Transition Zone Biopsies Research Articles

Transition zone biopsy and prediction of extraprostatic extension at radical prostatectomy.

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. 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. 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. 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.

Evaluation of transition zone and lateral sextant biopsies for prostate cancer detection after initial sextant biopsy

Objectives To assess the value of transition zone and lateral sextant biopsies for the detection of prostate cancer after a previous sextant biopsy was negative. Methods A total of 74 prostates after radical prostatectomy were used to perform biopsies ex vivo. First, a sextant biopsy was taken, then two different rebiopsy techniques were performed. Rebiopsy technique A consisted of a laterally placed sextant biopsy and two cores per side of the transition zones only. Rebiopsy technique B included a standard sextant biopsy and two cores per side from the lateral areas of the prostate. The biopsies were taken using ultrasound guidance to sample the areas of interest precisely. Results The initial sextant biopsy found 39 prostate cancers. Rebiopsy technique A found 12 cancers (34%). In this group, a laterally placed sextant biopsy found 12 cancers; transition zone biopsies revealed cancer in 5 cases, but no additional tumor was found. Rebiopsy technique B detected 23 prostate cancers (66%). Fourteen tumors were found after a second standard sextant biopsy, and nine additional tumors were found in the lateral areas. Conclusions Sextant biopsy has a low sensitivity of only 53%. A biopsy including the transition zones is not the ideal technique for detecting the remaining tumors. Therefore, transition zone biopsies should be reserved for patients with multiple previous negative biopsies of the peripheral zone. A subsequent sextant biopsy with additional cores from the lateral areas of the prostate is favorable if rebiopsy is necessary after a negative sextant biopsy.

Can total and transition zone volume of the prostate determine whether to perform a repeat biopsy?

Objectives To compare the ability of total prostate (TP) and transition zone (TZ) volume to predict the outcome of a repeat prostate biopsy in patients with serum prostate-specific antigen (PSA) levels of 4 to 10 ng/mL. Methods A total of 1137 patients were included and underwent transrectal ultrasound-guided needle sextant and two transition zone biopsies of the prostate. All patients with a prior negative biopsy (benign prostatic tissue) underwent a repeat biopsy after 6 weeks. The TP and TZ volumes of the prostate were measured by transrectal ultrasonography. Results Of the 1137 patients, prostate cancer was diagnosed in 364 (32%), in 276 (24.2%) after the first biopsy and in 88 (7.7%) after the repeated biopsy. The TP and TZ volumes were larger in the patients with prostate cancer detected on the repeated biopsy ( P <0.0001). Using a cutoff for TP volume of less than 20 cm 3 and greater than 80 cm 3 and for TZ volume of less than 9 cm 3 and greater than 41 cm 3 would have spared 7.1% and 10% of repeated biopsies, respectively. Conclusions The probability for a positive repeat prostate biopsy increases in a logarithmic function for larger prostates, as well as for larger TP and, especially, for larger TZ volumes. The probability of finding prostate cancer on a repeat biopsy in prostates with small (less than 20 cm 3) and large (greater than 79 cm 3) TP, as well as in small (less than 9.3 cm 3) and large (greater than 41 cm 3) TZ volumes, was very low. Therefore, a repeat prostate biopsy within 6 weeks is unnecessary. These patients should be followed up by serial PSA determination.

Dysplasia of the anal transitional zone after ileal pouch-anal anastomosis: results of prospective evaluation after a minimum of ten years.

