Prostate Cancer Treatment (PDQ®) 2/8 –Health Professional Version - National Cancer Institute

Prostate Cancer Treatment (PDQ®)–Health Professional Version - National Cancer Institute

Prostate Cancer Treatment (PDQ®)–Health Professional Version

Stage Information for Prostate Cancer

In This Section

• Staging Tests
  • Radionuclide bone scans
  • Serum prostate-specific antigen (PSA) level
  • Magnetic resonance imaging (MRI)
  • Pelvic lymph node dissection (PLND)
  • Transrectal or transperineal biopsy
  • Transrectal ultrasound (TRUS)
  • Computed tomography (CT) scans
• Staging Systems
• AJCC Stage Groupings and TNM Definitions

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% for a Gleason score of 5, 13% for a Gleason score of 6, and 23% for a Gleason score of 8.[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. 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] 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.[1]

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 TNM (tumor, node, metastasis) 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.[16]

Table 1. Definition of Histologic Grade Groupa

Grade Group	Gleason Score	Gleason Pattern
aAdapted from AJCC: Prostate. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 715–26.
1	≤6	≤3+3
2	7	3+4
3	7	4+3
4	8	4+4, 3+5, or 5+3
5	9 or 10	4+5, 5+4, or 5+5

Table 2. Definitions of TNM Stage Ia

Stage	TNM	Descriptionb,c,d,e	PSAf	Gleason Score; Gleason Pattern (Grade Group)g	Illustration
T = primary tumor; N = regional lymph nodes; M = distant metastasis; cT = clinical T; PSA = prostate-specific antigen; pT = pathological T.
aAdapted from AJCC: Prostate. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 715–26.
The explanations for superscripts b through g are at the end of Table 5.
I	cT1a–c, cT2a, N0, M0	cT1 = Clinically inapparent tumor that is not palpable.	<10	Gleason Score, ≤6; Gleason Pattern, ≤3+3 (1).	ENLARGE
		–cT1a = Tumor incidental histologic finding in ≤5% of tissue resected.
		–cT1b = Tumor incidental histologic finding in >5% of tissue resected.
		–cT1c = Tumor identified by needle biopsy found in one or both sides, but not palpable.
		cT2 = Tumor is palpable and confined within prostate.
		–cT2a = Tumor involves 1/2 of one side or less.
		N0 = No positive regional nodes.
		M0 = No distant metastasis.
	pT2, N0, M0	pT2 = Organ confined.	<10	Gleason Score, ≤6; Gleason Pattern, ≤3+3 (1).
		N0 = No positive regional nodes.
		M0 = No distant metastasis.

Table 3. Definitions of TNM Stages IIA, IIB, and IICa

Stage	TNM	Descriptionb,c,d,e	PSAf	Gleason Score; Gleason Pattern (Grade Group)g	Illustration
T = primary tumor; N = regional lymph nodes; M = distant metastasis; cT = clinical T; PSA = prostate-specific antigen; pT = pathological T.
aAdapted from AJCC: Prostate. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 715–26.
The explanations for superscripts b through g are at the end of Table 5.
IIA	cT1a–c, cT2a, pT2, N0, M0	See cT1a–c, cT2a descriptions in Table 2, Stage I.	≥10 <20	Gleason Score, ≤6; Gleason Pattern, ≤3+3 (1).	ENLARGE
		pT2 = Organ confined.
	cT2b–c, N0, M0	cT2 = Tumor is palpable and confined within prostate.	<20	Gleason Score, ≤6; Gleason Pattern, ≤3+3 (1).
		cT2b = Tumor involves >1/2 of one side but not both sides.
		cT2c = Tumor involves both sides.
		N0 = No positive regional nodes.
		M0 = No distant metastasis.
IIB	T1–2, N0, M0	T1 = Clinically inapparent tumor that is not palpable.	<20	Gleason Score, 7; Gleason Pattern 3+4 (2).	ENLARGE
		–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 found in one or both sides, but not palpable.
		cT2 = Tumor is palpable and confined within prostate.
		–cT2a = Tumor involves 1/2 of one side or less.
		–cT2b = Tumor involves >1/2 of one side but not both sides.
		–cT2c = Tumor involves both sides.
		pT2 = Organ confined.
		N0 = No positive regional nodes.
		M0 = No distant metastasis.
IIC	T1–2, N0, M0	See T1–2, N0, M0 descriptions above in Stage IIB.	<20	Gleason Score, 7; Gleason Pattern, 4 + 3 (3).	ENLARGE
	T1–2, N0, M0	See T1–2, N0, M0 descriptions above in Stage IIB.	<20	Gleason Score, 8; Gleason Pattern, 4+4, 3+5, or 5+3 (4).

