Patient characteristics
The cohort consisted of 42,834 patients with primary PDAC at a specific tumor site in the head, body, or tail of the pancreas. Table 1 shows the baseline characteristics of the patients including sex, race/ethnicity, age at diagnosis, insurance status, marital status, income, primary PDAC location, TNM stage, metastases to liver, and primary PDAC tumor size. Of these patients, 21,302 (49.10%) had M1 stage, and 16,207 (37.84%) had developed LM at the time of diagnosis. LM was present in the majority (77.07%) of PDAC patients with distant metastases. A slightly greater number of patients were men, and most diagnoses were among Non-Hispanic Whites (NHW). The most prevalent age at diagnosis in the cohort was 60–79 years, and most patients were insured. More than half of the patients (54.03%) were married at the time of diagnosis. The proportion of primary PDAC location was in the head (65.02%), body (17.25%), and tail (17.73%) of the pancreas, respectively. The detailed characteristics regarding TNM stage are presented in Table 1.
Table 1
Characteristics of the study population in SEER
Variable | Total No. | (%) |
All PDAC | 42,834 | 100.00 |
Sex | | |
Male | 21,925 | 51.19 |
Female | 20,909 | 48.81 |
Race | | |
NHW | 30,048 | 70.15 |
NHB | 5,205 | 12.15 |
Hispanic | 4,380 | 10.23 |
Others | 3,201 | 7.47 |
Age at diagnosis | | |
18–39 | 249 | 0.58 |
40–59 | 8,404 | 19.62 |
60–79 | 24,558 | 57.33 |
80 and up | 9,623 | 22.47 |
Insurance | | |
Insured | 36,031 | 84.12 |
Uninsured | 1,122 | 2.62 |
Others | 5,681 | 13.26 |
Marital status | | |
Single | 5,706 | 13.32 |
Married | 23,143 | 54.03 |
Others | 13,985 | 32.65 |
Incomea | | |
Quartile 1 | 10,499 | 24.51 |
Quartile 2 | 10,333 | 24.12 |
Quartile 3 | 10,710 | 25.00 |
Quartile 4 | 11,291 | 26.36 |
Location | | |
Head | 27,850 | 65.02 |
Body | 7,390 | 17.25 |
Tail | 7,594 | 17.73 |
T stage | | |
T1 | 1,667 | 3.89 |
T2 | 9,955 | 23.24 |
T3 | 18,379 | 42.91 |
T4 | 7,774 | 18.15 |
TX | 5,059 | 11.81 |
N stage | | |
N0 | 23,229 | 54.23 |
N1 | 15,595 | 36.41 |
NX | 4,010 | 9.36 |
M stage | | |
M0 | 21,802 | 50.90 |
M1 | 21,032 | 49.10 |
Metastases | | |
Liver (yes) | 16,207 | 37.84 |
Liver (no) | 26,627 | 62.16 |
Tumor size (cm) | | |
≤2 | 3,496 | 8.16 |
2.1-4 | 17,851 | 41.67 |
≥ 4 | 16,993 | 39.67 |
Unknown | 4,494 | 10.49 |
Abbreviations: NHW, non-Hispanic white; NHB, non-Hispanic black. |
a Unknown Income removed from model owing to nonconvergence (n = 1). |
Risk factors for developing LM
Of the 42,834 patients with primary PDAC stratified by age, LM occurred in the age groups 18–39, 40–59, 60–79, and ≥ 80 years at frequencies of 45.38%, 41.55%, 37.97%, and 34.06%, respectively (Fig. 1A). Non-Hispanic Black (NHB) race/ethnicity had a slightly higher incidence (41.46%) of LM than NHW (37.48%) and Hispanic (37.72%) (p < 0.01)(Fig. 1B). The cohorts of patients with primary PDAC in the tail (62.21%) or body (47.71%) of the pancreas had a significantly higher LM incidence than did the cohort with tumors in the head (28.57%) of the pancreas (p < 0.01)(Fig. 1C). There was a significantly higher incidence rate of LM in the cohort with primary PDAC tumor size larger than 4 cm (44.45%) or unknown primary tumor size (50.18%) than primary tumor size 2.1-4 cm (24.99%) or tumor size < 2 cm (23.86%) (p < 0.01) (Fig. 1D).
