Very rarely, prostate cancer starts in neuroendocrine cells. Some prostate cancers become resistant to treatment and turn into neuroendocrine tumors, which are more aggressive and have a poorer outlook.

Prostate cancer is the most common non-skin cancer and the second leading cause of cancer death in men in the United States. Non-Hispanic Black men are at the highest risk of receiving a prostate cancer diagnosis.

Almost all prostate cancers are adenocarcinomas. These cancers start in cells that create prostate fluid.

Neuroendocrine prostate cancer (NEPC) is rare and tends to be highly aggressive. Neuroendocrine tumors develop in cells that produce hormones in response to electrical signals from your nervous system.

NEPC can be a pure neuroendocrine tumor or share features with adenocarcinoma. The World Health Organization (WHO) classifies NEPC into four possible categories:

  • adenocarcinoma with neuroendocrine differentiation
  • well-differentiated neuroendocrine tumors
  • small-cell neuroendocrine carcinoma
  • large cell neuroendocrine carcinoma

Keep reading to learn more about how NEPC differs from adenocarcinoma.

NEPC develops in neuroendocrine cells that can secrete many different substances in response to neural signals, such as:

  • serotonin
  • histamine
  • chromogranin A
  • calcitonin
  • katacalcin

NEPC can develop as a new cancer or transform from adenocarcinoma that doesn’t respond to hormone therapy. Doctors call it “de novo” NEPC when it develops as a new cancer.

Researchers aren’t entirely sure why some people develop neuroendocrine tumors. But, like all cancers, they develop when mutated genes cause cells to replicate uncontrollably.

In a 2023 review of studies, researchers found the most frequently mutated genes in NEPC cells were:

  • TP53
  • RB1
  • PTEN

Adenocarcinoma transformation to neuroendocrine tumors

Almost everyone with prostate cancer has adenocarcinoma. This cancer develops in glands that produce prostate fluid.

Adenocarcinoma cells require androgen hormones to grow. Androgens are sex hormones that include testosterone and dihydrotestosterone. Doctors often administer medications to suppress androgen levels:

  • if your cancer has spread too far for treatment with surgery or radiation therapy
  • if your cancer comes back after surgery or radiation therapy
  • together with radiation therapy if you have a high risk of your cancer relapsing
  • before radiation therapy to shrink cancer cells

Cancers that continue to grow even when androgen levels are reduced are called castrate-resistant prostate cancers. As many as 17–40% of people with castrate-resistant prostate cancer develop neuroendocrine tumors.

Transformation to NEPC becomes more likely the longer hormone therapy continues.

How common is neuroendocrine prostate cancer?

De novo NEPC is very rare. Experts think it makes up 0.5–1% of newly diagnosed prostate cancers.

Most cases of NEPC are due to the transformation of castrate-resistant adenocarcinoma.

NEPC rates may be increasing due to the widespread use of a class of hormone therapy medications called androgen receptor pathway inhibitors. These medications keep androgens from binding to androgen receptors on prostate cancer cells. They include:

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Many of the early symptoms of NEPC are related to changes in how you urinate.

According to Neuroendocrine Cancer UK, symptoms of NEPC can include:

Later signs and symptoms may include:

NEPC that develops after hormone therapy has several characteristic features, such as:

A biopsy is the main tool for diagnosing all types of prostate cancer, including NEPC. It’s when a doctor takes a small tissue sample so a specialist called a pathologist can examine the cells under a microscope.

Other tests that doctors use to support a prostate cancer diagnosis include:

The most common imaging techniques are ultrasound and magnetic resonance imaging (MRI). Conventional imaging can’t yet differentiate neuroendocrine cancer from adenocarcinoma.

Researchers still have a poor understanding of NEPC, and few treatment options exist. There’s currently no standard effective therapy.

Treating NEPC often involves the removal of the prostate gland, followed by platinum-based chemotherapy regimens used to treat small cell lung cancer (SCLC). Treatment with cisplatin and carboplatin with either docetaxel or etoposide seems to have a relatively high response rate.

Researchers continue to examine treatments that may help treat NEPC in the future. Treatments under investigation include:

NEPC tends to have a poor outlook with rapid disease progression and a high risk of spreading to distant tissues. Its poor outlook is largely due to late diagnosis and lack of effective treatment.

About half of people with neuroendocrine cancer live less than a year. It most often spreads to the liver and bone.

Neuroendocrine tumors are responsible for about a quarter of deaths in people with castrate-resistant prostate cancer.

Adenocarcinoma tends to have a much better outlook. People with adenocarcinoma limited to the prostate or surrounding area are 99% as likely as people without prostate cancer to live at least 5 years.

NEPC is a rare type of prostate cancer that tends to be aggressive and has a poor outlook compared to adenocarcinoma, the most common type. NEPC can develop as a new cancer or develop from adenocarcinoma that becomes resistant to hormone therapy.

Researchers are still investigating how best to treat NEPC. There’s currently no standard treatment. Doctors often remove the prostate and use chemotherapy regimens for SCLC, an aggressive type of lung cancer.