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Keywords:

  • biopsy;
  • prostate-specific antigen;
  • prostatic neoplasms;
  • stage T1c prostate cancer

Abstract

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

Abstract  Aim:  The optimal biopsy strategy for prostate cancer detection, especially in men with isolated prostate-specific antigen (PSA) elevation, remains to be defined. We evaluated diagnostic yield and safety of transrectal ultrasound (TRUS)-guided transperineal systematic 14-core biopsy and compared the spatial distribution of cancer foci detected with this technique in men with and without abnormality on digital rectal examination (DRE).

Methods:  In a prospective study, 289 men aged between 50 and 87 years (median age, 70 years) underwent TRUS-guided transperineal systematic 14-core prostate biopsy because of elevated PSA and/or abnormal DRE findings. Using the fan technique, 12 cores from the peripheral zone and two cores from the transition zone were obtained systematically. To characterize the spatial distribution of cancer positive cores, site-specific overall and unique cancer detection rates were compared between stage T1c and T2 cancers.

Results:  Prostate cancer was detected in 105 of the 289 patients (36%). Major complications requiring prolonged hospital stay or re-hospitalization during a 4-week postbiopsy period were rare (1.4%). Sixty-seven stage T1c cancers were identified. These cancers were associated with significantly lower PSA and a smaller number of cancer positive cores when compared with stage T2 cancers (n= 38). The overall cancer detection rate was highest at the anterior peripheral zone and the posterior peripheral zone in stage T1c and stage T2 cancers, respectively. The unique cancer detection rate at the anterior peripheral zone was significantly higher in stage T1c cancers than in stage T2 cancers. Therefore, when the prostate is extensively biopsied using the transperineal approach, cancer positive cores are characteristically distributed anteriorly in stage T1c cancers and posteriorly in stage T2 cancers.

Conclusions:  TRUS-guided transperineal systematic 14-core biopsy showed an apico-anterior distribution of cancer foci in stage T1c prostate cancers.


Introduction

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

It has already been established that digital rectal examination (DRE) and prostate specific antigen (PSA) are the most useful front-line methods for assessing an individual's risk of prostate cancer.1 With the widespread use of PSA screening, an increasing number of prostate cancers have been diagnosed based on biopsy performed for isolated PSA elevation (stage T1c), in contrast to a palpable nodule on DRE (stage T2 or greater).2,3 Transrectal ultrasound (TRUS)-guided transperineal biopsy of the prostate, initially described in 1981,4 has been relegated to a secondary position by the TRUS-guided transrectal sextant biopsy,5 which has been widely practiced as the standard for prostate cancer detection. Transrectal sextant biopsy, however, has been criticized for its limited capacity to provide an adequate sampling of the prostate.6,7 Although various prostate biopsy schemes and biopsy needle trajectories have been evaluated8–11 and multiple-core biopsy protocols are now accepted as a general practice in detection of early prostate cancer,12 the optimal biopsy strategy for prostate cancer detection still remains to be defined.

At the apex of the gland, the peripheral zone extends anteriorly to the distal prostatic urethra;13 cancers that arise in this apico-anterior peripheral zone are difficult to palpate by DRE. Although the spatial distribution of stage T1c cancers has not been fully characterized, some of them have been located in areas such as the transition zone and the apico-anterior peripheral zone.14–16 From an anatomical point of view, transrectal biopsy is suitable to sample tissue from the posterior peripheral zone as well as from the far lateral peripheral zone.8,9,17,18 In contrast, tumors localized in the apico-anterior peripheral zone are readily accessible by transperineal biopsy. To date, however, only a few studies have been published on the sensitivity of TRUS-guided extensive transperineal prostate biopsy. Although stage T1c prostate cancer represents a stable majority of patients undergoing treatment for clinically localized disease, only a few studies have specifically addressed the location of stage T1c tumors.19 In the present study, we introduce a technique for TRUS-guided transperineal 14-core systematic prostate biopsy, and compare the spatial distribution of cancer foci detected by this strategy in men with and without abnormality on DRE.

