Neoadjuvant therapy offers longer survival than upfront surgery for poorly differentiated and higher stage pancreatic cancer

Figures & data

Table 1. Patient characteristics of PDAC patients operated in 2000–2015 according to preoperative treatment.

	NEO (n = 75)	US (n = 150)	p value
Age at operation, median (range)	65 (40–83)	66 (45–82)	NS
≥65 years	39 (50%)	79 (53%)	NS
Gender, female	42 (56%)	83 (55%)	NS
pTN* (AJCC 7th edition)
T0	3 (4%)	0	.001
T1	9 (12%)	5 (3%)
T2	18 (25%)	30 (20%)
T3	42 (58%)	115 (77%)
T4	1 (1%)	0
N0	38 (51%)	42 (28%)	.001
N1	36 (49%)	108 (72%)
LNR*
<20 %	66 (89%)	109 (74%)	.009
≥20 %	8 (11%)	39 (26%)
Stage* (AJCC 7th edition)
0	2 (3%)	0	.000
IA	5 (7%)	3 (2%)
IB	10 (14%)	16 (11%)
IIA	20 (27%)	23 (15%)
IIB	34 (47%)	107 (71%)
III	1 (1%)	0
IV**	1 (1%)	1 (1%)
pTumor size (mm), median (IQR)	25 (20–30)	30 (25–40)	.000
Grade*
1	11 (15%)	27 (18%)	NS
2	48 (66%)	97 (65%)
3	14 (19%)	26 (17%)
R0 resection*	58 (82%)	106 (75%)	NS
Vascular resection	34 (45%)	49 (33%)	NS
Perineural invasion*	47 (63%)	120 (81%)	.005
Perivascular invasion*	16 (21%)	58 (39%)	.010
Imaging (median in mm, range)
Tumor size pre-therapy	31 (10–89)
Tumor size post-therapy	23 (0–47)
Size difference	9 (0–42)
Missing/inadequate imaging	9 (12%)
Preoperative laboratory results***
CA 19–9 (ln(kU/l)), median (IQR)	4.4 (2.6–5.9)	4.8 (3.4–6.5)	NS
CEA (µg/l), median (IQR)	2.7 (1.7–3.9)	2.9 (1.8–5.0)	NS

NEO: neoadjuvant therapy; US: upfront surgery; AJCC: American Joint Committee on Cancer; LNR: lymph node ratio; IQR: interquartile range; NS: non-significant.

* Missing data: two patients lacked adequate TNM classification and stage; three patients’ lymph node metastases were inconclusive. Information on perineural and perivascular invasion was missing in one patient. Resection margin status was missing in seven patients. No grade available in two patients due to complete response.

** Preoperatively treated patient had an adrenal metastasis, and patient undergoing upfront surgery had a para-aortal lymph node metastasis. Metastases were not confirmed before surgery. These patients were excluded from survival analyses.

*** Mann–Whitney U-test. Natural logarithm was taken from CA19–9 value.

All 2 × 2 tests were done by using the Fisher’s exact test. Linear by linear association was used for tables with more than two rows. Missing data were excluded.

Significant values are shown in bold.

Figure 1. A. DSS in operated PDAC patients (2010–2015) according to preoperative treatment. Median survival for neoadjuvant therapy was 35 (95% CI 25–44) months and for upfront surgery 26 (95% CI 20–31) months, p = .008. B. DFS in operated PDAC patients (2010–2015) according to preoperative treatment. Median survival for neoadjuvant therapy was 25 (95% CI 13–36) months and for upfront surgery 13 (95% CI 6–21) months, p = .001.

Table 2. DSS and DFS in operated PDAC patients according to preoperative treatment.

	NEO (95% CI) months	US (95% CI) months	p value
Patients treated in 2000–2015 (n = 223)
DSS	34 (29–39)	26 (20–32)	.016
DFS	22 (17–27)	13 (9–17)	.001
Patients treated in 2000–2009 (n = 91)
DSS	30 (22–38)	27 (17–37)	NS
DFS	15 (10–19)	12 (10–15)	NS
Patients treated in 2010–2015 (n = 132)
DSS	35 (25–44)	26 (20–31)	.008
DFS	25 (13–36)	13 (6–21)	.001

NEO: neoadjuvant therapy; US: upfront surgery; DSS: disease-specific survival; DFS: disease-free survival; NS: non-significant. Survival was estimated with Kaplan–Meier and compared with the Breslow test.

Significant values are shown in bold.

Figure 2. A. DSS in patients with grade 3 tumor according to preoperative treatment. Patients: n(NEO) = 14, n(US) = 26. Median survival for neoadjuvant therapy 30 (95% CI 17–42) months and for upfront surgery 11 (95% CI 8–15) months, p = .004. NEO: neoadjuvant therapy; US: upfront surgery. B. DFS in patients with grade 3 tumor according to preoperative treatment. Patients: n(NEO) = 14, n(US) = 26. Median survival for neoadjuvant therapy was 21 (95% CI 11–31) months and for upfront surgery 7 (95% CI 5–8) months, p = .001. NEO: neoadjuvant therapy; US: upfront surgery.

Figure 3. A. DSS in operated stage IIB–III pancreatic cancer patients according to preoperative treatment. Patients: n(NEO) = 35, n(US) = 107. Median survival for neoadjuvant therapy was 34 (95% CI 29–40) months and for upfront surgery 20 (95% CI 14–26) months, p = .006. NEO: neoadjuvant therapy; US: upfront surgery. B. DFS in operated stage IIB–III pancreatic cancer patients according to preoperative treatment. Patients: n(NEO) = 35, n(US) = 107. Median survival for neoadjuvant therapy was 21 (95% CI 12–29) months and for upfront surgery 10 (95% CI 7–13) months, p = .001. NEO: neoadjuvant therapy; US: upfront surgery.

Table 3. DSS and DFS survival in operated PDAC patients according to different prognostic parameters and preoperative treatment.

	NEO (95% CI) months	p value	NEO vs. US p value	US (95% CI) months	p value
DSS
Tumor grade 1	36 (34–38)	NS	NS	43 (32–54)	.000
Tumor grade 2	31 (27–34)		NS	27 (20–35)
Tumor grade 3	30 (17–42)		.004	11 (8–15)
DFS
Tumor grade 1	23 (15–31)	NS	NS	18 (12–25)	.000
Tumor grade 2	18 (12–25)		NS	13 (8–18)
Tumor grade 3	21 (11–31)		.001	7 (5–8)
DSS
Stage 0–IIA	31 (25–37)	NS	NS	45 (33–56)	.004
Stage IIB–III	34 (29–40)		.006	20 (14–26)
DFS
Stage 0–IIA	19 (13–26)	NS	NS	24 (7–41)	.003
Stage IIB–III	21 (12–29)		.001	10 (7–13)
DSS
R0 margin	36 (34–38)	NS	NS	29 (21–37)	NS
R1 margin	31 (14–47)		NS	17 (12–21)
DFS
R0 margin	23 (17–29)	NS	.028	16 (11–21)	.001
R1 margin	17 (11–22)		.024	7 (2–11)

NEO: neoadjuvant therapy; US: upfront surgery; DSS: disease-specific survival; DFS: disease-free survival; NS: non-significant. Survival times were estimated with Kaplan–Meier and compared with the Breslow test. Stage according to AJCC 7th edition guidelines.

Significant values are shown in bold.