Clinical Presentation
In the United States, most prostate cancers are diagnosed as a result of screening; therefore, symptoms of cancer are infrequent at the time of diagnosis.[22] Nevertheless, local growth of the tumor may produce symptoms of urinary obstruction such as:
- Decreased urinary stream.
- Urgency.
- Hesitancy.
- Nocturia.
- Incomplete bladder emptying.
These symptoms are nonspecific and more indicative of benign prostatic hyperplasia than cancer.
Although rare in the current era of widespread screening, prostate cancer may also present with symptoms of metastases, including bone pain, pathologic fractures, or symptoms caused by bone marrow involvement.
Diagnostic Evaluation
Needle biopsy is the most common method used to diagnose prostate cancer. Most urologists now perform a transrectal biopsy using a bioptic gun with ultrasound guidance. Over the years, there has been a trend toward taking eight to ten or more biopsy samples from several areas of the prostate with a consequent increased yield of cancer detection after an elevated PSA blood test.[22] Less frequently, a transperineal, ultrasound-guided approach can be used in patients who may be at increased risk of complications caused by using a transrectal approach.[26]
Prophylactic antibiotics, especially fluoroquinolones, are often used before transrectal needle biopsies. There are reports of increasing rates of sepsis, particularly with fluoroquinolone-resistant E. coli, and hospitalization after the procedure.[27,28] Therefore, men undergoing transrectal biopsy should be told to seek medical attention immediately if they experience fever after biopsy.
Prognostic Factors
The survival of patients with prostate cancer is related to several factors, including the following:[29–33]
(Refer to the Surveillance, Epidemiology, and End Results’ 5-year and 10-year survival rates.)
Extent of tumor
When the cancer is confined to the prostate gland, long-term prognosis is excellent. Patients with locally advanced cancer are not usually curable, but 5-year survival is still very good. If prostate cancer has spread to distant organs, current therapy will not cure it. Median survival is usually 1 to 3 years, and most of these patients will die of prostate cancer. Even in this group of patients, indolent clinical courses lasting for many years may be observed.
Histologic grade of tumor
Poorly differentiated tumors are more likely to have metastasized before diagnosis and are associated with a poorer prognosis. The most commonly used method to report tumor differentiation is the Gleason score. (Refer to the Pathology section of the General Information About Prostate Cancer section of this summary for more information.)
Patient’s age and health
Any benefits of definitive local therapy with curative intent may take years to emerge. Therefore, therapy with curative intent is usually reserved for men with a sufficiently long life expectancy. For example, radical prostatectomy is often reserved for men with an estimated life expectancy of at least 10 years.
Prostate-specific antigen (PSA) level
PSA, an organ-specific marker, is often used as a tumor marker.[31,32,34–39] The higher the level of PSA at baseline, the higher is the risk for metastatic disease or subsequent disease progression. However, it is an imprecise marker of risk.
For example, baseline PSA and rate of PSA change were associated with subsequent metastasis or prostate cancer death in a cohort of 267 men with clinically localized prostate cancer who were managed by watchful waiting or active surveillance in the control arm of a randomized trial comparing radical prostatectomy with watchful waiting or active surveillance.[40,41] Nevertheless, the accuracy of classifying men into groups whose cancer remained indolent versus those whose cancer progressed was poor at all examined cut points of PSA or PSA rate of change.
Serum acid phosphatase levels
Elevations of serum acid phosphatase are associated with poor prognosis in both localized and disseminated disease. However, serum acid phosphatase levels are not incorporated into the American Joint Committee on Cancer’s (AJCC) staging system for prostate cancer.[34]
Related Summaries
Other PDQ summaries containing information related to prostate cancer include the following:
Stage Information for Prostate Cancer
Staging Tests
Most men are diagnosed with prostate cancer at an early clinical stage and do not have detectable metastases. Therefore, they generally do not have to undergo staging tests, such as a bone scan, computed tomography (CT), or magnetic resonance imaging (MRI). However, staging studies are done if there is clinical suspicion of metastasis, such as bone pain; local tumor spread beyond the prostate capsule; or a substantial risk of metastasis (prostate-specific antigen [PSA] >20 ng/mL and Gleason score >7).[1]
Tests used to determine stage include the following:
Radionuclide bone scans
A radionuclide bone scan is the most widely used test for metastasis to the bone, which is the most common site of distant tumor spread.
Serum prostate-specific antigen (PSA) level
Serum PSA can predict the results of radionuclide bone scans in newly diagnosed patients.
