The impact of intensified staging and combined therapies in locally advanced pancreatic cancer: a secondary analysis of prospective studies
Authors: Fiore Michele , Petrianni Gian Marco , Trecca Pasquale , D’Ercole Gabriele , Coppola Alessandro , La Vaccara Vincenzo , Taralli Silvia , Cimini Paola , Greco Carlo , Ippolito Edy , Calcagni Maria Lucia , Beomonte Zobel Bruno , Caputo Damiano , Coppola Roberto , Ramella Sara , D’Angelillo Rolando Maria 
Published: September 2023

Aim:
The aim was to investigate the use of comprehensive pretreatment staging with multiple diagnostic modalities, including functional imaging and minimally invasive surgical procedures, in locally advanced pancreatic cancer (LAPC) patients. The primary objective was to detect occult metastatic disease using staging laparoscopy and 18F-FDG-positron emission tomography (PET)/computed tomography (CT) scan. The study also evaluated treatment efficacy and outcomes in LAPC patients treated with combined therapies.

Materials and methods:
This study was a secondary analysis of three prospective studies of chemoradiotherapy (CRT) with or without induction chemotherapy (IC). The inclusion period was from December 2009 until February 2023. An intensified pretreatment staging was conducted for all LAPC patients. Patients without distant disease at initial staging, with borderline resectable or unresectable LAPC, were enrolled in CRT combination protocols (CRT with or without IC). IC regimens included GemOx or FOLFIRINOX for four cycles, followed by concurrent CRT with gemcitabine. The primary endpoint was the detection of occult metastatic disease, and secondary objectives included resection rate, treatment toxicity, overall survival (OS), progression-free survival (PFS), local control, and metastasis-free survival.

Results:
Out of the 134 LAPC patients, 33.5% were identified with metastatic disease. Of these, 23.1% had a positive exploratory laparoscopy. Additionally, 13.4% were identified as having distant metastases by 18-FDG PET/CT. The median PFS for all patients who completed CRT was 14.3 months, and the median OS was 17.2 months. Resected patients after the combined therapies demonstrated significantly improved outcomes compared tonon-resected patients (median PFS, 22.5 months vs. 9.5 months, P<0.001; median OS, 38.2 months vs. 13 months, P<0.001). Moreover, patients treated with IC followed by CRT showed significantly better outcomes compared to the upfront CRT group (median PFS, 19 months vs. 9.9 months, P<0.001; median OS, 19.3 months vs. 14.6 months, P<0.001). At univariate logistic regression analysis, the adding of IC was the only predictor for resection rate (95% CI: 0.12–1.02, P=0.05), and this data was confirmed at multivariate analysis (95% CI: 0.09–0.98, P=0.04). Hematological and gastrointestinal toxicities were observed during treatment, with manageable adverse events.

Conclusions:
The use of comprehensive pretreatment staging, including laparoscopy and 18F-FDG-PET/CT scan, is an effective approach in identifying occult metastatic disease in LAPC patients. Our findings offer valuable insights into accurate staging and treatment efficacy, providing evidence-based support for optimal management strategies in LAPC patients.