Methods

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

Subjects

From July 2000 to May 2002, 289 men aged 50–87 years (median age, 70 years) were enrolled in a prospective study of TRUS-guided transperineal 14-core systematic prostate biopsy. Informed consent was obtained from all study participants. Biopsy criteria included an elevated PSA level (above 2.5 ng/mL) and/or an abnormal DRE finding. Patients were excluded if they presented with a previous history of prostate cancer, acute prostatitis or proven urinary tract infection. Men with PSA levels greater than 40 ng/mL and palpable tumors were also excluded from the study. Seventy-one of the 289 subjects had an average of 1.4 (range 1–4) previous negative biopsies. The stage of the tumor was determined based on the 2002 tumour node metastasis (TNM) classification system.20

Biopsy technique

Before biopsy, all men underwent evaluation of total PSA (Tandem R), urinalysis and DRE. Biopsy was performed using an 18-gauge biopsy needle driven by an automatic Magnum Biopsy gun (C R Bard, Inc., Covington, GA) under spinal anesthesia. With the patient in the lithotomy position, the prostate gland was imaged with an ultrasound machine (ALOKA SSD-2000, Aloka, Tokyo, Japan) equipped with a biplanar 5/7.5 MHz transrectal probe (ALOKA UST-672). Prostate volume and transition zone volume were calculated using the prolate ellipsoid formula.21 PSA density (PSAD) and PSA transition zone density (PSATZD) were determined as the quotients of total PSA and ultrasound estimated total prostate volume, or transition zone volume, respectively. Using real-time image monitoring by TRUS, the biopsy needle was placed from the apex of the gland to the indicated sites in a systematic fashion to cover the entire peripheral zone (Fig. 1). Using the fan technique,22 12 cores were taken from six different sampling sites in the peripheral zone; anterior 1 (A1) and 2 (A2) from anterior peripheral zone, posterior 1 (P1) and 2 (P2) from posterior peripheral zone, anterior/far lateral (AL) and posterior/far lateral (PL) from far lateral peripheral zone. The transition zone was biopsied by introducing the needle to the peripheral zone/transition zone interface and then firing the gun (arrows indicated with TZ in Fig. 1). Tissue cores were labelled at the distal end with Indian Ink, and then placed in separate specimen containers labelled with the exact location from which they were taken. At the conclusion of this procedure, a Foley catheter was inserted until the next morning. Patients were discharged on the morning following biopsy, after appropriate criteria had been met. Any complications requiring prolonged hospitalization or re-hospitalization during the 4-week postbiopsy period were considered major. All other complications were considered minor.

image

Figure 1. Transverse, sagittal and coronal projections of the transperineal 14-core systematic biopsy technique. Using the fan technique, a total of 12 cores from the peripheral zone (four cores from anterior, four from posterior and four from the far lateral part of the peripheral zone) and two cores from the transition zone (TZ) were obtained.

Download figure to PowerPoint

Site-specific overall cancer detection rates were calculated according to the seven different sampling sites (A1, A2, P1, P2, AL, PL, TZ) and the anterior, posterior and far lateral parts of the peripheral zone. To characterize the spatial distribution of stage T1c and T2 cancer foci diagnosed with the transperineal 14-core biopsy, we calculated the site-specific unique cancer detection rate; the percent of cancers detected in the specified site only.

Statistical analyses

Association was evaluated based on the Fisher's exact test for nominal variables and a one-way analysis of variance (ANOVA) for continuous variables. All calculated P-values were 2-sided and P < 0.05 was considered statistically significant.

Results

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

Using the transperineal 14-core systematic biopsy technique, prostate cancer was detected in 105 out of the 289 men (36.3%). There was no statistical difference in cancer detection rate in men with previous negative biopsies (22/71; 31%) and men without previous biopsy (83/218; 38%) (P = 0.321). Univariate analyses of clinical parameters showed that a positive biopsy result was associated with abnormal DRE, higher PSA, higher PSAD, higher PSATZD, smaller prostate volume and smaller transition zone volume (Table 1). Cancer detection rates were 4 (1/25), 27 (40/148), 48 (39/82), and 74% (25/32) in men with PSA levels of 2.5–4.0, 4.1–10.0, 10.1–20.0, and 20.1–40.0 ng/mL, respectively. Men with normal DRE were associated with lower PSA, larger prostate volume and lower incidence of cancer than those with abnormal DRE (Table 2). Sixty-seven non-palpable (stage T1c) cancers were associated with significantly lower PSA levels, a smaller number of cancer positive cores and lower Gleason scores, compared with 38 palpable (stage T2) cancers (Table 3). There was, however, no statistical difference between stage T1c and T2 cancers with regard to mean prostate volume (Table 3). A stage breakdown of the 38 patients with T2 tumors showed that 12 patients had T2a tumours, 11 had T2b tumours and 15 had T2c tumors. Because of the relatively small number of patients within each of the T2 subcategories, statistical analyses were carried out between the groups as a whole (T1c vs T2).

