In patients who undergo resection of pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy, reduction in tumor size between diagnosis and surgery is associated with improved survival, according to a new single-center, retrospective analysis. The researchers compared tumor size as measured by endoscopic ultrasound (EUS) and found that a threshold of 47% or greater reduction in tumor size at resection was associated with a doubling in the 3-year survival rate.
The study, led by Rohit Das, MD, of the University of Pittsburgh Medical Center, was published in Clinical Gastroenterology and Hepatology.
The research represents only a small percentage of patients since most diagnosed with PDAC have locally advanced or metastatic disease that rules out surgery. Still, the work puts more emphasis on measuring tumor size while performing EUS, according to Robert Jay Sealock, MD, who is an assistant professor of medicine at Baylor College of Medicine, Houston.
“This is some helpful information that you can relay to the patient, saying that you have a significant decrease in the size of the tumor based on your initial EUS, and your chance of 3- to 5-year survival is going to be a lot higher, compared to somebody that didn’t have that tumor regression. Most of these patients will undergo an EUS anyway, and you’ll commonly if not always measure the tumor size while you’re in there. Now you can apply this information that you already have to give the patients some additional information if they do undergo surgery,” said Dr. Sealock, who was not involved in the research.
Previous efforts to prognosticate postsurgical survival focused on overall tumor burden using multidetector CT (MDCT), carbohydrate antigen 19-9 (CA19-9) levels, and histologic examination following surgery, but all suffer from various limitations. MDCT is not always accurate in its measurement of tumor size, other conditions can also raise CA19-9 levels, and pathologic findings are subjective because sometimes the amount of tumor before neoadjuvant therapy is uncertain.
The researchers mapped survival statistics to EUS and pathologic findings for 340 treatment-naive and 365 neoadjuvant-treated PDAC patients at the University of Pittsburgh Medical Center. They used a 200 patient cohort from the same center who had been treated with neoadjuvant therapy for validation.
Pathology examination revealed that, in the treatment-naive group, 71% of tumors were larger than the size determined during EUS. In 9% of cases there was no change in size (EUS versus pathology T-staging Pearson correlation coefficient, 0.586; P < .001). A similar analysis of MDCT showed a weaker correlation. There was no correlation between preoperative EUS/MDCT findings and postoperative pathology among patients who received neoadjuvant therapy.
In the neoadjuvant therapy group, tumor size was reduced in 31%, was unchanged in 53%, and actually grew in 16%. Three-year overall survival was highest in the reduced group (50%), and lower in the unchanged (37%) and tumor-growth (34%) groups. At 5 years, overall survival was 31%, 19%, and 16%, respectively (P = .003). Compared with those whose tumor size remained the same or grew, those with reduced tumor size had higher 3-year overall survival (50% vs. 33%) and 5-year overall survival (31% vs. 18%; P < .001).
The researchers used recursive positioning to identify the optimal threshold for tumor reduction, and found that a 47% or greater reduction was associated with 67% overall survival at 3 years and 47% at 5 years, compared with 32% and 16% for those with smaller reduction or tumors that maintained or increased in size (P < .001).
The researchers noted that, although their study is large, it remains retrospective in design. Another limitation they cited was that not all patients received the same neoadjuvant therapy. Furthermore, both EUS and pathologic evaluation can be subjective, and it can be difficult to correct for that.
“While additional studies are required, incorporating preoperative EUS and postoperative pathologic tumor size measurements into the standard evaluation of neoadjuvant-treated PDAC patients may guide subsequent management in the adjuvant setting,” the researchers concluded.
The study was funded in part by the National Pancreas Foundation, Sky Foundation, and the Pittsburgh Liver Research Center at the University of Pittsburgh. One author disclosed receiving an honorarium from Foundation Medicine, but the rest reported having nothing to disclose. Dr. Sealock has no relevant financial disclosures.
SOURCE: Das R et al. Clin Gastroenterol Hepatol. 2020 Dec 2. doi: 10.1016/j.cgh.2020.11.041.