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Keywords:

  • prostate biopsy;
  • prostate cancer;
  • radical prostatectomy;
  • single core positive

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Background: The objective of the present study was to analyze the pathological findings of radical prostatectomy specimens diagnosed on single core positive prostate biopsy in eight systematic transrectal ultrasonography (TRUS)-guided biopsies with a Gleason score ≤ 4.

Methods: Between January 1993 and March 2001, 975 patients underwent TRUS-guided prostate biopsy, and 32 patients were diagnosed as having prostate cancer based only on one positive core with a Gleason score ≤ 4. In this study, 14 of the 32 patients who underwent radical prostatectomy without any neoadjuvant therapies were enrolled, and the pathological findings of their radical prostatectomy specimens were evaluated.

Results: The clinical stage of the 14 patients was T1c in 10 and T2 in four. Cancer was detected in the prostate apex in seven patients, the middle in two, the base of the peripheral zone (PZ) in three, the lateral horn of the PZ in one and the transitional zone (TZ) one. Pathological stage of the 14 patients was pT2a in four, pT2b in six, pT3a in three and pT3b one. Gleason score of the radical prostatectomy specimens in 11 patients was also ≤ 4. Of the 10 patients diagnosed with cT1c, extraprostatic disease was found in only one radical prostatectomy specimen. All three patients whose cancer was detected from the base of the PZ showed pT3 disease. During the median follow-up period of 47.5 months, all patients were alive with no evidence of disease.

Conclusion: The prognosis of patients who were diagnosed with one core positive prostate biopsy with a Gleason score ≤ 4 is generally favorable; however, advanced disease tended to be observed in patients who were diagnosed with cT2a and/or whose cancer was detected from the base of PZ.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

The incidence and mortality rates of prostate cancer in Asian countries has been reported as remaining much lower than in Western countries; however, both incidence and mortality have markedly increased in Japan.1 In addition, Oesterling et al. reported that the mean prostate volume of American men is larger than that of Japanese men, and serum levels of prostate-specific antigen (PSA) in Japanese men without prostate disease are significantly lower than those in American men.2 Therefore, there may be differences in the characteristics of prostate cancer between Japanese and American men.

Systematic transrectal ultrasonography (TRUS)-guided prostate biopsy is widely used for the diagnosis of prostate cancer. This method has increased the detection of prostate cancer compared with biopsy targeting only the hypoechoic area.3,4 Features of systematic biopsy have been extensively investigated, and some of the useful factors for providing clinically relevant information have been clarified. Among them, the percentage of positive core as well as Gleason score in systematic TRUS-guided prostate biopsy have currently been regarded to be closely associated with disease progression and adverse outcomes after radical prostatectomy.5–7 Accordingly, it would be speculated that a well-differentiated cancer with a single positive prostate biopsy may be expected to predict a favorable clinical outcome or even ‘insignificant disease’.8,9 However, several studies conducted in Western counties have reported that a single positive core in TRUS-guided prostate biopsy is not predictive of a small volume of malignant lesion and does not guarantee a favorable outcome after radical prostatectomy.10–12

In the present study, to assess the significance of one core positive prostate biopsy with Gleason score ≤ 4 in Japanese men, we retrospectively analyzed the results of systematic TRUS-guided prostate biopsy performed for 975 consecutive cases in a single institution.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Between January 1993 and March 2001, 975 patients (median age, 67 years; range, 56–76 years) received TRUS-guided prostate biopsy of the prostate as indicated by either abnormal prostate findings on digital rectal examination or elevated serum PSA values. In this series, the previously reported cut-off value of serum PSA levels among Japanese men (2.0 ng/mL) was used,13 because it has been reported that Japanese men have low serum PSA values compared with American men and that the positive biopsy rate in Japanese men with serum PSA levels of 2.1–4.0 ng/mL is approximately 7%.2,14

TRUS examinations were performed using a Bruel and Kajer 1846 console with a multiplane transducer (model 8551; Bruel & Kajer, Naerum, Denmark). Transrectal biopsies of the prostate were obtained with a spring-loaded biopsy gun (Biopty, CR Bard, Covington, GA) and an 18-gauge Tru-cut biopsy needle under TRUS guidance. If hypoechoic areas were detected on TRUS, a specimen was taken from each of these areas. If no hypoechoic area was noted on the prostate, only systematic biopsy was performed as follows: specimens were taken from the prostate apex, the middle and base of the peripheral zone (PZ), and anterior lateral horn in each lobe. Furthermore, in patients undergoing repeat biopsy, specimens from the transition zone (TZ) of each lobe and midline of PZ were also taken.