Univariate analysis (Table 2) of patients with PDAC showed that primary tumor location at the tail (vs. head; odds ratio (OR), 4.12; 95% CI, 3.90–4.34; p < 0.01) and the body (vs. head; OR, 2.28; 95% CI, 2.17–2.40; P < 0.01) of the pancreas were associated with a significantly higher OR of developing LM at diagnosis of PDAC. Greater primary tumor size was significantly associated with a positive OR of LM in both univariate and multivariate analysis. Univariate analysis showed that male sex, younger age, and NHB race/ethnicity were associated with a higher incidence of LM. Univariate analysis of the roles of T and N stage showed that patients diagnosed at the T2 or TX stages had a greater likelihood of developing LM than those at the T1 stage (OR, 2.53; 95% CI, 2.26–2.84; P < 0.01, or OR, 6.04; 95% CI, 5.34–6.82; P < 0.01, respectively). Whereas, T3 stage and N1 stage primary PDAC tumors were associated with a lower incidence of LM than T1 stage or N0 stage (OR, 0.84; 95% CI, 0.75–0.94; P < 0.01, and OR, 0.85; 95% CI, 0.82–0.89; P < 0.01, respectively). Interestingly, on multivariable logistic regression, the OR of developing LM was 0.69 (95% CI, 0.61–0.79; P < 0.01) for T4 stage, whereas it was 1.32 (95% CI, 1.17–1.48; P < 0.01) on univariate regression.
Table 2
Univariate and multivariate logistic regression analyses of the presence of LM at diagnosis in patients with initial PDAC (diagnosed 2010–2015)
Variable | Univariate | | Multivariate | |
| OR (95%) | P Value | OR (95%) | P Value |
Sex | | | | |
Male | Ref | | Ref | |
Female | 0.83 (0.80–0.86) | < 0.01 | 0.88 (0.84–0.92) | < 0.01 |
Race | | | | |
NHW | Ref | | Ref | |
NHB | 1.18 (1.11–1.25) | < 0.01 | 1.11 (1.04–1.18) | < 0.01 |
Hispanic | 1.01 (0.95–1.08) | 0.76 | 0.98 (0.91–1.05) | 0.55 |
Others | 0.92 (0.82–0.99) | 0.03 | 0.89 (0.82–0.97) | 0.01 |
Age at diagnosis | | | | |
18–39 | Ref | | Ref | |
40–59 | 0.86 (0.66–1.10) | 0.23 | 0.84 (0.65–1.10) | 0.20 |
60–79 | 0.74 (0.51–0.95) | 0.02 | 0.75 (0.58–0.98) | 0.03 |
80 and up | 0.62 (0.48–0.80) | < 0.01 | 0.67 (0.51–0.87) | < 0.01 |
Insurance | | | | |
Insured | Ref | | Ref | |
Uninsured | 1.31 (1.16–1.47) | < 0.01 | 1.15 (1.01–1.31) | 0.03 |
Others | 1.15 (1.09–1.22) | < 0.01 | 1.10 (1.04–1.17) | < 0.01 |
Marital status | | | | |
Married | Ref | | Ref | |
Single | 1.13 (1.07–1.20) | < 0.01 | 1.07 (1.01–1.14) | 0.03 |
Others | 0.99 (0.95–1.01) | 0.77 | 1.07 (1.03–1.13) | < 0.01 |
Incomea | | | | |
Quartile 1 | Ref | | Ref | |
Quartile 2 | 1.01 (0.95–1.07) | 0.77 | NA | NA |
Quartile 3 | 1.05 (0.99–1.11) | 0.10 | NA | NA |
Quartile 4 | 0.95 (0.90–1.01) | 0.08 | NA | NA |
Location | | | | |
Head | Ref | | Ref | |
Body | 2.28 (2.17–2.40) | < 0.01 | 2.23 (2.12–2.36) | < 0.01 |
Tail | 4.12 (3.90–4.34) | < 0.01 | 3.82 (3.61–4.03) | < 0.01 |
T stage | | | | |
T1 | Ref | | Ref | |
T2 | 2.53 (2.26–2.84) | < 0.01 | 1.59 (1.40–1.80) | < 0.01 |
T3 | 0.84 (0.75–0.94) | < 0.01 | 0.53 (0.47–0.60) | < 0.01 |
T4 | 1.32 (1.17–1.48) | < 0.01 | 0.69 (0.61–0.79) | < 0.01 |