Stapling of the ileal pouch-anal anastomosis with preservation of the anal transitional zone remains controversial because of concerns about the potential risk of dysplasia and cancer. The natural history and optimal treatment of anal transitional zone dysplasia ten or more years after surgery are unknown. This study establishes the risk of dysplasia in the anal transitional zone and the outcome of a conservative management policy for anal transitional zone dysplasia, with a minimum of ten years' follow-up after ileal pouch-anal anastomosis. A total of 289 patients undergoing anal transitional zone-sparing stapled ileal pouch-anal anastomosis for inflammatory bowel disease between 1986 and 1990 were studied. Patients undergoing anal transitional zone-sparing ileal pouch-anal anastomosis who were studied with serial anal transitional zone biopsies for at least ten years postoperatively were included (n = 178). Median follow-up was 130 (range, 120-157) months. Anal transitional zone dysplasia developed in 8 patients 4 to 123 (median, 9) months after surgery. There was no association with gender, age, preoperative disease duration, or extent of colitis, but the risk of anal transitional zone dysplasia was significantly associated with cancer or dysplasia as a preoperative diagnosis or in the proctocolectomy specimen. Dysplasia was high grade in two patients and low grade in six. Two patients with low-grade dysplasia on two or more occasions after detection of low-grade dysplasia underwent completion mucosectomy and perineal pouch advancement with neo-ileal pouch-anal anastomosis. One patient with high-grade dysplasia on two occasions was to undergo completion mucosectomy, but this was not technically feasible. Partial mucosectomy with vigorous anal transitional zone biopsy was performed with close postoperative surveillance. Biopsies were negative for dysplasia. The second recently diagnosed patient with high-grade dysplasia underwent examination under anesthesia with negative anal transitional zone biopsies and will be kept under close surveillance. No cancer in the anal transitional zone was found during the study period. The 4 other patients with low-grade dysplasia on 1 or 2 occasions were treated expectantly and have been dysplasia free for a median of 119 (range, 103-133) months. Anal transitional zone dysplasia after stapled ileal pouch-anal anastomosis is infrequent and is usually self-limiting. Anal transitional zone preservation did not lead to the development of cancer in the anal transitional zone with a minimum of ten years of follow-up. Long-term surveillance is recommended to monitor dysplasia. If repeat biopsy confirms persistent dysplasia, mucosectomy with perineal pouch advancement and neo-ileal pouch-anal anastomosis is recommended.

Complexed prostate-specific antigen, complexed prostate-specific antigen density of total and transition zone, complexed/total prostate-specific antigen ratio, free-to-total prostate-specific antigen ratio, density of total and transition zone prostate-specific antigen: results of the prospective multicenter European trial

This prospective, multicenter European Prostate Cancer Detection study evaluated the value and performance of the molecular forms of prostate-specific antigen (PSA) and their derivatives in combination with prostate gland and transition zone volumes in early detection of prostate cancer in patients with PSA levels between 4 and 10 ng/mL. Of 750 men enrolled at 7 different European urology centers into the study between November 2001 and March 2002, 340 (45.3%) had a total PSA (tPSA) between 4 and 10 ng/mL (age range, 46 to 87 years). In all patients, the ratio of complexed PSA (cPSA) to tPSA (c/tPSA), cPSA density (cPSAD), cPSAD of the transition zone, PSA, free PSA (fPSA), ratio of fPSA to tPSA (f/tPSA), tPSA density (PSAD), and PSAD of the transition zone were measured and collected 5 to 10 minutes before the sextant biopsy with 2 additional transition zone cores. Measurements of tPSA and fPSA were done with the AxSYM test, whereas cPSA was measured with the ACS 180 cPSA assay. All patients had a transrectal ultrasound-guided sextant prostate biopsy, and 2 additional transition zone biopsies and total and transition zone volumes were measured at the time of biopsy. Histopathologic findings revealed benign histology in 237 patients and prostate cancer in 103 patients (69.7% and 30.3%, respectively). Statistically significant differences included larger total volumes, larger transition zone volumes, and f/tPSA in patients with benign disease ( P = 0.0009, P <0.0001, P <0.0001, respectively). At 90% and 95% sensitivity, specificity of cPSA was significantly greater than that for PSA ( P <0.0001). At sensitivity levels of 90% and 95%, the specificity of the cPSA assay using cutoff values of 3.06 and 2.52 ng/mL was 20.3% and 9.1%, respectively. A cPSA cutoff value of 6.95 ng/mL and 7.57 ng/mL afforded 90% and 95% specificity for detecting prostate cancer. The area under the curve (AUC) in the receiver operating characteristics curve of cPSA was statistically significantly higher compared with tPSA (60.8 vs 56.9, P = 0.032). AUC for volume-related parameters PSAD, cPSAD, PSAD of the transition zone, and cPSAD of the transition zone were 62.8%, 63.1%, 63.0%, and 63.6%, respectively. cPSA performs better than tPSA in the differentiation between benign disease and prostate cancer and provides similar information to the f/tPSA ratio. In addition, cPSA and cPSA volume-related parameters (cPSAD, cPSAD of the transition zone) further improved the specificity of PSA in early detection of prostate cancer.