- In one series, only 2 of 852 patients (0.23%) with a PSA of less than 20 ng/mL had a positive bone scan in the absence of bone pain.[2]
- In another series of 265 prostate cancer patients, 0 of 23 patients with a PSA of less than 4 ng/mL had a positive bone scan, and 2 of 114 patients with a PSA of less than 10 ng/mLhad a positive bone scan.[3]
Magnetic resonance imaging (MRI)
Although MRI has been used to detect extracapsular extension of prostate cancer, a positive-predictive value of about 70% and considerable interobserver variation are problems that make its routine use in staging uncertain.[4] Ultrasound and MRI, however, can reduce clinical understaging and thereby improve patient selection for local therapy. MRI with an endorectal coil appears to be more accurate for identification of organ-confined and extracapsular disease, especially when combined with spectroscopy.[1] MRI is a poor tool for evaluating nodal disease.
MRI is more sensitive than radionuclide bone scans in the detection of bone metastases, but it is impractical for evaluating the entire skeletal system.
Pelvic lymph node dissection (PLND)
PLND remains the most accurate method to assess metastasis to the pelvic nodes, and laparoscopic PLND has been shown to accurately assess pelvic nodes as effectively as an open procedure.[5]
The determining factor in deciding whether any type of PLND is indicated is when definitive therapy may be altered. For example, radical prostatectomy is generally reserved for men without lymph node metastasis. Likewise, preoperative seminal vesicle biopsy may be useful in patients with palpable nodules who are being considered for radical prostatectomy (unless they have a low Gleason score) because seminal vesicle involvement could affect the choice of primary therapy and predicts for pelvic lymph node metastasis.[6]
In patients with clinically localized (stage I or stage II) prostate cancer, Gleason pathologic grade and enzymatic serum prostatic acid phosphatase values (even within normal range) predict the likelihood of capsular penetration, seminal vesicle invasion, or regional lymph node involvement.[7] Analysis of a series of 166 patients with clinical stage I or stage II prostate cancer undergoing radical prostatectomy revealed an association between Gleason biopsy score and the risk of lymph node metastasis found at surgery. The risks of nodal metastasis for patients grouped according to their Gleason biopsy score was 2%, 13%, and 23% for Gleason scores of 5, 6, and 8, respectively.[8]
Whether to subject all patients to a PLND is debatable, but in patients undergoing a radical retropubic prostatectomy, nodal status is usually ascertained as a matter of course. In patients who are undergoing a radical perineal prostatectomy in whom the PSA value is less than 20 ng/mL and the Gleason sum is low, however, evidence is mounting that a PLND is probably unnecessary, especially in patients whose malignancy was not palpable but detected on ultrasound.[7,9]
Transrectal or transperineal biopsy
The most common means to establish a diagnosis and determine the Gleason score in cases of suspected prostate cancer is by needle biopsy. Most urologists now perform a transrectal biopsy using a bioptic gun with ultrasound guidance. Over the years, there has been a trend toward taking eight to ten or more biopsy samples at the same time.[1] Less frequently, a transperineal, ultrasound-guided approach can be used for those patients who may be at increased risk of complications from a transrectal approach.[10]
Transrectal ultrasound (TRUS)
TRUS may facilitate diagnosis by directing needle biopsy; however, ultrasound is operator dependent and does not assess lymph node size.
A prospective multi-institutional study of preoperative TRUS in men with clinically localized prostate cancer eligible for radical prostatectomy showed that TRUS was no better than digital rectal examination in predicting extracapsular tumor extension or seminal vesicle involvement.[11]
Computed tomography (CT) scans
CT scans can detect grossly enlarged lymph nodes but poorly define intraprostatic features;[12] therefore, it is not reliable for the staging of pelvic node disease when compared with surgical staging.[13]
Staging Systems
Historically, two systems have been in common use for the staging of prostate cancer.
- In 1975, the Jewett system (stage A through stage D) was described and has since been modified.[14] This staging system is no longer in common use, but older studies and publications may refer to it.