TX | 6.04 (5.34–6.82) | < 0.01 | 2.73 (2.36–3.15) | < 0.01 |
N stage | | | | |
N0 | Ref | | Ref | |
N1 | 0.85 (0.82–0.89) | < 0.01 | 0.87 (0.83–0.91) | < 0.01 |
NX | 3.54 (3.29–3.80) | < 0.01 | 3.05 (2.83–3.29) | < 0.01 |
Tumor size (cm) | | | | |
≤2 | Ref | | Ref | |
2.1-4 | 1.44 (1.32–1.56) | < 0.01 | 1.35 (1.24–1.48) | < 0.01 |
≥ 4 | 2.54 (2.34–2.76) | < 0.01 | 1.88 (1.72–2.05) | < 0.01 |
Unknown | 3.20 (2.90–3.53) | < 0.01 | 2.58 (2.31–2.88) | < 0.01 |
Abbreviations: NHW, non-Hispanic white; NHB, non-Hispanic black; OR, odds ratio |
a Unknown Income removed from model owing to nonconvergence (n = 1). |
OS among patients with PDAC and LM at diagnosis
The median OS for PDAC patients without LM was 9 months (95% CI: 8.81–9.19), whereas that in the cohort with PDAC and LM at diagnosis was 2 months (95% CI: 1.92–2.08). The presence of LM at initial diagnosis was associated with shorter survival time than that of patients presenting without baseline liver involvement. The median survival among all PDAC patients in the study group was longest in patients with a primary tumor in the head of the pancreas (7 months, 95% CI: 6.84–7.16) and shorter in those with a primary tumor in the body of the pancreas (5 months, 95% CI: 4.75–5.25). Patients with a primary PDAC tumor in the tail of pancreas had the shortest median survival (3 months, 95% CI: 2.84–3.16). In PDAC patients with LM sub-cohort, those with a primary tumor in the head of the pancreas had the longest median survival (3 months, 95% CI: 2.89–3.11), whereas those with a primary tumor in the body or tail of the pancreas had a slightly shorter median survival (2 months, 95% CI: 1.82–2.19;P < 0.01, and 2 months, 95% CI: 1.91–2.09; P < 0.01, respectively). Figure 2 shows the OS estimates (Fig. 2A), the OS estimates stratified by primary tumor location (Fig. 2B), and the OS estimates stratified by extent of identified LM at diagnosis (Fig. 2C). The median survival did not differ significantly according to tumor location among the three primary PDAC-with-LM groups (Fig. 2D).
Prognostic factors for OS in PDAC patients with LM
On multivariable Cox regression analysis (Table 3) of OS among PDAC patients with LM at diagnosis, female gender (vs. male gender; HR, 0.92; 95% CI, 0.89–0.95; P < 0.01) was associated with increased OS. However, other factors including age 40–59 years (vs. age 18–39 years; HR, 1.35; 95% CI, 1.10–1.67; P < 0.01), age 60–79 years (vs. age 18–39 years; HR, 1.81; 95% CI, 1.47–2.23; P < 0.01), age > 80 years (vs. age 18–39 years; HR, 2.98; 95% CI, 2.42–3.68; P < 0.01), uninsured status (vs. insured status ; HR, 1.25, 95% CI, 1.14–1.38; P < 0.01), primary PDAC location at the body (vs. head; HR, 1.06, 95% CI, 1.02–1.11; P < 0.01), at the tail (vs. head; HR, 1.16, 95% CI, 1.12–1.20 ; P < 0.01) of the pancreas, and primary tumor size ≥ 4 cm (vs. size < 2 cm ; HR, 1.16, 95% CI, 1.07–1.25 ; P < 0.01) were significantly associated with decreased OS.
