Prostate Gland

 

Protocol applies to all carcinomas of the prostate gland.

 

Procedures

·        Needle Biopsy

·        Transurethral Prostatic Resection

·        Suprapubic or Retropubic Enucleation (subtotal prostatectomy)

·        Radical Prostatectomy

 

 

This protocol is intended to assist pathologists in providing clinically useful and relevant information as a result of the examination of surgical specimens. Use of this protocol is intended to be entirely voluntary. If equally valid protocols or similar documents are applicable, the pathologist is, of course, free to follow those authorities. Indeed, the ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of the individual circumstances presented by a specific patient or specimen.

 

It should be understood that adherence to this protocol will not guarantee a successful result. Nevertheless, pathologists are urged to familiarize themselves with the document. Where a physician chooses to deviate from the protocol based on the circumstances of a particular patient or specimen, the physician is advised to make a contemporaneous written notation of the reason for the procedure followed.

 

The College recognizes that this document may be used by hospitals, attorneys, managed care organizations, insurance carriers, and other payers. However, the document was developed solely as a tool to assist pathologists in the diagnostic process by providing information that reflects the state of relevant medical knowledge at the time the protocol was first published. It was not developed for credentialing, litigation, or reimbursement purposes. The College cautions that any uses of the protocol for these purposes involve considerations that are beyond the scope of this document.

 

I.          Needle biopsy                        back     Top     Main Page

A.  CLINICAL INFORMATION

1.   Patient identification

a.   Name

b.   Identification number

c.   Age (birth date)

2.   Responsible physician(s)

3.   Date of procedure

4.   Other clinical information

a.   Relevant history (e.g. urinary obstruction)

b.   Relevant findings (e.g. digital rectal exam, PSA, ultrasound, MRI)

c.   Clinical diagnosis (e.g. carcinoma)

d.   Procedure (e.g. thick core [14 gauge] transrectal or transperineal biopsy, thin core [18 gauge] image-guided gun biopsies [sextant, octant, etc]

e.   Specific site of needle biopsy (e.g. peripheral zone, transition zone, apex, base, etc.)

B.   MACROSCOPIC EXAMINATION

1.    Specimen

a.  Number of pieces

b.  Unfixed/fixed (specify fixative)

c.  Dimensions

d.  Orientation (if designated by surgeon)

e.  Results of intraoperative consultation

2.   Tissue submitted for microscopic examination (e.g., all tissue), frozen section tissue fragment(s), unless saved for special studies)

3.   Special studies (specify) (e.g. histochemistry, immunohistochemistry,   morphometry, DNA analysis, cytogenetic analysis)

C.  MICROSCOPIC EVALUATION

1.   Tumor

a.   Histologic type (Note A)

b.   Gleason score with primary and secondary grades (Note B)

c.   Quantitation of tumor (e.g. proportion (%) of prostatic tissue involved by neoplasm) (Note C)

d.   Local invasion [Note D]

(1)  periprostatic fat

(2)  seminal vesicle

e.   Perineural invasion (Note E)

f.   Blood/lymphatic vessel invasion

2.   Additional pathologic findings, if present

a.  High grade prostatic intraepithelial neoplasia (PIN) (Note F)

b.  Therapy-related changes

            c.  Other

3.   Results/status of special studies (specify)

4.   Comments

a.   Correlation with intraoperative consultation, as appropriate

b.   Correlation with other specimens, as appropriate

c. Correlation with clinical information, as appropriate

II.  Transurethral prostatic resection                       back     Top     Main Page

1.             A. CLINICAL INFORMATION

2.      1.   Patient identification

a.  Name

b.  Identification number

c.   Age (birth date)

