Analysis of differences in clinicopathological features between prostate cancers located in the transition and peripheral zones

BACKGROUND: The objective of this study was to retrospectively characterize differences in the clinicopathological features of prostate cancer according to the zonal origin. METHODS: Among 185 consecutive patients who underwent radical prostatectomy without any neoadjuvant hormonal therapies, this study included 134 patients who were diagnosed as having either transition zone (TZ) or peripheral zone (PZ) cancer according to the following criteria: TZ or PZ cancers were considered when more than 70% of the cancer area was located in the TZ or PZ, respectively. The various clinicopathological features were then compared according to this classification. RESULTS: In this series, 27 patients were diagnosed as having TZ cancer, while the remaining 107 were diagnosed as having PZ cancer. The percent of positive biopsy cores in TZ cancers was significantly lower than that in PZ cancers; however, there were no significant differences in the anatomical location of positive cores between these two groups except for the middle of prostate where TZ cancer showed a significantly lower rate of positive biopsies than PZ cancer. The preoperative serum prostate-specific antigen (PSA) value in patients with TZ cancer was significantly higher than that in those with PZ cancer. Furthermore, tumor volume in TZ cancers was significantly greater than that in PZ cancers. However, there was no significant difference in biochemical recurrence-free survival between patients with TZ and PZ cancers. CONCLUSIONS: Despite the significantly high PSA value as well as great tumor volume compared with those of PZ cancers, TZ cancers had similar biochemical cure rates following radical prostatectomy, suggesting a less aggressive phenotype of TZ cancers than that of PZ cancers.     

A comparison of the biological features between prostate cancers arising in the transition and peripheral zones

OBJECTIVES: To investigate differences in the biological features of prostate cancer according to the zonal origin. PATIENTS AND METHODS: Among 172 consecutive patients who had a radical prostatectomy (RP), the study included 124 diagnosed as having either transition zone (TZ) or peripheral zone (PZ) cancer, defined according to whether there was > 70% of the cancer area in the TZ or PZ, respectively. The clinicopathological features were then compared between these groups. In addition, the RP specimens were stained immunohistochemically with antibodies to Ki-67, Bcl-2, matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF). RESULTS: Twenty-four patients were diagnosed as having TZ cancer and the remaining 100 as having PZ cancer. Prostate specific antigen (PSA) values in patients with TZ cancer were significantly higher than in those with PZ cancer. Tumour volume in TZ cancer was significantly greater than that in PZ cancer, but there was no significant difference in biochemical recurrence-free survival between the groups. Immunohistochemistry showed that despite there being no differences in Bcl-2 and VEGF expression between TZ and PZ cancers, there was significantly greater expression of Ki-67, MMP-2 and MMP-9 in PZ than TZ cancers. CONCLUSIONS: Despite there being no significant difference in biochemical recurrence-free survival after RP between patients with TZ and PZ cancers, there was less cell proliferation and biomarker levels related to invasive potential in TZ than in PZ cancers.     

Evaluation of a prostate biopsy strategy for cancer detection using a computer simulation system with virtual needle biopsy for three-dimensional prostate models

AIM: We evaluated a prostate biopsy strategy for cancer detection using a computer simulation system with virtual needle biopsy for three-dimensional (3D) prostate models. METHODS: Two 3D prostate models with a volume of 25 cc or 50 cc were constructed from computed tomographic images of radical prostatectomy specimens. The peripheral zone (PZ) and transition zone (TZ) were arranged in the prostate models according to the anatomical information. Four thousand patterns of cancer lesions were automatically inserted into each prostate model with a proportion of 75% in PZ and 25% in TZ. Average hit rates (AHR) in prostate models were evaluated both with an increased number of biopsy cores and various angles of virtual needle biopsy. The influence of adding secondary tumors for hit rates was also evaluated. RESULTS: For both sizes, the laterally angled biopsy in 4-8 core biopsy schemes showed higher AHR than the vertical plane biopsy, while the vertical plane biopsy in 10-18 core biopsy schemes showed higher AHR than the laterally angled biopsy. A higher number of biopsy cores increased the AHR of secondary tumors. CONCLUSIONS: Our results suggest that it is important in prostate cancer detection to change the needle placement according to the number of biopsy cores and the size of the prostate.     