Table 3
Multivariable Cox Regression for OS Among Patients with LM
Variable | All PDAC patients | PDAC patients with LM |
Patients, No. | Hazard Ratio (95% CI) | P Value | Patients, No. | Hazard Ratio (95% CI) | P Value |
Total | 42,834 | | | 16,207 | | |
Sex | | | | | | |
Male | 21,925 | Ref | | 8,762 | Ref | |
Female | 20,909 | 0.91 (0.89–0.93) | < 0.01 | 7,445 | 0.92 (0.89–0.95) | < 0.01 |
Race | | | | | | |
NHW | 30,048 | Ref | | 11,261 | Ref | |
NHB | 5,205 | 1.07 (1.04–1.11) | < 0.01 | 2,158 | NA | NA |
Hispanic | 4,380 | 1.03 (0.99–1.07) | 0.14 | 1,652 | NA | NA |
Other | 3,201 | 0.99 (0.95–1.03) | 0.57 | 1,136 | NA | NA |
Age | | | | | | |
18–39 | 249 | Ref | | 113 | Ref | |
40–59 | 8,404 | 1.32 (1.13–1.53) | < 0.01 | 3,492 | 1.35 (1.10–1.67) | 0.01 |
60–79 | 24,558 | 1.68 (1.44–1.95) | < 0.01 | 9,324 | 1.81 (1.47–2.23) | < 0.01 |
80 up | 9,623 | 2.81 (2.41–3.27) | < 0.01 | 3,278 | 2.98 (2.42–3.68) | < 0.01 |
Insurance | | | | | | |
Insured | 28,793 | Ref | | 10,371 | Ref | |
Uninsured | 1,122 | 1.22 (1.17–1.25) | < 0.01 | 490 | 1.25 (1.14–1.38) | < 0.01 |
Others | 12,919 | 1.26 (1.23–1.30) | < 0.01 | 4,986 | 1.22 (1.19–1.29) | < 0.01 |
Marital | | | | | | |
Married | 23,143 | Ref | | 8,679 | Ref | |
Single | 5,706 | 1.21 (1.17–1.25) | < 0.01 | 2,305 | 1.20 (1.14–1.26) | 0.09 |
Other | 13,985 | 1.23 (1.20–1.26) | < 0.01 | 5,223 | 1.24 (1.19–1.29) | < 0.01 |
Incomea | | | | | | |
Q1 | 10,499 | Ref | | 4,107 | Ref | |
Q2 | 10,333 | 0.93 (0.90–0.96) | < 0.01 | 4,042 | 0.96 (0.92–1.01) | 0.09 |
Q3 | 10,710 | 0.88 (0.85–0.91) | < 0.01 | 4,167 | 0.89 (0.85–0.93) | < 0.01 |
Q4 | 11,291 | 0.83 (0.81–0.86) | < 0.01 | 3,891 | 0.85 (0.81–0.89) | < 0.01 |
Location | | | | | | |
Head | 27,850 | Ref | | 7,957 | Ref | |
Body | 7,390 | 1.18 (1.15–1.21) | < 0.01 | 3,526 | 1.06 (1.02–1.11) | 0.01 |
Tail | 7,594 | 1.36 (1.32–1.40) | < 0.01 | 4,724 | 1.16 (1.12–1.20) | < 0.01 |
T stage | | | | | | |
T1 | 1,667 | Ref | | 471 | Ref | |
T2 | 9,955 | 1.39 (1.30–1.48) | < 0.01 | 4,970 | 0.91 (0.81–1.01) | 0.06 |
T3 | 18,379 | 0.93 (0.88-1.00) | 0.03 | 4,551 | 0.77 (0.69–0.86) | < 0.01 |
T4 | 7,774 | 1.21 (1.13–1.30) | < 0.01 | 2,654 | 0.80 (0.72–0.90) | < 0.01 |
TX | 5,059 | 1.66 (1.54–1.78) | < 0.01 | 3,561 | 0.99 (0.82–1.03) | < 0.01 |
N stage | | | | | | |
N0 | 23,229 | Ref | | 8,434 | Ref | |
N1 | 15,595 | 0.90 (0.88–0.92) | < 0.01 | 5,093 | 1.02 (0.98–1.06) | 0.36 |
NX | 4,010 | 1.51 (1.45–1.56) | < 0.01 | 2,680 | 1.13 (1.08–1.18) | < 0.01 |
Tumor size (cm) | | | | | | |
≤ 2 | 3,496 | Ref | | 834 | Ref | |
2.1-4 | 17,851 | 1.31 (1.26–1.37) | < 0.01 | 5,561 | 1.01 (0.94–1.10) | 0.74 |
≥4 | 16,993 | 1.64 (1.56–1.71) | < 0.01 | 7,554 | 1.16 (1.07–1.25) | < 0.01 |
Unknown | 4,494 | 1.99 (1.88–2.11) | < 0.01 | 2,255 | 1.22 (1.12–1.32) | < 0.01 |
Abbreviation: NHW, non-Hispanic white; NHB, non-Hispanic black. |
a Unknown Income removed from model owing to nonconvergence (n = 1). |
NHB was associated with poorer OS than NHW among all PDAC patients cohort but not among PDAC patients with LM sub-cohort. Although single (vs. married) was significantly associated with poor outcome in all PDAC patients cohort, the association was not significant in PDAC patients with LM sub-cohort. Higher T and N stage were not associated with worse OS in the two cohorts.