TNM Definitions
AJCC Stage Groupings
Jewett Staging System

Detection of asymptomatic metastatic disease in prostate cancer is greatly affected by the staging tests performed. Radionuclide bone scans are currently the most widely used tests for metastases to the bone, which is the most common site of distant tumor spread. Magnetic resonance imaging (MRI) is more sensitive than radionuclide bone scans but is impractical for evaluating the entire skeletal system. Some evidence suggests that serum prostate-specific antigen (PSA) levels can predict the results of radionuclide bone scan in newly diagnosed patients. In one series, only 2 of 852 patients (0.23%) with a PSA of less than 20 µg/L had a positive bone scan in the absence of bone pain.[1] In another series of 265 prostate cancer patients, 0 of 23 patients with a PSA of less than 4 μg/L had a positive bone scan, and 2 of 114 patients with a PSA of less than 10 μg/L had a positive bone scan.[2] Prognosis is worse in patients with pelvic lymph node involvement.

Whether to subject all patients to a pelvic lymph node dissection (PLND) is debatable, but in patients undergoing a radical retropubic prostatectomy, the nodal status is ascertained as a matter of course. In patients who are undergoing a radical perineal prostatectomy in whom the PSA value is less than 20 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.[3,4] A PLND remains the most accurate method to assess metastases to pelvic nodes, and laparoscopic PLND has been shown to accurately assess pelvic nodes as effectively as an open procedure.[5] The exact role of PLND in diagnosis and subsequent treatment is being evaluated, though it has already been determined that the length of hospital stay following laparoscopic PLND is shorter than that following an open procedure. The determining factor when deciding if any type of PLND is indicated is whether definitive therapy may be altered. 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 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.[3] Analysis of a series of 166 patients with clinical stage I and 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 node metastasis for patients grouped according to their Gleason biopsy score was 2%, 13%, and 23% for Gleason scores of 5, 6, and 8, respectively.[7]

Transrectal ultrasound (TRUS) may facilitate diagnosis by directing needle biopsy; however, ultrasound is operator dependent and does not assess lymph node size. Moreover, a prospective multi-institutional study of preoperative TRUS in men with clinically localized prostate cancer felt to be eligible for radical prostatectomy showed that TRUS was no better than digital rectal examination in predicting extracapsular tumor extension or seminal vesicle involvement.[8] Computed tomography (CT) can detect grossly enlarged nodes but poorly defines intraprostatic features;[9] therefore, it is not reliable for the staging of pelvic node disease when compared to surgical staging.[10] 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.[11] Ultrasound and MRI, however, can reduce clinical understaging and thereby improve patient selection for local therapy. Preliminary data with the endorectal MRI coil for prostate imaging report the highest sensitivity and specificity for identification of organ-confined and extracapsular disease.[3,12,13] MRI is a poor tool for evaluating nodal disease.

Two systems are in common use for the staging of prostate cancer. The Jewett system (stages A through D) was described in 1975 and has since been modified.[14] In 1997, the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer adopted a revised tumor, nodes, metastasis (TNM) system that employs the same broad T stage categories as the Jewett system but includes subcategories of T stage, such as a stage to describe patients diagnosed through PSA screening. This revised TNM system is clinically useful and more precisely stratifies newly diagnosed patients. In 2002, the AJCC further revised the TNM classification system.[15] Both staging systems are shown below, and both are used in this summary to discuss treatment options. A thorough review of the controversies of staging in prostate cancer has been published.[16]

Primary tumor (T)

• TX: Primary tumor cannot be assessed



• T0: No evidence of primary tumor



• T1: Clinically inapparent tumor not palpable nor visible by imaging
  • T1a: Tumor incidental histologic finding in 5% or less of tissue resected
  • T1b: Tumor incidental histologic finding in more than 5% of tissue resected
  • T1c: Tumor identified by needle biopsy (e.g., because of elevated PSA)



• T2: Tumor confined within prostate*
  • T2a: Tumor involves 50% or less of one lobe
  • T2b: Tumor involves more than 50% of one lobe but not both lobes
  • T2c: Tumor involves both lobes



• T3: Tumor extends through the prostate capsule**
  • T3a: Extracapsular extension (unilateral or bilateral)
  • T3b: Tumor invades seminal vesicle(s)



• T4: Tumor is fixed or invades adjacent structures other than seminal vesicles: bladder neck, external sphincter, rectum, levator muscles, and/or pelvic wall

* [Note: Tumor that is found in one or both lobes by needle biopsy but is not palpable or reliably visible by imaging is classified as T1c.]

