Pancreatic Cancer
- Recommendations
➡️ Diagnosis
▪️ Labs
▪️ Routine labs including LFTs, KFTs, and CBC should be included in the primary diagnosis of pancreatic cancer.
▪️CA 19-9 can be used as a serum marker to measure disease burden and potentially guide treatment decisions in patients with normal bilirubin.
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 recommendation, low grade evidence (1).
➡️ 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 “Pancreatic protocol”.
Strong recommendation, low grade evidence (2).
▪️ We recommend imaging before biliary drainage or stenting in case of jaundice due to an obstructive head PC.
Strong recommendation, very low grade evidence (3).
▪️ Imaging should be carried out in the 4 weeks before starting treatment.
Strong recommendation, low grade evidence (3).
▪️ Abdominal MRI may be used when CT cannot be carried out, or inconclusive or for pancreatic cystic lesions.
Conditional recommendation, very low grade evidence (4).
▪️ 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 recommendation, low grade evidence (5).
▪️ Hepatic MRI is recommended before surgery to confirm the absence of small liver metastases
Strong recommendation, low grade evidence (4).
➡️Pathology and immunophenotyping
▪️ CA19-9 (or CK19 according to availability), Chromogranin (or synaptophysin according to availability) are recommended for pathologic diagnosis.
Conditional recommendation, low grade evidence (6).
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 recommendation, low grade evidence (7).
▪️ We recommend assessing resectability by anatomical NCCN criteria
Strong recommendation, low grade evidence (8)
▪️ 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 recommendation, low grade evidence (9)
➡️Treatment of resectable PC
▪️We suggest performing frozen section analysis of pancreatic neck transection and of common bile duct transection margins.
Conditional recommendation, very low grade evidence (10)
▪️ Tumour clearance should be defined for all margins identified by the surgeon.
▪️ For adenocarcinomas of the pancreas head and uncinate, a pancreatoduodenectomy (Whipple procedure) should be done.
Strong recommendation, very low grade evidence (11)
▪️ 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 recommendation, very low grade evidence (12, 13)
▪️ Standard lymphadenectomy is recommended and should involve the removal of >16 lymph nodes to allow adequate pathological staging of the disease.
Strong recommendation, very low grade evidence (14).
▪️ 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 recommendation, very low grade evidence (14)
▪️ Patients undergoing surgery should receive perioperative thromboprophylaxis with either unfractionated heparin or low-molecular-weight heparin (LMWH), unless contraindicated.
Strong recommendation, high grade evidence (15, 16).
▪️ 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 recommendation, high grade evidence (17).
▪️ Neoadjuvant therapy is not recommended for resectable PC.
Conditional recommendation, moderate grade evidence (18-20).
▪️ Following resection of PC, completion of 6 months of adjuvant Chemotherapy is strongly recommended.
Strong recommendation, high grade evidence (21-2
▪️ Adjuvant mFOLFIRINOX is recommended for patients with resected PC and ECOG PS 0-1.
Strong recommendation, high grade evidence (23-25)
▪️ 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 recommendation, high grade evidence (23-25)
▪️ Adjuvant gemcitabine or 5-FU-LV should be limited to frail patients.
Strong recommendation, high grade evidence (23-25)
▪️ Adjuvant CRT is not recommended and should not be given to patients following surgery (in R0 cases).
Strong recommendation, high grade evidence (26).
➡️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 recommendation, high grade evidence (18-20)
▪️ 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 recommendation, low grade evidence (20, 27).
▪️ Gemcitabine combined with oxaliplatin or capecitabine may be considered, when FOLFIRINOX is not feasible.
Strong recommendation, low grade evidence (20,22).
▪️ CRT with capecitabine may be considered after induction Chemotherapy.
Conditional recommendation, low grade evidence (19)
▪️ Following induction therapy, medically fit patients without disease progression and with a decrease in CA 19-9 should undergo surgical exploration, unless contraindicated.
Strong recommendation, strong grade evidence (28).
➡️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 recommendation, strong grade evidence (29-31).
▪️ 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 recommendation, very low grade evidence (32,33).
➡️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).
▪️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 recommendation, high grade evidence (35).
Second-line treatment
▪️ After FOLFIRINOX treatment, gemcitabine alone may be offered to patients with ECOG PS 0-1 and a favorable comorbidity profile.
Conditional recommendation, low grade evidence (36-39).
▪️ 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 recommendation, low grade evidence (36-39).
▪️ For patients with ECOG PS 3-4, symptom directed, and palliative care is recommended.
Strong recommendation, low grade evidence (36-39).
▪️ 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 recommendation, low grade evidence (36-39).