A Simple Overview of Pancreatic Cancer Treatment for Clinical Oncologists

Abstract

Pancreatic cancer (PDAC) is one of the most aggressive solid tumors and is showing increasing incidence. The aim of our review is to provide practical help for all clinical oncologists and to summarize the current management of PDAC using a simple "ABC method" (A-anatomical resectability, B-biological resectability and C-clinical conditions). For anatomically resectable PDAC without any high-risk factors (biological or conditional), the actual standard of care is represented by surgery followed by adjuvant chemotherapy. The remaining PDAC patients should all be treated with initial systemic therapy, though the intent for each is different: for borderline resectable patients, the intent is neoadjuvant; for locally advanced patients, the intent is conversion; and for metastatic PDAC patients, the intent remains just palliative. The actual standard of care in first-line therapy is represented by two regimens: FOLFIRINOX and gemcitabine/nab-paclitaxel. Recently, NALIRIFOX showed positive results over gemcitabine/nab-paclitaxel. There are limited data for maintenance therapy after first-line treatment, though 5-FU or FOLFIRI after initial FOLFIRINOX, and gemcitabine, after initial gemcitabine/nab-paclitaxel, might be considered. We also dedicate space to special rare conditions, such as PDAC with germline BRCA mutations, pancreatic acinar cell carcinoma and adenosquamous carcinoma of the pancreas, with few clinically relevant remarks.

Keywords: pancreatic cancer; prognosis; therapy.

Figure 1

Treatment algorithm for PDAC patients using “ABC method” (A—anatomical resectabi- lity, B—biological resectability and C—clinical conditions). All PDAC patients should initiate systemic treatment apart from anatomically resectable PDAC without high-risk biological factors (absence of B factors) and fitness for surgery (absence of C factor), as demonstrated in the figure. In all cases, there are no rigid cut-offs for any high-risk aggressive features; therefore, these are left as considerations for the treating oncologists/surgeons. Note that before any systemic chemotherapy, biopsy for histological characterization is mandatory. High-risk biological features include suspicious hepatic or pulmonary lesions, the presence of positive lymph nodes (histologically proven or based on positivity of PET-FDG scan), large pancreatic primary tumors with dimension superior to 2–3 cm, elevated baseline level tumor biomarker CA 19-9 and several clinical characteristics such as celiac-type pain or significant weight loss (≥10% of body weight).

Figure 2

Treatment algorithm for metastatic PDAC. FOLFIRINOX and gemcitabine/nab-paclitaxel are the current standard of care in first-line settings. If patients are initiated with FOLFIRINOX with disease control, consider maintenance therapy with 5-FU/FOLFIRI after a minimum of 4 months of FOLFIRINOX. If patients are initiated with gemcitabine/nab-paclitaxel with disease control, consider maintenance therapy with gemcitabine after a minimum of 3 months of gemcitabine/nab-paclitaxel. Second-line chemotherapy changes the backbone: initial treatment with FOLFIRINOX is gemcitabine-based, while initial treatment with gemcitabine/nab-paclitaxel is 5-FU-based. Where possible, determine the three ESCAT level I alterations (germline BRCA1/2, MSI-high, NTRAK).

Figure 3

Outcome of patients affected by resectable/borderline resectable, locally advanced and metastatic PDAC. For metastatic PDAC patients, the OS outcome is less than 1 year; for locally advanced PDAC patients, the OS outcome is less than 2 years; for resectable PDAC patients who have undergone adjuvant FOLFIRINOX, an OS of 54 months has been reported [23,25,26,40,41,71].