2.   Responsible physician(s)

3.   Date of procedure

3.      4.   Other clinical information

a.  Relevant history (e.g. urinary obstruction)

b.  Relevant findings (e.g. digital rectal exam, PSA, ultrasound, MRI)

c.  Clinical diagnosis (e.g. carcinoma)

d.  Operative procedure (transurethral resection: TURP)

e.  Operative findings

B.  MACROSCOPIC EXAMINATION

4.      1. Specimen

a.  Organ(s)/tissues(s) included

b.  Unfixed/fixed (specify fixative)

c.  Weight

d.  Descriptive features

e.  Results of intraoperative consultation

2.  Tissue submitted for microscopic examination (Note G)

a.  All grossly suspicious chips (Note G)

b.  Specimen = 12 grams, submit entirely*

c.  Specimen > 12 grams, submit at least 12 grams (about 6-8 cassettes)*

d.  Frozen section tissue fragment(s) (unless saved for special studies)

*Note: If an unsuspected carcinoma is found in tissue submitted and it involves 5% or less of the tissue examined, all remaining tissue should be submitted for microscopic examination.

5.            3. Special studies (specify)

6.           

7.      C.  MICROSCOPIC EVALUATION

8.      1.   Tumor

a.  Histologic type (Note A)

b.  Gleason score with primary and secondary grades (Note B)

c.  Quantitation of tumor (Note C)

d.  Local invasion (Note D)

                  (1)   periprostatic fat

(2)   seminal vesicle

e.  Perineural invasion (Note E)

f.   Blood/lymphatic vessel invasion

2.   Additional pathological findings, if present

a.   Prostatic intraepithelial neoplasia (PIN) (Note F)

b.   Atypical adenomatous hyperplasia

c.   Therapy-related changes

d.   Other(s)

3.  Results of special studies

4.  Comments

a.  Correlation with intraoperative consultation, as appropriate

b.  Correlation with other specimens, as appropriate

c.   Correlation with clinical information, as appropriate

 

 

III.  Suprapubic or retropubic enucleation                      back     Top     Main Page

   A.  CLINICAL INFORMATION

1.  Patient identification

a.  Name

            b.   Identification number

c.  Age (birth date)

2. Responsible physician(s)
3.  Date of procedure
4.  Other clinical information

a.  Relevant history (e.g. urinary obstruction)

b.  Relevant findings (e.g. palpable mass, elevated PSA, imaging)

c.  Clinical diagnosis

d.  Procedure (e.g. enucleation)

e.  Operative findings

9.      B.  MACROSCOPIC EXAMINATION

10.  1.  Specimen

a.   Tissue(s)/organ(s) received

b.   Unfixed/fixed (specify fixative)

c.   Size (three dimensions)

d.   Weight

e.   Descriptive features (e.g. necrosis, nodular hyperplasia)

f.   Orientation (if indicated by surgeon)

g.   Identification of margins

h.   Results of intraoperative consultation

2.   Tumor (if identified)

a.   Location(s)

b.   Size(s)

c.   Descriptive features

d.   Extent of invasion (Note H)

3.   Blocks submitted for microscopic evaluation

a.   Tumor or areas suspicious for tumor

b.   Other representative blocks (approximately 8 cassettes)*

c.   Frozen section tissue fragment(s) (unless saved for special studies)

*Note: If an unsuspected carcinoma is found in tissue submitted and it involves 5% or less of the tissue      examined, additional blocks should be submitted for microscopic analysis.

       4.  Special studies (specify)

11.  C.  MICROSCOPIC EVALUATION

1.   Tumor

a.   Histologic type (Note A)

b.   Gleason score with primary and secondary grades (Note B)

c.   Quantitation of tumor

(1)   size of tumor(s) two or more dimension(s)

(2)   proportion(%) of specimen involved by tumor

d.   Location of tumor(s)

e.   Local invasion (Note H)

      f.   Perineural invasion (Note E)

       g.  Blood/lymphatic vessel invasion

 

2.   Margins (Note I)

 

3.   Additional pathologic findings, if present

a.  High grade prostatic intraepithelial neoplasia (PIN) ( Note E)

b.  Atypical adenomatous hyperplasia.

