Treatment options for pancreatic cancer.

Neoadjuvant treatment with chemotherapy and radiotherapy for patients with unresectable non-metastatic pancreatic cancer has been the subject of several recent studies that have shown promising results. This approach seeks to reduce tumor size, improve resectability rates, and prolong survival. Here are some key aspects supported by scientific evidence.

1. Concept of neoadjuvant treatment

Neoadjuvant treatment is administered before surgery with the intention of:

• Reducing the size of the primary tumor to make it resectable.

• Eliminating hidden micrometastases that are not detected with diagnostic imaging.

• Improving long-term survival rates compared to primary surgery followed by adjuvant chemotherapy.

2. Neoadjuvant chemotherapy

• FOLFIRINOX: One of the most commonly used regimens in advanced pancreatic cancer, including unresectable stage, is FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, and 5-fluorouracil). Studies have shown that this regimen can reduce tumor size and improve the chance of resection.

• Gemcitabine and nab-paclitaxel: This is another chemotherapy regimen used as neoadjuvant treatment. In clinical studies, it has been shown to improve the resectability rate in patients with locally advanced tumors.

• Relevant studies: According to a 2018 study in the Journal of Clinical Oncology, the neoadjuvant FOLFIRINOX regimen showed a conversion rate to resectability in 33% of patients with locally advanced pancreatic cancer, and patients who underwent resection achieved a median survival of more than 30 months.

3. Neoadjuvant radiotherapy

• Radiotherapy, in combination with chemotherapy (chemoradiotherapy), can help shrink the tumor.

• External beam radiotherapy (IMRT) and stereotactic body radiotherapy (SBRT) are advanced techniques that have been shown to be effective in precisely reducing tumor size, minimizing damage to surrounding tissues.

• Evidence: A study published in Annals of Surgical Oncology in 2020 showed that SBRT combined with neoadjuvant chemotherapy resulted in a resection rate of approximately 35% in patients with unresectable locally advanced pancreatic cancer. In addition, those who achieved resection showed a significant improvement in overall survival.

4. Survival and resectability

• Resectability rates: A meta-analysis published in Lancet Oncology in 2019 indicated that around 30-40% of patients with locally advanced pancreatic cancer who receive neoadjuvant treatment can undergo curative surgery.

• Overall survival: The median survival in patients who undergo resection after neoadjuvant treatment is significantly longer (24-30 months) compared to those who are not resectable, whose median survival is around 12-16 months.

5. Benefits of the neoadjuvant approach

• Improved resection rates with negative margins: Neoadjuvant treatment can help achieve clear surgical margins, which is crucial to improve long-term outcomes.

• Better local control: By reducing tumor size, the likelihood of local recurrence after surgery decreases.

• Identification of patients with aggressive disease: If a patient does not respond to neoadjuvant treatment, it may be an indication of aggressive disease and therefore avoiding surgery that would not offer benefit.

Evidence-based conclusions:

Neoadjuvant treatment with chemotherapy (FOLFIRINOX, gemcitabine/nab-paclitaxel) and radiotherapy (SBRT, IMRT) in patients with unresectable locally advanced pancreatic cancer has shown evidence of improving the resection rate and overall survival in some patients. Combining these treatments is a valid and effective option to improve outcomes, but patients who may benefit from this approach should be carefully selected.

Continued research is underway to identify optimal regimens and combinations, as well as to improve outcomes in this difficult-to-treat disease.