Neoadjuvant treatment for borderline resectable pancreatic adenocarcinoma is associated with higher R0 rate compared to upfront surgery

Figures & data

Figure 1. CONSORT diagram. BRPC: Borderline Resectable Pancreatic Cancer; MTB: Multidisciplinary Tumour Board.

Table 1. Patient and tumour baseline characteristics.

Variable	Total	Neoadjuvant treatment	Upfront surgery	p Value
	n = 79	n = 63	n = 16
Gender				0.78
Male	39 (49.4%)	32 (50.8%)	7 (43.8%)
Female	40 (50.6%)	31 (49.2%)	9 (56.2%)
Mean age (years)	63.4 (36–81)	62.3 (36–76)	67.9 (48–81)	0.02
Performance status				0.59
0–1	73	59	14
2	6	4	2
ASA score				0.14
1–2	72	59	13
>3	7	4	3
Median tumour size (mm)	30 (15–60)	31.5 (17–60)	25 (15–58)	0.01
Tumour location				0.58
Pancreatic head	74 (93.7%)	58 (92%)	16 (100%)
Pancreatic body	5 (6.3%)	5 (8%)	0
Median CA 19.9 at diagnosis (UI/ml)	211.3 (<0.8–6871)	189 (<0.8–6871)	457 (<0.8–4000)	0.68
Arterial contact	41 (51.9%)	35 (55.6%)	6 (37.5%)	0.27
SMA	24 (30.4%)	22 (34.9%)	2 (33.3%)	0.13
CT	2 (2.5%)	2 (3.2%)	0	1
CHA	19 (24.1%)	15 (23.8%)	4 (66.7%)	1
Venous contact	70 (88.6%)	57 (90.5%)	13 (81.3%)	0.38
SMV	65 (82.3%)	54 (85.7%)	11 (84.6%)	0.14
PV	24 (30.4%)	20	4	0.76

Table 2. Surgical and histological outcomes.

Variable	Total	Neoadjuvant treatment	Upfront surgery	p Value
	n = 55	n = 39	n = 16
Surgical outcomes
Procedure
Pancreaticoduodenectomy	50 (90.9%)	34 (87.2%)	16 (100%)	0.31
Distal pancreatectomy/splenectomy	1 (1.8%)	1 (2.6%)	0	1
Total pancreatectomy	4 (7.3%)	4 (10.3%)	0	0.31
Vascular resection	31 (56.4%)	21 (53.8%)	10 (62.5%)	0.76
Mean length of hospital stay (days)	16.81	16.83 (9–35)	16.43 (10–27)	0.41
Postoperative complications (all grades)
Pancreatic fistula	3 (5.5%)	2 (5.1%)	1 (6.3%)	1
Gastroparesis	11 (20%)	6 (15.4%)	5 (31.3%)	0.27
Haemorrhage	3 (5.5%)	3 (7.7%)	0	0.55
Severe postoperative complications (Dindo–Clavien grade ≥ 3)	5 (9.1%)	5 (12.8%)	0	0.31
Re-intervention	3 (5.5%)	3 (7.7%)	0	0.55
Rehospitalization within 90 days	4 (7.3%)	4 (10.3%)	0	0.31
Adjuvant chemotherapy	23 (41.8%)	12 (30.7%)	11 (68.8%)	0.02
Histological outcomes
Resection margins
R0 (0-mm margin)	48(87.3%)	37 (94.9%)	11 (68.8%)	0.02
R0 (1-mm margin)	42(76.4%)	35 (89.7%)	7 (43.8%)	<0.01
ypT stage
T0	4 (7.3%)	4 (10.3%)	0	0.31
T1	7 (12.7%)	7 (17.9%)	0	0.09
T2	4 (7.3%)	4 (10.3%)	0	0.31
T3	39 (70.9%)	24 (61.5%)	15 (93.8%)	0.02
T4	1 (1.8%)	0	1 (6.3%)	0.29
ypN stage				<0.01
N0	36 (65.5%)	31 (79.5%)	5 (31.3%)
N1	19 (34.5%)	8 (20.5%)	11 (68.7%)
ypTN stage
ypT0N0 (pCR)	4 (7.3%)	4 (10.3%)	0	0.31
ypT0-1N0 (pMR)	11 (20%)	11 (28.2%)	0	0.02

ASA: American Society of Anaesthesiologists; SMA: superior mesenteric artery; CT: coeliac trunc; CHA: common hepatic artery; SMV: superior mesenteric vein; PV: portal vein.