Does transurethral resection of the prostate facilitate detection of clinically significant prostate cancer that is missed with systematic sextant and transition zone biopsies?

BACKGROUND: A prospective study was conducted to determine whether transurethral resection of the prostate (TURP) facilitates detection of prostate cancer that is missed with systematic sextant biopsies associated with transition zone (TZ) biopsies. METHODS: A total of 139 consecutive patients underwent transperineal TZ biopsies of each lobe in addition to a transrectal systematic sextant peripheral zone (PZ) biopsy. Patients whose biopsies were negative for cancer received TURP for relief of lower urinary tract obstruction when indicated. RESULTS: Cancer was detected in biopsy specimens of 40 patients. Of these cancers, 18 originated in the PZ alone and 22 were located both in the TZ and the PZ. No cancers were detected in the TZ alone. Of 99 patients who were proven not to have cancer by the biopsies, 18 were indicated for TURP. Five of these patients (28%) had cancer in the resected tissues. All cancers were clinically organ confined and their Gleason sum scores were 2-5. Cancer-positive chips accounted for less than 10% of all resected specimens. Of the 66 patients with negative biopsies and without indication for TURP, four (6%) were revealed to have an elevation of the serum PSA level during follow up. They were later proven to have cancer by a second biopsy. CONCLUSION: Routine use of TZ biopsy is not warranted for detection of cancer. Transurethral resection of the prostate can detect cancers in patients with negative PZ and TZ biopsies. However, cancers detected by TURP may not always be clinically significant and only four of 66 patients who were not indicated for TURP and received a close follow up were later found to have cancer, although their follow-up period was short. Thus, it still remains to be elucidated whether TURP is necessary for all patients with negative biopsies of the prostate.     

Frequency and clinical significance of transition zone cancer in prostate cancer screening

Approximately 20% of prostate cancers originate in the transition zone (TZ). Although transrectal ultrasound (TRUS) and systematic biopsies have improved peripheral zone (PZ) cancer diagnosis, additional biopsies directed into the TZ may further improve cancer detection. To evaluate the frequency and clinical significance of TZ cancers, we added two TZ biopsies to the routinely performed sextant biopsies. Three hundred forty patients (aged 45–75) from our prostate-specific antigen (PSA) screening study (21,078 volunteers) with negative rectal examination findings underwent systematic and TZ biopsies with three-dimensional ultrasound equipment. All patients had elevated PSA levels according to age-specific reference ranges. Ninety-eight of 340 men (28.5%) had biopsies positive for cancer. Of these 98 cancers, 28 (28%) originated in the TZ only and 5 (5%) were located in the TZ as well as the PZ. Eight men showed TZ abnormalities on ultrasound images, of whom four had biopsies positive for TZ cancer. The TZ cancers detected were pathologically significant in 96% (27 of 28). Seventy-one percent (20 of 28) of pathologically staged cancers were found to be organ confined and all combined TZ and PZ cancers were advanced tumors. We conclude that TZ biopsies enhance the cancer detection rate in prostate cancer screening and should therefore be added to the routinely done sextant biopsies in men with PSA elevation and normal digital rectal examination findings. Prostate 30:130–135, 1997. © 1997 Wiley-Liss, Inc.     

Is transition zone biopsy valuable in benign prostatic hyperplasia patients with serum prostate-specific antigen >10 ng/ml and prior negative peripheral zone biopsy?

