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.     

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.     

Significance of lateral biopsy specimens during transrectal ultrasound-guided prostate biopsies in Japanese men

OBJECTIVES: Lateral biopsies are thought to have a better cancer detection rate compared with standard sextant biopsies. This study aimed to determine whether lateral peripheral zone biopsies in Japanese men who underwent transrectal ultrasound-guided prostate biopsies provided a significantly higher cancer detection rate than sextant biopsies. METHODS: Between 1999 and 2004, data were collected from 461 men who underwent prostate biopsy and had enough data regarding the performance of lateral biopsies for statistical analysis. There were two categories in this study: (i) patients who underwent sextant prostate biopsies; and (ii) patients who underwent sextant biopsies plus lateral biopsies. RESULTS: Prostate cancer was detected in 141 (30.6%) of 461 patients. It was detected in 24 (22.2%) of 108 patients who underwent sextant biopsies and 117 (33.1%) of 353 patients who underwent sextant plus lateral biopsies. Lateral biopsies were not associated with a statistically higher rate of positive biopsy findings; however, we found a significantly higher ratio of patients with positive findings in those with prostate specific antigen (PSA) levels 10 ng/mL (one of 71, 1.4%) among those who had positive cores only in lateral biopsy samples (P < 0.0001). CONCLUSIONS: Lateral biopsies did not show a significantly higher detection ratio of prostate cancer compared to sextant biopsies. However, lateral biopsies were more effective than sextant biopsies in patients with lower PSA levels. Our findings might be useful for the establishment of biopsy strategies to detect prostate cancer, especially in patients with lower PSA levels.     

Are extended biopsies really necessary to improve prostate cancer detection?

The aim of this study is to understand the value of specific sites in extended peripheral and transition zone biopsy schemes in order to define the optimal systematic biopsy regimen correlated with the percentage of positivity of each single bioptic site. A total of 165 consecutive patients underwent transrectal ultrasonography examination to detect prostate cancer followed by a lesion-directed and systematic 14-step biopsy scheme. The detection rate was examined for the lesion-directed and for each zone region biopsy. The frequency of positive biopsies in the various prostate regions was determined to evaluate the diagnostic yield of each biopsy site. Analysis was stratified for prostate-specific antigen (PSA), free-to-total PSA ratio, age, prostate size and digital rectal examination. The biopsy protocol detected 40% of patients (66/165) as positive and 55.1% (91/165) as negative for cancer. Standard sextant biopsy was expected to detect only 51 cancer on 66, lateral peripheral (PZ), transition (TZ) and central zone (CZ) biopsies only 56 cancer on 66, while the combination of sextant, PZ, TZ and CZ biopsies, for a total of 14 zone biopsies, detected 64 on 66 patients with cancer (97%) at recruitment. Sampling only the eight prostate regions with higher frequency of positive cancer biopsy was expected to detect 61 cancer patients against the 64 found with the 14-step scheme. This eight-biopsy regimen outperforms the conventional sextant regimen in cancer detection rate (93 vs 77%) and has an overall detection rate lower by only 3.1% (36.9 vs 40%) compared to the 14-biopsy regimen. This difference in detection rate is even smaller in patients with PSA values <10 ng/ml, age <70 y and prostate size <50 ml. This eight-biopsy scheme, including sampling in PZ and TZ toward the base, should be considered in an initial biopsy scheme to maintain a similar detection rate of an extensive biopsy scheme reducing the number of biopsies.     

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.     

Ultrasound-guided transrectal extended prostate biopsy： a prospective study

AIM: To evaluate the diagnostic value of the 10 systematic transrectal ultrasound-guided (TRUS) prostate biopsy compared with the sextant biopsy technique for patients with suspected prostate cancer. Methods: One hundred and fifty-two patients with suspected prostate cancer were included in the study. Patients were entered in the study because they presented with high levels of prostate specific antigen (PSA) (over 4 ng/mL) and/or had undergone an abnormal digital rectal examination (DRE). In addition to sextant prostate biopsy cores, four more biopsies were obtained from the lateral peripheral zone with additional cores from each suspicious area revealed by transrectal ultrasound. Sextant, lateral peripheral zone and suspicious area biopsy cores were submitted separately to the pathological department. Results: Cancer detection rates were 27.6% (42/152) and 19.7% (30/152) for the 10-core and sextant core biopsy protocols, respectively. Adding the lateral peripheral zone (PZ) to the sextant prostate biopsy showed a 28.6% (12/42) increase in the cancer detection rate in patients with positive prostate cancer (P < 0.01). The cancer detection rate in patients who presented with elevated PSA was 29.3% (34/116). When serum PSA was 4-10 ng/mL TRUS-guided biopsy detected cancer in 20.6%, while the detection rate was 32.4% and 47.0% when serum PSA was 10-20 ng/mL and above 20 ng/mL, respectively. Conclusion: The 10 systematic TRUS-guided prostate biopsy improves the detection rate of prostate cancer by 28.6% when compared with the sextant biopsy technique alone, without increase in the morbidity. We therefore recommend the 10-core biopsy protocol to be the preferred method for early detection of 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.     

