Prognosis of Upfront Surgery for Pancreatic Cancer: A Systematic Review and Meta-Analysis of Prospective Studies

BackgroundThe rate of patients with pancreatic ductal adenocarcinoma (PDAC) receiving neoadjuvant chemotherapy is increasing, but upfront resection is still offered to most patients with resectable or borderline resectable disease. Encouraging data reported in adjuvant chemotherapy trials prompts surgeons towards upfront surgery, but such trials are subject to a significant selection bias. This systematic review aims to summarize available high-quality evidence regarding survival of patients treated with upfront surgery for PDAC.MethodsPubmed, Cochrane, and Web of Science Databases were interrogated for prospective studies published between 2000 and 2021 that included at least a cohort of patients treated with upfront surgery for resectable or borderline resectable PDAC. The Cochrane Collaboration’s risk-of-bias tool for randomized trials (RoB-2) was used to assess risk of bias in all randomized studies. Patient weighted median overall survival (OS) and disease-free survival (DFS) were calculated.ResultsOverall, 8,341 abstracts were screened, 17 reports were reviewed in full text, and finally 5 articles and 1 conference abstract underwent data extraction. Included studies were published between 2014 and 2021. All studies were RCTs comparing different neoadjuvant treatment strategies to upfront surgery. Three studies included only resectable PDAC patients, two studies recruited patients with resectable and borderline resectable disease, and one study selected only borderline resectable patients. A total of 439 patients were included in the upfront resection cohorts of the 6 studies, ranging between 20 to 180 patients per study. The weighted median OS after upfront surgery was 18.8 (95% CI 12.4 – 20.6) months. Median DFS was 9 (95% CI 1.6 – 12.5) months. Resection rate was 74.5% (range 65-90%). Adjuvant treatment was initiated in 68% (range 43-77%) of resected patients.ConclusionsHigh-quality data for PDAC patients undergoing upfront surgery is scarce. Meta-analysis from the included studies showed a significantly shorter OS and DFS compared to recently published studies focusing on adjuvant combination chemotherapy, suggesting that the latter may overestimate survival due to the exclusion of most patients scheduled for upfront surgery.

P-P46 The use of FDG-PET/CT in the pre-operative staging of pancreatic ductal adenocarcinoma

Background The NICE Quality Standard for Pancreatic Cancer (December 2018) recommends that ‘adults with localised pancreatic cancer on CT(should) have staging using fluorodeoxyglucose positron emission tomography/CT(FDG-PET/CT) before they have surgery, radiotherapy or systemic therapy’. Such FDG-PET/CT staging aims to provide additional information to conventional cross-sectional imaging, thus presenting the most accurate staging of disease. However, the sensitivity and specificity of FDG-PET/CT to deliver relevant additional clinical information must be balanced with potential delays to treatment, and additional cost associated with its use, in the management of a time-critical pathology. Methods Consecutive pancreatic ductal adenocarcinoma(PDAC) patients deemed resectable on conventional imaging, and therefore referred for FDG-PET/CT assessment, were included for analysis. Data were derived from a single tertiary Hepatopancreaticobiliary(HPB) centre between May 2018 and June 2021. Data were collected and analysed from a combination of prospectively-collated electronic databases and paper patient records. Results Of 89 patients analysed, 55(61.7%) patients were male. Primary pancreatic lesions were PET avid in 81 cases(91%). Median time from request to FDG-PET/CT performance was 11 days(Range 1-35). Additional clinical information from FDG-PET/CT was provided in 61(68.5%) patients. Further investigations to assess FDG-PET/CT findings were arranged in 23 patients(25.8%; including liver MRI and EUS), demonstrating that FDG-PET/CT findings were true-positive in 6(26.1%), false-positive in 15(65.2%) and equivocal in 2(8.7%). There was a median delay of 60.5 days(Range 26 to 256) from FDG-PET/CT to surgery in those undergoing additional investigation. In total, a new diagnosis of metastatic/non-resectable disease was made in 14(15.7%) patients, preventing progression to planned operative intervention. Conclusions FDG-PET/CT provided additional information to conventional imaging that led to cancellation of planned operative resection in 14(15.7%) PDAC patients-8 directly and 6 following further investigation. However, there was a median delay of 11 days to FDG-PET/CT and 60.5 days from FDG-PET/CT to surgery in those undergoing additional investigation. Whilst FDG-PET/CT can lead to avoidance of unnecessary surgical intervention in PDAC patients with unsuspected metastatic/non-resectable disease, it can lead to delay, over-investigation, excess cost and anxiety in resectable patients. HPB units should audit their own findings to assess whether the use of FDG-PET/CT should be considered on a standard or selected basis.