Importance of Transition Zone Biopsies in Patients Undergoing Ultrasound-Guided Prostate Systemic Biopsies for the First Time

Introduction: We analyze the efficacy of routine transition zone biopsies in patients undergoing ultrasound-guided systemic prostate biopsies for the first time because of a suspicious digital rectal examination or an elevated serum prostate-specific antigen (PSA) level. Patients and Methods: During systemic prostate biopsy two or four additional transition zone biopsies were performed in 192 consecutive patients: in 182 because of a serum PSA concentration >4.1 ng/ml and in 10 because of a suspicious digital rectal examination and a serum PSA level <4.0 ng/ml. Results: The overall prostate cancer detection rate was 37.5% (72/192). In 24 patients (33.3%), cancer was only detected in the peripheral zone, in 3 (4.2%) only in the transition zone, and in 45 (62.5%) in both zones. Conclusion: Transition zone biopsies performed at the first time of systemic prostate biopsy seem to have a low efficacy.

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

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. 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. 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. 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.

Biopsies of the Transitional Zone of the Prostate

Purpose: In this prospective study we try to evaluate the necessity of performing additional transitional zone biopsies as part of the standard sextant biopsies procedure in order to detect prostate cancer. Materials and Methods: During a 12-month period we performed biopsies in 420 patients. All patients had two additional biopsies of the transitional zone biopsies. 289 of them were biopsies for the first time because they had an elevated PSA and/or a suspicious DRE. One hundred and thirty-one had a repeat biopsy because of the remaining elevated PSA after the previous negative one. Results: Of the 420 patients 143 (34%) had cancer, with 11 (7%) having cancer in the transitional zone only. Patients initially evaluated because of high PSA and or a positive DRE had only 2 (2.1%) cancers exclusively in the transitional zone. We found that this percentage rises (18.7%) when the patients had already at least one previous negative biopsy of the peripheral zone, and during the repeat biopsy the transitional zone is samples. Conclusions: The low yield of transitional zone biopsies (2.1%) during first time sampling of the prostate does not warrant their systematic use for the early detection of prostate cancer. Instead the effectiveness of biopsies in that area is higher when the biopsy is repeated after an initial previous negative biopsy of the peripheral zone.

PAIN AND MORBIDITY OF AN EXTENSIVE PROSTATE 10-BIOPSY PROTOCOL: A PROSPECTIVE STUDY IN 289 PATIENTS

Some studies imply that increasing the number of prostate biopsy cores may improve the cancer detection rate. We performed a prospective study to evaluate pain and morbidity after an extensive transrectal ultrasound guided 10-core biopsy protocol. A total of 289 consecutive men with abnormal digital rectal examination findings and/or increased prostate specific antigen underwent extensive prostate biopsy involving 6 sextant and 4 peripheral biopsies. Each received an information leaflet a few days before the procedure. A single dose of fluoroquinolone and a rectal enema were administered before biopsy. In no case was the procedure performed using anesthesia. Immediately after biopsy patients were asked to complete a self-administered nonvalidated questionnaire evaluating the degree of pain and/or discomfort using a visual analog scale. In another questionnaire they listed the side effects noticed during month 1 after biopsy. Although 48% of the 275 men who completed the initial questionnaire reported anxiety before the procedure, 78.8% of them were completely reassured by the information brochure. Of the 275 patients 47.6% described the procedure as painful, including only slightly painful (analog visual scale 3 or less) in 67.9%, while 33.8% described it as uncomfortable but not painful and 18.6% thought that it was neither painful nor uncomfortable. Of the 115 patients who engaged in sexual intercourse during month 1 after the procedure 78.3% noticed hematospermia an average of 10.9 days in duration. Of the 164 men who completed questionnaire 2, 74.4% noticed hematuria an average of 2.7 days in duration, 3.7% noticed pyrexia and 1.2% noticed acute prostatitis. In the 59 patients (36%) who reported delayed perineal pain it was slight in 64.4%, moderate in 30.5% and severe in 5.1%. No patient required hospitalization. Although minor complications are common, the extensive 10-core prostate biopsy protocol is associated with few major complications. The occurrence and intensity of pain and discomfort are in the range reported after the standard 6-core biopsy protocol.