Impact of additional sampling in the TRUS-guided biopsy for the diagnosis of prostate cancer

AIM: To evaluate the diagnostic value of 10+ systematic sampling technique when performing transrectal ultrasound-guided (TRUS) prostate biopsy, compared with the sextant biopsy technique for patients with suspected prostate cancer. METHODS: 286 patients with suspected prostate cancer were included in the study. Patients were eligible for the study if they had serum levels of prostate-specific antigen (PSA) >4 ng/ml or ratio PSA <0.25 and/or an abnormal digital rectal examination (DRE). The population sample was divided in three groups: (1) those with positive PSA, PSA ratio and DRE (70 patients); (2) those with positive PSA and PSA ratio but normal DRE (178 patients), and (3) those with positive PSA and PSA ratio, positive PSA velocity and a negative biopsy in the previous 6-month period (38 patients). In addition to the conventional sextant prostate biopsy cores, four more biopsies were obtained from the lateral peripheral zone (10 core biopsy protocol). Additional cores (total of 12-14) were also randomly selected in case of larger prostates (>60 ml) or from suspicious foci revealed by transrectal ultrasound. All additional biopsy cores were submitted separately to the pathological department. RESULTS: Cancer was detected in 55.7% (39/70) and 69% (48/70) of the patients (for sextant core and for the extended biopsy protocols, respectively) in the first study group, 11% (20/178) and 23% (41/178) of the patients (for the sextant and the extended biopsy protocols, respectively) in the second study group, and 42% (16/38) and 63% (24/38) of the patients (for the sextant and the extended biopsy protocols, respectively) in the third study group. The addition of the lateral peripheral zone (PZ) of the prostate to the sextant biopsy showed a 23, 105 and 50% increase in the number of cancers diagnosed in the first, second and third study groups, respectively. The improvement of cancer detection rate (sensitivity) was statistically significant for all groups evaluated. CONCLUSION: The 10+ systematic TRUS-guided prostate biopsy improves the detection rate of prostate cancer compared to the sextant biopsy technique alone, especially when performed in men with positive PSA, PSA ratio, and negative DRE.     

Extended 21-sample needle biopsy protocol for diagnosis of prostate cancer in 1000 consecutive patients

OBJECTIVE: To prospectively evaluate the diagnostic yield of a 21-sample ultrasound-guided needle biopsy protocol as the initial diagnostic strategy for detection of prostate cancer. MATERIALS AND METHODS: Between December 2001 and October 2005, 1000 consecutive patients underwent 21-sample needle biopsies under local anesthesia, comprising sextant biopsies, 3 additional posterolateral biopsies in each peripheral zone, 3 biopsies in each transition zone (TZ), and 3 biopsies in the midline peripheral zone. Each prostate core was numbered and analyzed separately. The patients were divided into subgroups according to the result of digital rectal examination (DRE), serum prostate-specific antigen (PSA), and prostate volume. We evaluated the cancer detection rate overall and in each subgroup. We compared the results of our biopsy protocol to those from 6-, 12-, and 18-core biopsy protocols by analyzing only those cores from our protocol that would correspond to these biopsy schemes. RESULTS: Cancer detection rates using 6 biopsy samples (sextant biopsies only), 12 samples (sextant plus lateral biopsies), 18 samples (sextant, lateral, and TZ biopsies), and 21 samples (sextant, lateral, TZ, plus midline biopsies) were 31.7%, 38.7%, 41.5%, and 42.5%, respectively. The 12-sample procedure improved the cancer detection rate by 22% compared with the 6-sample procedure (p=0.0001). The improvement in the diagnostic yield was most marked in patients with a prostate volume > or =55 ml (36.9%), in patients with normal DRE (26.6%), and in patients with PSA<4 (37.5%). The addition of TZ biopsies to a 12-biopsy scheme increased the diagnostic yield by 7.2% overall (p=0.023). Only 10 of 425 (2.3%) patients were diagnosed on the sole basis of midline biopsies. CONCLUSIONS: Patients with suspected localized prostate cancer should be offered at least 12 biopsies in the peripheral zone and far lateral peripheral zone (statistically significant). TZ biopsies have to be considered, because these biopsies improve the diagnostic yield. For patients with abnormal DRE and/or PSA> or =20 ng/ml, the 6-biopsy scheme seems sufficient (statistically), but 6 far lateral peripheral zone biopsies as well as the TZ biopsies add little incremental value (not significant). Evidence does not support the use of routine midline peripheral zone needle biopsies in the initial biopsy to enhance the detection of prostate cancer.     

