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Prostate Cancer Treatment (Professional) (cont.)

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:

  1. Radionuclide bone scans.
  2. Serum PSA level.
  3. MRI.
  4. Pelvic lymph node dissection (PLND).
  5. Transrectal or transperineal biopsy.
  6. Transrectal ultrasound (TRUS).
  7. CT scans.

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/ml had 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]

Prostate cancer staging; six panel drawing showing a side view of normal male anatomy and closeup views of Stage I, Stage IIA, Stage IIB, Stage III, and Stage IV showing cancer growing from within the prostate to nearby tissue and then to lymph nodes or other parts of the body.
Staging of prostate cancer.

Table 1. Definitions of TNM Stage I

StageTNMDescription
T = Primary tumor; N = Regional lymph nodes; M = Distant metastasis; G = Histopathologic grade.
Reprinted with permission fromAJCC: 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 ofTable 4.
IT1a, N0, M0, G1T1a = 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).

Table 2. Definitions of TNM Stage II

StageTNMDescription
T = Primary tumor; N = Regional lymph nodes; M = Distant metastasis; G = Histopathologic grade.
Reprinted with permission fromAJCC: 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 ofTable 4.
IIAT1a, N0, M0, G2–4T1a = 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).
IIAT1b, N0, M0, any GT1b = 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).
IIAT1c, N0, M0, any GT1c = 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).
IIBT1, N0, M0, any GT1 = 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 = Poorlly differentiated or undifferentiated (marked anaplasia) (Gleason score of 7–10).
IIBT2, N0, M0, any GT2 = 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).

Table 3. Definitions of TNM Stage III

StageTNMDescription
T = Primary tumor; N = Regional lymph nodes; M = Distant metastasis; G = Histopathologic grade.
Reprinted with permission fromAJCC: 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 ofTable 4.
IIIT3, N0, M0, any GT3 = 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).

Table 4. Definitions of TNM Stage IV

StageTNMDescription
T = Primary tumor; N = Regional lymph nodes; M = Distant metastasis; G = Histopathologic grade; p = Pathologic.
Reprinted with permission fromAJCC: 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.
a When more than one site of metastasis is present, the most advanced category (pM1c) is used.
b Tumor found in one or both lobes by needle biopsy, but not palpable or reliably visible by imaging, is classified as T1c.
c Invasion into the prostatic apex or into (but not beyond) the prostatic capsule is classified not as T3 but as T2.
IVT4, N0, M0, any GT4 = 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 GTX = 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 GTX = 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).

Table 5. Pathologic (pT)a,b

p = Pathologic; T = Primary tumor.
Reprinted with permission fromAJCC: 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.
a There is no pathologic T1 classification.
b Positive surgical margin should be indicated by an R1 descriptor (residual microscopic disease).
pT2Organ confined.
pT2aUnilateral, =½ of one side.
pT2bUnilateral, involving >½ of side but not both sides.
pT2cBilateral disease.
pT3Extraprostatic extension.
pT3aExtraprostatic extension or microscopic invasion of bladder neck.b
pT3bSeminal vesicle invasion.
pT4Invasion of rectum, levator muscles, and/or pelvic wall.

Table 6. Anatomic Stage/Prognostic Groupsa

GroupTNMPSA ng/mlGleason
T = Primary tumor; N = Regional lymph nodes; M = Distant metastasis; PSA = Prostate-specific antigen.
Reprinted with permission fromAJCC: 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.
a When either PSA or Gleason is not available, grouping should be determined by T stage and/or either PSA or Gleason as available.
IT1a–cN0M0PSA <10Gleason =6
T2aN0M0PSA <10Gleason =6
T1–2aN0M0PSA XGleason X
IIAT1a–cN0M0PSA <20Gleason 7
T1a–cN0M0PSA =10 <20Gleason =6
T2aN0M0PSA <20Gleason =7
T2bN0M0PSA <20Gleason =7
T2bN0M0PSA XGleason X
IIBT2cN0M0Any PSAAny Gleason
T1–2N0M0PSA =20Any Gleason
T1–2N0M0Any PSAGleason =8
IIIT3a–bN0M0Any PSAAny Gleason
IVT4N0M0Any PSAAny Gleason
Any TN1M0Any PSAAny Gleason
Any TAny NM1Any PSAAny Gleason

