Para-aortic Lymphnodes Removal During Upfront Pancreaticoduodenectomy

Pancreas Cancer Clinical Trial

— PALN  

Official title:

Para-aortic Lymphnodes Removal During Upfront Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoa: Should it be Performed? A Multicentre Randomized Controlled Trial.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04571294
• Other study ID #: 451/20
• Status: Recruiting
• Phase: N/A
• Start date: May 26, 2020
• Est. completion date: May 26, 2024

Study information

• Verified date: September 2020
• Source: Humanitas Hospital, Italy
• Contact: Gennaro Nappo, MD
• Phone: +39(0)282247701
• Email: gennaro.nappo[@]humanitas.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Pancreaticoduodenectomy (PD) associated with lymphadenectomy is the only curative option for patients affected by pancreatic ductal adenocarcinoma (PDAC). In 2014, the International Study Group on Pancreatic Surgery (ISGPS) defined the "standard lymphadenectomy", that is mandatory during PD for PDAC. Lymphadenectomy should include the removal of the hepatoduodenal ligament nodes (stations 5, 6, 12b1, 12b2, 12c according the classification of Japanese Pancreas Society), nodes along the hepatic artery (station 8a), the posterior surface of the pancreatic head (station 13a and 13b), the superior mesenteric artery (14a right lateral side, 14b right lateral side) and nodes of the anterior surface of the pancreatic head (stations 17a and 17b). The inclusion of para-aortic lymphnodes (PALN) (station 16) in standard lymphadenectomy is still matter of debate. Moreover, some retrospectives or prospective studies reported that the presence of PALN metastases has a significant negative prognostic impact. Until now, no randomized studies comparing PD associated with standard lymphadenectomy with or without removal of PALN have been published. The aim of this study is to evaluate if the removal of station 16 should be routinely included in standard lymphadenectomy during PD for PDAC.

Description:

Pancreaticoduodenectomy (PD) with lymphadenectomy is the current treatment of pancreatic ductal adenocarcinoma (PDAC). The optimal lymphadenectomy during PD (standard versus extended) has been largely debated during the last two decades. Four randomized controlled trials (RCTs) published afterward reported no survival benefit, and no arguments could be presented based on the evidence of these studies to support the role of extended lymphadenectomy during PD. A similar conclusion was underlined also in two meta-analyses, the first from Michalski et al., in which 3 RCTs were analyzed, and the second from Iqbal et al., in which both RCTs and cohort studies were included, both of which showed no benefit of extended lymphadenectomy. However, the definition of lymphadenectomy varied considerably between the RCTs. For this reason, in 2014, the International Study Group on Pancreatic Surgery (ISGPS) defined the "standard lymphadenectomy" during PD for PDAC. Lymphadenectomy should include the removal of the hepatoduodenal ligament nodes (stations 5, 6, 12b1, 12b2, 12c according the classification of Japanese Pancreas Society), nodes along the hepatic artery (station 8a), the posterior surface of the pancreatic head (station 13a and 13b), the superior mesenteric artery (14a right lateral side, 14b left lateral side) and nodes of the anterior surface of the pancreatic head (stations 17a and 17b). Para-aortic lymph nodes (PALN; station 16) are considered as "extra-regional" lymph nodes. Some questions about PALN still remain open: a) should the removal of station 16 be routinely included in the standard lymphadenectomy during PD for PDAC? b) in case of removal of station 16 and intraoperative demonstration of PALN metastases at frozen section, should PD be avoided ? Several retrospective reports described that the prognosis of patients with metastatic PALN is significantly worse if compared with patients with negative PALN. Two recent-metaanalyses have been published on this topic, confirming that PALN metastases correlated with poor prognosis in patients with PDAC. However, these meta-analyses concluded that, due to the presence of some long survivors even in cases of PALN metastases, the definitive avoidance of PD in these cases needs further investigation. Until now, no consensus in case of intraoperative metastatic PALN has been reached. Moreover, it's not still clear if the removal of PALN during PD should be routinely performed. Until now, no randomized studies comparing PD with or without removal of PALN have been published. In 2014, during the consensus meeting of ISGPS, there was extensive discussion about PALN removal: no strong recommendation was formulated on dissecting station 16 routinely and it was not included in standard lymphadenectomy. For this reason, we decided to plan this multicentric RCT that compares upfront PD with and without the removal of PALN, in order to evaluate if their removal should be routinely included in standard lymphadenectomy during PD for PDAC.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: May 26, 2024
• Est. primary completion date: May 26, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• pre-operative radiological or histological diagnosis of pancreatic head PDAC, including PDAC arising from IPMN (invasive-IPMN) (in case of not confirmation of PDAC at final pathological examination, the case will be considered as a "drop out" and excluded from the study);

• upfront PD associated with standard lymphadenectomy.

Exclusion Criteria:

• PD performed after neoadjuvant treatment;

• PALN metastases diagnosed by a pre-operative PET-FDG (if performed);

• intraoperative distant metastases;

• R2 resection.

Related Conditions & MeSH terms

• Lymphadenopathy
• Pancreas Adenocarcinoma
• Pancreas Cancer
• Pancreatic Neoplasms
• Pancreaticoduodenal Lymphadenopathy

Intervention

Procedure:
• removal of para-aortic lymphnodes (PALN)
During pancreaticoduodenectomy, para-aortic lymphnodes (PALN) will be removed for the surgeon

Locations

Country	Name	City	State
Italy	Humanitas Research Hospital	Rozzano	Italy/Milan

Sponsors (1)

Lead Sponsor	Collaborator
Humanitas Hospital, Italy

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	The primary endpoint is to compare overall survival (OS) in patients with (group A) and without (group B) removal of PALN	48 months
Secondary	PALN metastases	to evaluate the rate of PALN metastases (for group A, only)	12 months
Secondary	DFS in case of PALN metastases	to evaluate the prognostic impact, in terms of Disease Free Survival (DFS), of PALN metastases (for group A, only)	48 months
Secondary	OS in case of PALN metastases	to evaluate the prognostic impact, in terms of OS, of PALN metastases (for group A, only)	48 months
Secondary	predictive factors of PALN metastases	to evaluate possible pre- and intra-operative predictive factors of PALN metastases (for group A, only): diameter of PALN, jaundice, preoperative biliary stent, time to surgery from diagnosis)	12 months
Secondary	post-operative outcomes	to compare post-operative outcomes in both study groups (overall morbidity, Clavien-Dindoo classification, post-operative pancreatic fistula, hemorrhage, biliary fistula, other surgical and medical compliation, 30-day and 90-day mortality)	12 months