Minimally Invasive Surgery for Pancreatic Cancer

Are We There Yet? A Narrative Review

Manish S. Bhandare; Amir Parray; Vikram A. Chaudhari; Shailesh V. Shrikhande

Chin Clin Oncol. 2022;11(1):3

Abstract and Introduction

Abstract

Objective: The aim of this review article is to evaluate the current status of minimally invasive pancreatic resections (MIPR) for pancreatic ductal adenocarcinoma (PDAC), in light of the present evidence.

Background: Published data, largely in the form of retrospective studies and a few prospective/randomized controlled trials have confirmed feasibility, safety, and equivalent short-term outcomes of MIPR in experienced hands. Hence, several recent evidence-based international consensus guidelines have stated MIPR to be at par with the open approach, when these surgeries are performed at high-volume centers. However, longer operative duration, high conversion rates, inferior oncological outcomes, and increased mortality reported in low-volume centers, especially during minimally invasive pancreaticoduodenectomy remains a matter of concern, questioning its broad applicability. Hence, distal pancreatic resections are adopted more widely with a minimally invasive approach as compared to pancreatic head resections. Also, MIPR for PDAC in particular, remains controversial due to lack of high quality data evaluating long-term outcomes of MIPR for PDAC alone. Considering the ongoing impact of neoadjuvant treatment on pancreatic cancer surgery and the corresponding increase in vascular resections and arterial divestment procedures, applicability of MIPR in this setting remains questionable.

Methods: Medline, PubMed, Embase, Cochrane Library, and various international evidence-based guidelines were searched for the current status of minimally invasive resections for pancreatic cancer (PDAC).

Conclusions: The available evidence establishes the feasibility and safety of MIPR, however for PDAC the widespread application remains controversial owing to a dearth of literature evaluating the long-term outcomes. Apart from the outcomes, establishing the exact indications, appropriate patient selection, enhanced cost, and learning curve issues need further studies.

Introduction

Minimally invasive surgery (MIS) has gradually evolved, especially in the past two decades; and now is an integral part of management for almost all digestive diseases. In gastrointestinal (GI) cancers, MIS has shown equivalent results to the open approach for early gastric and colorectal cancers.^[1–3] Technological advances and the development of specific skill sets required for this approach by dedicated surgical teams led to rapid development in laparoscopic and robotic surgery for GI cancers.

The minimally invasive approach did not gain much popularity for pancreatic surgery for a long time since its first introduction in the early 1990s.^[4,5] Probable reasons being the anatomic disadvantages, i.e., retroperitoneal location of the organ, its intimate relations with major blood vessels and, the soft, friable, unforgiving nature of the gland. However, much progress has been made in the past decade and today MIS is widely accepted for managing benign pancreatic lesions or tumors with low malignant potential, especially in the distal pancreas.

MIPR has the potential to provide unreplaceable advantages to patients undergoing surgery for pancreatic cancer in terms of early recovery, fewer complications, reduced hospital stay, and cosmetically pleasing wounds. Several retrospective studies and a few randomized trials have demonstrated the safety and feasibility of minimally invasive pancreatic resections (MIPR), i.e., minimally invasive pancreaticoduodenectomy (MIPD), and minimally invasive distal pancreatectomy (MIDP). Although these studies reported favorable outcomes of certain parameters with MIS (lower blood loss, morbidity, and shorter hospital stay); the longer operative duration, high conversion rates, inferior oncological outcomes, and increased mortality reported in low-volume centers remain a matter of concern. Hospital volumes have a strong impact on postoperative outcomes for major pancreatic resections, even with the conventional open approach.^[6] With MIPR, the surgical complexity increases further, and hence it is recommended that such procedures are performed at specialized centers with a high volume of pancreatic surgery. Furthermore, the mid-term and long-term outcomes of MIPR for pancreatic ductal adenocarcinoma (PDAC) along with the issues of the indications and learning curve are controversial and need further assessment.

Also, as neoadjuvant therapy (NAT) is being more utilized for resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC), prospective evaluation of MIPR for PDAC after NAT remains the job at the fore.

