A prospective randomized trial comparing 6 versus 12 prostate biopsy cores: impact on cancer detection

PURPOSE: Several studies suggest that sextant transrectal ultrasound guided biopsy of the prostate provides insufficient material to detect all clinically important prostate cancer, and obtaining more biopsy cores may improve the cancer detection rate. We performed a prospective randomized trial comparing 6 to 12 prostate biopsy cores to determine the impact on the cancer detection rate. MATERIALS AND METHODS: We prospectively randomized 244 men, including 71 (29%) black men, with a mean age plus or minus standard deviation of 65 +/- 8 years to undergo biopsy with 6 or 12 peripheral zone tissue cores. In our study subjects serum total prostate specific antigen (PSA) was between 2.5 and 20 ng./ml., and/or digital rectal examination was suspicious for cancer. All men completed a self-administered pre-biopsy and 2 post-biopsy questionnaires at 2 and 4 weeks. Cancer detection rates were compared in the groups and correlated with race, biopsy history, digital rectal examination findings, total PSA, transrectal ultrasound volume and PSA density, as determined by the formula, total PSA/transrectal ultrasound volume. RESULTS: The cancer detection rate in the 6 and 12 core groups was almost identical (26% and 27%, p = 0.9). There was no significant difference in cancer detection in the 2 trial arms with respect to subject race, biopsy history, digital rectal examination findings, total PSA, transrectal ultrasound volume or PSA density. However, our study did not have the statistical power to rule out small differences. CONCLUSIONS: The overall cancer detection rate is not materially increased by 12 core, peripheral zone biopsy in men in whom prostate cancer was mainly detected by screening.     

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

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

CHARACTERISTICS OF SCREENING DETECTED PROSTATE CANCER IN MEN 50 TO 66 YEARS OLD WITH 3 TO 4 NG./ML. PROSTATE SPECIFIC ANTIGEN

Purpose

We defined the yield and nature of prostate cancer in the setting of population based, randomized prostate specific antigen (PSA) guided screening in men with PSA levels between 3 and 4 ng./ml. who were 50 to 65 years old at the time of randomization.

Materials and Methods

Sextant biopsies were performed in 243 men with PSA of 3 to 4 ng./ml. Therapy decisions were based on core cancer length, histological grade and life expectancy.

Results

Of the men 32 (13.2%) had prostate cancer constituting 23% of all of the 137 prostate cancers to date detected in the first round of our screening study. Age and PSA were similar in men with and without prostate cancer. Men with prostate cancer had significantly lower free PSA and free-to-total PSA ratio, and higher PSA density. Cancer was clinical stage T1c in 27 cases and stage T2 in 5. Hypoechoic areas were noted at transrectal ultrasound in 10 cases. Digital rectal examination and transrectal ultrasound were normal in 21 cases (66%). To date 14 patients have undergone prostatectomy. Surgical specimens showed a mean tumor volume of 1.8 cc (range 0.6 to 4.4) and significant amounts of high grade tumor were present in only 3 cases. Margins were positive in 5 cases, and pathological stage was pT2 in 8 cases and pT3 in 6.

Conclusions

By lowering the PSA cutoff from 4 to 3 ng./ml. an increase in cancer detection by 30% was achieved. While the addition of free-to-total ratio and PSA density may reduce the number of biopsies by about 15% with sensitivity maintained at 90%, systematic sextant biopsies were necessary in most of these men as 66% of the tumors were negative on transrectal ultrasound and digital rectal examination. The majority of these cancers were clinically significant and suitable for curative treatment. If therapy decisions are based on the pathological findings of the biopsies, the risk of treating insignificant cancers seems low.     

Transperineal extended biopsy improves the clinically significant prostate cancer detection rate: A comparative study of 6 and 12 biopsy cores

BACKGROUND: We evaluated the improvement in the rate of prostate cancer detection when using a 12-core transperineal biopsy protocol including transitional zone biopsy. METHODS: Between April 2003 and November 2004, 247 consecutive men underwent transperineal systemic 12-core biopsy of the prostate. Six cores were obtained at the peripheral zone, four at the transitional zone and two at the apex. We examined the cancer detection rate in each of the 12 cores, and also determined the improvement of cancer detection resulting from the extensive 12-core versus standard 6-core biopsy. RESULTS: Using the extensive 12-core biopsy, prostate cancer was detected in 98 cases (39.7%). Prostate-specific antigen (PSA), PSA density, the positive rate in digital rectal examination and transrectal ultrasound findings were significantly higher in the prostate cancer group than in the non-prostate cancer group, and prostate volume was larger in non-prostate cancer group. Every site showed almost the same positive rate, between 17.8 and 21.5%. There were 20 cases which were positive in the extended biopsy, but negative in the sextant. The detection improved significantly (20.4%). The improvement of cancer detection in extended biopsy was better in men with PSA levels of 10 ng/mL or less (28.9%), PSA density 0.3 or less (25.8%), negative digital rectal examination (23.3%), and negative transrectal ultrasound (21.6%). Of these twenty patients, no cases with insignificant tumor were detected in the six prostatectomy cases. In particular, three cases of the six were transitional-zone-only cancer. CONCLUSION: Transperineal extended 12-core biopsy including 4 transitional zone cores is a more useful procedure than transperineal 6-core biopsy. Routine transitional zone biopsy, that is different from transrectal biopsy, might be useful for detecting biologically significant cancer.     

Prevalence and Predictors of a Positive Repeat Transrectal Ultrasound Guided Needle Biopsy of the Prostate

Purpose

We determined the prevalence of and risk factors for carcinoma in patients with 1 previously negative prostate biopsy.

