Perineural invasion (PNI) means that cancer cells are growing inside or alongside a nerve.

A nerve is a bundle of fibers made up of cells called neurons. Nerves send and receive signals from your brain. If you have prostate cancer, PNI means the cancer is growing in or touching a nerve within the prostate.

PNI in prostate cancer could mean that there’s a higher chance your cancer will spread (metastasize) to other parts of the body, such as your bones. It could also mean that your cancer is more aggressive and has a less favorable outlook compared with prostate cancer without perineural invasion.

But PNI isn’t the only factor your doctor will consider when determining your outlook and treatment plan.

Language matters

Sex and gender exist on spectrums. This article uses “men” to reflect a term that has been historically used to gender people. It’s important to note that not everyone assigned male at birth identifies with the label “man.”

While we aim to create content that includes and reflects the diversity of our readers, specificity is key when reporting on research participants and clinical findings.

Unfortunately, the studies and surveys referenced in this article didn’t include data on, or include, participants who were transgender, nonbinary, gender nonconforming, genderqueer, agender, or genderless.

PNI doesn’t necessarily mean that cancer has spread to other parts of your body. But it does mean the chances are higher that your cancer has spread or will spread in the future.

A 2015 study found a strong relationship between PNI and bone metastasis (cancer that has spread to the bones). In the study, which included 633 men with prostate cancer, those with PNI had an 11 times higher risk for bone metastasis compared with men who didn’t have PNI.

PNI is a common way for prostate cancer cells to spread throughout your body. If your cancer invades the nerves, it now has a direct path to travel outside of the prostate via the nervous system. Cancer can also spread in the body through blood vessels and the lymphatic system.

Doctors can detect PNI in prostate cancer during a test known as a needle biopsy.

For a needle biopsy, a doctor removes several small samples of your prostate using a thin, hollow needle. They then examine the samples under a microscope so they can look more closely at the cancer cells.

A doctor will be able to see if the cancer cells are inside, around, or tracking alongside a nerve.

Doctors can also detect PNI after you have surgery to remove your prostate gland (radical prostatectomy). After the surgery, a doctor or pathologist will examine a sample of the prostate gland under a microscope to look for signs of PNI.

How common is perineural invasion in prostate cancer?

PNI is common in prostate cancer, but its prevalence varies from study to study.

In a 2018 review of studies with a total sample size of 13,412 men with prostate cancer, roughly 31% (4,197 people) had PNI. In another study of 721 people who underwent surgery to remove the prostate gland, nearly 74% had PNI.

The varied results could be due to the people diagnosing PNI as it is a complex diagnosis. A 2021 study found that observers disagreed on PNI diagnoses in about one out of every four cases.

PNI in prostate cancer on its own doesn’t cause symptoms. But you might experience symptoms if your cancer is able to spread outside the prostate through the nerves.

For example, advanced prostate cancer that has spread to the bones can lead to bone pain and fractures. Cancer that has spread to the brain can cause headaches, dizziness, and seizures.

Since PNI could mean that your cancer has a higher chance of becoming advanced or spreading throughout your body, a doctor might recommend a more aggressive treatment plan than if you didn’t have PNI.

But your doctor will consider many factors, including your diagnostic test results, age, and overall health, before deciding on a treatment plan.

If you have PNI and undergo surgery to remove the prostate gland, your doctor might also recommend removing the nerves that run on either side of the prostate. However, this might affect your ability to have an erection after the surgery.

Your doctor might also want to follow the surgery with radiation therapy, hormone therapy, or a systemic treatment like chemotherapy to kill cancer cells that may have already spread outside the prostate.

More randomized controlled trials with long-term follow-up are needed to help understand if a different treatment regimen for people with PNI can help prevent recurrence and improve the overall outlook.

As scientists better understand PNI and how it occurs in the prostate, new treatments may become available.

There’s still some controversy in the scientific community about the importance of PNI in prostate cancer diagnosis. In recent years, a growing body of evidence suggests PNI could be a useful tool in determining the outlook for prostate cancer.

Recent research shows a strong link between PNI and poorer outcomes. PNI is a sign of more aggressive cancer and is often present in more advanced tumors.

Still, PNI doesn’t always mean that your cancer has spread. And it isn’t the only factor a doctor will consider when determining your outlook.

Doctors also use a system known as the Gleason score or grade to help understand the severity of your cancer. In general, the higher your Gleason score, the more likely your cancer will spread quickly.

Other factors your doctor will look at when assessing your outlook include:

  • blood PSA level
  • the size of the tumor
  • lymph node involvement
  • if the cancer is in both sides of your prostate
  • the number of sample cores from the biopsy that contain cancer
  • results of imaging tests

In a 2018 study, PNI was associated with a higher Gleason score. People with PNI were also slightly more likely to have cancer return after treatment, but the difference wasn’t statistically significant. A 2020 study of 721 people with prostate cancer also found that PNI was linked to more aggressive disease and a higher chance of recurrence.

A 2017 study found that PNI was more common in people with high Gleason scores and associated with a higher mortality rate. Men in the study with PNI had a twofold higher risk of death from prostate cancer compared to those who were negative for PNI.

Perineural invasion (PNI) means that a diagnostic test found cancer inside or around a nerve in your prostate. It could mean that your cancer is more likely to spread to other parts of your body and could predict a worse outlook.

If you find out you have PNI following a biopsy, be sure to discuss what these results mean with your doctor. Keep in mind that your pathology report after a biopsy may not always include PNI results. If you have questions about this, it’s important that you ask your doctor.

Your doctor will likely use a few different diagnostic tools, such as Gleason scores, PSA, and imaging tests, to determine your outlook and decide on the best treatment plan.