- In 1997, the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer adopted a revised tumor, nodes, metastasis (TNM) system, which used the same broad T-stage categories as the Jewett system but included subcategories of T stage, such as a stage to describe patients diagnosed through PSA screening. This revised TNM system more precisely stratifies newly diagnosed patients. In 2010, the AJCC updated the TNM classification for prostate cancer.[15]
AJCC Stage Groupings and TNM Definitions
The AJCC has designated staging by TNM classification.[15]
| Stage | TNM | Description |
|---|---|---|
| G = histopathologic grade; M = distant metastasis; N = regional lymph nodes; T = primary tumor. | ||
| Reprinted with permission from AJCC: Prostate. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 457–68. | ||
| The explanation for superscript a is at the end of Table 4. | ||
| I | T1a, N0, M0, G1 | T1a = Tumor incidental histologic finding in ≤5% of tissue resected. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis.a | ||
| G1 = Well differentiated (slight anaplasia) (Gleason score of 2–4). | ||
| Stage | TNM | Description |
|---|---|---|
| G = histopathologic grade; M = distant metastasis; N = regional lymph nodes; T = primary tumor. | ||
| Reprinted with permission from AJCC: Prostate. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 457–68. | ||
| The explanations for superscripts a and b are at the end of Table 4. | ||
| IIA | T1a, N0, M0, G2–4 | T1a = Tumor incidental histologic finding in ≤5% of tissue resected. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis.a | ||
| G2 = Moderately differentiated (moderate anaplasia) (Gleason score of 5–6). | ||
| G3–4 = Poorly differentiated or undifferentiated (marked anaplasia) (Gleason score of 7–10). | ||
| IIA | T1b, N0, M0, any G | T1b = Tumor incidental histologic finding in >5% of tissue resected. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis.a | ||
| GX = Grade cannot be assessed. | ||
| G1 = Well differentiated (slight anaplasia) (Gleason score of 2–4). | ||
| G2 = Moderately differentiated (moderate anaplasia) (Gleason score of 5–6). | ||
| G3–4 = Poorly differentiated or undifferentiated (marked anaplasia) (Gleason score of 7–10). | ||
| IIA | T1c, N0, M0, any G | T1c = Tumor identified by needle biopsy (e.g., because of elevated PSA). |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis.a | ||
| GX = Grade cannot be assessed. | ||
| G1 = Well differentiated (slight anaplasia) (Gleason score of 2–4). | ||
| G2 = Moderately differentiated (moderate anaplasia) (Gleason score of 5–6). | ||
| G3–4 = Poorly differentiated or undifferentiated (marked anaplasia) (Gleason score of 7–10). | ||
| IIB | T1, N0, M0, any G | T1 = Clinically inapparent tumor neither palpable nor visible by imaging. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis.a | ||
| GX = Grade cannot be assessed. | ||
| G1 = Well differentiated (slight anaplasia) (Gleason score of 2–4). | ||
| G2 = Moderately differentiated (moderate anaplasia) (Gleason score of 5–6). | ||
| G3–4 = Poorly differentiated or undifferentiated (marked anaplasia) (Gleason score of 7–10). | ||
| IIB | T2, N0, M0, any G | T2 = Tumor confined within prostate.b |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis.a | ||
| GX = Grade cannot be assessed. | ||
| G1 = Well differentiated (slight anaplasia) (Gleason score of 2–4). | ||
| G2 = Moderately differentiated (moderate anaplasia) (Gleason score of 5–6). | ||
| G3–4 = Poorly differentiated or undifferentiated (marked anaplasia) (Gleason score of 7–10). | ||
| Stage | TNM | Description |
|---|---|---|
| G = histopathologic grade; M = distant metastasis; N = regional lymph nodes; T = primary tumor. | ||
| Reprinted with permission from AJCC: Prostate. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 457–68. | ||
| The explanations for superscripts a and c are at the end of Table 4. | ||
| III | T3, N0, M0, any G | T3 = Tumor extends through the prostate capsule.c |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis.a | ||
| GX = Grade cannot be assessed. | ||
| G1 = Well differentiated (slight anaplasia) (Gleason score of 2–4). | ||
| G2 = Moderately differentiated (moderate anaplasia) (Gleason score of 5–6). | ||
| G3–4 = Poorly differentiated or undifferentiated (marked anaplasia) (Gleason score of 7–10). | ||
| Stage | TNM | Description |
|---|---|---|
| G = histopathologic grade; M = distant metastasis; N = regional lymph nodes; p = pathologic; T = primary tumor. | ||
| Reprinted with permission from AJCC: Prostate. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 457–68. | ||
| aWhen more than one site of metastasis is present, the most advanced category (pM1c) is used. | ||
| bTumor found in one or both lobes by needle biopsy, but not palpable or reliably visible by imaging, is classified as T1c. | ||
| cInvasion into the prostatic apex or into (but not beyond) the prostatic capsule is classified not as T3 but as T2. | ||
