Types of Prostate Cancer

July 1, 2024

This page was reviewed under our medical and editorial policy by Wesley Yip, M.D., assistant professor, Division of Urology and Urologic Oncology, Department of Surgery, and Tanya Barauskas Dorff, M.D., professor, Department of Medical Oncology & Therapeutics Research, City of Hope^® Cancer Center Duarte

A vast majority of prostate cancer cases are adenocarcinomas, along with a number of less common cancers that affect this male reproductive gland.

The type of prostate cancer is assigned based on laboratory analysis of tissue samples obtained during a biopsy. Doctors who study tissue samples, called pathologists, use a microscope to determine how abnormal the prostate cancer cells appear to be. These tissue samples are then given a Gleason score, an indicator of how likely the cancer is to grow and spread. Faster-growing and faster-spreading cancers are considered high-grade.

A doctor may also order additional tests such as immunohistochemical (IHC) stains to help identify the type of prostate cancer. IHC pinpoints substances on cancer cells called antigens that trigger an immune response. These results may be combined with findings from tests like the prostate-specific antigen (PSA) test, which measures levels of PSA protein made by prostate cells, to help doctors understand characteristics of specific types of prostate cancer.

Prostatic Adenocarcinoma

Prostatic adenocarcinoma makes up 95% of all prostate cancers, and includes both acinar adenocarcinoma and ductal adenocarcinoma. These two types of cancer form in the prostate’s gland cells, which produce prostate fluid.

Adenocarcinoma starts in the protective epithelial layer of the prostate gland. Pathologists look for telltale markers of these cells and at glandular structures in tissue samples to help assign the type.

Adenocarcinoma is not typically an aggressive cancer, and it usually (though not always) grows slowly over a number of years. Overall, the relative prostate cancer survival rate is high.

Acinar Adenocarcinoma

Prostatic acinar adenocarcinoma (PAC) is by far the more common of the two types of prostatic adenocarcinomas, representing all but a small percentage of these cases. This type of cancer takes its name from the acinar epithelium (a layer of epithelial cells that line the prostate gland) from which it develops. Acini cells are groups of cells that form a round cluster.

PAC is usually a slower-growing, less aggressive cancer than prostatic ductal carcinoma (DAC). Men with PAC have better metastatic-free survival rates than those with DAC, meaning that once treatment begins, they are alive longer and free of cancer that spreads to other parts of the body. They also have greater overall survival rates.

Sometimes PAC has mixed acinar and ductal features, but it is considered acinar adenocarcinoma if its acinar features make up 50% or more of the total cancer features.

Ductal Adenocarcinoma

While acinar adenocarcinoma is the most common type of prostate cancer, ductal adenocarcinoma is considered rare. As its name suggests, it develops in the ducts of the prostate gland. It is characterized by tall, layered columns of abnormal epithelial cells.

Most cases of DAC include a PAC diagnosis as well.

Several factors make DAC different from PAC. For one, it is more likely to recur and spread to tissues and organs outside the prostate. It also has lower survival rates than PAC. DAC also does not respond as well as high-grade PAC to androgen deprivation therapy (ADT), one of the main types of hormone therapy used to treat it.

Less Common Prostate Cancer Types

Less common types of prostate cancers include those that are subtypes of other types, as well as those that are considered standalone conditions, such as squamous cell carcinoma of the prostate. Below are five less common types of prostate cancer.

Small Cell Prostate Cancer

Small cell carcinoma accounts for less than 1% of prostate cancer diagnoses. It is a subtype of another prostate cancer called neuroendocrine prostate cancer. It originates in the prostate’s neuroendocrine cells, which receive signals from the nervous system to release hormones. Small cell carcinoma of the prostate may also develop from treatment-related adenocarcinoma, specifically treatment with ADT drugs, such as abiraterone.

In this cancer type, a gene called RB1 that makes a protein to help stop tumors from growing is almost always “turned off.” It is common for another tumor-suppressing gene called TP53 to be turned off as well. This makes it easier for the cancer cells to grow and spread.

About half of patients diagnosed with small cell carcinoma are also diagnosed with adenocarcinoma.

Like ductal adenocarcinoma, small cell carcinoma is an aggressive cancer that does not respond well to treatment with ADT, and this may affect the survival outcomes of men diagnosed with the condition.

Squamous Cell Carcinoma of the Prostate

Squamous cells are flat, thin cells that resemble fish scales. Squamous cell carcinoma of the prostate begins in these cells. Specifically, it develops in one of three places: glands surrounding the urethra (the tube that carries urine out of the body), the basal cells or the acini cells.

Squamous cell tumors tend to be large, and men with these tumors may experience pain or burning when urinating, as well as difficulty urinating. The disease develops on its own or after ADT treatment for prostatic adenocarcinoma.

Although this type of prostate cancer is rare, it grows and spreads faster than adenocarcinoma of the prostate, particularly to the bone. Life expectancy is relatively short for men with this cancer, and research into new classification types and treatment plans aims to help improve treatment outcomes.

Urothelial Carcinoma

This condition, which was previously referred to as transitional cell carcinoma, starts in cells that line the bladder. These are called either urothelial cells or transitional cells (because of their ability to expand and contract).

Urothelial carcinoma may be distinguished from cancer that starts in the prostate gland through IHC stain testing, which shows whether urothelial cell markers are present.

Urothelial carcinoma is the most common type of bladder cancer. It is considered advanced (Stage 3 or Stage 4) if it has invaded the prostate gland or seminal vesicles and has become transitional cell cancer of the prostate. If this happens, men may notice symptoms, such as blood in the urine and pain, when they urinate.

For those diagnosed with the condition, doctors may recommend a multifaceted approach to treatment, including chemotherapy, radiation therapy, surgery and immunotherapy for prostate cancer. While the condition is challenging to treat, advances in targeted therapy for prostate cancer using a PARP inhibitor (which works by stopping DNA repair of cancer cells) show promise.

Neuroendocrine Prostate Cancer

Neuroendocrine prostate cancer (NEPC) is rare and includes three subtypes: small cell carcinoma, large cell neuroendocrine carcinoma and adenocarcinoma with neuroendocrine differentiation.

While some neuroendocrine tumors have features in common with adenocarcinoma, they may be distinguished using certain neuroendocrine markers, gene expressions and the absence of PSA secretions (patients with adenocarcinoma typically have elevated blood PSA levels).

NEPC develops from the neuroendocrine cells of the prostate gland. Treatment-related neuroendocrine prostate cancer may also develop after prostatic adenocarcinoma is treated with ADT drugs such as abiraterone and enzalutamide. This occurs in a small but significant group with a form of adenocarcinoma that is resistant to hormone therapy. Research is ongoing to determine the exact nature of underlying gene changes.

Neuroendocrine prostate cancer is considered an aggressive form of cancer, meaning it is a fast-growing type that quickly spreads to other organs. Treatment-related neuroendocrine cancer has contributed significantly to the lethal cases of prostate cancer, and its response to chemotherapy treatment is not usually long-lasting. Many clinical trials are now underway to find better treatments for this type of prostate cancer.

A blood test that helps distinguish NEPC from prostatic adenocarcinoma that is resistant to hormone therapy may help doctors more accurately diagnose the condition and provide targeted therapy for neuroendocrine tumors.