The resected prostatectomy specimens were fixed and whole-mount step sections were cut transversely at 5 mm intervals from the apex of the prostate to the tips of the seminal vesicles. Each section was examined for cancer location, capsular penetration and seminal vesicle invasion. Both the clinical and pathological stages were determined according to the UICC (TNM) tumor stage classification.15

Differences between the two groups were compared using the χ2 test, and probability values < 0.05 were considered significant.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Of the 975 patients who received TRUS-guided systematic prostate biopsy, 32 patients (3%) were diagnosed as having prostate cancer with a Gleason score ≤ 4 (1 + 2: 16 patients; 2 + 1: 13; 1 + 1: 2; and 2 + 2: 1) by a single positive biopsy. In this series, 14 of the 32 patients who underwent radical prostatectomy without any neoadjuvant therapy were analyzed. Characteristics of these 14 patients are summarized in Table 1. On final pathological examination of the prostatectomy specimens, three cases were diagnosed as moderately differentiated adenocarcinoma (Gleason score 5–7); that is, the diagnoses of tumor differentiation between biopsy and prostatectomy specimens were identical in 11 of the 14 cases (79%). As shown in Table 1, final pathological examination indicated that 10 patients (71%) diagnosed as either pT2a or pT2b had organ-confined disease. In addition, the remaining 18 patients who did not undergo radical prostatectomy without neoadjuvant therapy had similar clinical characteristics, including age, preoperative serum PSA, clinical stage and pathological features of biopsy specimens, to these 14 patients (data not shown).

Table 1.  Characteristics of patients diagnosed on single core positive prostate biopsy with a Gleason score ≤ 4
Characteristic 
  1. PSA, prostate-specific antigen; PZ, peripheral zone; TZ, transitional zone.

Median age
 Range (years)67 (56–76)
Median observation period
 Range (months)47.5 (1–81)
Median preoperative serum PSA
 Range (ng/mL) 4.4 (2.2–48)
Clinical stage  No. patients (%)
  T1c10 (71)
  T2a 4 (29)
Positive lesion of systematic biopsy No. patients (%)
  Apex 7 (50)
  Middle of PZ 2 (15)
  Base of PZ 3 (21)
  Anterior lateral horn  1 (7)
  TZ 1 (7)
Percentage of cancer volume in biopsy specimen: No. patients (%)
  ≤25 7 (50)
  >25 7 (50)
Pathological stage No. patients (%)
  T2a 4 (29)
  T2b 6 (43)
  T3a 3 (21)
  T3b 1 (7)
Gleason score in prostatectomy specimen No. patients (%)
  2–411 (79)
  5–7 3 (21)

We then analyzed the factors associated with tumor progression (i.e. organ confined compared to extraprostatic disease) among the 14 patients. As shown in Table 2, preoperative serum PSA levels and percentage of cancer volume in biopsy specimens were not associated with pathological stage. However, the patients who were diagnosed as cT2a or whose cancer was detected from the base of PZ showed a significantly higher incidence of extraprostatic progression.

Table 2.  Association of several factors with disease progression in patients diagnosed on single core positive prostate biopsy with Gleason score ≤ 4
VariableOrgan-confined disease (pT2)Extraprostatic disease (pT3)P-value
  1. PSA, prostate-specific antigen; PZ, peripheral zone.

Preoperative serum PSA (ng/mL)
 ≤4 710.12
 >4 33 
Clinical stage
 T1c 910.02
 T2a 13 
Percentage of cancer volume in biopsy specimen
 ≤25 610.24
 >25 43 
Positive lesion of systematic biopsy
 Base of PZ 030.02
 Other lesions101 

During the median follow-up period of 47.5 months, all patients were alive with no evidence of disease, although three of the four patients with extraprostatic disease received adjuvant therapies (hormonal therapy for two; hormonal therapy plus radiation for one).

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

To date, a number of studies have been carried out to identify clinically insignificant prostate cancer on the basis of various factors, including the percentage of positive core and cancer volume in needle biopsy specimens, serum PSA values, tumor volume and Gleason score in radical prostatectomy specimens.8,9 However, there is no consensus regarding whether an individual disease is clinically insignificant. This problem is particularly important for well-differentiated adenocarcinoma diagnosed on the single core positive prostate biopsy. Indeed, several studies have been conducted in Western countries to characterize the significance of prostate cancer diagnosed by single core positive in systematic biopsy and have reported that the result of single core positive biopsy should not be used as a surrogate for clinically insignificant disease,10–12 but it is a well accepted finding that the biological characteristics of prostate cancer between Japanese and American men are different.2,13 Furthermore, it has been reported that prostate cancers with a Gleason score ≤ 4 are almost of TZ origin with a low malignant potential.16 Therefore, in the present study, we retrospectively analyzed the outcome of TRUS-guided prostate biopsy performed for 975 consecutive cases in a single institution to clarify the significance of single core positive biopsy with well differentiated disease in Japanese men.