P-P58 The role of PET-CT in the management of pancreatic cancer. A Northern Ireland experience

Background Diagnosis and staging has proven to be difficult in 10-20% of patients with pancreatic cancer. The PET-PANC study found that PET-CT significantly influenced the staging and management of pancreatic cancer and therefore the NICE guidelines now advise PET-CT in all patients who have localised potentially resectable disease. This study aimed to investigate the impact of PET-CT on the management of pancreatic cancer patients in a single tertiary referral centre. Methods There were 288 patients with pancreatic cancer discussed at the Northern Ireland Regional Hepatobiliary MDM from January 2020 to March 2021. Of these patients, 176 were deemed to have inoperable disease based on initial CT, 5 had borderline resectable disease, 1 had holding chemotherapy due to COVID restrictions and 57 were excluded from surgical resection for a variety of reasons. These included the patient being unfit for surgery, the patient declining operative intervention and an alternative treatment offered as result of COVID-19 pandemic. Therefore, there were 49 patients with pancreatic adenocarcinoma which the MDT concluded should be considered for surgical resection. Results A total of 27 patients who were due to undergo a curative resection had a pre-operative PET-CT scan (55.1%). This demonstrated metastatic disease in 9 cases (33.3%). Four patients who did not have a preoperative PET-CT were found to have metastatic disease at operation (9.7%). This equated to a total metastatic incidence of 26.5% in those who had been initially deemed resectable based on CT scan alone. The time interval from MDM decision to surgery averaged 25.4 days in those who did not have a PET/CT compared to 40.43 days in those who did. This was an average delay of 15.07 days until treatment. Conclusions This study demonstrates the important role the PET-CT has in the management of patients with pancreatic cancer. A significant number of patients avoided an unnecessary operation which would have delayed the commencement of chemotherapy. However, there are limitations to PET-CT, demonstrated in the patient with an inconclusive result, who was found to have liver metastases at surgery. The introduction of PET-CT in the staging process does undoubtedly cause delays to surgical resection and a more streamlined pathway needs to be developed to limit the delay to curative treatment.

Neoadjuvant versus adjuvant management of resectable pancreas cancer: A review of the literature

SummaryNeoadjuvant therapy is well-accepted in the treatment of borderline resectable and locally advanced PC, the benefit of neoadjuvant chemotherapy in patients with resectable disease, however, is currently not so clear. Here we provide an up date on the literature.

Lurbinectedin in Refractory Diffuse Malignant Peritoneal Mesothelioma: Report of Two Cases

Mesothelioma is a malignancy of serosal membranes. Parietal pleura is the most common site, with peritoneum being the second most frequent location. Malignant peritoneal mesothelioma (MPM) is a rare and aggressive disease. The prognosis is often very poor with median overall survival ranging from 6 to 18 months in patients who are not candidates for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) due to non-resectable disease or comorbid conditions. For patients with resectable disease, CRS and HIPEC have become the standard of care. However, for patients with unresectable malignant mesothelioma there is unfortunately no effective systemic treatment beyond the first line. Based on the results of a recent phase II trial, lurbinectedin has clinical activity and acceptable toxicity in the second- and third-line treatment of malignant pleural mesothelioma. However, until present, no data have been available for patients with MPM and for patients who become refractory after multiple treatment lines. We report on two patients with metastatic MPM who achieved durable disease control of 10+ and 8 months with lurbinectedin in the fourth and fifth treatment line, respectively.

Optimal Upfront Treatment in Surgically Resectable Pancreatic Cancer Candidates: A High-Volume Center Retrospective Analysis

Pancreatic adenocarcinoma is a devastating disease with only 15–20% of patients resectable at diagnosis. Neoadjuvant chemotherapy for this cohort is becoming increasingly popular; however, there are no published randomized trials that support the use of neoadjuvant chemotherapy over upfront surgery in resectable disease. This retrospective cohort analysis was conducted to compare both treatment pathways and to identify any potential prognostic markers. Medical records from one large volume pancreatic cancer center from 2013–2019 were reviewed and 126 patients with upfront resectable disease were analyzed. Due to a change in practice in our center patients treated prior to December 2016 received upfront surgery and those treated after this date received neoadjuvant chemotherapy. Of these, 86 (68%) patients were treated with upfront surgery and 40 (32%) of patients were treated with neoadjuvant chemotherapy. Our results demonstrated that patients treated with upfront surgery with early-stage (1a) disease had a longer median OS compared to those treated with neoadjuvant chemotherapy (24 vs. 21 months, p = 0.028). This survival difference was not evident for all patients (regardless of stage). R0 resections were similar between groups (p = 0.605). We identified that both tumor viability (in neoadjuvant chemotherapy-treated patients) and tumor grade were useful prognostic markers. Upfront surgery for certain patients with low volume disease may be suitable despite the global trend towards neoadjuvant chemotherapy for all upfront resectable patients. A prospective clinical trial in this cohort incorporating biomarkers is needed to determine optimal therapy pathway.