Surgery Now a Realistic Option for More Patients with Pancreatic Cancer

While researchers race to find improved medical therapies for pancreatic ductal adenocarcinoma (PDAC), surgery remains the most effective treatment. 

Unfortunately, a large percentage of PDAC patients are not surgical candidates because by the time of diagnosis, the disease has metastasized. Even among those without metastases, choosing surgery can be tricky if there is too much risk of leaving live tumor behind. 

Borderline Resectable Pancreatic Cancer (BRPC)

Recently, however, cancer treatment teams have been extending surgery options to more patients previously considered “borderline resectable” by deploying a combination of chemotherapy and radiation before surgery. That aims to kill – and possibly shrink – the tumor, increasing the chances for surgical success. 

The minority of patients with localized, non-metastatic disease who are potential surgical candidates may be divided into two categories: those who have clearly resectable disease at initial diagnosis, and those with borderline resectable pancreatic cancer (BRPC).

BRPC represents an increasingly recognized, distinct clinical entity characterized by primary tumor involving surrounding vasculature with a high risk for margin-positive resection if resected de novo — that is, surgically removed in newly diagnosed patients.

Now, in one of the largest tests of its kind, a UCSF Pancreas Center team has found that using chemotherapy alone is an effective approach. Of 26 UCSF patients who underwent chemotherapy-only neoadjuvant therapy, more than 90 percent underwent surgery that successfully removed all tumor. The study was recently reported on in the Journal of Surgical Oncology.

Why Surgery Is a Challenging Decision 

“Until recently, fewer than 20 percent of PDAC patients at diagnosis have been realistic surgical candidates,” says cancer surgeon Eric Nakakura, MD, PhD. Many surgeons are reluctant to subject patients to a grueling surgery, only to have part of the tumor, one as lethal as PDAC, remain. 

Neoadjuvant therapy has improved the chances of these patients advancing to surgery, but Nakakura and his UCSF colleagues, Margaret Tempero, MD, and Andrew Ko, MD, were concerned that numerous randomized trials showed radiation having no benefit, and possibly even a negative effect, in patients with PDAC. 

Improving the Odds for Success 

Those concerns and others prompted the decision to use only chemotherapy before surgery for most of the 26 patients in the first UCSF study. Pancreas cancer is a systemic problem, and radiation is a local solution. About 58 percent of patients with borderline resectable PDAC also require vascular reconstruction, according to Dr. Nakakura, and radiation can make that aspect of the surgical procecure difficult, if not hazardous.

A combination of four chemotherapies – collectively known by the acronym FOLFIRINOX – completely removed the tumor in 92 percent of these patients, with 100 percent surviving the surgery. Moreover, at UCSF the median survival is 34 months for this challenging group of patients, compared to a median survival of only 24 months for patients nationally after surgery for PDAC. 

Future Clinical Studies

UCSF is now planning a clinical trial for up to 36 borderline resectable patients, which will use a combination chemotherapy (gemcitabine and nab-paclitaxel) with an enzyme called PEGPH20. 

“Pancreatic tumors are very fibrous, and that impedes the delivery of chemotherapy,” Nakakura says. “PEGPH20 breaks down the fibrotic wall and increases drug delivery. We successfully operated on our first patient recently and saw a dramatic response. We are encouraged.”