"Patients who have a radiological or biochemical response and are borderline resectable should be given the option of surgery after neoadjuvant chemotherapy," Dr. Amanda Arrington of the University of Arizona in Tucson told Reuters Health by email. "Even if there is a microscopic positive margin, patients have better survivals than those who only undergo chemotherapy alone."
"Patients who underwent chemotherapy before surgery . . . had the best overall survival," she said. "With better options for neoadjuvant chemotherapy, response rates are better."
Dr. Arrington and colleagues point out in the Journal of the American College of Surgeons that R0 resection for pancreatic cancer is considered standard of care, but is not always achieved. Therefore, the team looked at R1/R2-resection outcomes, hypothesizing that patients with margin-positive disease would have better outcomes than with chemotherapy alone.
They identified close to 11,700 patients, of whom 81% were treated with chemotherapy alone, 16% with upfront surgery and 3% with neoadjuvant therapy with surgery. The mean ages ranged from 63 to 70 years in the three groups, and about half the patients were men; more than 80% were white.
The R1/R2 neoadjuvant group had the best overall survival, with a mean of 19.75 months versus 17.77 months in the upfront-surgery group and 10.12 months in the chemotherapy-alone group. The adjusted hazard ratios with chemotherapy alone as reference were 0.46 for the upfront-surgery group and 0.54 for the neoadjuvant group (both P<0.0001).
Even with R2 resection, survival was better in surgical compared to chemotherapy-only groups (15.76 months vs. 10.22 months, P=0.06).
Patients who underwent R1/R2 resections and received neoadjuvant/adjuvant chemotherapy had improved survival, though survival rates were significantly lower than for standard R0 resection.
Regardless of the analysis method - Cox regression, unmatched groups adjusted by inverse probability of treatment weights, propensity match - the findings were consistent throughout and statistically significant.
The authors conclude, "Even in the setting of margin positive disease, no matter how you slice and look at the data presented, surgery, particularly in combination with neoadjuvant therapy, improves survival in otherwise aggressive and, ultimately, potentially lethal pancreatic cancers."
Dr. Arrington said, "Our team is continuing this research by looking at the resection margins, recurrence-free survivals, and tumor biology based on the specific chemotherapy regimen in patients treated at our own institution."
Dr. Christos Fountzilas, a medical oncologist at Roswell Park Comprehensive Cancer Center in Buffalo, New York, told Reuters Health by email, "In general, patients with pancreatic cancer who can have resection of the primary tumor along with multi-agent chemotherapy live longer. This is not related to removal of the primary pancreatic tumor per se, but mostly to favorable disease anatomy and biology, as well as patients' characteristics and overall health condition allowing aggressive multidisciplinary care."
In the current study, he said, "Only about 20% of patients had an R1/2 resection, a very highly selected population. Given that all patients had stage-II disease and almost all had R1 resection, the intention was not to undergo surgery with a positive margin. Further, we don't know the type of chemotherapy (multi-agent vs. single agent) that was received and if this has played a role in the observed results."
"Every patient's treatment plan should be individualized to achieve the best outcomes possible," said Dr. Fountzilas, who was not involved in the study. "We should still make every effort to avoid a margin-positive resection with more extensive use of pre-operative chemotherapy and, if needed, chemoradiotherapy. We also need to identify new targets and use novel drugs and approaches to really make steps forward in our efforts to cure this disease and encourage patient participation in clinical trials.
SOURCE: https://bit.ly/2PzONKx Journal of the American College of Surgeons, online March 26, 2021.
By Marilynn Larkin
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