# Two Cases of Neuroendocrine Transformation of Prostate Carcinoma in the Era of Expanding Therapeutic Options: Do the Increased Number of Available Treatments Translate Into Improved Patient Outcomes?

**Authors:** Rita Aranha, Filipe Veiga, Rafael Marques, Joana Melo, Sofia A Oliveira

PMC · DOI: 10.7759/cureus.99831 · Cureus · 2025-12-22

## TL;DR

This paper discusses two cases of aggressive prostate cancer that transformed into neuroendocrine cancer, highlighting diagnostic and treatment challenges.

## Contribution

The paper contributes two clinical case reports illustrating neuroendocrine transformation in prostate cancer and its implications for treatment.

## Key findings

- Neuroendocrine transformation occurred in two patients with metastatic prostate cancer after androgen receptor-directed therapy.
- Clinical progression was not reflected by prostate-specific antigen levels, complicating diagnosis.
- Current treatments show limited effectiveness against this aggressive cancer type.

## Abstract

Neuroendocrine prostate cancer is an aggressive and increasingly recognized resistance phenotype arising in advanced prostate adenocarcinoma, particularly after prolonged androgen receptor-directed therapy. We describe two patients with metastatic prostate cancer who developed rapid clinical progression accompanied by disproportionately low prostate-specific antigen (PSA) levels, ultimately revealing transformation to neuroendocrine carcinoma. These cases highlight the diagnostic challenges associated with this entity, the importance of obtaining new tissue for histologic confirmation when radiologic progression diverges from biochemical markers, and the limited effectiveness of current therapeutic options. Overall, these cases emphasize the critical need for improved clinical recognition and for continued research into targeted therapeutic approaches capable of addressing this highly aggressive phenotype.

## Linked entities

- **Diseases:** prostate cancer (MONDO:0005159)

## Full-text entities

- **Genes:** AR (androgen receptor) [NCBI Gene 367] {aka AIS, AR8, DHTR, HPCX3, HUMARA, HYSP1}, KLK3 (kallikrein related peptidase 3) [NCBI Gene 354] {aka APS, KLK2A1, PSA, hK3}
- **Diseases:** neuroendocrine carcinoma (MESH:D018278), Neuroendocrine Transformation (MESH:D018358), prostate adenocarcinoma (MESH:D000230), Prostate Carcinoma (MESH:D011472), Neuroendocrine prostate cancer (MESH:D011471)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12822179/full.md

## References

12 references — full list in the complete paper: https://tomesphere.com/paper/PMC12822179/full.md

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Source: https://tomesphere.com/paper/PMC12822179