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Keywords:

  • prostate;
  • neoplasm;
  • prostatectomy;
  • tumor TNM staging;
  • classification

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

BACKGROUND

Clinicopathologic staging of prostate adenocarcinoma provides a method for assessing the extent of tumor and predicting patient prognosis. The American Joint Committee on Cancer (AJCC) TNM staging system has undergone recent revisions for T2 prostate tumors. T2 tumors currently are subclassified as T2a (less than one-half of one lobe involvement), T2b (greater than one-half of one lobe involvement), and T2c (bilateral involvement). Despite general acceptance of the system, controversy and uncertainty still exist with regard to the application of the TNM staging system, particularly the use of the T2 staging subclassification.

METHODS

The study population was comprised of 369 patients with prostate carcinoma who were treated with radical retropubic prostatectomy. Radical prostatectomy specimens were evaluated histologically by complete embedding and whole-mount processing. Tumor specimens were staged initially using the 1998 AJCC TNM system and then reevaluated according to the 2002 TNM staging guidelines.

RESULTS

The weights of the prostate specimens ranged from 14–149 g (median, 38 g). Prostate tumor specimens were multifocal in 312 patients (85%). The majority of the specimens were classified pathologically as T2 (n = 276 [75%]). Using the 2002 TNM staging criteria, 54 of the tumor specimens (15%) were classified as pT2a, 222 (60%) were pT2c, 75 (20%) were pT3a, and 18 (5%) were pT3b. No pathologic T2b tumor specimens were identified.

CONCLUSIONS

Taking into consideration the average weight of the prostate specimens (38 g), as well as the predominance of tumor multifocality, it would be unusual to identify tumors involving greater than one-half of 1 lobe (approximately an 8-cm3 tumor) without involving the other lobe. The authors question the existence of a true pT2b tumor. Cancer 2004. © 2004 American Cancer Society.

The development of a staging system with both clinical and pathologic accuracy is essential in understanding the biologic characteristics of prostate carcinoma, as well as for determining prognosis and appropriate therapeutic management. In 1992, the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) adopted a unified TNM staging system for prostate carcinoma.1, 2 T2 disease was defined as palpable prostate-confined tumor and was subdivided into three categories: T2a (unilateral tumor involving one-half of a lobe or less), T2b (unilateral tumor involving greater than one-half a lobe), and T2c (bilateral disease). In 1998, the TNM staging system was revised by the AJCC3 to reduce the number of T2 subdivisions. Unilateral disease was combined into a single subdivision, T2a, and bilateral tumor involvement was reclassified as T2b (Table 1). The sixth edition of the AJCC staging system, adopted in 2002, reincorporated the three clinical subdivisions for T2 tumors.4 Controversy exists regarding the appropriate subclassification of T2 prostate carcinoma.

Table 1. Comparison of 1992/2002 and 1998 AJCC Staging Systems for T2 Organ-Confined Prostate Adenocarcinoma
1992/20021998Definition
  1. AJCC: American Joint Committee on Cancer.

T2aT2aTumor involves one-half of one lobe or less
T2bT2aTumor involves greater than one-half of one lobe, but not both lobes
T2cT2bTumor involves both lobes (bilateral disease)

In the current study, we analyzed the AJCC subclassification for prostate carcinoma in a large series of patients with radical retropubic prostatectomy specimens evaluated by complete embedding and whole-mount processing.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Three hundred sixty-nine consecutive patients were treated with radical retropubic prostatectomy from 1999 to 2003 at Indiana University Hospital (Indianapolis, IN). The radical prostatectomy specimens were evaluated as previously described.5–10 After removal of the seminal vesicles, the prostate specimens were weighed, measured, inked, and fixed in 10% neutral formalin. After fixation, the apex and base were amputated and serially sectioned at 3–5-mm intervals in the vertical, parasaggital plane. The seminal vesicles were sectioned parallel to their junction with the prostate and submitted in their entirety for evaluation. The remaining prostate specimen was serially sectioned perpendicular to the long axis from the apex of the prostate to the base and whole-mount sections were prepared. Specimens were evaluated histologically, graded, and staged by a single pathologist (L.C.). The 1998 TNM system was used initially for pathologic staging.3 The 1998 T2a tumors were analyzed retrospectively to determine whether they represented 2002 T2a or T2b disease. Tumors involving less than one-half of the area of a single lobe per whole-mount section were reclassified as T2a and tumors involving greater than one-half of a single lobe, but not both lobes, were reclassified as T2b. Bilateral disease was reclassified as T2c. Tumors were graded according to the Gleason system.11, 12 Surgical margins were considered positive when carcinoma cells were in contact with the inked margin.6

The current study was approved by the institutional review board at Indiana University.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Three hundred sixty-nine totally embedded, serially sectioned, whole-mount radical prostatectomy specimens were evaluated. Table 2 shows the characteristics of the patients and the tumor specimens. The average age of the patients at the time of surgery was 60 years (range, 41–77 years). The median and mean weights of the prostate specimens were 38 g and 42 g, respectively (range, 14–149 g). The Gleason scores were 4 (n = 1 patient), 5 (n = 65 patients), 6 (n = 115 patients), 7 (n = 153 patients), and 8–9 (n = 35 patients). The majority of the specimens were pathologic T2 (276 specimens [75%]) and 93 specimens (25%) were pathologic T3. Using the 2002 TNM staging criteria, 54 of the tumor specimens (15%) were pT2a, 222 (60%) were pT2c, 75 (20%) were pT3a, and 18 (5%) were pT3b. No pathologic T2b tumor specimens were identified. The majority of tumor specimens were multifocal (312 specimens [85%]). Eighty-six specimens (23%) were found to have positive surgical margins.