OBJECTIVES: To evaluate the importance of transition zone (TZ) biopsy in benign prostatic hyperplasia (BPH) patients with serum prostate-specific antigen (PSA) >10 ng/ml and prior negative peripheral zone (PZ) biopsy and to estimate the sensitivity of TZ biopsy. MATERIAL AND METHODS: A total of 273 BPH patients with PSA >10 ng/ml and prior negative PZ biopsy underwent an extended biopsy protocol. In patients with a TZ volume <25 cm(3), four TZ biopsies were taken (two cores per side from the apex and base). In patients with a TZ volume > or =25 cm(3) (n=183), six TZ biopsies were taken (three cores per side from the apex, middle and base). Overall, 215 patients were subjected to either transurethral resection of the prostate (n=162) or open enucleation of the adenoma (n=53). RESULTS: The extended biopsy revealed prostate cancers in 21.2% of cases (58/273). The zonal distribution of the positive cores was as follow: PZ cancers only in 67.2% of cases (39/58), TZ cancers only in 13.8% (8/58) and PZ+TZ cancers in 19% (11/58). Overall, 73.6% (14/19) and 36.8% (7/19) of TZ cancers were detected at the apex and middle of the TZ, respectively, while no TZ cancers at all were detected at the base (p=0.00015). The incidence of carcinoma on definitive pathology was 5.6% (12/215). Consequently, TZ biopsy detected only 61.3% (19/31) of TZ cancers. The incidence of pure TZ cancers was 7.3%. On the chi(2) test, patient age, serum PSA, transrectal ultrasonography findings and PSA density did not correlate significantly with the detection rate of TZ cancer. Prostate volume (p=0.023), TZ volume (p=0.027) and PSA/TZ density (p=0.007) were predictive of TZ cancers. CONCLUSIONS: Although TZ biopsy was the sole site of cancer in only 2.9% of cases (8/273), it improved the cancer detection rate by 14% in this selected group of patients. The majority (74%) of TZ cancers were detected at the apex site. TZ biopsy has a low sensitivity (61%).     

Relationship between clinical stage and histological zone of origin in early prostate cancer: morphometric analysis.

A detailed morphometric analysis of 96 radical prostatectomy specimens (13 clinical stage A1, 29 A2, 34 B1 and 20 B2) was undertaken to examine the relationship of zone of origin to volume, grade and extraprostatic extension of cancer. In patients with stage A disease, transition zone (TZ) cancer (present in 81%) was significantly larger but of lower grade than peripheral zone (PZ) cancer (present in 90%). The total volume of cancer in stage A1 patients averaged 1.55 ml with 72% of TZ origin. In patients with stage A2 disease, tumour volume averaged 5.83 ml with only 57% of TZ origin. Specimens taken during transurethral resection of the prostate (TURP) revealed TZ cancer in 82% and PZ cancer either alone or with TZ cancer in 22%. The 9 patients with PZ cancer in the TURP specimen included 5 of the 11 with extracapsular extension and all 5 of those with seminal vesicle invasion. Every patient with stage B disease had PZ cancer which, in all except 3 cases, was of significantly larger volume and higher grade than any TZ cancer (present in 43%) in the same gland. In patients with stage B cancer, total tumour volume was 5.13 ml with 91% of PZ origin. TZ cancer tended to be well differentiated in all patients, even at large volumes, whereas PZ cancer was often moderately or poorly differentiated even at low volumes. In patients with stage B disease, TZ cancer appeared to be incidental and of no clinical importance, while in stage A patients PZ cancers were sometimes large, poorly differentiated and extended outside the prostate. Progression of a stage A cancer seems more likely to result from PZ cancer than TZ cancer, and the finding of PZ cancer in a TURP specimen should probably preclude its classification as stage A1.     

Elevation of dipeptidylpeptidase iv activities in the prostate peripheral zone and prostatic secretions of men with prostate cancer: possible prostate cancer disease marker

PURPOSE: Dipeptidylpeptidase IV (DPIV) is a multifunctional type II plasma membrane glycoprotein with serine-type exopeptidase activity that is secreted by the prostate and increased in prostate cancer. We determined whether changes in DPIV activities in prostatic tissue zones and expressed secretions were associated with the presence of cancer. MATERIALS AND METHODS: Expressed prostatic secretion (EPS), and biopsy of the transition (TZ) and peripheral (PZ) zones were collected from men undergoing ultrasound guided prostate biopsy. DPIV activities were measured by glypro-p-nitroanalide hydrolysis. RESULTS: DPIV activities were significantly higher in TZ than in PZ tissues in men with no evidence of malignancy. However, activities in EPS were negatively associated with TZ volume and positively associated with PZ volume. Mean and median DPIV activities in EPS from men with biopsy determined cancer were significantly higher than in men with no evidence of malignancy. DPIV activities in TZ and PZ biopsies were higher in men with cancer but most markedly in the PZ. CONCLUSIONS: These data indicate that secreted DPIV originates from the TZ and PZ. Increased DPIV activities in cancer are strongly associated with the PZ, which is the zone most commonly involved with cancer. Measuring DPIV levels in expressed EPS or post-digital rectal prostate examination urine may be useful for evaluating men for prostate cancer.     