Transition zone biopsy and prediction of extraprostatic extension at radical prostatectomy

BACKGROUND: There is limited data in the literature that suggests that transition zone (TZ) biopsy might be useful for the prediction of extraprostatic extension (EPE) in clinically localized prostate cancer. We studied the role of TZ biopsy in the prediction of EPE. METHODS: Transition zone biopsies were performed in addition to systematic peripheral zone (PZ) biopsies between November 1995 and December 1999. During this period, 59 patients underwent radical prostatectomy for clinically localized disease. Final pathological results were compared with preoperative clinical and biopsy findings. RESULTS: Of the 59 patients who underwent radical prostatectomy, 46 had cancer only in the PZ cores and 13 had cancer both in the PZ and the TZ cores at the biopsy. Final histopathological results revealed EPE in 19 (32%) patients and positive surgical margins in 22 (37%). In univariate analysis of age, prostate-specific antigen (PSA), mean percentage of positive PZ cores, mean biopsy Gleason score and positive TZ biopsy, there was a significant difference for serum PSA levels (P = 0.021), presence of positive TZ cores (P = 0.018) and percentage of positive PZ cores in patients with and without EPE (P < 0.001). In multivariate analysis, the single independent predictor of EPE was the percentage of positive PZ biopsy cores (P = 0.0227). There was agreement between the side of positive TZ biopsy and EPE in seven of eight patients. CONCLUSION: Taking two TZ cores in addition to peripheral sextant biopsy did not result in better prediction of EPE. The relationship between TZ involvement and the presence of EPE can be investigated further in radical prostatectomy specimens.     

Critical evaluation of the current indications for transition zone biopsies

Objectives. Two primary indications for the performance of anteriorly directed transition zone (TZ) biopsies are (a) an elevated prostate-specific antigen (PSA) level and an enlarged, non-nodular prostate and (b) prior negative sextant biopsies of the prostate. These indications are, however, based on a study population evaluated early in the PSA era (1989 to 1992). The current analysis targeted a more contemporary series of patients (1995 to 2000) presenting with these two indications for TZ biopsies, who underwent ultrasound scanning and biopsies by the same examiner and with the same equipment as in the earlier series.Methods. We evaluated 390 men, 274 (70.3%) of whom underwent sextant plus TZ biopsies for elevated PSA levels and an enlarged, non-nodular prostate; 116 (28.7%) underwent this biopsy strategy because of an elevated or rising PSA in whom prior sextant biopsies had not revealed cancer.Results. Of the 274 patients who underwent initial sextant biopsies plus anterior biopsies for an enlarged, non-nodular prostate, 49 (17.9%) were found to have adenocarcinoma and in only 4 (1.5%) did only the TZ biopsies reveal cancer. Of the 116 patients who underwent TZ biopsies after prior negative sextant biopsies, 36 (31.0%) were found to have prostate cancer and in 11 (9.5%) only the TZ biopsies demonstrated cancer.Conclusions. The cancer detection rate for sextant plus TZ biopsies in this contemporary series of patients presenting with enlarged, non-nodular prostates was substantially lower than the rate in earlier reports (1.5% compared with 36.9%), despite the consistency in the equipment and examining physician. This may have been due to the stage migration of prostate cancer, which has been observed as a result of the widespread use of PSA measurement for early detection. Sextant plus TZ biopsies are more productive in patients with prior negative biopsies who have a persistent clinical suspicion for prostate cancer on the basis of an elevated and/or rising PSA level.     

