What are the latest developments and treatment approaches for pancreatic cancer?

Latest Developments in Pancreatic Cancer Treatment

Radical surgical resection with adjuvant chemotherapy remains the only potential curative treatment for pancreatic cancer, with multimodal approaches offering the best outcomes for survival and quality of life. 1

Diagnosis and Staging

• CT scan is the preferred imaging modality for initial staging of pancreatic cancer, providing essential information about tumor extent and vascular involvement 1
• MRI/MRCP may provide additional information about biliary and pancreatic ducts and can better distinguish solid from cystic masses, particularly in patients with liver or renal failure 1
• Endoscopic ultrasound (EUS) is valuable for assessing vascular and nodal involvement and obtaining pathological samples when needed 1
• Laparoscopy may detect small peritoneal and liver metastases in approximately 15% of patients, changing treatment strategy, and should be considered before resection of large left-sided tumors or when neoadjuvant treatment is planned 1

Surgical Advances

• Pylorus-preserving pancreaticoduodenectomy is the procedure of choice for pancreatic head tumors, while distal pancreatectomy (typically including splenectomy) is standard for body and tail tumors 1
• Achieving negative resection margins (R0) is the most critical prognostic factor for patients undergoing radical resection 1
• Tumor size, nodal involvement, histological grade, and post-resection CA19.9 levels are strong prognostic indicators 1
• The experience of the surgical team significantly impacts outcomes, supporting the case for specialized centers 1

Treatment Approaches by Stage

Resectable Disease (Stage I)

• Radical pancreatic resection remains the standard treatment option 1
• Adjuvant chemotherapy with either 5-fluorouracil (5-FU) or gemcitabine (GEM) for six cycles is recommended following resection 1
• No substantial difference in disease-free or overall survival has been demonstrated between 5-FU and gemcitabine as adjuvant therapy 1

Borderline Resectable Disease (Stage IIA)

• Neoadjuvant approaches (chemotherapy or chemoradiation) may increase R0 resection rates 1
• Preoperative gemcitabine-based chemoradiation can identify patients unlikely to benefit from surgical resection without compromising survival in those who ultimately undergo surgery 1
• Patients should be encouraged to participate in clinical trials for neoadjuvant treatment 1

Locally Advanced Disease (Stages IIB and III)

• Patients with borderline resectable disease may benefit from preoperative therapy (chemoradiation or induction chemotherapy followed by chemoradiation) 1
• In unresectable disease, 5-FU chemoradiation can be considered, though trials comparing chemoradiation with chemotherapy alone have shown contradictory results 1
• Patients treated with gemcitabine who do not progress after 3 months and maintain good performance status may benefit from the addition of chemoradiation 1

Metastatic Disease (Stage IV)

• FOLFIRINOX has proven superior to gemcitabine alone for patients with good performance status (ECOG 0-1) and normal or near-normal bilirubin levels, despite increased toxicity 1
• Gemcitabine remains a reasonable choice for patients who cannot tolerate more aggressive regimens 1
• The combination of gemcitabine and erlotinib showed a statistically significant but clinically modest survival improvement (12 days) over gemcitabine alone 1
• For second-line treatment, 5-FU/oxaliplatin should be considered as standard for patients who have progressed on first-line therapy 1

Palliative Care

• For biliary obstruction, endoscopic placement of a metallic biliary stent is strongly recommended over percutaneous insertion 1
• Duodenal obstruction is preferentially managed by endoscopic placement of an expandable metal stent rather than surgery 1
• Pain management is a major priority and should follow standard guidelines, with consideration of radiotherapy for coeliac pain control 1
• Coeliac plexus block can improve pain control and decrease systemic medication requirements, with EUS guidance representing a newer, safer approach 1

Emerging Approaches

• Intraoperative radiotherapy (IORT) has shown improved local control and overall survival in European centers, particularly in patients with lower tendency for systemic disease spread, though it is not yet recommended as routine practice 1
• Functional imaging techniques are increasingly being adopted in early phase clinical trials to better assess treatment response, particularly in locally advanced disease where conventional imaging may underestimate response 1
• Neoadjuvant protocols for borderline resectable tumors are being explored in randomized phase II studies, with R0 resection rates as a potential endpoint 1
• Molecular biomarkers such as hENT1 may help identify patients more likely to benefit from gemcitabine therapy 1

Future Directions

• The FOLFIRINOX regimen, successful in metastatic disease, is being evaluated for potential use in neoadjuvant and adjuvant settings, though its increased toxicity requires careful consideration in trial design 1
• Uniform classifications for disease stage, radiological resectability, and treatment results reporting are needed to advance clinical research 1
• Exploratory early proof-of-concept studies and randomized phase II studies with objective endpoints are recommended to select the best therapeutic approaches for phase III trials 1
• Treating patients within prospective clinical studies with translational components, including dynamic imaging, is strongly encouraged 1