Differences in biopsy features between prostate cancers located in the transition and peripheral zone

OBJECTIVE: To identify the zonal location of prostate cancers before surgery, by analysing the mapping of ultrasonography-guided systematic sextant biopsies for differences between cancers located in the transition zone (TZ) and peripheral zone (PZ); and to compare the correlation between Gleason scores of needle biopsies and those of radical prostatectomy (RP) specimens. PATIENTS AND METHODS: In all, 186 patients with TZ (46) and PZ cancers (140) underwent ultrasonography-guided systematic sextant biopsy and RP at the same institution. The clinical and pathological characteristics, and the anatomical location of positive biopsies, were determined and compared using t-tests and chi-square tests. Differences between Gleason scores of needle biopsies and those of RP specimens were evaluated and compared by Cohen kappa testing. RESULTS: TZ cancers had a significantly lower rate of positive biopsies in the middle (63% vs 80%) and base (50% vs 80%) of the prostate than had PZ cancers. Positive biopsies were exclusively obtained from the apex in 19.6% of TZ and 5% of PZ cancers (P = 0.002). There was exact agreement between Gleason scores of needle biopsies and those of RP specimens in 15.2% of TZ (kappa = 0.02) and 55% of PZ cancers (kappa = 0.25), respectively. CONCLUSION: Compared with PZ cancers, TZ cancers had a different anatomical pattern of positive biopsies, with lower rates in the middle and base of the prostate. The finding of positive biopsies exclusively in the apex favoured prostate cancer located in the TZ. Furthermore, the correlation between needle biopsy Gleason scores and those of the RP specimens was clearly lower in TZ cancers.     

Dynamic Contrast-Enhanced MRI for Preoperative Identification of Localised Prostate Cancer

ObjectivesTo assess the value of pelvic-phased array (PPA) dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting intraprostatic tumour location and volume for clinically localised prostate cancers.MethodsSuspicious areas on prospective prebiopsy MRI were located with respect to anatomic features, gland side, and transition zone (TZ) and peripheral zone (PZ) boundaries. These MRI findings were compared with histopathology findings for the radical prostatectomy specimens. Literature review of original studies correlating MRI and histologic results was performed.ResultsDCE-MRI with a PPA is superior to T2-weighted sequences for the detection and depiction of intraprostatic prostate cancer. In a series of 24 cases with 56 separate cancer foci, sensitivity, specificity, and positive and negative predictive values for cancer detection by MRI were, respectively, 77%, 91%, 86%, and 85% for foci >0.2 cc, and 90%, 88%, 77%, and 95% for foci >0.5 cc. Median focus volume was 1.37 cc (range: 0.338–6.32) for foci >0.2 cc detected by MRI in PZ, and 0.503 cc (range: 0.337–1.345) for those not detected by MRI (p < 0.05). The corresponding values for TZ foci were 2.54 (range: 0.75–16.87) and 0.435 (range: 0.26–0.58).ConclusionsPrebiopsy PPA DCE-MRI is an accurate technique for detecting and quantifying intracapsular TZ or PZ tumour foci >0.2 cc. It has several applications, such as screening for prostate cancer and excluding cancer in patients with a raised PSA level, targeting of biopsies, estimating cancer volume and prognosis, and, in the future, monitoring of disease both during active surveillance and after focal therapy.     