Transition zone biopsy in the detection of prostate cancer

OBJECTIVE: About 25% of all prostate cancers occur in the transition zone (TZ). We analyzed the impact of 4 systematic TZ and 2 systematic apex (AP) biopsies in addition to systematic sextant biopsies in an effort to establish the diagnostic importance of early prostate cancer. METHODS: One hundred and thirty patients underwent systematic transperineal multipoint prostate biopsy (biopsy of 12 sites, including 4 TZ and 2 AP biopsies). RESULTS: Forty-one of 130 men (31.5%) had biopsy specimens positive for cancer, and cancer originated in the TZ alone in 4 of these 41 patients (9.8%). Fourteen patients underwent radical retropubic prostatectomy. We compare the pathological findings of radical prostatectomy specimens and biopsy results. Prostate cancers predicted to be stage T(2c) by TZ biopsy were all classified as pT(2c) or greater. CONCLUSIONS: Routine TZ biopsy does not substantially increase the prostate cancer detection rate; however, it can be useful in patients who require repeat biopsy.     

An extended 10-core transrectal ultrasonography guided prostate biopsy protocol improves the detection of prostate cancer

OBJECTIVE: To evaluate the efficacy of TRUS guided 10-core biopsy strategy for Turkish patients who had biopsy of the prostate for the first time. METHODS: Between February 2001 and May 2003, 303 consecutive men with suspected prostate cancer were included in the study. Indications for TRUS guided prostate biopsy were: abnormal digital rectal examination and/or a serum PSA over 2.5 ng/ml. All of the patients underwent a 10-core biopsy protocol with additional core from the each suspicious area detected by TRUS. Besides the sextant technique, 4 more biopsies were obtained from the lateral peripheral zone. We aimed to analyze whether cancer detection improved with the extended versus the standard sextant biopsy in our series overall and in each subgroup. RESULTS: Of 303 patients 94 (31%) were positive for prostate cancer. Median age and PSA of prostate cancer patients were significantly higher than of the non-cancer patients. Besides prostate volumes of the cancer patients were significantly lower than of the non-cancer ones. The cancer detection rates were 31% (94/303) and 23.1% (70/303) for the 10-core biopsy strategy and sextant biopsy strategies, respectively. Thus the 10-core biopsy technique increased cancer detection rate by 25.5% (24/94) for the whole group of patients. A statistically significant number of additional cancers were detected with 10-core biopsy strategy for all the subgroups of the patients. Furthermore 10-core biopsy protocol detected more cancers (at least 6.4%) than all the probable different combinations of 8-core biopsy protocols. Among the 94 cancer patients, biopsy from a suspicious area revealed cancer in 31.9% of them; however, in all of these patients cancer was already present in the 10-core biopsy. On the other hand, lesion biopsies revealed 5.7% additional cancers if sextant technique was used. There were only 3 (0.9%) serious complications requiring hospitalization and all 3 were infections controlled by appropriate antibiotics. CONCLUSION: Adding 4 lateral peripheral biopsies to the conventional sextant biopsy (10-core biopsy strategy) technique has increased the cancer detection rate by 25.5% without significant morbidity and without increasing the number of insignificant cancers. 10-core biopsy protocol was superior to all probable 8-core biopsy protocols in our study group. Additional biopsies from suspicious areas detected by transrectal ultrasonography revealed no further benefit if 10-core technique was used. We therefore suggest that 10-core biopsy protocol should be the preferred strategy in early detection of prostate cancer.     

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.     

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.     