** [Note: Invasion into the prostatic apex or into (but not beyond) the prostatic capsule is classified as T2 not T3.]

Regional lymph nodes (N)

• Regional lymph nodes are the nodes of the true pelvis, which essentially are the pelvic nodes below the bifurcation of the common iliac arteries. They include the following groups (laterality does not affect the N classification): pelvic (not otherwise specified [NOS]), hypogastric, obturator, iliac (i.e., internal, external, or NOS), and sacral (lateral, presacral, promontory [e.g., Gerota], or NOS). Distant lymph nodes are outside the confines of the true pelvis. They can be imaged using ultrasound, CT, MRI, or lymphangiography and include: aortic (para-aortic, periaortic, or lumbar), common iliac, inguinal (deep), superficial inguinal (femoral), supraclavicular, cervical, scalene, and retroperitoneal (NOS) nodes. Although enlarged lymph nodes can occasionally be visualized, because of a stage migration associated with PSA screening, very few patients will be found to have nodal disease, so false-positive and false-negative results are common when imaging tests are employed. In lieu of imaging, risk tables are generally used to determine individual patient risk of nodal involvement. Involvement of distant lymph nodes is classified as M1a.
  • NX: Regional lymph nodes were not assessed
  • N0: No regional lymph node metastasis
  • N1: Metastasis in regional lymph node(s)

Distant metastasis (M)*

• MX: Distant metastasis cannot be assessed (not evaluated by any modality)
• M0: No distant metastasis
• M1: Distant metastasis
  • M1a: Nonregional lymph node(s)
  • M1b: Bone(s)
  • M1c: Other site(s) with or without bone disease

* [Note: When more than one site of metastasis is present, the most advanced category (pM1c) is used.]

Histopathologic grade (G)

• 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 I

• T1a, N0, M0, G1

Stage II

• T1a, N0, M0, G2–4
• T1b, N0, M0, any G
• T1c, N0, M0, any G
• T1, N0, M0, any G
• T2, N0, M0, any G

Stage III

• T3, N0, M0, any G

Stage IV

• T4, N0, M0, any G
• Any T, N1, M0, any G
• Any T, any N, M1, any G

Stage A

Stage A is clinically undetectable tumor confined to the prostate gland and is an incidental finding at prostatic surgery.

• Substage A1: well differentiated with focal involvement and usually left untreated
• Substage A2: moderately or poorly differentiated or involves multiple foci in the gland

Stage B

Stage B is tumor confined to the prostate gland.

• Substage B0: nonpalpable and PSA detected [17]
• Substage B1: single nodule in one lobe of the prostate
• Substage B2: more extensive involvement of one lobe or involvement of both lobes

Stage C

Stage C is tumor clinically localized to the periprostatic area but extending through the prostatic capsule; seminal vesicles may be involved.

• Substage C1: clinical extracapsular extension
• Substage C2: extracapsular tumor producing bladder outlet or ureteral obstruction

Stage D

Stage D is metastatic disease.

• Substage D0: clinically localized disease (prostate only) but persistently elevated enzymatic serum acid phosphatase titers
• Substage D1: regional lymph nodes only
• Substage D2: distant lymph nodes and metastases to bone or visceral organs
• Substage D3: D2 prostate cancer patients who relapsed after adequate endocrine therapy

References

1. 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]
   
   
2. 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]
   
   
3. 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]
   
   
4. 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.  [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. 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.  [PUBMED Abstract]
   
   
8. 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.  [PUBMED Abstract]
   
   
9. 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]
   
   
10. 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]
    
    
11. 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]
    
    
12. Consensus conference. The management of clinically localized prostate cancer. JAMA 258 (19): 2727-30, 1987.  [PUBMED Abstract]
    
    
13. Schiebler ML, Schnall MD, Pollack HM, et al.: Current role of MR imaging in the staging of adenocarcinoma of the prostate. Radiology 189 (2): 339-52, 1993.  [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: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 309-316. 
    
    
16. Montie JE: Staging of prostate cancer: current TNM classification and future prospects for prognostic factors. Cancer 75 (7 Suppl): 1814-1818, 1995. 
    
    
17. Bostwick DG, Myers RP, Oesterling JE: Staging of prostate cancer. Semin Surg Oncol 10 (1): 60-72, 1994 Jan-Feb.  [PUBMED Abstract]
    
    

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