Zonal origin of localized prostate cancer does not affect the rate of biochemical recurrence after radical prostatectomy

OBJECTIVE: To investigate whether transition zone (TZ) prostate cancers demonstrate different rates of biochemical recurrence after radical prostatectomy compared to peripheral zone (PZ) cancers. METHODS: In 1262 consecutive patients treated with radical prostatectomy, computerized planimetry defined tumour origin as either TZ tumours (>70% TZ location) or PZ. Kaplan-Meier and multivariate Cox regression models tested the association between zonal origin and the rate of biochemical recurrence (prostate-specific antigen >0.1ng/ml and rising). We used the Harrell's concordance index to quantify the accuracy of various Cox regression models. RESULTS: TZ prostate cancers were diagnosed in 115 patients (9.1%). Biochemical recurrence was recorded in 16 TZ and in 201 PZ prostate cancers patients. In multivariate Cox models, the rate of biochemical recurrence was not significantly different between TZ and PZ prostate cancers (p=0.4). Combined multivariate predictive accuracy of biochemical recurrence predictions was 81.2% accurate when zonal origin was included versus 81.0% when zonal origin was omitted. CONCLUSIONS: The zonal origin of prostate cancers does not affect the rate of biochemical recurrence after radical prostatectomy.     

Significance of routine transition zone biopsies in Japanese men undergoing transrectal ultrasound-guided prostate biopsies

BACKGROUND: The objective of this study was to evaluate the clinical significance of additional routine transition zone (TZ) biopsies in Japanese men undergoing transrectal ultrasound (TRUS)-guided systematic 8-core peripheral zone (PZ) biopsies. METHODS: Between October 2002 and December 2004, a total of 788 consecutive patients underwent TRUS-guided systematic biopsy of the prostate for the fi rst time. As a rule, 10 cores were taken from each patient; that is, 8 cores from the PZ, including the standard sextant cores and 2 cores from the anterior lateral horns, and 2 additional cores from the bilateral TZ. The cancer detection rate was calculated according to several parameters. We also assessed the disease extent on radical prostatectomy specimens according to the cancer location within the biopsy specimens. RESULTS: Prostate cancer was detected by 10-core biopsies in 209 (26.5%) of the 788 patients, and 11 of these patients had positive cores only in the TZ; that is, the increase in cancer detection rate by sampling two additional cores from the TZ was 5.3%. Among 209 patients diagnosed as having prostate cancer, radical prostatectomy without any neoadjuvant therapy was performed in 59 patients with positive biopsy cores in the PZ, 7 in the TZ and 32 in both the PZ and TZ. Patients with positive cores in both zones showed significantly less favorable characteristics, indicating more advanced disease than that in those with positive cores in either zone. CONCLUSIONS: Routine TZ biopsy did not significantly increase the detection rate of prostate cancer; however, the anatomical location of positive biopsy cores could provide additional information concerning disease extension in patients undergoing radical prostatectomy.     

Biochemical recurrence following radical prostatectomy: a comparison between prostate cancers located in different anatomical zones

BACKGROUND: To assess whether differences of biochemical recurrence after radical prostatectomy exist between prostate cancers located in the transition zone (TZ) and peripheral zone (PZ). METHODS: The 5-year biochemical recurrence rate of 307 patients was evaluated. A serum prostate specific antigen (PSA) level > or =0.1 ng/ml was defined as biochemical failure. Cancers were characterized by the location of the largest tumor area as TZ or PZ cancers. Pure PZ cancers were matched to TZ cancers by comparable pathological tumor stage, Gleason score, and surgical margin status. RESULTS: In 63 (20.5%) patients the largest tumor area was located in the TZ. A Kaplan-Meier analysis of the matched pairs calculated an 80% actuarial cure rate of TZ cancers compared to 89% of pure PZ cancers (log-rank test P = 0.742). CONCLUSIONS: TZ and pure PZ cancers matched by comparable pathological tumor stage, Gleason score, and surgical margin status showed no statistical difference in regard to biochemical cure following radical prostatectomy.     