Figure 2. (a) Recurrence-free survival and (b) overall survival in the whole population (n = 79) and (c) recurrence-free survival and (d) overall survival among operated patients (n = 55). NAT: Neoadjuvant treatment.

Table 3. Prognostic factors (a) in the entire population (n = 79) and (b) for operated patients (n = 55).

	Recurrence-free survival				Overall survival
Variables	Univariate analysis		Multivariate analysis		Univariate analysis		Multivariate analysis
	HR (95% CI)	p Value	HR (95% CI)	p Value	HR (95% CI)	p Value	HR (95% CI)	p Value
(a)
Neoadjuvant treatment	0.5 (0.3–0.8)	0.01	0.1 (0.1–0.3)	<0.01	0.6 (0.3–1.0)	0.07	0.1 (0.0–0.4)	<0.01
Surgical resection	0.4 (0.2–0.7)	<0.001	0.3 (0.2–0.5)	<0.01	0.4 (0.2–0.7)	<0.01	0.3 (0.2–0.6)	<0.01
Adjuvant chemotherapy	0.8 (0.4–1.3)	0.33	0.5 (0.2–1.2)	0.11	0.6 (0.3–1.2)	0.18	0.3 (0.1–0.9)	0.03
Tumour size (≥35 mm)	0.9 (0.5–1.5)	0.58			0.9 (0.5–1.7)	0.86
CA19-9 at diagnosis	1.0 (0.6–1.8)	0.96			1.0 (0.5–1.9)	0.95
Arterial contact	0.9 (0.6–1.5)	0.82			1.1 (0.6–1.9)	0.79
Venous contact	0.9 (0.4–1.9)	0.80			1.2 (0.5–2.9)	0.76
Age (<65 years old)	0.7 (0.5–1.2)	0.19	0.5 (0.3–0.8)	<0.01	0.6 (0.3–1.0)	0.07	0.5 (0.3–0.9)	0.03
(b)
Neoadjuvant Treatment	0.2 (0.1–0.5)	<0.01	0.2 (0.1–0.4)	<0.01	0.3 (0.1–0.6)	<0.01	0.1 (<0.1–0.4)	<0.01
Adjuvant Chemotherapy	1.1 (0.6–2.1)	0.73	0.5 (0.2–1.1)	0.08	1.0 (0.5–2.2)	0.94	0.2 (0.1–0.6)	<0.01
R1 (0 mm-margin) (vs. R0)	1.6 (0.7–3.9)	0.28			1.7 (0.6- 5.0)	0.33
R1 (1 mm-margin) ( vs. R0)	2.1 (0.9–4.3)	0.06			2.8 (1.2–6.7)	0.02
N1 ( vs. N0)	2.5 (1.3–4.6)	<0.01	2.2 (1.0- 4.9)	0.04	2.5 (1.2–5.3)	0.02
ypT0-1 N0 R0 (vs. no)	0.5 (0.2–1.1)	0.07	0.5 (0.2–1.3)	0.13	0.3 (0.1–0.9)	0.04	0.2 (0.1–0.8)	0.02
ypT0 N0 R0 (vs. no)	0.7 (0.2–2.2)	0.49			0.3 (0.1–2.3)	0.26
Tumour size (≥ 35 mm)	0.9 (0.4–1.6)	0.64			0.9 (0.4–2.1)	0.87
CA 19-9 at diagnosis	1.0 (0.5–1.9)	0.94			0.9 (0.4–1.9)	0.72
Arterial contact	1.0 (0.6–1.9)	0.88			1.2 (0.6–2.4)	0.69
Venous contact	0.6 (0.2–1.4)	0.22	0.4 (0.1–1.1)	0.07	0.7 (0.3–2.1)	0.58
Age (<65 years old)	0.9 (0.5–1.6)	0.73	0.4 (0.2–0.8)	0.01	0.7 (0.3–1.5)	0.38	0.5 (0.2–1.1)	0.1

HR: Hazard Ratio; CI: Confidence Interval; CT: chemotherapy.