c.  Therapy related changes

d.  Other(s)

 

4.   Results/status of special studies (specify)

 

5.   Comments

a.    Correlation with intraoperative consultation, as appropriate

b.   Correlation with other specimens, as appropriate

c.       Correlation with clinical information, as appropriate

 

IV.       Radical prostatectomy              back     Top     Main Page

        A.            CLINICAL INFORMATION

        1. Patient identification

a.  Name

b.  Identification number

c.  Age (birth date)

       

        2. Responsible physician(s)

        

  3. Date of procedure

              

              4. Clinical information

                        a.  Relevant history (previous diagnosis, treatment, includes PSA, imaging)

b.  Relevant findings

c.   Procedure

(1)  perineal procedure

(2)  retropubic procedure

i.    nerve sparing

ii.    standard radical

d.  Operative findings

e.  Anatomic site(s) of specimen(s)

B. MACROSCOPIC EXAMINATION

1.  Specimen

a.   Organ(s)/tissues included

b.  Unfixed/fixed (specify fixative)

c.  Opened/unopened

d.  Orientation (if indicated by surgeon)

e.  Structures included in specimen

(1)  prostate

(2)  seminal vesicles

(3)  segments of vasa deferentia

(4)  bladder neck

(5)  urethra

(6)  other(s) (specify)

f.   Size (three dimensions)

g.  Weight (prostate separately)

h.  Obstruction of urethra (partial/complete)

i.   Descriptive features (e.g. necrosis, nodular hyperplasia)

j.   Results of intraoperative consultation

 

2.  Tumor (if identified)

a.  Location(s)

b.  Size(s)

c.  Descriptive features

d.  Extent of local invasion

 

3.  Regional lymph nodes

a.  Location

b.  Number (each location, if possible)

 

4.  Blocks submitted for microscopic evaluation (include diagrams, if appropriate) (Note G)

a.   Tumor(s) (each grossly recognizable tumor)

b.  Blocks from other anatomic locations within the prostate (to evaluate for multicentricity)

c.  Blocks to determine extent of invasion (Note H)

(1)  prostatic capsule and periprostatic tissue adjacent to each tumor including inked margins

(2)  seminal vesicles

(3)  periprostatic tissue at bases of seminal vesicles

d.   Apex (Note I)

e.   Vesical neck margin

f.   All lymph nodes

g.   Frozen section tissue fragment(s)(unless saved for special studies)

h.   Other tissues (specify)

        

          5.Special studies (specify) (e.g. immunohistochemistry, ploidy analysis, S phase fraction)

C.        MICROSCOPIC EVALUATION

1.   Tumor

a.  Histologic type (Note A)

      b.  Gleason score with primary and secondary grades (Note B)

c.  Location(s)

       d.  Extent of local invasion (Note H)

(1)  Extraprostatic extension

(2)  Seminal vesicle involvement

     

      2.   Margins (location and extent of margins involved with tumor) (see Note I)

 

3.   Regional lymph nodes

a.  Number (specify location)

      b.  Number involved by tumor

(1)  specify location, if possible

(2)  size of metastatic deposit (i.e. if <2 mm = micrometastasis)

(3)  extracapsular extension, if present

     

4.   Additional pathologic findings, if present

a.  High grade intraepithelial neoplasia (PIN)

b.  Therapy-related changes

c.  Other(s)

 

5.   Metastasis to other organ(s) or structure(s) (specific sites)

 

6.   Other tissue(s)/organ(s)

 

7.   Results/status of special studies (specify)

 

8.   Comments

a.  Correlation with intraoperative consultation, as appropriate

b.  Correlation with other specimens, as appropriate

c.  Correlation with clinical information, as appropriate

EXPLANATORY NOTES

A. Histologic Type     back     Top     Main Page

This protocol applies only to carcinomas of the prostate gland. The histologic classification of prostate carcinoma is recommended and shown below.(1) However, this protocol does not preclude the use of other systems of classification or histologic types. Mixtures of different histologic types should be indicated.