Morbidity of transrectal ultrasound-guided prostate needle biopsy in patients receiving immunosuppression

Objectives. To prospectively evaluate the safety and early and delayed morbidity of transrectal ultrasound-guided needle biopsies in patients receiving immunosuppressive therapy. Methods. A total of 59 men receiving immunosuppressive agents after kidney transplantation, with a total prostate-specific antigen level between 4 and 10 ng/mL, were prospectively studied. All patients underwent transrectal ultrasound (TRUS)-guided sextant biopsy plus two additional transition zone biopsies. Biopsy samples were also obtained from suspicious areas identified during TRUS and digital rectal examination. The immediate and delayed morbidity, patient satisfaction, and complication rates were recorded and compared with the morbidity data recorded in the same period from 1051 men in the European Prostate Cancer Detection study. Results. Of the 59 subjects, prostate cancer was detected in 17; 231 men were found to have cancer in the European Prostate Cancer Detection Study. Minor or no discomfort was observed in 88% and 92% of the transplant recipients and controls, respectively ( P = 0.31). Twelve percent versus 8% experienced pain. Early morbidity included rectal bleeding (2.6% versus 2.1%, P = 0.19), severe hematuria (0.8% versus 0.7%, P = 0.08), and moderate to severe vasovagal episodes (1.9% versus 2.8%, P = 0.04). Late morbidity included fever (3.5% versus 2.9%, P = 0.1), hematospermia (11.0% versus 9.8%, P = 0.1), recurrent mild hematuria (17.4% versus 16.8%, P = 0.08), persistent dysuria (6.4% versus 7.2%, P = 0.2), and urinary tract infections (12.0% versus 10.9%, P = 0.08). Major complications were rare: urosepsis (0% versus 0.1%). Conclusions. The results of our study demonstrate that TRUS-guided biopsy of the prostate is generally well tolerated, with minor morbidity, in patients receiving immunosuppression. No differences were noted in pain apprehension or early and delayed morbidity, suggesting that TRUS-guided biopsies can be performed safely in these patients.

DOES INCREASED NEEDLE BIOPSY SAMPLING OF THE PROSTATE DETECT A HIGHER NUMBER OF POTENTIALLY INSIGNIFICANT TUMORS?