In this series, 14 patients were diagnosed based on one positive biopsy core with Gleason score ≤ 4, and subsequently underwent radical prostatectomy without any neoadjuvant therapies. Final pathological examination of radical prostatectomy specimens revealed that four of the 14 cases showed extraprostatic progression. However, during the median observation period of 47.5 months, despite three patients receiving adjuvant therapies, all patients were alive with no evidence of disease, suggesting a favorable clinical course after radical prostatectomy in cases diagnosed by a single positive core biopsy. Despite the lack of long-term follow-up, these findings were similar to those in previous studies performed in Western countries.10–12 For example, D’Amico et al. reported that patients diagnosed on the basis of a single positive biopsy with a Gleason score ≤ 7 had favorable pathological findings, but 10% of the patients failed biochemically within 5 years.12

It is of interest to determine which factor is associated with disease progression among cases detected by single biopsy core. Wang et al. reported that serum PSA> 10 ng/mL strongly suggested the presence of clinically significant cancer even in cases presenting with cancer limited to one core biopsy irrespective of tumor differentiation.11 Moreover, Ravery et al. reported that the percentage of tumor on the biopsy specimen is closely associated with tumor volume in cases with a single positive needle biopsy.10 In this series; however, serum PSA levels and percentage of cancer volume in biopsy specimens were not associated with tumor progression, while the incidence of extraprostatic progression was significantly higher in patients who were diagnosed as cT1c or those whose cancer was detected at the base of PZ. This discrepancy might be explained by several reasons, such as the different characteristics of prostate cancer between Japanese and American men, especially in serum levels of PSA and the different biopsy strategies and techniques in different institutions.

In conclusion, the prognosis of Japanese men with prostate cancer who were diagnosed with one core positive biopsy with a Gleason score ≤ 4 is generally favorable; however, approximately 30% of such cases showed extraprostatic progression, which tended to be observed in patients who were diagnosed as cT2a and/or whose cancer was detected at the base of the PZ.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References
  • 1
    Egawa S, Suyama K, Ohori M et al. Early detection of prostate cancer. Cancer 1995; 76: 46372.
  • 2
    Oesterling JE, Kumamoto Y, Tsukamoto T et al. Serum prostate-specific antigen in a community-based population of healthy Japanese men: lower values than for similarly aged white men. Br. J. Urol. 1995; 75: 34753.
  • 3
    Stamey TA. Making the most out of six systematic sextant biopsies. Urology 1995; 45: 212.
  • 4
    Hodge KK, McNeal JE, Terris MK, Stamey TA. Random systematic versus detected ultrasound guided transrectal core biopsies of the prostate. J. Urol. 1989; 142: 715.
  • 5
    D’Amico AV, Whittington R, Malkowicz SB et al. Clinical utility of the percentage of positive prostate biopsies in defining biochemical outcome after radical prostatectomy for patients with clinically localized prostate cancer. J. Clin. Oncol. 2000; 18: 116472.
  • 6
    Gohji K, Okamoto M, Takenaka A, Nomi M, Fujii A. Predicting the extent of prostate cancer using the combination of systematic biopsy and serum prostate-specific antigen in Japanese men. BJU Int. 1999; 83: 3942.
    Direct Link:
  • 7
    Gilliland FD, Hoffman RM, Hamilton A et al. Predicting extracapsular extension of prostate cancer in men treated with radical prostatectomy: results from the population based prostate cancer outcomes study. J. Urol. 1999; 162: 13415.
  • 8
    Stamey TA, Freiha FS, McNeal JE, Redwine EA, Whittemore AS, Schmid HP. Localized prostate cancer: relationship of tumor volume to clinical significance for treatment of prostate cancer. Cancer 1993; 71: 9338.
  • 9
    Epstein JI, Chan DW, Sokoll LJ et al. Nonpalpable stage T1c prostate cancer: prediction of insignificant disease using free/total prostate specific antigen levels and needle biopsy findings. J. Urol. 1998; 160: 240711.
  • 10
    Ravery V, Szabo J, Toublanc M et al. A single positive prostate biopsy in six does not predict a low-volume prostate tumor. Br. J. Urol. 1996; 77: 7248.
  • 11
    Wang X, Brannigan RE, Rademaker AW, McVary KT, Oyasu R. One core positive prostate biopsy is a poor predictor of cancer volume in the radical prostatectomy specimen. J. Urol. 1997; 158: 14315.
  • 12
    D’Amico AV, Wu Y, Chen MH, Nash M, Renshaw AA, Richie JP. Pathological findings and prostate specific antigen outcome after radical prostatectomy for patients diagnosed on the basis of a single microscopic focus of prostate carcinoma with a Gleason score = 7. Cancer 2000; 89: 18107.
  • 13
    Egawa S, Koh H, Satoh T et al. Preoperative serum prostate-specific antigen, clinical stage and Gleason sum as basis for predicting final pathological stage in Japanese prostate cancer. Jpn J. Clin. Oncol. 1996; 26: 43844.
  • 14
    Egawa S, Suyama K, Ohori M et al. Early detection of prostate cancer. Results of a prostate specific antigen based detection program in Japan. Cancer 1995; 76: 46372.
  • 15
    International Union Against Cancer. In: Sobin LH, Wittekind CH (eds). TNM Classification of Malignant Tumors, 5th edn. John Wiley & Sons, New York, 1997; 1703.
  • 16
    Ro YJ, Grignon DJ, Amin MB. Atlas of Surgical Pathology of the Male Reproductive Tract. W.B. Saunders, Philadelphia, 1997.