Histologic Classification of Carcinoma of the Prostate                  

·        Adenocarcinoma (conventional, not otherwise specified)

·        Special variants of adenocarcinoma and other carcinomas

- Prostatic duct adenocarcinoma

-  Mucinous (colloid) adenocarcinoma

-  Signet ring cell carcinoma

-  Adenosquamous carcinoma

-  Squamous cell carcinoma

-  Basaloid and adenoid cystic carcinoma

-  Transitional cell carcinoma

-  Small cell carcinoma

-  Sarcomatoid carcinoma

-  Lymphoepithelioma-like carcinoma

-  Undifferentiated carcinoma, not otherwise specified

B. Gleason Score                   back     Top     Main Page

The Gleason grading system is recommended for use in all prostatic cancer specimens.(2-6) The Gleason score is the sum of the primary (most predominant) Gleason grade and the secondary (second most predominant) Gleason grade. Where no secondary Gleason grade exists, the primary Gleason grade is doubled to arrive at a Gleason score. The primary and secondary grades should be reported in parenthesis after the Gleason score, i.e. Gleason score 7(3,4) or 7(3+4). In needle biopsy specimens when there are more than two patterns present and the worst grade is neither the predominant nor the secondary grade, the predominant and the highest grade should be chosen to arrive at a score (e.g. 60% grade 3, 30% grade 2, 10% grade 4 = score 3+4 = 7). When multiple needle biopsy specimens are submitted and they have differing Gleason scores, an overall (composite) Gleason score for the case should be clearly reported in a note.

In radical prostatectomy specimens, where more than one separate tumor is identified, the Gleason scores of the individual tumors may be reported separately or at the very least the Gleason score of the most significant lesion should be recorded. For instance if there is a large Gleason score 5 transition zone cancer and a separate smaller Gleason score 7 peripheral zone cancer, both scores or at least the latter score should be reported rather than the scores being averaged.

Another grading system may be used according to institutional preference (e.g. WHO, MD Anderson) but the Gleason score must be included to facilitate comparison of data.

Gleason Grades (Patterns):

·        Grade 1- single, separate, closely packed acini

·        Grade 2-single acini, more loosely arranged, less uniform

·        Grade 3-single acini of variable size, and separation, cribriform and papillary patterns

·        Grade 4-irregular masses of acini and fused epithelium, can show clear cells

·        Grade 5-anaplastic carcinoma

Gleason scores may be grouped into differentiation (prognostic) categories:

2-4       Well differentiated

5-6       Moderately well differentiated

7          Moderately poorly differentiated

8-10  Poorly differentiated or

2-6       Well differentiated

7          Moderately differentiated

8-10     Poorly differentiated

C. Quantitation of Tumor                  back     Top     Main Page

There are many methods of estimating the amount of tumor in prostatic specimens.(7-16) In core biopsies, the absolute number and/or percentage of cores involved, the linear extent of involvement in millimeters and the proportion (percent)of surface area of prostatic tissue involved may be used. In transurethral resectates, the proportion (percent) of tissue involved by carcinoma and the number of positive chips (foci) may be used. In subtotal and radical prostatectomy specimens, the percentage of tissue involved by tumor can also be “eyeballed”. Additionally, in these latter specimens it may be possible to measure a dominant tumor nodule in at least two dimensions and to indicate the number of blocks involved by tumor over the total number of prostatic blocks submitted.

For the purpose of this protocol, it is recommended that at the very least, the proportion (percentage) of prostatic tissue involved by tumor be included for all specimens.