| IV | T4, N0, M0, any G | T4 = Tumor is fixed or invades adjacent structures other than seminal vesicles such as external sphincter, rectum, bladder, levator muscles, and/or pelvic wall. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis.a | ||
| GX = Grade cannot be assessed. | ||
| G1 = Well differentiated (slight anaplasia) (Gleason score of 2–4). | ||
| G2 = Moderately differentiated (moderate anaplasia) (Gleason score of 5–6). | ||
| G3–4 = Poorly differentiated or undifferentiated (marked anaplasia) (Gleason score of 7–10). | ||
| Any T, N1, M0, any G | TX = Primary tumor cannot be assessed. | |
| T0 = No evidence of primary tumor. | ||
| T1 = Clinically inapparent tumor not palpable or visible by imaging. | ||
| T1a = Tumor incidental histologic finding in ≤5% of tissue resected. | ||
| T1b = Tumor incidental histologic finding in >5% of tissue resected. | ||
| T1c = Tumor identified by needle biopsy (e.g., because of elevated PSA). | ||
| T2 = Tumor confined within prostate.b | ||
| T2a = Tumor involves ≤50% of one lobe. | ||
| T2b = Tumor involves >50% of one lobe but not both lobes. | ||
| T2c = Tumor involves both lobes. | ||
| T3 = Tumor extends through the prostate capsule.c | ||
| T3a = Extracapsular extension (unilateral or bilateral). | ||
| T3b = Tumor invades seminal vesicle(s). | ||
| T4 = Tumor is fixed or invades adjacent structures other than seminal vesicles such as the bladder, external sphincter, rectum, levator muscles, and/or pelvic wall. | ||
| N1 = Metastasis in regional lymph node(s). | ||
| M0 = No distant metastasis.a | ||
| GX = Grade cannot be assessed. | ||
| G1 = Well differentiated (slight anaplasia) (Gleason score of 2–4). | ||
| G2 = Moderately differentiated (moderate anaplasia) (Gleason score of 5–6). | ||
| G3–4 = Poorly differentiated or undifferentiated (marked anaplasia) (Gleason score of 7–10). | ||
| Any T, any N, M1, any G | TX = Primary tumor cannot be assessed. | |
| T0 = No evidence of primary tumor. | ||
| T1 = Clinically inapparent tumor not palpable or visible by imaging. | ||
| T1a = Tumor incidental histologic finding in ≤5% of tissue resected. | ||
| T1b = Tumor incidental histologic finding in >5% of tissue resected. | ||
| T1c = Tumor identified by needle biopsy (e.g., because of elevated PSA). | ||
| T2 = Tumor confined within prostate.c | ||
| T2a = Tumor involves ≤50% of one lobe. | ||
| T2b = Tumor involves >50% of one lobe but not both lobes. | ||
| T2c = Tumor involves both lobes. | ||
| T3 = Tumor extends through the prostate capsule.c | ||
| T3a = Extracapsular extension (unilateral or bilateral). | ||
| T3b = Tumor invades seminal vesicle(s). | ||
| T4 = Tumor is fixed or invades adjacent structures other than seminal vesicles such as the bladder, external sphincter, rectum, levator muscles, and/or pelvic wall. | ||
| NX = Regional lymph nodes were not assessed. | ||
| pNX = Regional nodes not sampled. | ||
| N0 = No regional lymph node metastasis. | ||
| pN0 = No positive regional nodes. | ||
| N1 = Metastasis in regional lymph node(s). | ||
| pN1 = Metastases in regional node(s). | ||
| M1 = Distant metastasis.a | ||
| M1a = Nonregional lymph node(s). | ||
| M1b = Bone(s). | ||
| M1c = Other site(s) with or without bone disease. | ||
| GX = Grade cannot be assessed. | ||
| G1 = Well differentiated (slight anaplasia) (Gleason score of 2–4). | ||
| G2 = Moderately differentiated (moderate anaplasia) (Gleason score of 5–6). | ||
| G3–4 = Poorly differentiated or undifferentiated (marked anaplasia) (Gleason score of 7–10). | ||
| Stage | Description |
|---|---|
| p = pathologic; T = primary tumor. | |
| Reprinted with permission from AJCC: Prostate. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 457–68. | |
| aThere is no pathologic T1 classification. | |
| bPositive surgical margin should be indicated by an R1 descriptor (residual microscopic disease). | |
| pT2 | Organ confined. |
| pT2a | Unilateral, ≤½ of one side. |
| pT2b | Unilateral, involving >½ of side but not both sides. |
| pT2c | Bilateral disease. |
| pT3 | Extraprostatic extension. |
| pT3a | Extraprostatic extension or microscopic invasion of bladder neck.b |
| pT3b | Seminal vesicle invasion. |
| pT4 | Invasion of rectum, levator muscles, and/or pelvic wall. |
| Site-Specific Factors | Testing and Grading |
|---|---|
| Reprinted with permission from AJCC: Prostate. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 457–68. | |
| Required for staging | PSA. |
| Gleason score. | |
| Clinically significant | Gleason primary and secondary patterns. |
| Gleason tertiary pattern. | |
| Clinical staging procedures performed. | |
| Number of biopsy cores examined. | |
| Number of biopsy cores positive for cancer. | |
| Grade | Description |
|---|---|
| Reprinted with permission from AJCC: Prostate. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 457–68. | |
| Gleason X | Gleason score cannot be processed. |
| Gleason ≤6 | Well differentiated (slight anaplasia). |
| Gleason 7 | Moderately differentiated (moderate anaplasia). |
| Gleason 8–10 | Poorly differentiated/undifferentiated (marked anaplasia). |