Table 1.   Patients characteristics according to the biopsy result.
ParametersBiopsy result
Overall (n = 289)Positive (n = 105)Negative (n = 184)P-value
  • , Fisher's exact test;

  • , anova. DRE, digital rectal examination; PSAD, prostate specific antigen density; PSATZD, prostate specific antigen transition zone density.

No. abnormal DRE (%)54 (19)38 (36)16 (9)<0.0001
Mean age (years)70.170.969.7 0.15
Mean PSA (ng/mL)10.713.9 8.9<0.00001
Mean prostate volume (mL)47.039.651.0 0.0002
Mean transition zone volume (mL)24.918.228.5<0.0001
Mean PSAD 0.30 0.50 0.19<0.0001
Mean PSATZD 0.82 1.59 0.40<0.0001
Table 2.   Comparison of biopsy result and clinical parameters according to DRE finding.
 DRE
Overall (n = 289)Normal (n = 235)Abnormal (n = 54)P-value
  • , Fisher's exact test;

  • , anova. PSA, prostate specific antigen.

No. positive biopsy (%)105 (36)67 (29)38 (70)<0.0001
Mean age (years) 70.170.070.6 0.51
Mean PSA (ng/mL) 10.7 9.416.4<0.0001
Mean prostate volume (mL) 47.049.535.8 0.0003
Table 3.  Comparisons of clinicopathologi cal parameters between stage T1c and T2 prostate cancer detected by the transperineal 14-core biopsy.
 Clinical stage
Overall (n = 105)T1c (n = 67)T2 (n = 38)P-value
  • , anova.

Mean age (years)70.971.469.9 0.5
Mean PSA (ng/mL)13.910.919.7<0.0001
Mean prostate volume (mL)39.642.933.8 0.079
Mean number of positive cores 3.9 3.0 5.3 0.0002
Mean Gleason score 6.8 6.6 7.1 0.039

Minor complications were observed in 35% of the patients, with gross hematuria being most prevalent complication (28%). Major complications requiring prolonged hospital stay or re-hospitalization during the 4-week postbiopsy period were rare (1.4%) and included persistent gross hematuria in two patients, clot retention in one, and persistent headache (probably due to spinal anesthesia) in one patient. No acute bacterial prostatitis was observed as a complication of this procedure.

The overall cancer detection rate was highest at the P2 site and lowest at the AL site among the seven different sampling sites, regardless of the DRE finding (Table 4). Among the three parts of the peripheral zone, the overall cancer detection rate was highest at the anterior peripheral zone in stage T1c cancers (65.7%), whereas it was highest at the posterior peripheral zone in stage T2 cancers (79.0%). Because the number of cancer positive cores per patient was significantly smaller in stage T1c cancers (average 3.0) than in stage T2 cancers (average 5.3), direct comparison of overall cancer detection rates between stage T1c and T2 cancers was inappropriate. Therefore, we calculated site-specific unique cancer detection rates (Table 5). Again, high unique cancer detection rates at the A1 and the A2 sites resulted in the highest unique cancer detection rate at the anterior peripheral zone in stage T1c cancers (22.4%), which was significantly higher than that in stage T2 cancers (5.3%; P= 0.02). Fifteen out of 67 stage T1c cancers would not have been diagnosed if four cores from the anterior peripheral zone had been omitted from the biopsy protocol. In clear contrast, the unique cancer detection rate in stage T2 cancers was highest at the posterior peripheral zone.

Table 4.  Site-specific overall cancer detection rates (%).
Sampling siteClinical stage
Total (n = 105)T1C (n = 67)T2 (n =  38)
Anterior 1 (A1)43.840.350.0
Anterior 2 (A2)48.640.363.2
Posterior 1 (P1)37.528.852.6
Posterior 2 (P2)55.2 4.873.7
Anterior/far lateral (AL)32.423.947.4
Posterior/far lateral (PL)41.932.857.9
Transition zone (TZ)37.129.950.0
Anterior (A1 + A2)69.565.776.3
Posterior (P1 + P2)62.553.079.0
Far lateral (AL + PL)52.441.871.1
Table 5.  Comparison of site-specific unique cancer detection rates (%) between stage T1c and T2 prostate cancer.
Sampling siteClinical stage
Total (n = 105)T1c (n = 67)T2 (n = 38)P-value
  • , Fisher's exact test.