D.  Local Invasion in Needle Biopsies         back     Top     Main Page                

Occasionally in needle biopsies, periprostatic fat is present and involved by tumor.(7-9) This observation should be noted since it indicates that the tumor is at least stage pT3a. Furthermore, if seminal vesicle tissue is present [either serendipitously or intentially as in a directed biopsy] and involved by tumor, this should be reported since it indicates that the tumor is at least pT3b. Seminal vesicle invasion is defined by involvement of the muscular wall.(7-9,17) At times, especially in needle biopsy specimens, it is difficult to distinguish between seminal vesicle and ejaculatory duct-type tissue. It is important not to over-interpret ejaculatory duct as seminal vesicle-type tissue. Ejaculatory duct epithelium is generally surrounded by loose fibrous connective tissue with abundant blood vessels, whereas the seminal vesicle epithelium is surrounded by smooth muscle bundles constituting its wall.

E. Perineural Invasion                       back     Top     Main Page

Perineural invasion on core needle biopsies has been associated with a high risk of extraprostatic extension in some studies although the exact prognostic significance remains to be determined.(18-21) Perineural invasion has also been found to be an independent risk factor for predicting an adverse outcome in patients treated with external beam radiation. The value of perineural invasion as an independent prognostic factor, however, has been questioned in a multi-variate analysis.(22)

F.  Prostatic Intraepithelial Neoplasia (PIN)                        back     Top     Main Page

The diagnostic term PIN (prostatic intraepithelial neoplasia), unless qualified, refers to high grade PIN.(23) Low grade PIN is not reported. The presence of PIN should be reported in all biopsy specimens including those with carcinoma.(9) High grade PIN in a biopsy without evidence of carcinoma is a significant risk factor for the presence of carcinoma on subsequent biopsies.(24,25) The reporting of high grade PIN in prostatectomy specimens is optional.

G. Submission of  Tissue for Microscopic Evaluation in Transurethral Resection and Radical Prostatectomy Specimens.back     Top     Main Page

Specimens weighing (<=12 grams should be submitted in their entirety, usually in 6-8 cassettes.(26,27) For specimens > 12 grams, the initial 12 grams are submitted (6-8 cassettes) and one cassette for every additional 5 grams may be submitted.

In general, random chips are submitted, however, if some chips are firmer or have a yellow or orange-yellow appearance, they should be preferentially submitted.

In radical prostatectomy specimens with no grossly visible tumor, the specimen may be submitted in its entirety or partially sampled in a systematic fashion. One method of partial sampling involves submitting the entire apical segment and bladder neck along with alternating posterior transverse sections. Two or three random blocks demonstrating the anterior surface are also submitted along with samples of each seminal vesicle including their juncture with prostate proper.

H.  Extraprostatic Extension             back     Top     Main Page

Extraprostatic extension(EPE)is the preferred term for the presence of tumor beyond the confines of the prostate gland.(8,28) Tumor abutting on or admixed with fat constitutes extraprostatic extension. EPE may also be reported when tumor involves perineural spaces in the neurovascular bundles, even in the absence of periprostatic fat involvement. In certain locations, such as the anterior prostate and bladder neck regions, there is a paucity of fat and in these locations, EPE is determined when the tumor extends beyond the confines of the normal glandular prostate. Sometimes there is a distinct bulging tumor nodule which may be associated with a desmoplastic stromal reaction. 

I.  Margins                 back     Top     Main Page

The entire surface of the prostate should be inked to evaluate the surgical margins.(29-36) Usually, surgical margins should be designated as “negative” if tumor is not present at the inked margin and is “positive” if tumor cells touch the ink at the margin. Positive surgical margins should not be interpreted as extra-prostatic extension. If the surgical margin is positive, the pathologist should state this explicitly, although this finding is not relied upon for pathologic staging. The specific locations of the positive margins should be documented and there should be some indication (e.g. number of positive blocks, linear extent in millimeters) of the extent of margin positivity.

J. Apex and Bladder Neck                back     Top     Main Page

The apex should be closely examined because of its unusual susceptibility to positive margins.(29-31) At the apex, tumor admixed with skeletal muscle elements does not constitute extraprostatic extension. The apical and bladder neck surgical margins should be sectioned entirely, preferably with a perpendicular orientation. Microscopic involvement of bladder neck muscle fibers in radical prostatectomy specimens should not be equated with a pT4 designation. The latter generally requires gross involvement of the bladder neck.