Table 7. Prognostic Factors (Site-Specific Factors)

Reprinted with permission fromAJCC: 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 stagingPSA.
Gleason score.
Clinically significantGleason primary and secondary patterns.
Gleason tertiary pattern.
Clinical staging procedures performed.
Number of biopsy cores examined.
Number of biopsy cores positive for cancer.

Table 8. Histologic Grade

Reprinted with permission fromAJCC: 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 XGleason score cannot be processed.
Gleason =6Well differentiated (slight anaplasia).
Gleason 7Moderately differentiated (moderate anaplasia).
Gleason 8–10Poorly differentiated/undifferentiated (marked anaplasia).

References:

  1. Zelefsky MJ, Eastham JA, Sartor AO: Cancer of the prostate. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1220-71.
  2. Oesterling JE, Martin SK, Bergstralh EJ, et al.: The use of prostate-specific antigen in staging patients with newly diagnosed prostate cancer. JAMA 269 (1): 57-60, 1993.
  3. Huncharek M, Muscat J: Serum prostate-specific antigen as a predictor of radiographic staging studies in newly diagnosed prostate cancer. Cancer Invest 13 (1): 31-5, 1995.
  4. Schiebler ML, Yankaskas BC, Tempany C, et al.: MR imaging in adenocarcinoma of the prostate: interobserver variation and efficacy for determining stage C disease. AJR Am J Roentgenol 158 (3): 559-62; discussion 563-4, 1992.
  5. Schuessler WW, Pharand D, Vancaillie TG: Laparoscopic standard pelvic node dissection for carcinoma of the prostate: is it accurate? J Urol 150 (3): 898-901, 1993.
  6. Stone NN, Stock RG, Unger P: Indications for seminal vesicle biopsy and laparoscopic pelvic lymph node dissection in men with localized carcinoma of the prostate. J Urol 154 (4): 1392-6, 1995.
  7. Oesterling JE, Brendler CB, Epstein JI, et al.: Correlation of clinical stage, serum prostatic acid phosphatase and preoperative Gleason grade with final pathological stage in 275 patients with clinically localized adenocarcinoma of the prostate. J Urol 138 (1): 92-8, 1987.
  8. Fournier GR Jr, Narayan P: Re-evaluation of the need for pelvic lymphadenectomy in low grade prostate cancer. Br J Urol 72 (4): 484-8, 1993.
  9. Daniels GF Jr, McNeal JE, Stamey TA: Predictive value of contralateral biopsies in unilaterally palpable prostate cancer. J Urol 147 (3 Pt 2): 870-4, 1992.
  10. Webb JA, Shanmuganathan K, McLean A: Complications of ultrasound-guided transperineal prostate biopsy. A prospective study. Br J Urol 72 (5 Pt 2): 775-7, 1993.
  11. Smith JA Jr, Scardino PT, Resnick MI, et al.: Transrectal ultrasound versus digital rectal examination for the staging of carcinoma of the prostate: results of a prospective, multi-institutional trial. J Urol 157 (3): 902-6, 1997.
  12. Gerber GS, Goldberg R, Chodak GW: Local staging of prostate cancer by tumor volume, prostate-specific antigen, and transrectal ultrasound. Urology 40 (4): 311-6, 1992.
  13. Hanks GE, Krall JM, Pilepich MV, et al.: Comparison of pathologic and clinical evaluation of lymph nodes in prostate cancer: implications of RTOG data for patient management and trial design and stratification. Int J Radiat Oncol Biol Phys 23 (2): 293-8, 1992.
  14. Jewett HJ: The present status of radical prostatectomy for stages A and B prostatic cancer. Urol Clin North Am 2 (1): 105-24, 1975.
  15. 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.
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