Anterior 1 (A1) 7.611.90.00.02
Anterior 2 (A2) 7.610.42.60.14
Posterior 1 (P1) 1.0 1.50.00.64
Posterior 2 (P2) 6.7 7.65.30.50
Anterior/far lateral (AL) 3.8 3.05.30.46
Posterior/far lateral (PL) 1.0 1.50.00.64
Transition zone (TZ) 3.8 4.52.60.54
Anterior (A1 + A2)16.222.45.30.02
Posterior (P1 + P2)10.512.07.90.38
Far lateral (AL + PL) 6.7 7.55.30.50

Discussion

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

Some of the limited sensitivity experienced with prostate biopsies might be explained by the fact that many cancers are too small to be detected and that some cancers localize in areas that are not systematically sampled (e.g. those located anteriorly or apically). To circumvent these issues we introduced a TRUS-guided transperineal 14-core systematic prostate biopsy that demonstrated a 36% cancer detection rate. Although comparisons must be made with caution, because of differences in sample size, population and biopsy protocol, this figure is better than those of sextant transperineal or transrectal biopsy.11,23–25 Similarly, using systematic 12-core transperineal biopsy, Emiliozzi and his colleagues reported a 45% cancer detection rate in men with PSA between 4.1 and 10 ng/mL.22 Igel et al. reported a 43% cancer detection rate using a systematic transperineal template biopsy for re-biopsy in high-risk men.26

As reported for other extensive biopsy protocols, the present study showed that minor complications such as self-limiting hematuria were frequent, but that major complications requiring hospitalization were rare.27,28 Major infective complications did not occur in the current study. Reviews of contemporary studies on transrectal biopsy demonstrated that 0.8–20% rates of febrile infection, with at least two deaths from anaerobic sepsis, have been reported following transrectal prostate biopsy.29–32 Although, to our knowledge, there have been no randomized prospective studies comparing complication rates between transperineal and transrectal approaches, transperineal biopsy might have a lower incidence of serious infective complications than that of transrectal biopsy, as proposed previously.29

Stage T1c cancers, representing two thirds of the cancers diagnosed in the current study, were characterized with lower PSA and a smaller number of cancer positive cores compared with stage T2 cancers, suggesting that the volume of stage T1c cancers is smaller than that of stage T2 cancers. These results, which are consistent with previous studies that showed a lower cancer volume for stage T1c cancers compared with stage T2 cancers,14 support a diagnostic advantage of the transperineal 14-core systematic biopsy, especially in men without abnormality on DRE.

Both the apical entry and the longitudinal trajectory of the biopsy needle allow us to obtain full-stroke peripheral zone tissue, even from the apex and the anterior portion of the gland. Tumors that arise in these areas are often difficult to palpate on DRE, or to sample by transrectal biopsy. The biopsy protocol used in the present study produced the highest unique cancer detection rate in these areas, consistent with previous studies that indicate the importance of apical sampling of the prostate.33–36 Therefore, the benefits of sampling from the apico-anterior peripheral zone is clearly indicated, especially in men without abnormality on DRE.

Several studies have revealed a high incidence of anteriorly located tumors in radical prostatectomy specimens of non-palpable prostate cancer.14–16 These studies, however, analyzed only prostate cancers detected by conventional transrectal biopsy. In the present study, we found that cancer positive cores were characteristically distributed anteriorly in stage T1c cancers and posteriorly in stage T2 cancers, when the prostate was extensively biopsied using a transperineal approach. Whether the apico-anterior cancer foci revealed by the transperineal 14-core biopsy are undetectable by transrectal biopsy remains to be examined. In the era of PSA-driven prostate biopsy, transperineal extensive biopsy can be a useful alternative method for early diagnosis of stage T1c prostate cancer.

Conclusions

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

TRUS-guided transperineal systematic 14-core biopsy revealed an apico-anterior distribution of cancer foci in non-palpable T1c prostate cancers.

References

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