K.  TNM and Stage Groupings                     back     Top     Main Page

The protocol recommends the use of the TNM Staging System for carcinoma of the prostate of the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) as shown below.(37,38)

By AJCC/UICC convention, the designation “T” of the TNM classification refers exclusively to the first resection of a primary tumor. The prefix symbol “p” refers to the pathologic classification of the TNM (pTNM), as opposed to the clinical classification. Pathologic classification is based on gross and microscopic examination. Therefore, pT entails a resection of the primary tumor or biopsy adequate to evaluate the highest pT category; pN entails removal of nodes adequate to validate lymph node metastasis; and pM implies microscopic examination of distant lesions. Clinical classification (cTNM) is usually carried out by the referring physician before treatment during initial evaluation of the patient or when pathologic classification is not possible.

Primary Tumor, Clinical (cT)

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% 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 the prostate*

   T2a               Tumor involves one lobe

   T2b               Tumor involves both lobes

T3        Tumor extends through the prostatic capsule**

   T3a               Extracapsular extension (unilateral or bilateral)

   T3b   Tumor invades the seminal vesicle(s)

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

12.  * Tumor found in one or both lobes by needle biopsy, but not palpable or visible by imaging, is classified as T1c.

** Invasion into the prostatic apex or into (but not beyond) the prostatic capsule is not classified as T3, but as T2. Tumor extension into periprostatic soft tissue, as opposed to organ confined cancer (T2), is T3.

Primary Tumor, Pathologic (pT)

pT2***                        Organ confined

    pT2a                                    Unilateral

    pT2b                                    Bilateral

pT3                  Extraprostatic extension

    pT3a                                    Extraprostatic extension

    pT3b                                    Seminal vesicle extension

pT4****          Invasion of bladder, rectum

*** There is no pathologic T1 category.

**** Invasion of bladder indicates direct spread into the wall of the urinary bladder. The basal prostatic stroma blends imperceptively into the bladder neck  musculature and in most instances involvement of the bladder neck margin in a radical prostatectomy does not indicate that the tumor is pT4.

Regional Lymph Nodes (N)

NX      Regional lymph nodes cannot be assessed

N0       No regional lymph node metastasis

N1       Metastasis in regional lymph node or nodes

Distant Metastasis†  (M)

MX      Distant metastasis cannot be assessed

M0       No distant metastasis

M1       Distant Metastasis

   M1a -                       non-regional lymph node(s)

   M1b -                       bone(s)

   M1c -                       other site(s)

† When more than one site of metastasis is present, the most advanced category (pM1c) is used.

Stage Groupings (TNM)                               Grade

Stage I                         T1a      N0       M0       G1

Stage II                        T1a      N0       M0       G2, G3-4

                        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

Residual Tumor in the Patient

Tumor remaining in a patient after therapy with curative intent (e.g., surgical resection) is categorized by a system known as R classification, shown below. This classification may be used by the surgeon to indicate the known or assumed status of the completeness of the surgical resection. For the pathologist, the R classification is relevant only to the margins of surgical resection specimens; patients with tumor involving the resection margins on pathologic examination may be assumed to have residual tumor. Such patients may be classified as to whether the involvement is macroscopic or microscopic.

RX       Presence of residual tumor cannot be assessed

R0        No residual tumor

R1        Microscopic residual tumor

R2        Macroscopic residual tumor.

Residual Tumor in a Specimen

Tumor remaining in a resection specimen following previous (neoadjuvant) treatment of any type (radiation therapy alone, chemotherapy therapy alone, or any combined modality treatment) is codified by the TNM using a prescript “y” to indicate the post-treatment status of the tumor (e.g., ypT1). The classification of residual disease may be a predictor of postoperative outcome. In addition, the ypTNM classification provides a standardized framework for the collection of data needed to accurately evaluate new neoadjuvant therapies.

