Pancreatic Cancer

Recommendation

Strength of recommendation

     Diagnosis

· Labs

· Routine labs including LFTs, KFTs, and CBC should be included in the primary diagnosis of pancreatic cancer. 

Good practice statement

· CA 19-9 can be used as a serum marker to measure disease burden and potentially guide treatment decisions.

Good practice statement.         

· Cytology in localized pancreatic lesion, preferably by EUS guidance or biopsy from metastatic site “preferred” should be obtained before initiation of chemotherapy.

Strong

· Imaging

· Multiphasic contrast-enhanced thoracic-abdominal and pelvic CT, including late arterial phase and portal venous phase, should be used as the first-line imaging modality for suspected PC.

Strong

· We recommend imaging before biliary drainage or stenting in case of jaundice due to an obstructive head PC.

 Strong

·Imaging should be carried out in the 4 weeks before starting treatment.

Strong

·  Abdominal MRI may be used when CT cannot be carried out, or inconclusive or for pancreatic cystic lesions.

Conditional

· We do not recommend PET/CT for diagnosis of primary tumors but may be useful for staging localized tumors and in cases where the presence of distant metastases is uncertain (e.g. Doubtful imaging or high CA 19-9).

Conditional

·  Hepatic MRI is recommended before surgery to confirm the absence of small liver metastases

Strong

Pathology and immunophenotyping

· CA19-9 (or CK19 according to availability), Chromogranin (or synaptophysin according to availability) are recommended for pathologic diagnosis.

Conditional

Staging and Risk assessment

· MDT discussion in expert centers is required to define a recommended treatment strategy for patients with PC.

Good clinical practice

· Tumors should be staged according to the AJCC staging system

Strong

·  We recommend assessing resectability by anatomical NCCN criteria.

Strong

· We prefer staging laparoscopy in patients who meet any of the followings:

CA19.9 > 150U/ml, low volume ascites, tumor in the body or tail of pancreas, borderline resectable tumor (after neoadjuvant treatment), or tumor > 3 cm in size.

Conditional

Treatment of resectable PC

· We suggest performing frozen section analysis of pancreatic neck transection and of common bile duct transection margins.

Conditional

·  Tumour clearance should be defined for all margins identified by the surgeon

Good clinical practice

· For adenocarcinomas of the pancreas head and uncinate, a pancreatoduodenectomy (Whipple procedure) should be done.

Strong

· For patients with tumours in the body or tail, radical anterograde modular pancreatosplenectomy with dissection of the left hemi-circumference of the SMA to the left of the coeliac trunk is recommended.

Strong

· Standard lymphadenectomy is recommended and should involve the removal of >16 lymph nodes to allow adequate pathological staging of the disease.

Strong

· The total number of lymph nodes examined and lymph node ratio (number of involved lymph nodes as a proportion of the number of lymph nodes examined) should be reported in the pathological analysis.

Strong

· Patients undergoing surgery should receive perioperative thromboprophylaxis with either unfractionated heparin or low-molecular-weight heparin (LMWH), unless contraindicated.

Strong

· If the bilirubin level is >14 mg/l (250 mmol/l), endoscopic drainage is recommended for those planned to receive neoadjuvant treatment or those in whom surgery will be delayed for longer than 2 weeks.

Strong

· Neoadjuvant therapy is not recommended for resectable PC.

Conditional

· Following resection of PC, completion of 6 months of adjuvant Chemotherapy is strongly recommended.

Strong

·  Adjuvant mFOLFIRINOX is recommended for patients with resected PC and ECOG PS 0-1.            

Strong

· In patients who are not candidates for mFOLFIRINOX (age >75 years, ECOG PS 2 or contraindication to mFOLFIRINOX), we recommend gemcitabine-capecitabine as an alternative option.

Strong

· Adjuvant gemcitabine or 5-FU-LV should be limited to frail patients.

Strong

· Adjuvant CRT is not recommended and should not be given to patients following surgery.

Strong

Treatment of borderline resectable tumors (BRPC)

· Patients with BRPC have a high probability of an R1 resection and should be considered for induction treatment.

Strong

·  A period of induction chemotherapy (FOLFIRINOX) followed by CRT on a case-by-case basis and subsequent surgery, is recommended according to MDT recommendations

Strong

· Gemcitabine combined with oxaliplatin or capecitabine may be considered, when FOLFIRINOX is not feasible.

Strong

· CRT with capecitabine may be considered after induction Chemotherapy.

Conditional

 ·  Following induction therapy, medically fit patients without disease progression and with a decrease in CA 19-9 should undergo surgical exploration, unless contraindicated.

Strong

Treatment of locally advanced pancreatic cancer (LAPC)

· A conversion surgery strategy utilizing the standard of care of up to 6 months of combination Chemotherapy (e.g. FOLFIRINOX) should be chosen.

Strong

·  Arterial resection after induction therapy is not recommended but can be considered as a possibility in experienced centers on a case-by-case basis in selected patients according to MDT recommendations.

Conditional

Treatment of advanced pancreatic cancer

First-line treatment

· Options to treat patients with metastatic PC should be dependent on PS:

o In patients with ECOG PS 0-1 and bilirubin level <1.5 times the ULN, the regimen  

   FOLFIRINOX should be considered.

             Strong recommendation, high grade evidence (34)

o For patients with ECOG PS 2, Karnofsky PS (KPS) >70 and bilirubin level <1.5 times

   the ULN, gemcitabine-cisplatin can be considered.

             Strong recommendation, high grade evidence (34).

o For patients with ECOG PS 2, KPS <70 and/or bilirubin level >1.5 times the ULN,   

   gemcitabine monotherapy should be considered.

             Strong recommendation, high grade evidence (34).

o For patients with ECOG PS 3-4, symptom-directed and palliative care should be

   considered

              Strong recommendation, high grade evidence (34).

Strong

· The efficacy of treatment should be typically evaluated every 8-12 weeks and should be based on clinical status, CA 19-9 trajectory and imaging.

Strong

Second-line treatment

· After FOLFIRINOX treatment, gemcitabine alone may be offered to patients with ECOG PS 0-1 and a favorable comorbidity profile.

Conditional

·  Oxaliplatin-based second-line treatment (mFOLFOX6 or OFF) may be considered as an alternative in patients with ECOG PS 0-2 if not given previously.

Conditional

· For patients with ECOG PS 3-4, symptom directed, and palliative care is recommended.

Strong

· Maintenance therapy with capecitabine (after discussion with patient) may be indicated till disease progression or unacceptable toxicity on a case- by case basis according to MDT recommendations.

Conditional