Metastatic solid pseudopapillary neoplasms of the pancreas: current treatment status and exploration of endocrine therapy

<h3>Background</h3> Solid pseudopapillary neoplasm (SPN) of the pancreas is rare and indolent. However, some patients with malignant potential develop metastasis. We aimed to analyze current treatment status and explore optimized clinical management of metastatic SPNs. <h3>Patients and methods</h3> Clinical data of metastatic SPN patients were collected from literature and two hospitals. Gene set enrichment analysis of RNA expression profiles of tumor tissues versus normal pancreatic tissues from the GEO database was carried out to explore functionally enriched pathways. Fresh tumor tissues from 10 SPN patients were cultured and <i>in vitro</i> hormonal agent sensitivity testing was conducted. Six patients received endocrine therapy with tamoxifen and megestrol acetate. <h3>Results</h3> A total of 115 metastatic SPN patients were included. Eighty-four patients underwent local treatment, including surgery, interventional therapy, and radiotherapy. Cytoreductive therapy significantly improved overall survival (<i>P</i> < 0.05, hazard ratio 0.11, 95% confidence interval 0.02-0.68). Thirty-six patients received chemotherapy and only one achieved partial response. Concurrent enrichment of the Wnt signaling pathway and progesterone receptor signaling pathway in SPNs was revealed. Drug sensitivity testing showed inhibition rates (IRs) of 50% for megestrol acetate, 40% for tamoxifen, and 30% for testosterone propionate, and 20% for gemcitabine at 10 × peak plasma concentration (Cmax). There was a trend toward higher IR for megestrol acetate and tamoxifen in the 100% progesterone receptor expression subgroup. Six patients received endocrine therapy with tamoxifen plus megestrol acetate. Tumor regression was observed in two patients. <h3>Conclusions</h3> This largest-to-date retrospective study demonstrated the chemoresistant nature of SPN, survival benefits from cytoreductive therapy, and preliminary clinical response of endocrine therapy. The combination of tamoxifen and megestrol acetate is worthy of further exploration.