Table 2.

Clinical questions discarded from the REDISCOVER guidelines (from Ann Surg. 2024 Feb 26. 10.1097/SLA.0000000000006248)

	LoE	SoR	Expert agreement%	Audience agreement%
Discarded after audience discussions and voting
Following neoadjuvant treatments, in patients with radiologic encasement of the superior mesenteric artery does tumor resection improve survival when compared to continued medical treatments?
In the absence of progression with good biological response complete surgical resection should be considered to improve survival. All patients should be discussed at MDT board. Only high-volume centers should perform these surgeries	Low	Expert opinion	88.1	72
In patients fit for surgery with non-metastatic LA-PDAC involving the superior mesenteric artery who, for any reason, cannot receive preoperative multi-agent chemotherapy, does surgery improve survival when compared to alternative treatments?
In patients with non-metastatic LA-PDAC involving the superior mesenteric artery who are fit for surgery but, for any reason, are unable to receive preoperative multi-agent chemotherapy, chemoradiotherapy should be considered as an alternative to upfront surgery. Given the high level of complexity involved in these procedures, upfront surgery should generally be avoided in these patients. If R2 resection may be avoided, pancreatectomy with resection and reconstruction of the superior mesenteric artery may be carefully evaluated in centers with specific experience and positive postoperative outcomes	Low	Weak	80.2	55
In patients with LA PDAC who received neoadjuvant medical treatments and are fit for surgery but have oligometastic disease, do continued medical treatments improve survival when compared to tumor resection?
In patients with LA-PDAC who received neoadjuvant medical treatments and are fit for surgery but have oligometastic disease, there is no evidence that resection improves survival when compared continued medical treatments. The best approach to oligometastasis in PDAC is determined by a variety of factors, including oncology and patient characteristics. In some patients with oligometastasis who responded to multi-agent chemotherapy, preliminary data suggest that tumor resection may be beneficial, particularly when tumor markers showed a clear decline, patients were in good clinical condition, and resection of the primary tumor aimed to local radicality. The option of resection should be carefully discussed in a multidisciplinary tumor board considering also the burden of surgery, candidly presented to patients, and documented in a written informed consent. Patients should be closely monitored, and outcome information should be entered into prospective databases	Low	Weak	85.1	67
Discarded by the validation committee
In patients fit for surgery with non-metastatic LA-PDAC involving the celiac trunk who, for any reason, cannot receive preoperative multi-agent chemotherapy, does surgery improve survival when compared to alternative treatments?
Chemo-radiotherapy should be taken into consideration instead of upfront surgery in patients with non-metastatic LA-PDAC involving the celiac trunk who are fit for surgery but, for any reason, are unable to receive preoperative multi-agent chemotherapy. In high-volume centers, upfront surgery may be carefully considered if R2 resection can be avoided	Low	Weak	86.1	81
What is the best timing for surgical resection in patients with BR- or LA-PDAC who received primary/neoadjuvant chemo-radiation?
There is no clear evidence about the best timing of surgery in patients with BR- or LA-PDAC following primary/neoadjuvant chemo-radiation. However, delaying surgery > 10 or > 20 weeks, while adding a short course of additional chemotherapy, can improve pathologic response	Low	Weak	81.2	80
Is there an ideal number of chemotherapy cycles before surgery?
There is no clear evidence about the ideal number of chemotherapy cycles before surgery. While more preoperative chemotherapy cycles could prolong survival, the decision when chemotherapy is completed and the patient can be considered for surgery, should be taken on an individual basis by a multidisciplinary pancreas tumor board	Low	Weak	97	95
In patients with BR-PDAC undergoing pancreatic resection, does neoadjuvant chemo-radiation improve oncologic outcomes compared to chemotherapy alone?
Chemo-radiation does not appear to improve oncologic outcomes of patients with BR-PDAC undergoing pancreatic resection, despite higher rates of R0 resection and improved pathological response	High	Strong	91.1	92
In patients with LA-PDAC, does primary chemo-radiation improve oncologic outcomes when compared to chemotherapy alone?
Currently available data do not fully support the hypothesis that chemo-radiation improves oncologic outcomes of LA-PDAC when compared to chemotherapy alone. Well-designed randomized control trials are required to answer this question	Low	Weak	92.1	91
In patients with BR-PDAC who are fit for surgery, do ablation therapies improve oncologic outcomes compared to pancreatic resection?
No study has compared ablation therapies to surgery in patients with BR-PDAC fit for surgery. Therefore, at the present time, there is no evidence supporting the hypothesis that ablation therapies could improve oncologic outcomes compared to pancreatic resection	Low	Weak	92.1	98
In patients with LA-PDAC who are fit for surgery, do ablation therapies improve oncologic outcomes compared to pancreatic resection?
Currently available studies have a retrospective design and are at high risk of selection bias. Therefore, there is no evidence that ablation therapies can improve oncologic outcomes compared to pancreatic resection in patients with LA-PDAC. Preliminary data suggest that ablation therapies could be worth of further investigation	Low	Weak	91.1	96
In patients with LA PDAC who received primary/neoadjuvant medical treatments, are fit for surgery, and have no evidence of distant metastasis but show rising Ca 19.9 levels do continued medical treatments improve survival when compared to tumor resection?
There is no evidence that continued medical treatments improve survival when compared to tumor resection in patients with LA-PDAC who received neoadjuvant medical treatments, are fit for surgery, and have no evidence of distant metastasis but show rising Ca 19.9 levels. Response of Ca 19.9 to neoadjuvant medical treatments provides relevant prognostic information and is used to select surgical candidates. Probably because of this background, the literature does not provide specific information. Whether or not these patients could be offered resection (after chemotherapy switch), should be carefully defined in a multidisciplinary pancreatic tumor board. Potential advantages of pancreatic resection should be carefully balanced against predictably high postoperative morbidity and mortality rates	Low	Weak	94.1	89
In patients requiring resection and reconstruction of the celiac trunk/hepatic artery and the superior mesenteric artery, that typically includes also resection and reconstruction of the superior mesenteric-portal vein, does total pancreatectomy improves postoperative outcomes when compared to partial pancreatectomy?
Partial pancreatectomy is barely ever feasible in patients undergoing pancreatectomy with simultaneous resection and reconstruction of the celiac trunk/hepatic artery and the superior mesenteric artery. In this specific setting, total pancreatectomy facilitates both venous and arterial reconstruction	Low	Weak	96	88

LoE Level of evidence, SoR strength of recommendation