Resection of isolated liver oligometastatic disease in pancreatic ductal adenocarcinoma: Is there a survival benefit? A systematic review

Table 1 Characteristics of included studies

Ref.	Country and Units	Single or multicentre	Metastasectomy timing	Control group?	Total patients included	Total no controls	Gender (% male)	Pancreas resection types included
Dünschede et al[23], 2010	Germany	Single	Metachronous and synchronous	Yes	13	10	54	PD, DP, TP
Hackert et al[31], 2017	Germany	Single	Metachronous and synchronous	No	85	-	55	PD, DP, TP
Hamad et al[24], 2022	United States	Single	Synchronous only	Yes	137	-	-	PD only
Klein et al[25], 2012	Germany	Single	Synchronous only	Yes	22	22	64	PD, DP, TP
Shi et al[32], 2016	China	Single	Synchronous only	Yes	30	39	67	PD, DP, TP
Schwarz et al[26], 2020	Germany, Austria and United States	Multicentre	Metachronous only	Yes	25	8	42	NR
Tachezy et al[27], 2016	Greece, France, Italy and Germany	Multicentre	Synchronous only	Yes	69	69	63	PD, DP, TP
Takeda et al[28], 2023	Japan	Single	Synchronous only	Yes	5	-	80	NR
Yang et al[29], 2020	China	Single	Synchronous only	Yes	48	10	58	PD, DP
Zanini et al[30], 2015	Italy	Single	Metachronous and synchronous	No	15	-	53	PD, DP, TP

PDAC: Pancreatic ductal adenocarcinoma; PD: Pancreatoduodenectomy; DP: Distal pancreatectomy; TP: Total pancreatectomy; NR: Not reported.

Table 2 Synchronous isolated liver metastases resection outcomes

Ref.	n of patients	n of metastases (median, IQR)	Mean diameter of LM, cm	Type of liver resection	Primary resection R0 rate	Post op morbidity	Post op mortality	DFS (months)	OS (months)	5-yr survival
Dünschede et al[23], 2010	9	3 (1-5)	3.5 (1-9)	NAR (6), Seg (1), HH (2)	100%	33%	0%	-	8	0%
Hackert et al[31], 2017	62	-	-	NAR (59), Seg (2), HH (1)	-	47%	1.60%	-	10.6	-
Hamad et al[24], 2022	137	-	-	-	-	-	-	-	15.6	-
Klein et al[25], 2012	22	-	-	NAR (15), Seg (7)	32%	27%	0%	-	7.4	0%
Shi et al[32], 2016	30	-	-	-	-	-	-	-	15.7	3.3%
Tachezy et al[27], 2016	69	2 (1-2)	-	-	58%	68%	1%	-	14.5	5.8%
Takeda et al[28], 2023	5	2 (2-2)	-	-	-	23% CD3+	0%	20.9	33	-
Yang et al[29], 2020	48	-	-	NAR (43), Seg (4), HH (1)	100%	15%	4.1%	-	7.8	0%
Zanini et al[30], 2015	11	2 (1-2)	2.4 (1.75-2.5)	NAR (1), Seg (10)	-	27% CD3+; 54% overall	0%	5.2	9.1	0%

Seg: Segmentectomy; HH: Hemihepatectomy; NAR: Non-anatomical resection; CD: Clavien-Dindo; DFS: Disease free survival; OS: Overall survival.

Table 3 Synchronous isolated liver metastases resection outcomes vs controls

Ref.		Treatment modality	n of patients	Median age	n of mets	Max met diameter	Adjuvant chemotherapy	OS	P value
Dünschede et al[23], 2010	Control	Gemcitabine, no surgical resection	5	63	1	3.5 (1-9)	NR	Median 11 mo	NR
	Intervention	Synchronous resection of pancreatic primary and liver metastases	9	55	3	Mean 3.5 cm	NR	Median 8 mo
Klein et al[25], 2012	Control	Pancreatic primary resection only. No liver metastases	22	Mean 57.5	-	-	22 (100)	Median 14.6 mo	0.015
	Intervention	Synchronous resection of pancreatic primary and liver metastases	22	Mean 57.5	-	-	22 (100)	Median 7.6 mo
Shi et al[32], 2016	Control	Palliative bypass and gemcitabine	39	Mean 63	-	-	NR	Median 16.9 mo	0.085
	Intervention	Synchronous resection of pancreatic primary and liver metastases	30	Mean 62.2	-	-	NR	Median 15.7 mo
Tachezy et al[27], 2016	Control	No resection, palliative bypass/exploration and chemotherapy (FOLFIRINOX or Gemcitabine)	69	Median 62	2 (1-8)	-	58 (84)	Median 7.5 mo	< 0.001
	Intervention	Synchronous resection of pancreatic primary and liver metastases	69	Median 65	2 (1-11)	-	58 (84)	Median 14.5 mo
Yang et al[29], 2020	Control	Systemic gemcitabine-based chemotherapy, no surgery	31	Mean 61.1	-	-	NR	Median 7.6 mo	0.37
	Intervention	Synchronous resection of pancreatic primary and liver metastases	48	Mean 61.1	-	-	NR	Median 7.8 mo

NR: Not reported; OS: Overall survival.

Table 4 Metachronous isolated liver metastases resection outcomes

Ref.	n of patients	Age (median IQR)	n of Mets (median, IQR)	Mean diameter of LM, cm	Type of liver resection	Time to metastases detection or resection	Postop morbidity	Postop mortality	OS1 (median, months)	5-yr survival
Dünschede et al[23], 2010	4	42 (41–81)	1.75 (1–2)	2.2 (1–3)	NAR (3), Seg (1), HH (6)	92	0	0	31	0%
Hackert et al[31], 2017	23	60.4 (mean, for SM and MM)			NAR (14), Seg (3), HH (6)	18.43	34%	4.30%	14.8	-
Schwarz et al[26], 2020	25	63.8	1 (1,2)	-	NAR (8), Seg (15), HH (2)	17.83	32% CD1; 12% CD3	0%	36.8	0%
Zanini et al[30], 2015	4	48 (40.5-55.25)	1 (1-1)	2.2 (2-2.5)	NAR (3), HH (1)	8.02	25% CD3+; 75% overall	0%	11.4	0%

¹All median overall survival values are from liver metastases resection except Dünschede et al[23]. Which is reported from time of diagnosis.

²Time from primary resection to detection of LM.

³time from primary resection to resection of LM.

Seg: Segmentectomy; HH: Hemihepatectomy; NAR: Non-anatomical resection; CD: Clavien-Dindo; OS: Overall survival.

Table 5 Metachronous isolated liver metastases resection outcomes vs controls

Ref.		Treatment modality	n of patients	Median age	n of mets	Max met diameter	Overall survival1 (median, months)	P value
Dünschede et al[23], 2010	Control	Systemic chemotherapy (gemcitabine), no surgery	5	42	1.75	2.2 cm (average)	11 (8-19)	< 0.05
	Intervention	Resection of liver metastases	4	42	1.75	2.2 cm (average)	31 (20-51)
Schwarz et al[26], 2020	Control	Systemic chemotherapy (gemcitabine), no surgery	8	Median 69.4	2	-	9.2	0.0007
	Intervention	Resection of liver metastases	25	Median 63.8	1	-	36.8

¹All median overall survival values are from liver metastases resection except Dünschede et al[23]. Which is reported from time of diagnosis.