Ronald Evans, MD
Despite improvements in the treatment of many formerly intractable cancer, the prognosis for pancreatic cancer remains dismal, with a 5-year survival rate of 8.2% (Figure).1
Novel multimodal approaches that address the unique, aggressive biology of pancreatic cancer are needed, experts say.
“It is a very challenging diagnosis, but there are new therapies coming along based on science. This kind of knowledge is what we need to crack open the problem,” said Ronald Evans, MD, director of the Gene Expression Laboratory at the Salk Institute for Biological Studies in La Jolla, California.
In recent years, there have been significant developments in the management of pancreatic cancer, including neoadjuvant chemotherapy and radiation for patients with resectable disease and frontline use of multiagent cytotoxic therapy for metastatic disease. Several promising novel approaches that target the stem cell pathway and the tumor stroma are in the early stages of development and would be a big step forward for a subgroup of patients if they prove successful, according to Evans. Additionally, early-stage clinical trials are exploring the potential for immunotherapies including checkpoint blockade agents and chimeric antigen receptor therapies. However, much progress is still needed to improve toxicity with current chemotherapy regimens, standardization of molecular subtyping, utility of genomics testing, and screening recommendations for high-risk patients.
Optimizing Treatment Regimens
For the small percentage of patients with resectable disease, treatment has traditionally involved surgery followed by chemotherapy and radiation therapy. However, treatment in the neoadjuvant setting may improve outcomes for patients with resectable disease, according to Emma C. Fields, MD, radiation oncologist at the Virginia Commonwealth University Massey Cancer Center in Richmond, Virginia. A retrospective analysis2
by Fields and colleagues showed that approximately 40% of patients had positive margins after resection; a positive margin was associated with shorter progression-free survival (PFS) than a negative margin.
According to Fields, maximizing tumor shrinkage with neoadjuvant therapy prior to surgery would help improve the likelihood of negative margins and thus survival outcomes. Furthermore, she stated that surgery for pancreatic cancer requires a lengthy recovery period during which the cancer could recur or metastasize. “Someone receives a pancreatic duodenectomy or Whipple [procedure], their recovery is 6 to 8 weeks, and then they have a CT scan showing development of disease elsewhere.”
Furthermore, Fields noted that patients may be able to tolerate intense regimens of chemotherapy and radiation better prior to surgery, which is associated with high morbidity and incidence of postoperative complications. A retrospective analysis3
showed completion of multimodality treatment in 83% of patients who received neoadjuvant therapy versus 58% of patients who received surgery first. Patients who completed multimodality therapy had better median overall survival (OS) at 36 months, compared with 11 months for those who received an incomplete regimen. Neoadjuvant treatment also tests the responsiveness of the tumor to chemotherapy and radiation, and patients unlikely to bene t from treatment could avoid unnecessary burdens from surgery and receive palliative care earlier.
According to Fields, providing radiation in the neoadjuvant setting also allows for a smaller volume of tissue to be treated. “Preoperatively, we can see the tumor and treat just around the tumor itself. Postoperatively, we treat a much larger volume because you’re dealing with an operative bed and it’s very hard to know where the tumor was with the reconstructed anatomy. So, we cover everywhere the surgeon potentially was and areas at risk.” Fields also noted that the tissues and tumor regions have better blood ow and oxygenation before surgery, which likely improve the efficacy of chemotherapy and radiation.
Although the role of neoadjuvant radiation and chemotherapy for early-stage pancreatic cancer is promising, Fields said that prospective studies in specific categories of patients (eg, those with resectable, borderline resectable, or locally advanced disease) are currently ongoing to deter- mine the benefits of neoadjuvant therapy and surgical eligibility at each stage of disease.Chemotherapy for Metastatic Disease