Several studies have documented that increased biopsy sampling, that is 6 versus 12 biopsy cores, can detect more prostate cancer. It is unknown whether increased sampling of the prostate will detect a higher number of potentially insignificant tumors. We searched the surgical pathology files at The Johns Hopkins Hospital for patients in whom prostate needle biopsy was performed by a single urologist between April 1993 and April 2000, and subsequently underwent radical prostatectomy. Patients who underwent radical prostatectomy and had 8 core biopsies or less between March 1994 and August 1999 were also studied. Clinically significant tumors were defined as those with volume greater than 0.5 cc, Gleason score 7 or greater or nonorgan confined disease. A total of 297 patients with a mean age of 60 years (range 36 to 75) were evaluated. Group 1 consisted of 107 men with 8 core biopsies or less, including 51 with 6, and group 2 comprised 190 men with 9 cores or greater, including 145 with 12. The 2 groups were equal in regard to prostate specific antigen, age, digital rectal examination and transrectal ultrasound gland volume at biopsy. The only difference between the groups was a higher number of cores with cancer in group 2 (mean 2.8 versus 2.1, p = 0.0006). Of the patients who underwent radical prostatectomy 59.6% had Gleason score 6 or less, 26.3% 3+4, 6.7% 4+3 and 7.4% 8 to 9. There were 12.4% of patients with positive margins, 36.4% extraprostatic extension, and 5.4% seminal vesicle invasion and/or lymph node metastasis. Tumor volumes averaged 1.1 cc (range 0.01 to 10.7) and 60.9% of tumors were greater than 0.5 cc. Clinically significant tumors were seen in 77.4% of patients in group 1 and 74.6% in group 2. There was no significant difference in Gleason score, margin status, tumor volume, seminal vesicle invasion, or lymph node metastasis between groups 1 and 2, or in a subset analysis of men with 6 versus 12 core biopsies. However, patients in whom cancer was diagnosed with 9 core biopsies or greater were more likely to have organ confined disease (p = 0.02). Although increased sampling of the prostate does not increase the detection of potentially insignificant tumors, it does appear to detect earlier stage cancer.

PROSPECTIVE EVALUATION OF PROSTATE CANCER DETECTED ON BIOPSIES 1, 2, 3 AND 4: WHEN SHOULD WE STOP?

We evaluated biochemical parameters and pathological features, as well as biopsy related morbidity of prostate cancer detected on biopsies 2, 3 and 4 in men with total serum prostate specific antigen (PSA) between 4 and 10 ng./ml. These features were compared to those detected on prostate biopsy 1. In this prospective European Prostate Cancer Detection study 1,051 men with total PSA between 4 and 10 ng./ml. underwent transrectal ultrasound guided sextant biopsy and 2 additional transition zone biopsies. All patients in whom biopsy samples were negative for prostate cancer underwent biopsy 2 after 6 weeks. If also negative, biopsies 3 and even 4 were performed at 8-week intervals. Those patients with clinically localized cancer underwent radical prostatectomy. Pathological and clinical features of patients diagnosed with cancer on either biopsy 1 or 2 and clinically organ confined disease who agreed to undergo radical prostatectomy were compared. Cancer detection rates on biopsies 1, 2, 3 and 4 were 22% (231 of 1,051), 10% (83 of 820), 5% (36 of 737) and 4% (4 of 94), respectively. Overall, of the patients with clinically localized disease, which was 67% of cancers detected, 86% underwent radical prostatectomy and 14% opted for watchful waiting or radiation therapy. Overall, 58.0%, 60.9%, 86.3% and 100% of patients had organ confined disease on biopsies 1, 2, 3 and 4, respectively. Despite statistically significant differences in regard to multifocality (p = 0.009) and cancer location (p = 0.001), including cancer on biopsy 2 showing a lower rate of multifocality and a more apico-dorsal location, there were no differences in regard to stage (p = 0.2), Gleason score (p = 0.3), percent Gleason grade 4/5 (p = 0.2), serum PSA and patient age between biopsies 1 and 2. However, cancer detected on biopsies 3 and 4 had a significantly lower Gleason score (p = 0.001 and 0.001), lower rate of grade 4/5 (p = 0.02), and lower volume (p = 0.001 and 0.001) and stage (p = 0.001), respectively. Despite differences in location and multifocality, pathological and biochemical features of cancer detected on biopsies 1 and 2 were similar, suggesting comparable biological behaviors. Cancer detected on biopsies 3 and 4 had a lower grade, stage and volume compared with that on biopsies 1 and 2. Morbidity on biopsies 1 and 2 was similar, whereas biopsies 3 and 4 had a slightly higher complication rate. Therefore, biopsy 2 in all cases of a negative finding on biopsy 1 appears justified. However, biopsies 3 and 4 should only be obtained in select patients with a high suspicion of cancer and/or poor prognostic factors on biopsy 1 or 2.

