From the Guidelines
Neuroendocrine prostate cancer (NEPC) is the type of prostate cancer that expresses Prostate-Specific Membrane Antigen (PSMA) but has low Prostate-Specific Antigen (PSA) levels. This aggressive variant of prostate cancer develops in patients with castration-resistant prostate cancer, often after hormonal therapy, and is associated with a poor prognosis 1. Key characteristics of NEPC include:
- High levels of PSMA expression
- Low PSA levels despite large metastatic burden and visceral disease
- Resistance to androgen deprivation therapy
- Rapid disease progression NEPC cells undergo a lineage switch, losing their androgen receptor signaling dependency while maintaining PSMA expression on their cell surface, which creates a diagnostic challenge since PSA, the traditional prostate cancer marker, remains low despite disease progression 1. The discordance between PSMA expression and PSA levels makes PSMA-PET imaging particularly valuable for detecting these tumors when conventional PSA monitoring might suggest the disease is under control. Treatment typically involves cytotoxic chemotherapy regimens, such as cisplatin/etoposide, carboplatin/etoposide, docetaxel/carboplatin, or cabazitaxel/carboplatin, rather than hormonal approaches due to the loss of androgen receptor dependence in these tumors 1.
From the Research
Prostate Cancer Type with High PSMA and Low PSA Expression
- The type of prostate cancer that expresses Prostate-Specific Membrane Antigen (PSMA) but has low Prostate-Specific Antigen (PSA) levels is often associated with metastatic castration-resistant prostate cancer (mCRPC) 2, 3.
- mCRPC is a form of prostate cancer that no longer responds to traditional hormonal treatment alone and has spread to other parts of the body 2.
- Studies have shown that PSMA is highly expressed in mCRPC, making it a potential target for treatment with radioligand therapies such as Lutetium-177 (177Lu)-PSMA-617 3, 4.
- While PSA levels are often used as a biomarker for prostate cancer, some patients with mCRPC may have low PSA levels despite having aggressive disease 4, 5.
- The use of 177Lu-PSMA-617 has been shown to be effective in treating mCRPC, even in patients with low PSA levels, and has been approved for treatment of mCRPC based on positive phase III studies 2, 3.
Characteristics of Prostate Cancer with High PSMA and Low PSA Expression
- High expression of PSMA on the surface of cancer cells 3, 4
- Low levels of PSA in the blood 4, 5
- Aggressive disease that has spread to other parts of the body (metastatic) 2, 3
- Resistance to traditional hormonal treatment (castration-resistant) 2, 3
- Potential for treatment with radioligand therapies such as 177Lu-PSMA-617 2, 3, 4, 5