Recommendations for research

The guideline committee has made the following recommendations for research. The committee's full set of research recommendations is detailed in the full guideline.

1 Neoadjuvant therapy

Prospective randomised trials should be undertaken to compare preoperative (neoadjuvant) therapy with standard postoperative therapy in people with resectable pancreatic cancer.

Why this is important

The survival rate of pancreatic cancer after surgical resection is very low, which suggests that most patients have metastatic disease at the time of surgery. In addition, complications of surgery may stop people from having adjuvant therapy. This makes neoadjuvant therapy an attractive option. However, the evidence for neoadjuvant therapy is limited and low quality. Using neoadjuvant therapy means delaying surgery, and it is possible that during this delay pancreatic cancer will progress and become unresectable in some people, negating any benefit of neoadjuvant therapy.

Research is needed to compare neoadjuvant treatments (which might be chemotherapy, radiotherapy or both) with surgery followed by adjuvant chemotherapy. The outcomes of interest are:

  • feasibility of delivering neoadjuvant treatment

  • feasibility of randomising patients

  • objective response rate of neoadjuvant therapy

  • R0 resection rate

  • surgical complications, length of hospital stay, mortality of surgery

  • delivery of planned treatment

  • disease-free survival and overall survival after surgery

  • quality of life, patient experience and patient-reported outcome measures.

2 Cachexia interventions

A cohort study followed by phase 2 and 3 studies should be undertaken in people with pancreatic cancer and cachexia or pre-cachexia, to compare cachexia assessment methods and anti-cachexia interventions with standard care.

Why this is important

Most people with advanced and metastatic pancreatic cancer also have cachexia. This causes severe reductions in their quality of life and is associated with reduced overall survival. Cachexia has 3 phases: pre‑cachexia, cachexia and refractory cachexia. The condition cannot be stopped by conventional nutritional support and leads to progressive functional impairment. Complete or partial reversal of cachexia would cause major improvements in quality of life, and potentially improve survival if people recover enough to have more effective cancer treatments. The outcomes of interest are:

  • prevention or reversal of cachexia

  • overall survival

  • quality of life

  • pain relief

  • lean tissue mass

  • tolerance to treatment.

3 Minimally invasive pancreatectomy

Prospective randomised trials should be undertaken to compare the effectiveness of minimally invasive pancreatectomy or pancreatoduodenectomy (laparoscopic or robotic) with open pancreatectomy or pancreatoduodenectomy in people with pancreatic cancer.

Why this is important

Minimally invasive surgery is generally considered to be more acceptable to patients than open surgery. It has been introduced successfully for several other types of cancer and has been shown to improve quality of life. However, there is not enough evidence to determine whether minimally invasive surgery improves morbidity and mortality for people with pancreatic cancer, compared with open surgery. Prospective randomised trials are therefore needed in this area. The outcomes of interest are:

  • conversion rate to open surgery

  • R0 resection rate

  • lymph node yield

  • blood loss

  • duration of surgery

  • complications

  • need for critical care

  • length of hospital stay

  • time to return to normal activity

  • mortality of surgery

  • long-term survival after surgery

  • quality of life, patient experience and patient-reported outcome measures.

4 Pain management

A randomised trial should be undertaken comparing early endoscopic ultrasound-guided neurolytic coeliac plexus (EUS‑guided NCP) interventions with on‑demand EUS‑guided NCP interventions in people with unresectable pancreatic cancer.

Why this is important

There is a limited number of randomised trials in this area, and the methods used to perform NCP intervention are heterogeneous. It is not clear if early NCP intervention is superior to on‑demand NCP intervention in terms of the important outcomes for the patient and duration of effect of the procedure. On‑demand NCP intervention may benefit people with uncontrolled pain, people receiving escalating doses of analgesia, people experiencing unacceptable analgesic side effects, and others. However, people who receive early NCP intervention may not need on‑demand NCP intervention later on. Further research should clarify if the timing of the intervention confers any advantage. The outcomes of interest are:

  • reduction in pain

  • patient experience (including nutritional status)

  • health-related quality of life

  • adverse events

  • analgesic use

  • survival.

5 Psychological support needs

A qualitative study should be undertaken to evaluate information and support interventions to address psychological needs at different points in the care pathway for people with pancreatic cancer.

Why this is important

People with pancreatic cancer often have unmet psychological support needs that impact on their quality of life. These can be related to anxiety and depression, and to the psychological impact of fatigue, pain, gastrointestinal symptoms (particularly changes to appetite) and nutritional status. There has been very little research into the information and support interventions that would meet these needs. Research would help identify effective information and support interventions that would improve quality of life for people with pancreatic cancer and their family members or carers. Outcomes of interest are:

  • quality of life

  • psychological wellbeing

  • ability to carry out normal activities

  • patient experience and patient-reported outcome measures.

  • National Institute for Health and Care Excellence (NICE)