SAFETY AND MORBIDITY OF FIRST AND REPEAT TRANSRECTAL ULTRASOUND GUIDED PROSTATE NEEDLE BIOPSIES: RESULTS OF A PROSPECTIVE EUROPEAN PROSTATE CANCER DETECTION STUDY

We prospectively evaluate the safety, morbidity and complication rates for first and repeat transrectal ultrasound guided prostate needle biopsies. In this prospective European Prostate Cancer Detection Study 1,051 men, with total prostate specific antigen between 4 and 10 ng./ml., underwent transrectal ultrasound guided sextant biopsy plus 2 additional transition zone biopsies. Biopsy samples were also obtained from suspicious areas identified during transrectal ultrasound and digital rectal examination. All 820 patients with biopsy samples negative for prostate cancer underwent re-biopsy after 6 weeks. Immediate and delayed (range 1 to 7 days) morbidity, patient satisfaction and complication rates were recorded. Of the 1,051 subjects the initial biopsy was positive for prostate cancer in 231 and negative, including benign prostatic hyperplasia or benign tissue, in 820. Of these 820 patients prostate cancer was detected in 10% (83) on re-biopsy. Minor or no discomfort was observed in 92% and 89% of patients at first and re-biopsy, respectively (p = 0.29). Immediate morbidity was minor and included rectal bleeding (2.1% versus 2.4%, p = 0.13), mild hematuria (62% versus 57%, p = 0.06), severe hematuria (0.7% versus 0.5%, p = 0.09) and moderate to severe vasovagal episodes (2.8% versus 1.4%, respectively, p = 0.03). Delayed morbidity of first and re-biopsy was comprised of fever (2.9% versus 2.3%, p = 0.08), hematospermia (9.8% versus 10.2%, p = 0.1), recurrent mild hematuria (15.9% versus 16.6%, p = 0.06), persistent dysuria (7.2% versus 6.8%, p = 0.12) and urinary tract infection (10.9% versus 11.3%, respectively, p = 0.07). Major complications were rare and included urosepsis (0.1% versus 0%) and rectal bleeding that required intervention (0% versus 0.1%, respectively). Furthermore, an age dependent pattern of pain apprehension during biopsy was observed with the highest scores in patients younger than 60 years. Transrectal ultrasound guided biopsy is generally well tolerated with minor morbidity only rarely requiring treatment. Re-biopsy can be performed 6 weeks later with no significant difference in pain or morbidity. Patients younger than 60 years should be counseled in regard to a higher level of discomfort, and local and topical anesthesia if desired.

PROSTATE CANCER DIAGNOSIS USING A SATURATION NEEDLE BIOPSY TECHNIQUE AFTER PREVIOUS NEGATIVE SEXTANT BIOPSIES

We hypothesized that markedly increasing the number of cores obtained during prostate needle biopsy may improve the cancer detection rate in men with persistent indications for repeat biopsy. We performed saturation ultrasound guided transrectal prostate needle biopsy in 224 men under anesthesia in an outpatient surgical setting in whom previous negative biopsies had been performed in the office. The mean number of previous sextant biopsy sessions plus or minus standard deviation before saturation biopsy was 1.8 (range 1 to 7). A mean of 23 saturation biopsy cores (range 14 to 45) were distributed throughout the whole prostate, including the peripheral, medial and anterior regions. Indications for repeat biopsy were persistent elevated serum prostate specific antigen (PSA) in 108 cases, persistent elevated PSA and abnormal rectal examination in 27, persistent abnormal rectal examination in 4, high grade prostatic intraepithelial neoplasia in the previous biopsy in 64 and atypia in the previous biopsy in 21. Cancer was detected in 77 of 224 patients (34%). The number of previous negative sextant biopsies was not predictive of subsequent cancer detection by saturation biopsy. Median PSA was 8.7 ng./ml. and median PSA velocity was 0.63 ng./ml. yearly. Of the 77 patients in whom cancer was detected radical prostatectomy was performed in 52. Pathological stage was pT2 in 48 patients and pT3 in 4, while Gleason score was 4 to 5, 6 to 7 and 8 in 5, 46 and 1, respectively. At prostatectomy median cancer volume was 1.04 cc and 85.7% of removed tumors were clinically significant, assuming a 3-year doubling time. The overall complication rate for saturation needle biopsy was 12% and hematuria requiring hospital admission was the most common event. Saturation needle biopsy of the prostate is a useful diagnostic technique in men at risk for prostate cancer with previous negative office biopsies. This technique allows adequate sampling of the whole prostate gland and has a detection rate of 34% in this cohort of patients.

