Prostate cancer staging

Overview
Prostate cancer staging is the process by which physicians evaluate the spread of prostate cancer. This is important because in a good cancer staging system, the stage of disease helps determine prognosis and assists in selecting therapies. A combination of physical examination, blood tests, and medical imaging is used to determine the clinical stage; if tissue is obtained via biopsy or surgery, examination of the tissue under a microscope can provide pathologic staging.

There are two schemes commonly used to stage prostate cancer. The most common is the TNM system, which evaluates the size of the tumor, the extent of involved lymph nodes, and any metastasis (distant spread). As with many other cancers, these are often grouped into four stages (I–IV). Another scheme, used less commonly, is the Whitmore-Jewett stage.

Briefly, Stage I disease is cancer that is found incidentally in a small part of the sample when prostate tissue was removed for other reasons, such as benign prostatic hypertrophy, and the cells closely resemble normal cells and the gland feels normal to the examining finger. In Stage II more of the prostate is involved and a lump can be felt within the gland. In Stage III, the tumor has spread through the prostatic capsule and the lump can be felt on the surface of the gland. In Stage IV disease, the tumor has invaded nearby structures, or has spread to lymph nodes or other organs. Grading is based on cellular content and tissue architecture from biopsies (Gleason) which provides an estimate of the destructive potential and ultimate prognosis of the disease.

The most important distinction made by any staging system is whether or not the cancer is still confined to the prostate. In the TNM system, clinical T1 and T2 cancers are found only in the prostate, while T3 and T4 cancers have spread elsewhere. Several tests can be used to look for evidence of spread. These include computed tomography to evaluate spread within the pelvis, bone scans to look for spread to the bones, and endorectal coil magnetic resonance imaging to closely evaluate the prostatic capsule and the seminal vesicles. Bone scans should reveal osteoblastic appearance due to increased bone density in the areas of bone metastasis - opposite to what is found in many other cancers that metastasize.

Computed tomography (CT) and magnetic resonance imaging (MRI) currently do not add any significant information in the assessment of possible lymph node metastases in patients with prostate cancer according to a meta-analysis. The sensitivity of CT was 42% and specificity of CT was 82%. The sensitivity of MRI was 39% and the specificity of MRI was 82%. For patients at similar risk to those in this study (17% had positive pelvic lymph nodes in the CT studies and 30% had positive pelvic lymph nodes in the MRI studies), this leads to a positive predictive value (PPV) of 32.3% with CT, 48.1% with MRI, and negative predictive value (NPV) of 87.3% with CT, 75.8% with MRI.

After a prostate biopsy, a pathologist looks at the samples under a microscope. If cancer is present, the pathologist reports the grade of the tumor. The grade tells how much the tumor tissue differs from normal prostate tissue and suggests how fast the tumor is likely to grow. The Gleason system is used to grade prostate tumors from 2 to 10, where a Gleason score of 10 indicates the most abnormalities. The pathologist assigns a number from 1 to 5 for the most common pattern observed under the microscope, then does the same for the second most common pattern. The sum of these two numbers is the Gleason score. The Whitmore-Jewett stage is another method sometimes used. Proper grading of the tumor is critical, since the grade of the tumor is one of the major factors used to determine the treatment recommendation.

TNM staging
From the AJCC 6th edition (2002) and UICC 6th edition.

Evaluation of the (primary) tumor ('T')

 * TX: cannot evaluate the primary tumor
 * T0: no evidence of tumor
 * T1: tumor present, but not detectable clinically or with imaging
 * T1a: tumor was incidentally found in less than 5% of prostate tissue resected (for other reasons)
 * T1b: tumor was incidentally found in greater than 5% of prostate tissue resected
 * T1c: tumor was found in a needle biopsy performed due to an elevated serum PSA
 * T2: the tumor can be felt (palpated) on examination, but has not spread outside the prostate
 * T2a: the tumor is in half or less than half of one of the prostate gland's two lobes
 * T2b: the tumor is in more than half of one lobe, but not both
 * T2c: the tumor is in both lobes
 * T3: the tumor has spread through the prostatic capsule (if it is only part-way through, it is still T2)
 * T3a: the tumor has spread through the capsule on one or both sides
 * T3b: the tumor has invaded one or both seminal vesicles
 * T4: the tumor has invaded other nearby structures

It should be stressed that the designation "T2c" implies a tumor which is palpable in both lobes of the prostate. Tumors which are found to be bilateral on biopsy only but which are not palpable bilaterally should not be staged as T2c.

