Pancreatic cancer is the third-leading cause of cancer-related death in the U.S. and is on track to become number two in 2020, surpassing colorectal cancer. Outcomes have not improved substantially in 40 years, with just a 9 percent five-year survival rate today versus 5 percent in the late 1970s. However, a combination of new approaches is transforming the treatment and survival of pancreatic cancer patients.

Andrew L. Warshaw, MD, FACS, FRCSEd(Hon), will discuss advances in pancreatic cancer treatment during Wednesday afternoon’s Commission on Cancer Oncology Lecture, Pancreatic Cancer: Progress and Prospects. A Past-President of the American College of Surgeons, Dr. Warshaw is senior consultant, international and regional clinical relations, Massachusetts General Hospital, and the W. Gerald Austen Distinguished Professor of Surgery, Harvard Medical School, Boston.

Gemcitabine, introduced in the 1990s, offered the first significant improvement in long-term survival, he said. First approved for unresectable metastatic disease, gemcitabine soon was being used in the adjuvant setting.

Gemcitabine was followed by FOLFIRINOX, a four-drug regimen combining leucovorin with 5-fluorouracil, irinotecan, and oxaliplatin, that led to improved survival with gemcitabine alone. Then came gemcitabine plus nab-paclitaxel (gem nab-paclitaxel). Both agents were introduced for nonresectable disease, then expanded into the adjuvant and neoadjuvant settings.

“FOLFIRINOX and gem nab-paclitaxel are pretty much equivalent in terms of survival, but patients who responded to FOLFIRINOX didn’t respond to gem nab-paclitaxel, and vice versa,” Dr. Warshaw said. “That was a clue that not all pancreatic cancers are the same. That recognition opens up the possibility of highly targeted treatments based on tumor genomics.”

The development of effective chemotherapeutic agents has transformed pancreatic cancer surgery, he added. Before gemcitabine, only about 20 percent of pancreatic cancer patients were candidates for surgery. Adding neoadjuvant chemotherapy to downstage tumors means that up to 60 percent of pancreatic cancer patients are now good candidates for surgery.

In theory, tripling the number of surgical candidates could triple long-term survival following surgery, Dr. Warshaw said, but the reality could be higher.

Early results suggest that neoadjuvant chemotherapy allows surgeons to deal with locally advanced cancers that were unresectable just a few years ago. Not only are more patients with more advanced cancers being resected, 55−60 percent of patients leave the operating room with an R0 resection. Clear margins could become the expected outcome of surgery, not the exception, Dr. Warshaw said.

Other treatment tweaks could improve survival even further, he added. Pancreatic cancers are protected by a stroma, which protects the tumor from chemotherapeutic agents and promotes tumor progression. Adding losartan appears to help drugs penetrate the stroma and improve therapeutic effects. Prospective trials that combine losartan, FOLFIRINOX, and nivolumab, an immunotherapeutic used to treat lung and other cancers, are under way.

Meanwhile, the development of targeted therapies will change biopsy strategies. Rather than simply confirming the presence of pancreatic cancer, biopsies in the future could be used to screen for specific genetic forms of the disease that respond to specific treatments. “We are already able to resect pancreatic cancers that we wouldn’t have dreamed of touching in the past,” Dr. Warshaw said. “After a long period of stagnation, we have better surgical tools, better chemical tools, and we are poised to see major changes in five-year cure rates.”

The Commission on Cancer Oncology Lecture was established in 1988 and is sponsored by the Commission on Cancer to explore major developments in oncology and to focus on the surgeon’s role in caring for cancer patients.