Locally Recurrent Tumor

Tumor that is locally recurrent after a documented disease-free interval following surgical resection is classified according to the TNM categories but modified with the prefix “r” (e.g., rpT1).

References     back     Top     Main Page

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2.   Gleason DR, Mellinger GT, the Veterans Administration Cooperative Urological Research Group. Prediction of prognosis for prostate adenocarcinoma by combined histological grading and clinical staging. J Urol. 1974;111:58-64.

3.   Gleason DF: Histologic grading of prostate cancer: A perspective. Hum Pathol. 1992;23:273-279

4.   Bostwick DG: Gleason grading of prostatic needle biopsies: Correlation with grade in 316 matched prostatectomies. Am J Surg Pathol. 1994; 18:796-803.

5.      Steinberg DM, Sauvageot J, Piantadosi S, Epstein JI: Correlation of prostate needle biopsy and radical prostatectomy Gleason grade in academic and community settings. Am J Surg Pathol. 1997; 21:566-576.

6.     Partin AW, Kattan MW, Subong ENP, et al. Combination of prosate-specific antigen, clinical stage, and Gleason            score to predict pathological stage of localized prostate cancer: A multi-institutional update. JAMA. 1997; 277:1445- 1451.

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9.         Bostwick DG. Evaluating prostate needle biopsy: Therapeutic and prognostic importance. CA-A. Cancer J Clin. 1997; 47:297-319.

10.       Cupp MR, Bostwick DG, Myers RP, Oesterling JE. The volume of prostate cancer in the biopsy specimen cannot reliably predict the quantity of cancer in the radical prostatectomy on an individual basis. J Urol. 1995; 153:1543-1548.

11.       Peller PA, Young DC, Marmaduke DP, et al. Sextant prostate biopsies: A histopathologic correlation with radical prostatectomy specimens. Cancer. 1995; 75:530-538.

12.       Ravery V, Boccon-Gibod LA, Dauge-Geffroy, et al. Systematic biopsies accurately predict extracapsular extension of prostate cancer and persistent/recurrent detectable PSA after radical prostatectomy. Urology.

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14.       Terris MK, Haney DJ, Johnstone IM, et al. Prediction of prostate cancer volume using prostate specific antigen levels, transrectal ultrasound, and systematic sextant biopsies. Urology. 1995; 45:75-80.

15.       Stamey TA, Freiha FS, McNeal JE, et al. Localized prostate cancer. Relationship of tumor volume to clinical significance for treatment of prostate cancer. Cancer. 1993; 71;933-938.

16.       Humphrey PA, Vollmer RT. Percentage carcinoma as a measure of prostatic tumor size in radical prostatectomy tissues. Mod Pathol. 1997; 10:326-333.

17.       Ohori M, Scardino PT, Lapin SL, Seale-Hawkins C, Link J, Wheeler TM. The mechanisms and prognostic significance of seminal vesicle involvement by prostate cancer. Am J Surg Pathol. 1993; 17:1252-1261.

18.       Anderson PR, Hanlon Al, Patchefsky A, Al-Saleem T, Hanks GE. Perineural invasion and Gleason 7-10 tumors predict increased failure in prostate cancer patients with pretreatment PSA <10 ng/ml treated with conformal external beam radiation therapy. Int J Radiat Oncol Biol Phys. 1998; 41:1087-1092

19. Bastacky SI, Walsh PC, Epstein JI. Relationship between perineural tumor invasion on needle biopsy and radical prostatectomy capsular penetration in clinical stage B adenocarcinoma of the prostate. Am J Surg Pathol. 1993; 17:336-

20.       Holmes GF, Walsh PC, Pound CR, Epstein JI. Excision of the neurovascular bundle at radical prostatectomy in cases with perineural invasion on needle biopsy. Urology. 1999; 53:752-756.

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