Resection rates and intention-to-treat outcomes in borderline and locally advanced pancreatic cancer: real-world data from a population-based, prospective cohort study (NORPACT-2)

Abstract

Background: Systemic chemotherapy is the initial treatment strategy for borderline resectable and locally advanced pancreatic cancer to facilitate curative resection. The aim of this study was to investigate the resection rates and overall survival in patients with borderline resectable pancreatic cancer and locally advanced pancreatic cancer.

Methods: Consecutive patients with borderline resectable pancreatic cancer/locally advanced pancreatic cancer discussed by Oslo University Hospital multidisciplinary team between 2018 and 2020, serving a population of 3.1 million within a geographically defined area in south-eastern Norway, were included in this prospective Norwegian Pancreatic Cancer Trial-2 study, according to intention-to-treat principles. The total number of patients with pancreatic cancer was sought from the Cancer Registry of Norway.

Results: A total of 1178 patients were diagnosed with pancreatic cancer, of whom 618 were referred to Oslo University Hospital. After multidisciplinary team evaluation, 230 patients were considered to have borderline resectable pancreatic cancer/locally advanced pancreatic cancer. The final study group consisted of 188 patients (borderline resectable pancreatic cancer n = 96, locally advanced pancreatic cancer n = 92) who were fit to receive primary chemotherapy. Resection rates were 46.9% (45 of 96) for borderline resectable pancreatic cancer and 13% (12 of 92) for locally advanced pancreatic cancer (P <0.001). Median overall survival was 14.6 months (borderline resectable pancreatic cancer 16.4 months; locally advanced pancreatic cancer 13.7 months, (P = 0.2)). Adjusted for immortal time bias, median overall survival for patients undergoing resection versus only chemotherapy was 24.4 months versus 10.1 months (P <0.001) for borderline resectable pancreatic cancer and 28.4 months versus 12.6 months for locally advanced pancreatic cancer (P = 0.001).

Conclusion: Resection rates and survival in patients with borderline resectable pancreatic cancer and locally advanced pancreatic cancer treated at a high-volume centre in a universal healthcare system compare well with those treated at international expert centres.Registration number: NCT04423731 (http://www.clinicaltrials.gov).

Fig. 1

Study design ERC, endoscopic retrograde cholangiography; PTC, percutaneous transhepatic cholangiogram; BRPC, borderline resectable pancreatic cancer; LAPC, locally advanced pancreatic cancer; MDT, multidisciplinary team.

Fig. 2

Flow diagram of the study stratified by resectability status according to the National Comprehensive Cancer Network classification (borderline resectable or locally advanced), primary treatment (best supportive care, primary chemotherapy or upfront surgery) and first-line chemotherapy regimen (FOLFIRINOX, gemcitabine/nab-paclitaxel, gemcitabine, other) Outcome of surgery is classified as resected or explored only. *Secondary CT performed in six patients before initiation of planned neoadjuvant chemotherapy showed distant metastasis, and the patients received palliative chemotherapy. ^†Two patients with borderline resectable pancreatic cancer underwent upfront surgery followed by adjuvant chemotherapy. One patient with borderline resectable pancreatic cancer received fluorouracil/leucovorin/oxaliplatin and underwent subsequent resection. CT, computed tomography; FOLFIRINOX, fluorouracil, leucovorin, oxaliplatin and irinotecan; GnP, gemcitabine nab-paclitaxel.

Fig. 3

Overall survival for the 188 patients, regardless of being resected or not, receiving chemotherapy stratified by resectability status (borderline resectable versus locally advanced) according to the National Comprehensive Cancer Network classification BRPC, borderline resectable pancreatic cancer; LAPC, locally advanced pancreatic cancer.

Fig. 4

Overall survival for the study cohort a Overall survival adjusted for immortal time bias for 188 patients with borderline resectable and locally advanced pancreatic cancer receiving chemotherapy stratified by treatment (resection versus no resection). b Overall survival adjusted for immortal time bias for 96 patients with borderline resectable pancreatic cancer receiving chemotherapy stratified by treatment (resected versus non-resected). c Overall survival adjusted for immortal time bias for 92 patients with locally advanced pancreatic cancer receiving chemotherapy stratified by treatment (resected versus non-resected).