In the present article, we intend to provide an overview of the progress made so far and the current position of MIPR for PDAC. We present the following article in accordance with the Narrative Review reporting checklist (available at https://cco.amegroups.com/article/view/10.21037/cco-21-131/rc).

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Table 1. Oncological and perioperative outcomes of minimally invasive vs. open distal pancreatectomy for pancreatic cancer
Authors/year	Procedure/numbers	Propensity matching	Oncological outcomes								Per-operative outcomes
Authors/year	Procedure/numbers	Propensity matching	R0 resection (%)	P value	LN Harvest	P value	Overall survival (months)	P value	Adjuvant chemotherapy (%)	P value	Operative time (min)	P value	Blood loss (mL)	P value	Hospital stay (days)	P value	Post-operative complication	P value
Kooby et al. 2010 (14)	Lap/Open; 23/189	–	74/73	NS	13.8±8.4; 12.5±8.5	NS	MST 11 months; 11 months	NS	57; 70	NS	238.4±68.1; 230.4±80.4	NS	422±473; 790±828	0.004	7.4±3.4; 10.7±6.3	0.03	–	–
Magge et al. 2013 (15)	MIS (Lap &Robotic)/ Open; 28/34	–	86/88	NS	11 (IQR: 8–20); 12 (IQR: 6–19)	NS	Only comparison provided	NS	–	–	317±23; 294±24	NS	790±828; 290±60	0.006	6 (IQR: 3); 8 (IQR: 2.75)	0.03	39% vs. 50%	NS
Hu et al. 2014 (16)	Lap/Open; 11/23	–	100/100	NS	14.8±4.5; 16.1±5.7	NS	42.0±8.6 months; 54.0±5.8 months	>0.05	–	–	150.0±54.0; 160±48.0	NS	100 [50–400]; 150 [50–350]	NS	5.2±2.5; 8.6±3.9	0.01	–	–
Rehman et al. 2014 (17)	Lap/Open;8/14	–	88/86	NS	16 [1–27]; 14 [0–26]	NS	MST; 33 vs. 52 months	NS	–	–	376 [300–534]; 274 [180–420]	0.009	306 [250–535]; 650 [145–1,300]	NS	8 [5–14]; 12 [6–21]	0.05	37% vs. 42%	NS
Lee et al. 2014 (18)	MIS (Lap &Robotic)/ Open; 10/40	Yes	100/87.5	NS	11.7±7.2; 12.1±8.1	NS	Only comparison provided	0.05	70; 65	NS	330±168.2; 253.3±124.7	NS	440±382.1; 625.4±878.8	NS	12.7±7.1; 22.1±27.1	0.05	20% vs. 32.5%	NS
