June 11, 2019
About 55,000 people in the U.S. are diagnosed with pancreatic cancer each year. In about a third, the tumor has not spread to other organs, but has grown outside the pancreas to wrap around veins and arteries. These cancers are considered borderline resectable or locally advanced.
Historically, most patients with pancreatic cancer whose tumors grow outside the pancreas to encompass veins and arteries have been told the cancer is inoperable and they should prepare for an average survival time of 12 to 18 months. A Mayo Clinic study published in the Annals of Surgery in 2019 finds that a pre-surgery treatment plan focused on three factors can extend life years beyond that.
The study followed 194 Mayo Clinic patients with pancreatic ductal adenocarcinoma over a seven-year period who received chemotherapy followed by radiation and surgery.
All study participants, 123 (63%) with borderline resectable and 71 (37%) with locally advanced pancreatic ductal adenocarcinoma, underwent resection after receiving treatment with total neoadjuvant therapy, followed by long-course chemoradiation therapy. A group of 165 patients (85%) were treated with FOLFIRINOX, 65 (34%) patients received gemcitabine along with nab-paclitaxel, and 36 patients (19%) required a change in chemotherapeutic agent before they received long-course chemoradiation therapy and subsequent resection. The majority (94%) were able to achieve negative margin operations.
Mayo Clinic researchers assessed operative morbidity, mortality and survival to help them define outcome predictors and response endpoints. An average survival time of 58.8 months, or just under five years, was achieved. The researchers found that patients with these three factors had significantly longer survival times than those who did not:
- Extended (≥ 6 cycles) preoperative chemotherapy before surgery; the more cycles patients had, the longer the survival.
- A CA 19-9 tumor marker that fell to a normal level after chemotherapy.
- Major pathological response to preoperative chemotherapy.
Lead author Mark J. Truty, M.D., M.S. an oncologic surgeon at Mayo Clinic's campus in Rochester, Minnesota, estimates that roughly half of his patients with vein and artery involvement came to him after being told elsewhere that their cancer was inoperable. He hopes the study findings convince physicians that for many such patients, long-term survival is possible if they receive appropriate treatment before surgery.
"We now have more-advanced surgical techniques and more-effective chemotherapy and radiation therapy. We can take all of these advances and put them together to get the outcomes we are looking for," says Dr. Truty. "The goal is to extend patients' lives and maintain or improve their quality of life."
The conventional wisdom has been that surgery gives patients with pancreatic cancer the only chance at long-term survival, but that these patients are inoperable due to a high risk that cancer will be left behind and their prognosis for survival will be poor. The Mayo Clinic study refutes that conventional wisdom.
The 194 patients treated at Mayo and followed over seven years all received modern chemotherapy followed by radiation and radical operations, many of which are only performed at Mayo Clinic. For most patients, the surgery included removing and reconstructing veins, arteries or both, ensnared by pancreatic tumors. Crucial to their care before surgery was finding the right chemotherapy and continuing it until the CA 19-9 tumor marker was normal and the PET scan showed that the tumor was dead, says Dr. Truty.
The more of those three factors the patients had, the better they did. Because the three factors are all related to chemotherapy and the response to it, it may be possible to help many more patients achieve them by adjusting their chemotherapy before surgery, says Dr. Truty.
Additional findings and conclusions
- 29% of the patients had all three factors identified in the study; their median survival time has not yet been calculated because more than half are still alive. An additional 29% had two factors; their median survival was 58.6 months.
- 31% had one factor and a median survival of 29.7 months.
- 11% had none of the factors and a median survival of 18.5 months.
"The bottom line is patients with these advanced cancers can do very well if they're treated in the right manner prior to the operation," says Dr. Truty. "Our data show there's no difference in survival long term if you had a vein or an artery involved or not. It's those three factors related to how chemotherapy was administered, and if it was effective, only then moving on to radiation and surgery."
Just as important as identifying who is a good candidate for surgery is pinpointing who is a poor candidate, says Dr. Truty. The operation is more complex than surgery in patients whose cancer has not spread beyond the pancreas, and the risks must be weighed against the predicted benefit. Given the magnitude of the surgery, it is only performed at a few centers in the U.S., including Mayo Clinic.
For more information
Truty MJ, et al. Factors predicting response, perioperative outcomes, and survival following total neoadjuvant therapy for borderline/locally advanced pancreatic cancer. Annals of Surgery. In press.