Table 2. Patient and Tumor Characteristics
CharacteristicsNo. (%)
  1. PSA: prostate-specific antigen; AJCC: American Joint Committee on Cancer.

Mean age (yrs) (range) 60 (41–77)
Mean preoperative PSA (ng/mL) (range)8.4 (0.3–150)
Mean prostate weight (g) (range) 42 (14–149)
Mean tumor volume (cm3) (range)2.5 (0.03–38)
2002 AJCC pathologic classification 
 pT2a 54 (15)
 pT2b  0 (0)
 pT2c222 (60)
 pT3a 75 (20)
 pT3b 18 (5)
Gleason score 
 4  1 (0.3)
 5 65 (18)
 6115 (31)
 7153 (42)
 8–9 35 (9)
Extraprostatic extension 
 Negative280 (76)
 Positive 89 (24)
Seminal vesicle invasion 
 Negative351 (95)
 Positive 18 (5)
Lymph node metastasis 
 Negative363 (98)
 Positive  6 (2)
Surgical margin 
 Negative283 (77)
 Positive 86 (23)
Tumor multifocality 
 Negative 57 (15)
 Positive312 (85)

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

The TNM staging system for prostate carcinoma was adopted initially for worldwide use in 1992, with subsequent revisions published in 1998 and 2002. The 1998 revision merged palpable tumors occupying less than one-half a lobe with larger tumors in a single lobe (formerly 1992 T2a and T2b) into a single category (T2a) and changed the T2b category to designate palpable tumors involving both lobes (formerly 1992 T2c). In 2002, the sixth edition of the AJCC staging system refuted the two-tiered classification and reverted to the three-tiered system for T2 tumors. In our series of 369 totally embedded, serially sectioned, whole-mount radical prostatectomy specimens, unilateral tumors histologically occupying greater than one-half of a single lobe (pT2b) were not identified. To our knowledge, this is the first report indicating a lack of pathologic 2002 T2b tumors in a large series of whole-mount prostatectomy specimens. Previous whole-mount prostate series have combined T2a and T2b into one category in the analysis.

The extent of clinically evident tumor (T) is determined by findings at digital rectal examination, transrectal ultrasonography, or the results of other imaging techniques. Pathologic staging of prostate adenocarcinoma with the TNM system (pT) requires histologic identification of the extent of tumor within the prostate and surrounding tissues. Although the criteria for assessment of the clinical staging of prostate carcinoma are well defined, ambiguity still exists with regard to translating these criteria into pathologic staging after radical prostatectomy. Anatomically distinct lobes are not macroscopically or histologically definable in the prostate, despite use of this distinction in the staging system.13, 14 In addition, prostate tumors are often multifocal,15 and to the best of our knowledge, clear methods for the pathologic staging of multifocal small tumors have not been defined to date.

Agreement between both clinical and pathologic stages facilitates the assessment of patient prognosis and guides appropriate therapy. However, the ability of clinical stage to predict final pathologic stage is limited.16 Bostwick et al.7 found that 59% of clinical T2, T3, and T4 prostatic tumor specimens from men undergoing radical prostatectomy were understaged when compared with the final pathologic stage. Approximately 5% of the tumor specimens were clinically staged higher than the pathologic stage. Therefore, the clinical and pathologic stages corresponded in only 36% of the cases. Hoedemaeker et al.17 observed similar results in their study, with 53% of tumor specimens clinically understaged, 7% clinically overstaged, and 41% in agreement.

Subclassification of T2 prostate carcinoma is controversial. Han et al.18 reported significantly different biochemical recurrence-free survival rates for men with 1992 T2a versus 1992 T2b disease after radical prostatectomy, but similar rates for men with 1992 T2b versus 1992 T2c disease. The authors support the division of unilateral disease into two subclassifications, with possible combination of the 1992 T2b and 1992 T2c categories for the purpose of simplification. Cagiannos et al.19 also reported statistically significant biochemical recurrence-free survival rates for the 1992 T2a and T2b subclassifications, but not for T2b versus T2c subclassifications.

In contrast to previous studies, we evaluated T2 tumors based on histologic assessment, not clinical staging criteria. Using the whole-mount technique for processing prostatectomy specimens, we did not find any pT2b tumors using the 2002 TNM staging criteria. Given that the average weight of the prostate specimens in the current series is 38 g, a tumor occupying greater than one-fourth of the prostate would approach 8 cm3 in volume (Fig. 1). It appears unlikely that such a large tumor would remain confined within a single lobe, especially given the predominance of multifocality observed with prostate carcinomas.

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Figure 1. Whole-mount section of a radical prostatectomy specimen with 2002 American Joint Committee on Cancer pT2a prostate carcinoma (PCA). It is estimated that a tumor occupying greater than one-half of one lobe (pT2b carcinoma) would have a tumor volume of at least 8 cm3.

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The current study does not support a distinct subclassification for tumors occupying greater than one-half of a single lobe, but fewer than two lobes (pT2b). The three-tiered T2 classification system for staging organ-confined prostate carcinoma is not necessary, taking into consideration the biology and anatomy of prostate carcinoma. Further study is needed to determine the optimal staging system for organ-confined prostate carcinoma.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES
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