Evaluation of the regional lymph nodes ('N')

 * NX: cannot evaluate the regional lymph nodes
 * N0: there has been no spread to the regional lymph nodes
 * N1: there has been spread to the regional lymph nodes

Evaluation of distant metastasis ('M')

 * MX: cannot evaluate distant metastasis
 * M0: there is no distant metastasis
 * M1: there is distant metastasis
 * M1a: the cancer has spread to lymph nodes beyond the regional ones
 * M1b: the cancer has spread to bone
 * M1c: the cancer has spread to other sites (regardless of bone involvement)

Evaluation of the histologic grade ('G')
Usually, the grade of the cancer (how different the tissue is from normal tissue) is evaluated separately from the stage; however, for prostate cancer, grade information is used in conjunction with TNM status to group cases into four overall stages.


 * GX: cannot assess grade
 * G1: the tumor closely resembles normal tissue (Gleason 2–4)
 * G2: the tumor somewhat resembles normal tissue (Gleason 5–6)
 * G3–4: the tumor resembles normal tissue barely or not at all (Gleason 7–10)

Of note, this system of describing tumors as "well-", "moderately-", and "poorly-" differentiated based on Gleason score of 2-4, 5-6, and 7-10, respectively, persists in SEER and other databases but is generally outdated. In recent years pathologists rarely assign a tumor a grade less than 3, particularly in biopsy tissue. A more contemporary consideration of Gleason grade is:


 * Gleason 3+3: tumor is low grade (favorable prognosis)
 * Gleason 3+4 / 3+5: tumor is mostly low grade with some high grade
 * Gleason 4+3 / 5+3: tumor is mostly high grade with some low grade
 * Gleason 4+4 / 4+5 / 5+4 / 5+5: tumor is all high grade

Prostate: Adenocarcinoma (Gleason grade 1)


Prostate : Adenocarcinoma (Gleason grade 2)


Prostate : Adenocarcinoma (Gleason grade 3)


Prostate: Adenocarcinoma (Gleason grade 4)


Prostate: Adenocarcinoma (Gleason grade 5)


Overall staging
The tumor, lymph node, metastasis, and grade status can be combined into four stages of worsening severity.

Whitmore-Jewett staging
The Whitmore-Jewett system is similar to the TNM system, with approximately equivalent stages. Roman numerals are sometimes used instead of Latin letters for the overall stages (for example, Stage I for Stage A, Stage II for Stage B, and so on).


 * A: tumor is present, but not detectable clinically; found incidentally
 * A1: tissue resembles normal cells; found in a few chips from one lobe
 * A2: more extensive involvement
 * B: the tumor can be felt on physical examination but has not spread outside the prostatic capsule
 * BIN: the tumor can be felt, it does not occupy a whole lobe, and is surrounded by normal tissue
 * B1: the tumor can be felt and it does not occupy a whole lobe
 * B2: the tumor can be felt and it occupies a whole lobe or both lobes
 * C: the tumor has extended through the capsule
 * C1: the tumor has extended through the capsule but does not involve the seminal vesicles
 * C2: the tumor involves the seminal vesicles
 * D: the tumor has spread to other organs

Risk groups
While TNM staging is important, the TNM stage alone is not sufficient for deciding what treatment is best for a patient with prostate cancer. Instead, a different category called "risk groups" is used, which is based on the T-stage of the TNM system and adds additional information from the Gleason score and prostate specific antigen (PSA) value. The risk can be described as low risk, intermediate risk, or high risk. The risk is a useful predictor of having extraprostatic extension, which is spread of the cancer beyond the prostate gland itself. Although slightly different criteria are used for assigning risk, one such system defines low risk as a PSA less than 10, a Gleason score of 6 or lower, and a T-stage of T2a or lower; high risk is a PSA more than 20, a Gleason score of 8 or higher, or T2c; intermediate risk is a PSA of 10 to 20, T2b, or a Gleason of 7.

Patients with low risk disease may be treated with prostatectomy or radiotherapy alone. Patients with intermediate risk disease are usually treated with radiotherapy and a short duration (less than 6 months) of hormonal ablation (medical castration using a gonadotropin-releasing hormone analog), and those with high risk disease are usually treated with radiotherapy and a long duration of hormonal ablation.