Determining your best path forward begins with learning as much as possible about your type of prostate cancer. That may be easier once you understand more about the results of your diagnostic tests and how they, along with your personal and family medical histories, contribute to your personalized treatment plan.

Your doctor may perform any of the following tests to diagnose your tumor and begin planning your treatment. Some tests may be used for monitoring once treatment begins.

Physical Exam

A digital rectal exam (DRE) is a common test to screen for prostate cancer, as well as to determine how large the tumor is. The doctor will insert a lubricated, gloved finger into your rectum and feel for any abnormalities in the prostate.

Blood Tests

Prostate-specific antigen (PSA) is one of the most accurate cancer biomarkers available. PSA is a protein produced only by prostate cells, both normal and cancerous. Some of this protein enters the bloodstream and can be measured in a small sample of blood. Generally, higher PSA levels indicate a greater risk that prostate cancer cells are present. However, infection, inflammation, enlargement or other injuries to the prostate can also raise a man’s PSA level. 

In men with an elevated PSA, the Prostate Health Index (phi) and 4Kscore tests can help avoid unnecessary biopsies without missing more than an occasional high grade, aggressive cancer, which would likely be found on the next screening test.

Biomarkers are molecules produced by cancer cells or by other cells in response to cancer and can be measured in blood or urine samples and used to indicate whether a cancer is present and how aggressive it may be.

If your PSA level is consistently elevated, your doctor may recommend some of the following related tests to help determine if a biopsy is needed or how serious the cancer may be:

• PSA density (PSAD) helps to determine how likely you are to have an aggressive cancer. It is calculated by dividing the PSA by the size of the prostate measured by ultrasound or MRI.

• PSA velocity measures how fast PSA levels change over time. It can be used to decide if a biopsy is needed but is most valuable as an indicator of how fast the cancer may be growing if it recurs after treatment.

• PSA doubling time is the time it takes for the PSA level to double. A shorter doubling time is associated with a more aggressive cancer. Your doctor may use this information to choose the best options for your therapy.

• Percent free PSA measures the proportion of the total PSA that circulates "freely" in the blood, not bound to another molecule. The higher the percent, the more likely the elevated PSA level is coming from benign enlargement of the prostate (BPH) rather than cancer. 

• Prostate Health Index (phi) measures PSA, free PSA and proPSA and uses a formula to predict the presence of a high grade (Grade Group 2 or more) cancer in the prostate in men with an elevated PSA.

• 4Kscore test measures PSA, free PSA, intact PSA and hK2 in a blood sample and combines these results with age and DRE, and whether a man had a previous negative biopsy into an algorithm to predict the likelihood that a biopsy would show a high-grade cancer.

PSA level may increase with age. It is important to be tested regularly so your doctor can compare these levels over time and watch for an increase, which may indicate a need for further evaluation. 

Urine Tests

Several tests help predict the likelihood that cancer is present within the prostate by measuring the level of abnormal RNA in cells excreted into the urine. Some require a vigorous prostate massage before the urine sample is collected (MiPS, PCA3, Select MDx) and some are geared to help predict whether a high grade cancer (Grade Group 2 or more) is present (MiPS, Select MDx, ExoDx or EPI).

Biopsies

A biopsy is the only way to definitively diagnose prostate cancer. Multiple tissue samples (typically 12 to 14 of them) are usually collected.

• Core needle biopsy is the most commonly used test for detecting the presence and grade of cancer in the prostate. 
• Transrectal ultrasound (TRUS)-guided biopsy uses sound waves to visualize the prostate and evaluate for cancer and other conditions. The ultrasound image is also used by the doctor to guide needles to the correct areas during the biopsy.   
• Transperineal, ultrasound-guided biopsy removes tissue with a thin needle that is inserted through the skin between the scrotum and rectum and into the prostate. 

• MRI-US fusion biopsy fuses, or combines, detailed MRI images with live, real-time ultrasound images of the prostate. An MRI is done first. At another appointment, an ultrasound of the prostate is performed. Fusion software combines the images from both tests and gives the doctor a detailed three- dimensional ultrasound/MRI view to help guide the biopsy needles more precisely to areas suspicious for cancer. 

• Pelvic lymphadenectomy is a surgical procedure to remove lymph nodes in the pelvis to see if they contain cancer. This procedure helps to determine the cancer’s stage.

• Seminal vesicle biopsy uses a needle to remove a sample of tissue from the seminal vesicles to check for spread of the cancer. 

• Prostate “bed” biops y may be performed after prostate cancer surgery if an abnormal lump arises in the area where the prostate was removed. 

The Grade of Prostate Cancer

The grade of a cancer refers to its appearance under a microscope and can only be determined from a tissue sample. Prostate cancer grade groups range from 1-5. In group 1, the cancer cells appear nearly normal and form recognizable glands - these are the most favorable, slowest growing cancers. Group 5 consists of sheets of disorganized, irregular cells hardly recognizable as coming from the prostate - these are the most aggressive, fastest growing. Since prostate cancers are usually composed of more than one grade, the grade of the largest area of cancer is listed first and the second largest, second (for example, 4+3). These combinations of grades are then grouped into the 5 grade groups, which powerfully predict the behavior of the tumor.

