EAU Lab: Biological insights for neuroendocrine tumours
Prof. Maurizio Colecchia (IT) and Prof. Carmen Jeronimo (PT) co-chaired the session, “Uro-oncology: Integrating biological insights with clinical care,” which was part of the new EAU Lab at the EAU25 Congress. This initiative was developed in collaboration with the EAU Section of Uropathology and the EAU Section of Urological Research. This report covers lectures on neuroendocrine differentiation, from understanding its biology to clinical challenges, moderated by Prof. Eva Comperat (AT) and Prof. Kjetil Tasken (NO).
In her presentation ‘Neuroendocrine prostate cancer’, Ms. Martine Duterque Coquillaud (FR) stated that over the past decade, there has been an increase in incidence of neuroendocrine prostate cancer (NEPC). She elaborates on the main characteristics of neuroendocrine prostate cancer (NEPC). “AR is absent or inactive, PSA is low, small cell phenotype, the neuroendocrine marker expressions are synaptophysin (SYP), chromogranin A (CHGA), and enolase 2 (ENO2 or NSE).
According to Ms. Duterque Coquillaud, there are at least two hypotheses about where NEPC’s come from. “Clonal evolution of t-NEPC from basal or neuroendocrine cells, or mechanism of trans-differentiation from epithelial adenocarcinoma cells to neuroendocrine cells.”
She stated that diagnosis is often late due to lack of biomarkers during ARPIs therapies, patients have a poor prognosis due to lack of specific drugs, and there is a limited understanding. “In vivo models must be developed (organoids, PDX).” And she concluded with the question, can NEPC characteristics be detected non-invasively, and with what biomarkers?
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A pathologist’s perspective was presented by Prof. Ronald De Krijger (NL) in his lecture ‘Neuroendocrine tumours of the genitourinary tract’.
According to Prof. De Krijger, urologists need to know that all paragangliomas (PGL) are malignant, and most abdominal paragangliomas produce catecholamines. “Up to 40% of PGL are hereditary and there are more than 20 genes involved, so all patients should be referred to clinical genetics.”
When defining neuroendocrine neoplasms, he stated that well-differentiated neuroendocrine (NET) has replaced carcinoid. “Neuroendocrine carcinomas are more frequent than NET. Small cell NE carcinomas in kidney, bladder, and prostate contain an NE component. Part of the NE carcinoma in the prostate arise through trans-differentiation from adenocarcinomas treated with anti-androgenic drugs.”
“Treatment-related neuroendocrine prostatic carcinoma arises by trans-differentiation of castration-resistant prostate cancer after androgen-deprivation therapy. Lineage plasticity plays an important role in this. Epigenetic events appear to play a role in specific genomic conditions, such as with loss of TP53, RB1, and PTEN. There is a poor prognosis with medium survival after trans-differentiation of 7 months.”
You can watch the full webcast via the EAU25 Resource Centre.