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.

Morbidity and Discomfort of Ten-Core Biopsy of the Prostate Evaluated by Questionnaire

Transition zone biopsies have been found to increase the detection rates of cancer of the prostate in patients with negative digital rectal examination. There are however no data available whether the higher biopsy rate is associated with greater morbidity. The present study was therefore designed to evaluate the complication rate of extended sextant biopsy. In this prospective study, 162 consecutive patients who presented for prostatic evaluation were included. After starting prophylactic antibiotic treatment 48 h prior to the procedure, transrectal ultrasound-guided core biopsies were obtained from each lobe: three each from the peripheral zone (apex, mid-zone and base) and two from the transition zone of each prostatic lobe. In all patients a questionnaire was obtained 10–12 days after the procedure. Major complications occurred in 3 patients. In 2 of the 3 cases major macroscopic hematuria was treated by an indwelling catheter for 1 or 2 days and 1 patient developed fever >38.5°C for 1 day. Minor macroscopic hematuria was present in 68.5% of the patients. In 17.9% of these cases, the hematuria lasted for more than 3 days. Hematospermia was observed in 19.8% and minor rectal bleeding occurred in 4.9%. Ten-core biopsies did not lead to an increase in adverse effects or complications when compared to the results of sextant biopsies reported in the literature.

SYSTEMATIC TRANSPERINEAL ULTRASOUND GUIDED TEMPLATE BIOPSY OF THE PROSTATE IN PATIENTS AT HIGH RISK

A negative biopsy result does not necessarily equate with cancer in specific high risk groups. We describe an alternative systematic biopsy technique for evaluating this subgroup of patients. From March 1997 to May 1999 a total of 88 men underwent systematic ultrasound guided biopsy using the transperineal template technique. All patients had undergone at least 1 and 75 (85%) had undergone 2 or more previous sets of biopsies. In addition, study inclusion required high risk parameters, including prostate specific antigen (PSA) velocity greater than 0.75 ng./ml., PSA greater than 10 ng./ml. or previous prostatic intraepithelial neoplasia on biopsy, and/or atypical small cell acinar proliferation. Cancer was identified in 38 of the 88 men (43%) in this high risk subgroup undergoing repeat biopsy. A mean of 15.1 previous biopsy cores had been obtained. The most common biopsy grade was 6 (range 4 to 9). Adenocarcinoma was identified in the transition zone area in 29 of 38 cases (76%), including 15 (39%) in which disease was detected in the transition zone only. Persistent PSA acceleration greater than 0.75 ng./ml. was the major indicator for transperineal template biopsy in 83 of the 88 patients (94%). The only significant independent variable predictive of positive biopsy was prostate volume. Mean prostate volume in the positive and negative biopsy groups was 48 and 73 gm., respectively (p <0.001). Complications were rare and self-limiting, consisting primarily of hematuria and urinary retention requiring overnight catheterization in 2 patients. Systematic transperineal template biopsy of the prostate is a safe and precise repeat biopsy technique in patients who remain at high risk for adenocarcinoma.

Transition zone biopsy in the detection of prostate cancer.

Transition zone biopsy in the detection of prostate cancer.