Shin et al. 2015 (19)	Lap/Open; 70/80	–	75.7/83.8	NS	12 [1–34]; 10 [1–64]	NS	MST; 33 vs. 29 months	NS	78.6; 68.8	NS	239 [125–397]; 254 [115–573]	NS	–	–	9 [5–29]; 12 [7–87]	<0.001	20% vs. 25.7%	NS
Sulpice et al. 2015 (20)	Lap/Open; 347/2406	–	–	–	–	–	MST; 62.5 vs. 36.7 months	0.0001	–	–	–	–	–	–	14.9±8.9; 19.6±14.6	<0.0001	6.6% vs. 10.4%	NS
Sharp et al. 2015 (21)	Lap/Open; 144/625	–	87/78	0.04	14.9±10.0; 13.3±9.9	NS	–	–	–	–	–	–	–	–	6.8±4.6; 8.9±7.5	<0.001	–	–
Zhang et al. 2015 (22)	Lap/Open; 17/34	–	94/85	NS	9 [5–15]; 8 [2–22]	NS	MST; 14 vs. 14 months	NS	76.5; 76.5	NS	190 [100–390]; 245 [155–420]	NS	50 [30–500]; 400 [100–3,900]	0.000	13 [4–23]; 15.5 [6–40]	0.022	35.2% vs. 41%	NS
Stauffer et al. 2016 (23)	Lap/Open; 44/28	–	95/82	NS	25.9 [5–48]; 12.7 [1–45]	0.0001	MST; 26.6 vs. 26.4 months	NS	75.6; 75	NS	254 [99–521]; 266 [131–543]	NS	332 [10–2,650]; 874 [150–3,400]	0.00012	5.1 [2–17]; 9.4 [4–36]	0.0001	13.6% vs. 25%	NS
Anderson et al. 2017 (24)	MIS (Lap &Robotic)/ Open; 505/1302	–	85/79	<0.001	12 [7–19]; 12 [7–19]	NS	3 yr OS 55%; 3 yr OS 52%	NS	57.8; 53.8	NS	–	–	–	–	6 [5–8]; 7 [6–10]	0.0001	–	–
Plotkin et al. 2017 (25)	MIS (Lap &Robotic)/ Open; 166/335	–	–	–	–	–	–	–	–	–	239±9.0; 250±6.2	NS	–	–	5±0.31; 7±0.51	0.009	31% vs. 42%	NS
Kantor et al. 2017 (26)	Lap/Open; 349/1,205	–	82/75	<0.001	14.0±11.7; 14.8±12.0	NS	MST; 29.9 vs. 24 months	NS	67.9; 61.8	NS	–	–	–	–	7.1±6.0; 8.7±7.3	<0.01	–	–
Bauman et al. 2017 (27)	Lap/Open; 33/46	–	77/87	NS	14.5±1.1; 17.5±1.2	NS	MST; 17.9 vs. 15.1 months	NS	61; 63	NS	3.9±0.2 (h); 4.2±0.2 (h)	NS	310±68; 597±95	0.016	7.6±1.4; 9±0.7	0.44	52% vs. 70%	NS
Raoof et al. 2018 (28)	Lap/Open; 563/563	Yes	85/81	NS	12 [7–18]; 1 [6–18.5]	NS	3 yr OS 41.6%; 3 yr OS 36.0%	NS	–	–	–	–	–	–	6 [5–8]; 7 [5–9]	<0.001	–	–
van Hilst et al. 2019 (29)	MIS (Lap &Robotic)/ Open; 340/340	Yes	67/58	0.01	14 [8–22]; 22 [14–31]	<0.001	MST; 28 vs. 31 months	NS	76; 73	NS	240 [180–295]; 230 [178–286]	NS	200 [60–400]; 300 [150–500]	0.001	8 [6–12]; 9 [7–14]	<0.001	18% vs. 21%	NS