Imaging Tests

Transrectal ultrasound (TRUS) uses sound waves to visualize organs and evaluate them for cancer and other conditions. During this test, the technician will insert a lubricated transducer (a small instrument that emits sound waves) into the rectum. As the sound waves reach the prostate and create echoes, images of the prostate will appear on the monitor for the technician to view.

Magnetic resonance imaging (MRI) uses magnetic fields instead of X-rays to visualize internal organs in the body; the MRI is particularly helpful in showing a detailed view of the prostate.

A bone scan may be performed if the patient has bone pain or is at high risk for bone metastases based on other test results.

Computed tomography (CT) is primarily performed to look for the spread of cancer to lymph nodes and other organs but is not especially helpful at showing details inside the prostate.

Positron emission tomography (PET) involves intravenous administration of a tiny dose of radioactivity, which hones in on cancer, to identify its spread. A new version of PET, the PSMA PET, hones in on any clusters of prostate cancer more accurately than CT or MRI and is particularly valuable in men with advanced or very aggressive cancer.

ProstaScint scan detects the presence of PSMA on the surface of prostate cancer cells using an antibody carrying a radioactive molecule that can be detected by single photon emission computed tomography (SPECT). It is more accurate than a standard bone scan but less accurate than a PSMA PET scan.

Understanding Staging and Grading

The results of a thorough exam, imaging studies, blood tests and a biopsy are used to stage and grade the cancer. Staging determines the extent of your cancer, where it is located and whether it has metastasized (spread) to nearby organs, tissues or lymph nodes, or to other parts of your body. 

The TNM system is used to classify prostate cancer. The tumor (T) is categorized by its size, including how much of the prostate is occupied by cancer and whether it has spread to adjacent structures such as the seminal vesicles, rectum, bladder and/or pelvic wall; whether cancer has affected nearby lymph nodes (N); and whether the cancer has metastasized (M), or spread, to other parts of the body. The TNM classification, Gleason grade group, PSA level and other factors are considered in assigning a stage.Prostate cancer can be described as localized, locally advanced, regional or metastatic: 

• Localized cancer is found only in the prostate or the closely surrounding tissue. 
• Locally advanced cancer has spread outside the prostate to the bladder or rectum or is fixed to the nearby muscles. 
• Regional cancer has spread to the pelvic lymph nodes.  
• Metastatic prostate cancer has spread to distant parts of the body. 

Table 1. TNM system for classifying prostate cancer

Classification	Definition
Tumor (T)
TX	Primary tumor cannot be assessed.
T0	No evidence of primary tumor.
T1   T1a   T1b   T1c	Clinically inapparent (produces no signs or symptoms) tumor that is not palpable (noticeable by touch). Tumor incidental histologic finding in 5 percent or less of tissue resected. Tumor incidental histologic finding in more than 5 percent of tissue resected. Tumor identified by needle biopsy found in one or both sides, but not palpable (noticeable by touch).
T2   T2a   T2b   T2c	Tumor is palpable (noticeable by touch) and confined within prostate. Tumor involves one-half of one side (one prostate lobe) or less. Tumor involves more than one-half of one side (one prostate lobe) but not both sides (both lobes). Tumor involves both sides (prostate lobes).
T3   T3a   T3b	Extraprostatic tumor (tumor extends beyond the prostate gland) that is not fixed or does not invade adjacent structures. Extraprostatic extension (tumor extends beyond the prostate gland) (unilateral or bilateral). Tumor invades seminal vesicle(s) (gland on each side of the bladder).
T4	Tumor is fixed or invades adjacent structures other than seminal vesicles such as external sphincter, rectum, bladder, levator muscles and/or pelvic wall.
Node (N)
NX	Regional nodes were not assessed.
N0	No positive regional nodes.
N1	Metastases in regional node(s).
Metastasis (M)
M0	No distant metastasis.
M1   M1a   M1b   M1c	Distant metastasis. Nonregional lymph node(s). Bone(s). Other site(s) with or without bone disease.

Table 2. AJCC Prognostic Stage Groups

Group/stage	TNM classification	Grade group	Prostate-specific antigen (PSA) level
I	T1a-c, N0, M0 T2a, N0, M0	1 1	Less than 10 Less than 10
IIA	T1a-c, N0, M0 T2a, N0, M0 T2b-c, N0, M0	1 1 1	Greater than or equal to 10, but less than 20 Greater than or equal to 10, but less than 20 Less than 20
IIB	T1-2, N0, M0	2	Less than 20
IIC	T1-2, N0, M0 T1-2, N0, M0	3 4	Less than 20 Less than 20
IIIA	T1-2, N0, M0	1-4	Greater than or equal to 20
IIIB	T3-4, N0, M0	1-4	Any level
IIIC	Any T, N0, M0	5	Any level
IVA	Any T, N1, M0	Any grade	Any level
IVB	Any T, Any N, M1	Any grade	Any level

Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original and primary source for this information is the AJCC Cancer Staging Manual, Eighth Edition (2017) published by Springer Science+Business Media.

Illustrated Stages of Prostate Cancer

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