Prostate Biopsy Protocols: 3D Visualization-Based Evaluation and Clinical Correlation

Objectives: Systematic needle core biopsy is commonly used for the diagnosis of prostate cancer by urologists worldwide. As accurate and early diagnosis will result in more and better options for treatment, it is critical that the best possible protocols for biopsy be used clinically. In this study, we develop three-dimensional (3D) modeling and simulation technologies to evaluate most of the biopsy protocols in current clinical use, and correlate the results with those from clinical cases.Materials and Methods: Using deformable modeling techniques, 3D computerized prostate surface models were reconstructed from step-sectioned, whole-mounted radical prostatectomy specimens with localized prostate cancer. A 3D computer simulation system was developed to accurately depict the anatomy of the prostate and all individual tumor foci. A user-friendly interface was developed in the system so that a physician can easily and interactively use it for prostate needle core biopsy. A total of 281 prostate models were reconstructed, and 18 biopsies were performed by a urologist on each model to determine the detection rates of seven different biopsy protocols. Clinical biopsies from 35 patient cases were also reviewed and correlated with the simulation results.Results: The most commonly used sextant biopsy had only a 71.5% detection rate, while rates for the 10-pattern and 12-pattern protocols were much higher (96.4% and 97.2%, respectively). Even the lateral 4-pattern protocol performed better than the sextant protocol, with a detection rate of 89.3%. The lateral sextant biopsy protocol (using sites similar to, but more lateral than, those in the sextant protocol) achieved a rate of 92.5%. Although the rate of the 14-pattern biopsy was a little higher (97.5%), it used four more biopsies to achieve this increase, which, according to McNemar's test, is not statistically significant when compared to results with the 10-pattern protocol. The 5-region protocol, which uses 12 biopsies, had a detection rate of 89.7%. Transition zone and seminal vesicle biopsies did not result in a significantly increased detection rate when added to the patterns above. The clinical correlation also confirmed that the 10-pattern protocol was significantly superior to the traditional sextant biopsy pattern.Conclusions: The 10-pattern biopsy protocol was the most optimized among all the protocols evaluated. This protocol supplemented the sextant biopsy protocol with four more lateral biopsies in the mid and apical sites on both sides.

Incidence and natural history of dysplasia of the anal transitional zone after ileal pouch-anal anastomosis: results of a five-year to ten-year follow-up.

Preservation of the anal transitional zone during ileal pouch-anal anastomosis is still controversial because of the risk of dysplasia and the theoretical risk of associated cancer. Without long-term follow-up data, the natural history and optimal treatment of anal transitional zone dysplasia are unknown. The aim of this study was to determine the long-term risk of dysplasia in the anal transitional zone and to evaluate the outcome of a conservative management policy for anal transitional zone dysplasia. Two hundred ten patients undergoing anal transitional zone-sparing ileal pouch-anal anastomosis for ulcerative or indeterminate colitis between 1987 and 1992 and who were studied with serial anal transitional zone biopsies for at least five years postoperatively were included. Median follow up was 77 (range, 60-124) months. Anal transitional zone dysplasia developed in seven patients 4 to 51 (median, 11) months postoperatively. There was no association with gender, age, preoperative disease duration or extent of colitis, but the risk of anal transitional zone dysplasia was significantly increased in patients with prior cancer or dysplasia in the colon or rectum. Dysplasia was high grade in one and low grade in six. Two patients each with low-grade dysplasia detected on three separate occasions underwent mucosectomy 29 and 38 months after detection of low-grade dysplasia, but no cancer was found. The five other patients with dysplasia on one or two occasions were treated expectantly and were apparently dysplasia-free for a median of 72 (range, 48-100) months. Anal transitional zone dysplasia after ileal pouch-anal anastomosis is infrequent, is most common in the first two to three years postoperatively and may apparently disappear on repeated biopsy. Anal transitional zone preservation did not lead to the development of cancer in the anal transitional zone after five to ten years of follow-up. Long-term surveillance is recommended to monitor dysplasia. If repeat biopsy confirms persistent dysplasia, anal transitional zone excision with neoileal pouch-anal anastomosis is recommended.