MIDP, minimally invasive distal pancreatectomy; ODP, open distal pancreatectomy; LDP, laparoscopic distal pancreatectomy; RDP, robot-assisted distal pancreatectomy; MIPD, minimally invasive pancreatoduodenectomy; OPD, open pancreatoduodenectomy; LPD, laparoscopic pancreatoduodenectomy; RPD, robot-assisted pancreatoduodenectomy.

Table 2. Ongoing randomized controlled trials evaluating minimally invasive pancreatic resection, MIPR
Trial/region/design	Sample size	Results expected	Arms	Primary outcome measure
DIPLOMA (NCT04483726), International, Multicentre Patient- and assessor blinded	258	2021	MIDP (RDP or LDP) vs. ODP	R0 resection
(NCT03957135), Korean, Multicentre Non-blinded	244	2025	LDP vs. ODP	2-year survival
(NCT03792932), Chinese, Multicentre Non-blinded	306	2024	LDP vs. ODP	2-year disease free survival
PORTAL (NCT04400357), China, Phase III Multicentre Patient blinded	244	2024	RPD vs. OPD	Time to functional recovery
(NCT04171440), USA, Phase III Single-centre Patient-blinded	240	2025	MIPD (RPD or LPD) vs. OPD	Time to functional recovery

Table 3. Oncological and perioperative outcomes of minimally invasive *vs.* open pancreaticoduodenectomy for pancreatic cancer
Authors/year	Procedure/numbers	Propensity matching	Oncological outcomes								Per-operative outcomes
Authors/year	Procedure/numbers	Propensity matching	R0 resection (%)	P value	LN harvest	P value	Overall survival (months)	P value	Adjuvant chemotherapy (%)	P value	Operative time (min)	P value	Blood loss (mL)	P value	Hospital stay (days)	P value	Post-operative complication	P value
Croome et al. 2014 (57)	Lap/Open; 108/214	–	77/76.6	NS	21.4±8.1; 20.1±7.5	NS	MST 25 months; 21.8 months	NS	76; 76	NS	379.4±93.5; 387.6±91.8	NS	492.4±519.3; 866.7±733.7	0.001	6 [4–118]; 9 [5–73]	<0.001	5.6% vs. 13.6%	NS
Sharpe et al. 2015 (58)	Lap/Open; 384/4,037	–	80/74	0.02	18±9.7; 16±9.6	0.008	–	–	–	–	–	–	–	–	10±8.0; 12±9.7	<0.0001	–	–
Nussbaum et al. 2016 (59)	MIS (Lap &Robotic)/Open; 1,191/6,776	–	79.8/77.9	NS	17.4±10.0; 16.5±9.6	<0.01	2 yr OS 43%; 2 yr OS 47%	NS	55.3; 52.7	NS	–	–	–	–	11.4±10.3; 12.3±9.5	<0.01	–	–
Staufer et al. et al. 2017 (60)	Lap/Open; 58/193	–	84.5/79.8	NS	27 [9–70]; 17 [1–63]	<0.001	MST;18.5 vs. 20.3 months	NS	75.9; 73.5	NS	518 [313–761]; 375 [159–681]	<0.001	250 [50–8,500]; 600 [50–7,800]	0.001	6 [4–68]; 9 [4–71]	<0.001	53% vs. 66%	NS
Kantor et al. 2017 (61)	Lap/Open; 828/7,385	–	79.1/76.8	NS	18.1±9.5; 17.1±9.6	0.01	MST;20.7 vs. 20.9 months	NS	61.4; 60.4	NS	–	–	–	–	10.2±8.5; 11.8±9.3	<0.01	–	–
Chapman et al. 2018 (62)	Lap/Open; 248/1,520	–	77.4/73	NS	–	–	MST;19.8 vs. 15.6 months	0.02	35.9; 36	NS	–	–	–	–	10 [7–15]; 10 [7–15.5]	0.06	–	–
Kuesters et al. 2018 (63)	Lap/Open; 62/278	–	87/71	0.01	17 [7–28]; 16 [2–47]	NS	5 yr OS 20%; 5 yr OS 14%	NS	–	–	477 [295–686]; 428 [245–714]	<0.001	–	–	14 [7–39]; 16 [5–379]	0.03	53% vs. 55%	NS
Zhou et al. 2019 (64)	Lap/Open; 55/93	Yes	100/94.6	NS	18 [13–25]; 11 [7–14.5]	0.001	MST; 20 vs. 18.7 months	NS	47.3; 50.5	NS	330 [260–360]; 260 [07.5– 325.5]	<0.001	150 [100–200]; 200 [150–350]	0.001	13 [11–20]; 14 [10–20]	NS	49% vs. 71%	0.008
Choi et al. 2020 (65)	Lap/Open; 27/34	–	92.5/70.5	NS	13.33±9.21; 20.65±9.47	NS	MST;44.6 vs. 45.2 months	NS	77.7; 79.4	NS	477.7±60.75; 471.21±78.62	NS	232.59±178.68; 448.82±343.83	0.003	21.19±11.13; 19.94±9.79	NS	–	–
Girgis et al. 2021 (66)	Robotic/Open; 226/330	–	21.3/18	NS	25.7±11.5; 31.7±13.8	0.0001	MST, 25 vs. 23 months	0.055	90.7/89.2	NS	403±125; 353±109	0.0001	–	–	7 vs. 9	0.001	32% vs. 12% (wound infection)	0.0001
Kwon et al. 2020 (67)	MIPD/Open; 76/972	Yes	75/71	NS	18.6±9.9; 22±10.6	0.006	MST, 25 vs. 23 months	0.055	79; 68	0.001	392±96; 368±99	0.04	–	–	12±5.5; 15±8.6	0.001	30% vs. 35.0%	0.3