 IIB IIIB T2N3bM0 IIIA IIIB T3N3bM0 IIIB IIIC Down-staged T4bN0M0 IIIB IIIA T4aN2M0 IIIB IIIA T4bN2M0 IIIC IIIB T4aN3aM0 IIIC IIIB Abbreviation: AJCC, American Joint Committee on Cancer.

Supplementary Figure legend

Supplementary Figure 1. Comparison of overall (OS) and cancer-specific survival (CSS) between N3a and N3b groups. a, OS in all patients; b, OS in patients with more than 15 lymph nodes examined; c, CSS in all patients; d, CSS in patients with more than 15 lymph nodes examined.

Supplementary Figure 2. Comparison of cancer-specific survival between N3a and N3b groups stratified by pT categories in AJCC 8th edition. a, T1 group, b, T2 group, c, T3 group, d, T4a group, e, T4b group. The P value was calculated by log-rank test.

Supplementary Figure 3. Comparison of cancer-specific survival among groups with stage migration. a, T1N3b shifts from IIB to IIIB; P1 for

T1N3b and IIB, P2 for T1N3b and IIIB. b, T2N3b, shifts from IIIA to IIIB C; P1 for T2N3b and IIIA, P2 for T2N3b and IIIB. c, T3N3b shifts from IIIB to IIIC; P1 for T3N3b and IIIB, P2 for T3N3b and IIIC. d, T4aN2 shifts from IIIB to IIIA; P1 for T4aN2 and IIIB, P2 for T4aN2 and IIIA. e, T4aN3a shifts from IIIC to IIIB; P1 for T4aN3a and IIIB, P2 for T4aN3a and IIIC. f, T4bN0 shifts from IIIB to IIIA; P1 for T4bN0 and IIIB, P2 for T4bN0 and

IIIA. g, T4bN2 shifts from IIIC to IIIB; P1 for T4bN2 and IIIB, P2 for T4bN2 and IIIC. Supplementary Figure 1. Supplementary Figure 2. Supplementary Figure 3.