The utility of apical anterior horn biopsies in prostate cancer detection

We sought to determine the utility of adding apical anterior horn biopsies to systematic prostate sampling regimens in detecting cancer in men with measured prostate volume < or =50 cc. We reviewed the biopsy data of consecutive men referred for an abnormal digital rectal exam or PSA elevation > or =4.0 ng/mL. All of these patients underwent lesion directed biopsy as well as a systematic 12-core biopsy regimen consisting of the standard sextant, bilateral lateral mid- and lateral base-sites, and bilateral apical anterior horn sites. Overall cancer detection and unique cancer detection rates were calculated for each of the 12 sites, stratified by race, age, PSA, and findings on digital rectal exam. In addition, cancer detection rates of various biopsy schemes were calculated and compared. There were 255 men undergoing biopsy who had calculated prostate volume < or =50 cc, and the prostate cancer detection rate was 47%. The overall cancer detection rate of apical anterior horn biopsies ranged between 29% and 56%. The utility of these biopsies was greatest in men with normal rectal exam and PSA <10 ng/mL, with unique cancer detection rates of 6% and 4%, respectively. Including the apical anterior horn biopsies in an 8-biopsy scheme (anterior, apex, lateral mid, lateral base) yielded cancer detection rates greater than 91% in all subgroups that were not statistically different from extended 10- and 12-core biopsy regimens. Apical anterior horn prostate biopsies target cancers that are potentially in the anterior region of the prostate, a region under-sampled using traditional schemes. The use of these biopsies as part of an 8-core biopsy pattern provides high cancer detection in all groups of patients and may represent a new standard.     

Extensive repeat transrectal ultrasound guided prostate biopsy in patients with previous benign sextant biopsies

PURPOSE: Standard sextant prostate biopsy may underestimate cancer in men in whom clinical findings are suspicious for localized prostate cancer. We describe our experience with extensive transrectal ultrasound guided prostate biopsy in men in whom previous sextant biopsy was negative. MATERIALS AND METHODS: Between November 1997 and March 1999, 57 men 47 to 72 years old (mean age 61.4) underwent extensive transrectal ultrasound guided biopsy of the prostate using intravenous sedation at our institution. An average of 22.5 cores (range 15 to 31) were obtained depending on prostate size. Biopsies were obtained from each of 6 sagittal regions, including samples from the far lateral and mid transitional zones. Each patient had undergone at least 1 previous benign transrectal ultrasound guided sextant biopsy (mean 2.1, range 1 to 4). Indications for repeat biopsy were persistently elevated prostate specific antigen (PSA) in 89% of the cases, increased PSA velocity in 63%, suspicious free-to-total PSA in 39% and a previous suspicious biopsy finding in 32%. Clinical factors (PSA, PSA velocity, free-to-total PSA and previous suspicious biopsy) were analyzed for the ability to predict positive biopsy, and tumor parameters were assessed pathologically in patients undergoing radical prostatectomy. RESULTS: Adenocarcinoma was identified in 17 of the 57 men (30%). Biopsy revealed a Gleason score of 6 to 8 (mean 6.4). In 7 of the 17 patients (41%) in whom cancer was identified only 1 biopsy core was positive. Of the 15 patients in whom previous sextant biopsy had demonstrated high grade prostatic intraepithelial neoplasia or atypical small acinar proliferation extensive biopsy revealed cancer in 7 (47%). Although serum PSA was higher and free-to-total PSA was lower in those with cancer, the only statistically significant predictor of positive biopsy was PSA velocity (p <0.001). Prostate cancer was noted in 64% of the men with PSA velocity 1 ng./ml. or greater. Of the 13 patients undergoing radical prostatectomy pathologically significant disease was identified in all but 1 (92%). Complications of extensive biopsy included urinary retention in 6 patients and limited rectal bleeding in 1. CONCLUSIONS: Extensive prostate biopsy identifies significant prostate cancer in many men in whom previous sextant biopsy was benign. This procedure should be considered when findings are suspicious for adenocarcinoma despite previously negative sextant biopsy.     

Prostate specific antigen adjusted for transition zone epithelial volume: the powerful predictor for the detection of prostate cancer on repeat biopsy

PURPOSE: The indications for repeat prostate biopsy for persistently increased prostate specific antigen (PSA) in men with prostate cancer never detected on previous biopsy are not clear. In this study we determined that PSA adjusted for transition zone (TZ) epithelial volume is the most powerful predictor for detecting prostate cancer on repeat biopsy. MATERIALS AND METHODS: Repeat prostate biopsies including additional TZ cores were performed in 75 men with PSA between 4.0 and 10.0 ng/ml. TZ epithelial volume was calculated by multiplying TZ volume by the percent of epithelium, which was measured by morphometric analysis using image analysis computer software. RESULTS: Prostate cancer was detected on repeat biopsy in 19 of the 75 patients. Patients with prostate cancer had a significant smaller percent area of epithelium or glandular lumen than those without cancer. In patients without prostate cancer TZ epithelial volume significantly correlated with total PSA. According to ROC analysis PSA adjusted for TZ epithelial volume had the greatest AUC for cancer detection (0.879). This parameter was able to avoid more than 90% of unnecessary repeat biopsies with 90% sensitivity. Multiple logistic regression analysis showed that PSA complex adjusted for TZ epithelial volume was the significant independent predictor of cancer. CONCLUSIONS: PSA adjusted for TZ epithelial volume is the most powerful predictor of cancer in men who have undergone previous negative prostate biopsies and in whom PSA remains between 4.0 and 10.0 ng/ml.     

