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Título

177Lu-PSMA and 177Lu-DOTATATE as Therapy Alternatives for Metachronous Transdifferentiated Prostate and Neuroendocrine Tumors - Case Report

Introdução/Justificativa

Prostate cancer is among the most common cancers in males. The PSMA (Prostate-Specific Membrane Antigen), a protein expressed in prostate cancer cells, has been used in the control of that cancer and can also be taken up in the neovasculature of other non-prostatic tumors, where it should may be a useful tool.
In a normal prostate, the neuroendocrine (NE) cells represent a smaller population than the epithelial cells and may play a role in the regulation. In cases of prostatic adenocarcinoma, a portion of the carcinomatous cell population undergoes transdifferentiation processes, becoming cells that express NE markers related to progression and poor prognosis. The carcinoembryonic antigen (CEA) is one of the main markers for monitoring patients who have undergone transdifferentiation.
Studies indicate that the transdifferentiation is often accelerated by conventional androgen deprivation therapy, leading to the progression of the cancer, which highlights the need for new therapeutic strategies.
Neuroendocrine tumors (NETs) are a diverse group of neoplasms originating from NE cells present in different organs. Radioactive therapy with 177Lu-DOTA is considered an innovative approach in treating NETs, specifically targeted to tumor tissues, minimizing the impact on healthy tissues.
Considering the similarities between the cells of NETs and the NE cells from prostate adenocarcinoma, this report aims to demonstrate the application of 177Lu-PSMA and/or 177Lu-DOTA in a case where metachronous tumors with NE cells exist.

Relato

Male, 73 years old, with a neuroendocrine pancreatic cancer (since 2000) being treated with Octreotide. Was diagnosed with prostatic adenocarcinoma, Gleason 4+4=8, ECIVB (T3aN0M1b) in 2021, started androgenic deprivation with Gosserelina and Zoledronato, associated with Abiraterone+Prednisone. The PSA had decreased by 98,73% with treatment, but during the evaluation, sonographic imaging demonstrated liver lesions compatible with metastatic disease and an increase in liver enzymes, which led to the suspension of Abiraterone.
A 1007-PSMA-PET/CT (from 2023) with high uptake on the pancreas, liver, and multiple bone lesions led to the therapy with 177Lu-PSMA.
After the first cycle of therapy, he presented a facial flush, which was solved spontaneously. After the second cycle of 177Lu-PSMA therapy, the laboratory demonstrated a significant reduction in PSA (52,4%) and Chromogranin A (58,7%), comparing before treatment. In the second PSMA-18F PET-CT (from 2024), the pancreatic mass has reduced by 30,7% and the hepatic lobes by 15,7% in comparison with the SUV from 2023. However, bone injuries have an increase of 15,8% on SUV in the thoracic spine, which leaves the doubt of flare phenomenon or disease progression. A Ga68-DOTA-PET/CT demonstrated intense uptake at the same lesions detected by PSMA-18F PET-CT.
The patient has two different possibilities of radionuclide therapy. Behold, 177Lu-PSMA can be an alternative to prostate adenocarcinoma and NET dedifferentiation due to its increase in angiogenesis, demonstrated by 1007-PSMA-PET/CT and 177Lu-DOTA due to its increased uptake on neuroendocrine cells demonstrated by Ga68-DOTA-PET/CT.

Conclusão

The case demonstrates the possibility of treating prostate and neuroendocrine tumors with 177Lu-PSMA and/or 177Lu-DOTA, depending on the pathology stage.

Palavras Chave

177Lu-PSMA; 177Lu-DOTA; Prostate cancer; Neuroendocrine Tumors