Table 4. Definitions of TNM Stages IIIA, IIIB, and IIICa

Stage	TNM	Descriptionb,c,d,e	PSAf	Gleason Score; Gleason Pattern (Grade Group)g	Illustration
T = primary tumor; N = regional lymph nodes; M = distant metastasis; cT = clinical T; PSA = prostate-specific antigen; pT = pathological T.
aAdapted from AJCC: Prostate. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 715–26.
The explanations for superscripts b through g are at the end of Table 5.
IIIA	T1–2, N0, M0	See T1–2, N0, M0 descriptions in Table 3, Stage IIB.	≥20	Gleason Score, ≤6; Gleason Pattern, ≤3+3 (1).	ENLARGE
				Gleason Score, 7; Gleason Pattern 3+4 (2).
				Gleason Score, 7; Gleason Pattern, 4+3 (3).
				Gleason Score, 8; Gleason Pattern, 4+4, 3+5, or 5+3 (4).
IIIB	T3–4, N0, M0	cT3 = Extraprostatic tumor that is not fixed or does not invade adjacent structures.	Any value	Gleason Score, ≤6; Gleason Pattern, ≤3+3 (1).	ENLARGE
		–cT3a = Extraprostatic extension (unilateral or bilateral).		Gleason Score, 7; Gleason Pattern 3+4 (2).
		–cT3b = Tumor invades seminal vesicle(s).		Gleason Score, 7; Gleason Pattern, 4+3 (3).
		pT3 = Extraprostatic extension.		Gleason Score, 8; Gleason Pattern, 4+4, 3+5, or 5+3 (4).
		–pT3a = Extraprostatic extension (unilateral or bilateral) or microscopic invasion of bladder neck.
		–pT3b = Tumor invades seminal vesicle(s).
		cT4 or pT4= 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 positive regional nodes.
		M0 = No distant metastasis.
IIIC	Any T, N0, M0	TX = Primary tumor cannot be assessed.	Any value	Gleason Score, 9 or 10; Gleason Pattern, 4+5, 5+4, or 5+5 (5).	ENLARGE
		T0 = No evidence of primary tumor.
		T1 = Clinically inapparent tumor that is not palpable.
		–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 found in one or both sides, but not palpable.
		cT2 = Tumor is palpable and confined within prostate.
		–cT2a = Tumor involves 1/2 of one side or less.
		–cT2b = Tumor involves >1/2 of one side but not both sides.
		–cT2c = Tumor involves both sides.
		–pT2 = Organ confined.
		cT3 = Extraprostatic tumor that is not fixed or does not invade adjacent structures.
		–cT3a = Extraprostatic extension (unilateral or bilateral).
		–cT3b = Tumor invades seminal vesicle(s).
		pT3 = Extraprostatic extension.
		–pT3a = Extraprostatic extension (unilateral or bilateral) or microscopic invasion of bladder neck.
		–pT3b = Tumor invades seminal vesicle(s).
		cT4 or pT4 = 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 positive regional nodes.
		M0 = No distant metastasis.

Table 5. Definitions of TNM Stages IVA and IVBa

Stage	TNM	Descriptionb,c,d,e	PSAf	Gleason Score; Gleason Pattern (Grade Group)g	Illustration
T = primary tumor; N = regional lymph nodes; M = distant metastasis; cT = clinical T; PSA = prostate-specific antigen; pT = pathological T.
aAdapted from AJCC: Prostate. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 715–26.
bWhen either PSA or Grade Group is not available, grouping should be determined by T category and/or either PSA or Grade Group as available.
cThere is no pathological T1 classification.
dPositive surgical margin should be indicated by an R1 descriptor, indicating residual microscopic disease.
eWhen more than one site of metastasis is present, the most advanced category is used. M1c is most advanced.
fPSA values are used to assign this category.
gRecently the Gleason system has been compressed into so-called Grade Groups.[17]
IVA	Any T, N1, M0	Any T = See descriptions in Table 4, Stage IIIC.	See Any PSA values in Table 4, Stage IIIC.	Gleason Score, ≤6; Gleason Pattern, ≤3+3 (1).	ENLARGE
				Gleason Score, 7; Gleason Pattern 3+4 (2).
				Gleason Score, 7; Gleason Pattern, 4+3 (3).
		N1 = Metastases in regional node(s).		Gleason Score, 8; Gleason Pattern, 4+4, 3+5, or 5+3 (4).
		M0 = No distant metastasis.		Gleason Score, 9 or 10; Gleason Pattern, 4+5, 5+4, or 5+5 (5).
IVB	Any T, Any N, M1	Any T = See descriptions in Table 4, Stage IIIC.	See Any PSA values Table 4, Stage IIIC.	Any Gleason Score; Gleason Pattern (Grade Group) = See above in Stage IVA.	ENLARGE
		NX = Regional nodes were not assessed.
		N0 = No positive regional nodes.
		N1 = Metastases in regional node(s).
		M1 = Distant metastasis.
		–M1a = Nonregional lymph node(s).
		–M1b = Bone(s).
		–M1c = Other site(s) with or without bone disease.

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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
8. Fournier GR, Narayan P: Re-evaluation of the need for pelvic lymphadenectomy in low grade prostate cancer. Br J Urol 72 (4): 484-8, 1993. [PUBMED Abstract]
9. Daniels GF, McNeal JE, Stamey TA: Predictive value of contralateral biopsies in unilaterally palpable prostate cancer. J Urol 147 (3 Pt 2): 870-4, 1992. [PUBMED Abstract]
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. [PUBMED Abstract]
11. Smith JA, 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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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.
16. Prostate. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 715–26.
17. Epstein JI, Egevad L, Amin MB, et al.: The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System. Am J Surg Pathol 40 (2): 244-52, 2016. [PUBMED Abstract]