Predictive value of prostate specific antigen density in the detection of prostate cancer in patients with elevated prostate specific antigen levels and normal digital rectal findings or stage A prostate cancer

We compared the usefulness of PSA and PSA density (PSAD) in diagnosing prostate cancer in 102 men who had a PSA value higher than 4.0 ng/ml and normal digital rectal examination and who had undergone transrectal ultrasonography-guided systematic sextant biopsies of the prostate between August 1996 and October 1999. In addition, for a group of 53 patients who underwent retropubic simple prostatectomy, PSA, PSAD and PSA transition zone (PSA-TZ) examination results for those with stage A prostate cancer were compared with the results for those with benign prostatic hyperplasia (BPH). Of the former 102 men, 20 (19.6%) had prostate cancer. There was no significant difference in mean PSA level between patients with negative and those with positive biopsy results (mean 9.3 and 11.8, respectively, p = 0.295), but the mean PSAD of patients with positive biopsy results was significantly higher than that of those with negative results (mean 0.55 and 0.29, respectively, p = 0.0007). Of the 53 men who underwent retropubic simple prostatectomy, 10 (18.9%) were diagnosed with stage A prostate cancer. There was no significant difference in mean PSA, PSAD and PSA-TZ examination results between patients with BPH and those with stage A prostate cancer. For all 102 patients and for 71 patients with PSA levels of 4.1-10.0 ng/ml, a PSAD cutoff value of 0.1 reduced the number of biopsies 15.7% (16 of 102 cases), and 22.5% (16 of 71 cases), respectively. These results suggest that by measurement of PSAD some patients with benign disease could be spared a biopsy which would have been performed based on PSA results alone.     

Is extended 11-core biopsy valuable in benign prostatic hyperplasia patients with intermediate serum prostate-specific antigen (4.1-10 ng/ml) and prior negative sextant biopsy?

OBJECTIVE: To evaluate the importance of extended 11-core biopsy in benign prostatic hyperplasia (BPH) patients with intermediate prostate-specific antigen (PSA; 4.1-10 ng/ml) and prior negative sextant biopsy. MATERIAL AND METHODS: A total of 381 BPH patients with intermediate PSA (4.1-10 ng/ml) and prior negative sextant biopsy underwent extended 11-core biopsy, which included conventional sextant biopsy in addition to five cores from three alternative sites. Two cores were taken from the right and left anterior horns of the peripheral zone (PZ), two from the right and left anterior transition zones (TZs) and one from the midline of the PZ. Overall, 315 patients were subjected to transurethral resection of the prostate (n = 272) or open prostatectomy (n = 43). RESULTS: Repeat 11-core biopsy revealed prostate cancer in 66/381 cases (17.3%). The distribution of positive cores on repeat 11-core biopsy was as follows: sextant biopsy sites only in 50% of cases (33/66); alternative sites only in 31.8% (21/66); and sextant plus alternative biopsy sites in 18.2% (12/66). The anterior horn of the PZ was the most frequently positive alternative site (25/33; 75.8%), followed by the TZ (5/33; 15.2%), while the midline site was involved in 9% of cases (3/33). Eleven-core biopsy had a significantly better cancer detection rate compared to sextant biopsy when digital rectal examination was normal (p = 0.009), prostate volume was in the range 30-50 cm (p = 0.033) and PSA density was > or =0.15 (p = 0.024). Six cancer cases out of 315 (1.9%) were diagnosed as a result of the definitive pathology. The sensitivity of 11-core biopsy was 91.6%, compared to 62.5% for sextant biopsy (p < 0.001). CONCLUSION: An extended 11-core biopsy protocol is valuable in BPH patients with intermediate PSA (4.1-10 ng/ml) and prior negative sextant biopsy as it significantly improved the overall detection rate in our study by 32% (p = 0.019).