Prognostic significance of prostate cancer originating from the transition zone

PurposeTransition zone (TZ) cancers are reported to have better biochemical relapse-free survival (bRFS) after radical prostatectomy (RP) than cancers from the peripheral zone (PZ). To understand the influence of tumor location, we compared bRFS for TZ and PZ cancers stratified for risk using known clinical and pathological prognostic factors.Patients and MethodsThe surgical pathology and outcomes of 494 patients were reviewed. Cancers originating from the TZ and PZ were identified from step sectioning of surgical specimens and tumor mapping. Univariate and multivariate analyses of bRFS after RP were compared.ResultsTZ cancers were present in 89 (18%) patients. On univariate analysis, most factors predicted bRFS, although cancer location did not: 5-year bRFS was 85% for TZ vs. 77% for PZ (P = 0.12). However, on multivariate analysis, all factors except SV involvement were significant, including TZ cancer location (P = 0.04, HR = 1.88 [1.02–3.47]). Interestingly, TZ location was correlated with improved 5-year bRFS for cancers > 2 cc (81% for TZ vs. 65% for PZ, P = 0.017), for preop PSA >10 (80% for TZ vs. 59% for PZ, P = 0.027), and for PSAV > 2 (85% for TZ vs. 66% for PZ, P = 0.08). However, TZ cancers showed no difference in outcome for small volumes, low preop PSA, low PSAV, or high Gleason grade.ConclusionsTZ cancers that are large, with high preop PSA, low Gleason scores, and high PSAV show better outcomes than their PZ counterparts. However, high-grade cancer tumor location had no apparent influence on outcome. Tumor location could be considered in subsets for optimal prognostication.     

Transition zone cancers undermine the predictive accuracy of Partin table stage predictions

PURPOSE: The Partin tables represent the most widely used predictor of pathological stage in men with localized prostate cancer (PCa). The accuracy and performance of the tables have been tested across different populations. However, to our knowledge the potential limitations that may stem from differences between transition zone (TZ) and peripheral zone (PZ) prostate cancers has not been explored. We tested the predictive accuracy and performance of the Partin tables according to TZ vs PZ tumor predominance. MATERIALS AND METHODS: Preoperative serum prostate specific antigen, clinical stage and biopsy Gleason sum data on 1,990 patients treated with radical retropubic prostatectomy were used to define the 2001 Partin probabilities of organ confinement and seminal vesicle invasion (SVI). Data on 1,320 patients who underwent staging pelvic lymphadenectomy and radical retropubic prostatectomy were used to define the probabilities of lymph node invasion (LNI) and organ confined disease (OC). ROC area under the curve was used to assess the predictive accuracy of the 2001 Partin tables relative to observed extracapsular extension (ECE), SVI, LNI and OC. Performance characteristics for each prediction were explored graphically with local regression, nonparametric smoothing plots. Results were compared between 222 TZ cancers and 1,768 PZ cancers. RESULTS: The 1,990 radical retropubic prostatectomy specimens demonstrated ECE in 689 cases (34.6%) (TZ in 58 or 27.1% and PZ in 631 or 35.8%) and SVI in 224 (TZ in 13 or 6.1% and PZ in 211 or 11.9%). The 1,320 lymphadenectomy specimens demonstrated LNI in 56 cases (TZ in 2 or 0.9% and PZ in 54 or 4.6%). OC was found in 784 cases (59.4%) (TZ in 95 or 69.9% and PZ in 689 or 58.2%). Predictive accuracy was for ECE 76.4% (TZ 69.0% and PZ 77.2%), 78.0% for SVI (TZ 73.5% and PZ 78.3%), 78.6% for LNI (TZ 44.5% and PZ 79.9%) and 79.4% for OC (TZ 73.8% and PZ 80.0%). CONCLUSIONS: The biological tumor characteristics of TZ PCa differ from those of PZ PCa. These differences appear to undermine the accuracy of pathological stage predictions.     

Effects of age,sex steroids,and family relationships on volumes of prostate zones in men with and without prostate cancer

Benign prostatic hyperplasia (BPH) and prostate cancer commonly occur together. This suggests that common familial, hormonal, and environmental factors contribute to their development. In men at risk for the development of prostate cancer (at 40 men in 19 families) and aged-matched unrelated controls (n = 46), we have determined whether familial factors, age, and blood hormone concentrations are related to the transition zone (TZ), peripheral zone (PZ), or total volume of the prostate measured by transrectal ultrasound (TRUS). We determined that the influences of age, prostate cancer (n = 15), and familial status did not significantly affect the relationships reported. Therefore, data from all groups were combined for this study. TZ correlated positively with age (P = 0.003) after controlling for family status, but total prostate volume correlated insignificantly with age (P = 0.08). In addition, the ratio of TZ to PZ volumes also correlated significantly with age in the control group (r = 0.27, P = 0.014). Both TZ and PZ volumes correlated highly (r = 0.91, P < 0.0001, n = 86) with total volume. In addition, total volume correlated significantly (r = 0.71, P < 0.001) with the ratio of the TZ/PZ volumes, which also correlated significantly with each other (r = 0.61, P < 0.0001, n = 86). In contrast to the increase of TZ volume related to total prostate volume, PZ volume declined compared with total volume. Prostate volumes up to 50 ml are predominated by the PZ and above 50 ml by the TZ, which may compress and shrink the PZ. Both TZ and total prostate volume correlated positively with serum estrone concentrations (P = 0.04 and P = 0.003, respectively). These results suggest that the risk of prostate cancer does not contribute to generalized overgrowth of the prostate, including the TZ. However, estrogens and age strongly influence TZ but not PZ volume. Both PZ and TZ volumes rise together until the prostate exceeds 50 ml, when the growth of the TZ appears to exceed the PZ and then to compress it.     

