Combined phosphorus-32 implantation and chemotherapy versus chemotherapy alone for locally advanced pancreatic cancer: a propensity-score weighted landmark analysis.

Background and aims: Combined standard chemotherapy and phosphorus-32 (³²P) microparticle intra-tumoral implantation has revealed encouraging results in locally advanced pancreatic cancer (LAPC). We compared chemotherapy and ³²P implantation with standard therapy (chemotherapy +/- chemoradiotherapy) using a propensity-score weighted analysis (PSWA).

Method: We conducted a retrospective cohort study comparing clinical outcomes of combined chemotherapy and endoscopic ultrasound (EUS)-guided ³²P implantation against standard therapy for patients with LAPC from 2 tertiary hospitals. Landmark analysis was used to address immortal time bias. PSWA was applied to reduce bias due to confounding. The primary outcome was overall survival within 30 months after first-line treatment initiation, with treatment effect expressed as restricted mean survival time (RMST).

Results: 104 patients were considered. The landmark date was designated as 3 months after initiation of first-line chemotherapy. After excluding patients who died before the landmark, or had ³²P implantation after it, 86 patients were included (35 combination vs. 51 standard). The RMST within 30 months after chemotherapy commencement was an estimated 189 days longer for patients with combination therapy (527.2 [95% CI 437.8-634.8] vs. 338.0 [95%CI 284.2-402]; p=0.002). The local progression free RMST within 30 months was estimated to be 168.6 days (95%CI 79.9-257.2) longer and the probability of downstaging was 23.9% higher (95%CI 6.3-41.3, p=0.008) in patients treated with combination therapy.

Conclusion: In this comparative study between combined chemotherapy and ³²P microparticles implantation with standard chemotherapy for patients with LAPC, the combination showed better survival, disease control and downstaging. The outcomes highlight the need for a randomized controlled trial.