What is the respectability of pancreatic cancer?

From the Guidelines

Pancreatic cancer is a highly respectable and serious medical condition that demands immediate attention and comprehensive treatment, with the most recent guidelines from 2021 recommending a multidisciplinary approach for diagnosis, evaluation, treatment, and follow-up 1. When diagnosed with pancreatic cancer, patients should seek care from a team including oncologists, surgeons, and gastroenterologists. Treatment typically involves a combination approach that may include:

• Surgical resection (such as Whipple procedure for tumors in the head of the pancreas)
• Chemotherapy regimens (commonly FOLFIRINOX or gemcitabine plus nab-paclitaxel)
• Sometimes radiation therapy Patients should understand that pancreatic cancer often presents with vague symptoms like abdominal pain, weight loss, and jaundice, which contributes to late-stage diagnosis and poorer outcomes. The aggressive nature of pancreatic cancer stems from its tendency to metastasize early and its resistance to many treatments. Supportive care is essential throughout treatment, including:
• Pain management
• Nutritional support (often with pancreatic enzyme supplements like Creon)
• Psychological support Early genetic testing may be beneficial for family members of patients with pancreatic cancer, especially if there is a family history of the disease or known genetic mutations like BRCA1/2. According to the American Society of Clinical Oncology, a multiphase CT scan of the chest, abdomen, and pelvis should be performed to assess the extent of disease, and the baseline performance status, symptom burden, and comorbidity profile of a patient with metastatic pancreatic cancer should be evaluated carefully 1. The goals of care, patient preferences, and support systems should be discussed with every patient with metastatic pancreatic cancer and their caregivers. Multidisciplinary collaboration to formulate treatment and care plans and disease management for patients with metastatic pancreatic cancer should be the standard of care. Every patient with pancreatic cancer should be offered information about clinical trials, which include therapeutic trials in all lines of treatment as well as palliative care, biorepository/biomarker, and observational studies. The NCCN Guidelines for Pancreatic Adenocarcinoma provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pancreatic cancer, and emphasize the importance of a multidisciplinary approach and patient-centered care 1. In terms of resectability, the guidelines recommend that patients with resectable disease should undergo radical surgery, and that adjuvant chemotherapy should be considered for patients who have undergone surgical resection 1. The guidelines also emphasize the importance of supportive care, including pain management, nutritional support, and psychological support, throughout treatment. Overall, the management of pancreatic cancer requires a comprehensive and multidisciplinary approach, with a focus on patient-centered care and evidence-based treatment recommendations. The most effective treatment approach for pancreatic cancer is a combination of surgical resection, chemotherapy, and radiation therapy, with a focus on supportive care and patient-centered care, as recommended by the most recent guidelines from 2021 1.

From the FDA Drug Label

The efficacy of gemcitabine was evaluated in two trials (Studies 5 and 6), a randomized, single-blind, two-arm, active-controlled trial (Study 5) conducted in patients with locally advanced or metastatic pancreatic cancer who had received no prior chemotherapy and in a single-arm, open-label, multicenter trial (Study 6) conducted in patients with locally advanced or metastatic pancreatic cancer previously treated with fluorouracil or a fluorouracil-containing regimen In Study 5, patients were randomized to receive either gemcitabine 1000 mg/m2 intravenously over 30 minutes once weekly for 7 weeks followed by a one-week rest, then once weekly for 3 consecutive weeks every 28-days in subsequent cycles (n=63) or fluorouracil 600 mg/m2 intravenously over 30 minutes once weekly (n=63) The major efficacy outcome measure in both trials was "clinical benefit response" A patient was considered to have had a clinical benefit response if either of the following occurred: ● The patient achieved a ≥50% reduction in pain intensity (Memorial Pain Assessment Card) or analgesic consumption, or a 20-point or greater improvement in performance status (Karnofsky Performance Status) for a period of at least 4 consecutive weeks, without showing any sustained worsening in any of the other parameters. ● The patient was stable on all of the aforementioned parameters, and showed a marked, sustained weight gain (≥7% increase maintained for ≥4 weeks) not due to fluid accumulation. Patients treated with gemcitabine had statistically significant increases in clinical benefit response, survival, and time to disease progression compared to those randomized to receive fluorouracil.

The respectability of pancreatic cancer is supported by the fact that gemcitabine demonstrated a statistically significant increase in clinical benefit response compared to fluorouracil in patients with locally advanced or metastatic pancreatic cancer, with a clinical benefit response rate of 22.2% versus 4.8% for fluorouracil 2. Key points include:

• Improved survival: Gemcitabine showed a statistically significant increase in overall survival compared to fluorouracil.
• Increased time to disease progression: Gemcitabine demonstrated a statistically significant increase in time to disease progression compared to fluorouracil.
• Clinical benefit response: Gemcitabine had a statistically significant increase in clinical benefit response, which includes improvements in pain intensity, performance status, and weight gain.

From the Research

Overview of Pancreatic Cancer

• Pancreatic ductal adenocarcinoma (PDAC) is a relatively uncommon cancer, with approximately 60,430 new diagnoses expected in 2021 in the US 3.
• The incidence of PDAC is increasing by 0.5% to 1.0% per year, and it is projected to become the second-leading cause of cancer-related mortality by 2030 3.

Treatment Approaches

• A multidisciplinary management approach is recommended for pancreatic cancer patients 3, 4.
• For patients with resectable disease at presentation (10%-15%), surgery followed by adjuvant chemotherapy with FOLFIRINOX represents a standard therapeutic approach with an anticipated median overall survival of 54.4 months 3.
• Neoadjuvant systemic therapy with or without radiation followed by evaluation for surgery is an accepted treatment approach for resectable and borderline resectable disease 3, 5.
• For patients with locally advanced and unresectable disease due to extensive vascular involvement, systemic therapy followed by radiation is an option for definitive locoregional disease control 3.

Surgical Management

• Pancreaticoduodenectomy, the Whipple resection, is a complex operation that is commonly performed for patients with pancreatic ductal adenocarcinoma and other malignant or benign lesions in the head of the pancreas 5, 6.
• The surgical technique and perioperative clinical outcomes of pancreaticoduodenectomy have been evaluated in several studies, with mortality rates below 5% reported at high-volume experienced centers 6.

Respectability of Pancreatic Cancer

• The respectability of pancreatic cancer is determined by the degree of arterial and venous involvement by tumor, typically of the superior mesenteric vessels 3.
• Localized pancreas cancer includes resectable, borderline resectable (localized and involving major vascular structures), and locally advanced (unresectable) disease based on the degree of arterial and venous involvement by tumor 3.
• The intra-observer agreements in multidisciplinary team assessments of pancreatic cancer patients have been evaluated, with moderate to high agreement reported for TNM-stage and resectability assessment, but low agreement for treatment allocation 4.