Tumor formation of prostate cancer cells influenced by stromal cells from the transitional or peripheral zones of the normal prostate

This study was designed to investigate the different involvements of prostatic stromal cells from the normal transitional zone (TZ) or peripheral zone (PZ) in the carcinogenesis of prostate cancer (PCa) epithelial cells (PC-3) in vitro and in vivo co-culture models. Ultra-structures and gene expression profiles of primary cultures of human prostatic stromal cells from the normal TZ or PZ were analyzed by electron microscopy and microarray analysis. In vitro and in vivo co-culture models composed of normal TZ or PZ stromal cells and human PCa PC-3 cells were established. We assessed tumor growth and weight in the in vivo nude mice model. There are morphological and ultra-structural differences in stromal cells from TZ and PZ of the normal prostate. In all, 514 differentially expressed genes were selected by microarray analysis; 483 genes were more highly expressed in stromal cells from TZ and 31 were more highly expressed in those from PZ. Co-culture with PZ stromal cells and transforming growth factor-β1 (TGF-β1) increased the tumor growth of PC-3 cells in vitro and in vivo, as well as Bcl-2 expression. On the other hand, stromal cells of TZ suppressed PC-3 cell tumor growth in the mouse model. We conclude that ultra-structures and gene expression differ between the stromal cells from TZ or PZ of the normal prostate, and stroma–epithelium interactions from TZ or PZ might be responsible for the distinct zonal localization of prostate tumor formation.     

Improving prostate cancer detection with an extended-core transrectal ultrasonography-guided prostate biopsy protocol

OBJECTIVE: To investigate whether taking two transition zone (TZ) and four lateral peripheral zone (PZ) biopsies in addition to routine parasaggital sextant biopsies would improve detection rates in men with suspected prostate cancer. PATIENTS AND METHODS: The study included 493 consecutive men (mean age 68.7 years, sd 8.2) with elevated serum prostate-specific antigen (PSA) levels and/or abnormal findings on a digital rectal examination who underwent transrectal ultrasonography-guided prostate biopsy. In addition to sextant biopsies, six further biopsies were obtained, two from the TZ (mid-gland) and four from the lateral PZ (base and mid-gland). Pathological findings for the additional biopsies were compared with those of the sextant regions. RESULTS: Prostatic adenocarcinoma was diagnosed in 164 of the 493 (33%) men biopsied. Men with cancer were older, had smaller prostates and higher median PSA levels than men with negative biopsies. Sextant biopsies were positive for cancer in 133 of 164 (81%) men. All three sets of biopsies were positive in 53 (32%) cases. In 50 (30%) men both the sextant and lateral PZ biopsies were positive, while in six (4%) men, both sextant and TZ biopsies were positive. Thirty-one (19%) tumours were not detected by sextant biopsies, 10 (6%) where the lateral PZ biopsies alone were positive, 17 (10%) where the TZ biopsies alone were positive and four (3%) where both the TZ and lateral PZ together were positive. There were no differences in median PSA concentration, total prostate volume or TZ volume between men with an isolated TZ cancer and men with cancer elsewhere in the prostate. However, 77% of men with TZ cancer had a PSA of > 10 ng/mL, compared with 60% of men with cancer at other sites within the prostate (P = 0.015). CONCLUSION: An extended-core biopsy protocol significantly improves the detection rate for prostate cancer when compared with the standard sextant biopsy protocol alone. Routine TZ biopsies should be considered for men with serum PSA levels of >10 ng/mL.     

Clinicopathological study of prostate cancer patients who had a serum PSA level of more than 20 ng/ml and were treated by a radical prostatectomy

PURPOSE: In order to assess the validity of radical prostatectomy for the prostate cancer with PSA greater than 20 ng/ml, we reviewed the clinicopathological characteristics and prognoses of radical prostatectomy cases with PSA greater than 20 ng/ml. MATERIAL AND METHODS: Twenty-one radical prostatectomy cases who had a serum PSA level greater than 20 ng/ml were reviewed regarding their clinicopathological characteristics. Step-sectioned specimens were used for pathological evaluation. RESULT: The serum PSA level ranged from 21 to 65 ng/ml (median : 27 ng/ml). As for the clinical stage, there were 8 T1c cases, 5 T2b cases, 5 T2c cases, and 3 T3a cases (2001. TNM classification). According to the tumor location, 10 cases were diagnosed as peripheral zone (PZ) cancer, and 10 cases were diagnosed as transition zone (TZ) cancer. One case had several small cancer foci both in PZ area and TZ area. In 10 PZ cancer cases, 2 cases had lymph node metastasis, and 8 had seminal vesicle invasion. All of 10 PZ cancer cases showed extraprostatic extension, and 7 showed positive surgical margin. On the other hands in 10 TZ cancer cases, no cases had lymph node metastasis and seminal vesicle invasion. Five TZ cancer cases showed extraprostatic extension, and 6 showed positive surgical margin. The findings of digital rectal examination (DRE) and transrectal ultrasonography (TRUS) were positive in all PZ cancer cases, but these findings were unclear in TZ cancer cases. In addition, no significant difference were observed between the PZ cancer cases and the TZ cancer cases regarding age, PSA, prostate volume, PSA density, cancer volume, and Gleason scores. PSA failure was observed in 9 PZ cancer cases, and 2 TZ cancer cases. CONCLUSION: Based on our findings, the prognosis of TZ cancer cases was better than that of PZ cancer cases among the radical prostatectomy cases with PSA greater than 20 ng/ml. Radical prostatectomy might be one of the effective treatment option for TZ cancer even if the PSA shows greater than 20 ng/ml. It seems to be important to detect TZ cancer properly based on DRE and TRUS findings.     

Are Transition Zone Biopsies Still Necessary to Improve Prostate Cancer Detection?: Results from the Tyrol Screening Project

OBJECTIVES: The present retrospective study was designed to investigate the value of transition zone (TZ) biopsies for prostate cancer (PC) detection rate in a combined contrast enhanced color Doppler targeted (CECD) and gray-scale systematic biopsy (SB) approach. METHODS: PSA screening participants totalling 1475 with tPSA of >1.25 ng/ml (fPSA< or =18%) were assessed. Ten SB and additionally 5 or fewer CECD were performed. The impact of TZ biopsies on the PC detection rate and the biological significance of the detected TZ-cancers were analyzed. RESULTS: Out of 1475 biopsied patients, 395 (26.8%) were identified as PC patients; 5925 biopsy cores from these patients were analyzed. In 86 patients (21.8% of PC), we found 102 PC- positive cores in the TZ, and only in 9 of them solitary TZ-cancers without any other PC-location (2.3% of PC or 0.6% of all investigated patients). Pathologic findings after retropubic prostatectomy (RPE) revealed multifocal adenocarcinoma including involved peripheral zone (PZ) in eight of these nine patients, and solitary TZ-cancer in one patient. There was no positive correlation between prostate volume and TZ-detection rate and no patient with solitary TZ-PC after rebiopsy. CONCLUSION: Biopsy revealed 9 solitary TZ cancers (1.8%) and RPE revealed only one of them to be truly TZ-confined cancer (0.6%). Furthermore PC-detection did not improve, even in patients with rebiopsy, and there was no correlation between detection of TZ-cancers and prostate volume. A combined use of CECD and SB to investigate participants of a PSA-screening program suggests that TZ-biopsies do not improve PC detection rate and are therefore unnecessary.