Materials and Methods

Transrectal ultrasound guided prostate needle biopsies were repeated in 130 men. Risk factors analyzed included age, pathological result of initial biopsy, inter-biopsy interval, prostate specific antigen (PSA), PSA density, PSA velocity, digital rectal examination, abnormal transrectal ultrasound and family history of prostate cancer.

Results

A total of 39 patients (30%) had positive biopsies for cancer. Univariate analysis revealed that PSA more than 20 ng./ml. and abnormal transrectal ultrasound were more frequent in men with positive second biopsies. Using multivariate logistic regression analysis only PSA more than 20 ng./ml. was a significant risk factor (adjusted odds ratio 4.48, 95% confidence interval 1.02 to 20.1). We determined the incidence of carcinoma in patients who represent the lowest risk group as defined by PSA less than 10 ng./ml., PSA density less than 0.15 mg./ml./cm.³, PSA velocity less than 0.75, ng./ml. per year, no prostatic intraepithelial neoplasia plus negative transrectal ultrasound, digital rectal examination and family history. Of 21 patients who fit this cohort 5 (23.8%) had carcinoma on repeat biopsy.

Conclusions

A significant false-negative rate for initial transrectal ultrasound guided prostate biopsies exists. Baseline risk in lowest risk patients is sufficiently high such that one cannot define a subset of patients for whom repeat biopsy is unnecessary. We recommend repeat biopsy in all patients who meet the criteria for a transrectal ultrasound guided biopsy and in whom the initial biopsy is negative.     

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.     

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.     

Transperineal prostate biopsy after abdominoperineal resection

PURPOSE: Prostate cancer evaluation in men who have undergone abdominoperineal resection poses a challenge for urologists. Diagnosis and staging methods are limited because as access to the prostate via digital rectal examination is not possible. Prostate specific antigen (PSA) has been used to screen for malignancy in this population. However, the conventional diagnostic technique with transrectal ultrasound guided biopsies cannot be used. Transperineal ultrasound and biopsy have been described to evaluate the prostate in this setting. We report our experience with transperineal ultrasound biopsy for evaluating the prostate in patients with elevated PSA who have previously undergone abdominoperineal resection. MATERIALS AND METHODS: We reviewed the records of 28 patients treated at 2 institutions. All patients had a history of abdominoperineal resection and subsequent transperineal ultrasound guided prostate biopsy for evaluating elevated PSA. Mean serum PSA in this population was 22 ng./ml. (median 9.5, range 4.1 to 237). Abdominoperineal resection was done in 16 patients (57%) for colorectal cancer, in 11 (39%) for ulcerative colitis and in 1 (4%) for familial polyposis coli. Average time since resection was 14 years (range 1 to 33). Five patients had previously undergone radiation therapy as part of treatment for colorectal cancer before transperineal ultrasound biopsy. RESULTS: Of the 28 biopsies performed 23 revealed prostate cancer, 2 revealed prostatitis and 3 were benign. Average Gleason grade was 6.6 (range 3 to 9). Of the 23 patients with prostate cancer 22 were treated with androgen deprivation therapy (7), prostatectomy (8), external beam (6) and high dose (1) radiation therapy. Of the 8 patients who underwent prostatectomy pathological stage was T2 in 3 and T3 in 4, while pathological findings were not determined in 1 patient in whom the prostate was removed in pieces. CONCLUSIONS: In patients with a history of abdominoperineal resection and elevated PSA transperineal ultrasound guided biopsy of the prostate can provide an accurate tissue diagnosis.     

Prospective detection of clinically relevant prostate cancer in the prostate specific antigen range 1 to 3 ng./ml. combined with free-to-total ratio 20% or less: the Aarau experience

PURPOSE: Little is known about the incidence rate and clinical relevance of prostate cancer in a low prostate specific antigen (PSA) level. In a prospective PSA based screening study we investigated the incidence and clinicopathological features of prostate cancer that occurred within PSA range 1 to 3 ng./ml. when the free-to-total ratio was 0.20 or less. MATERIALS AND METHODS: Men participating in the Aarau, Switzerland, section of the European Randomized Study of Screening for Prostate Cancer between October 1998 and July 2000 were included in the study. As a side study, all men with PSA between 1 and 3 ng./ml. and free-to-total ratio 0.20 or less were invited to undergo further evaluation with ultrasound guided sextant prostate biopsy. RESULTS: Overall, 168 (7.8%) participants fulfilled inclusion criteria. A total of 158 (94%) patients underwent prostate biopsy, and prostate cancer was detected in 17 (10.8%). There were no statistically significant differences between prostate cancer and benign prostatic hyperplasia in regard to patient age (60.7 versus 59.8 years), prostate volume (23.9 versus 23.0 cc), PSA (1.98 versus 1.86 ng./ml.), free-to-total ratio (0.161 versus 0.160), PSA density (0.089 versus 0.076 ng./ml.) or PSA transition zone density (0.33 versus 0.24 ng./ml., respectively). Median Gleason score was 5 on prostate biopsy versus 6 on retropubic prostatectomy specimen. Of the 14 patients who underwent surgery there were positive lymph nodes in 1, stage pT3b Gleason 7 disease in 1, and pathologically organ confined Gleason 5 in 2, Gleason 6 in 5 and Gleason 7 in 5. Mean tumor volume was 1.01 cc (range 0.02 to 5.17). There were 2 (14.3%) insignificant (less than 0.2 cc, Gleason grade 3 or less), 1 (7.1%) minimal (less than 0.5cc, Gleason grade 3 or less) and 11 (78.6%) clinically relevant and potentially harmful cancers. CONCLUSIONS: There is a significant number of prostate cancer cases diagnosed at PSA as low as 1 to 3 ng./ml. A majority of these tumors are clinically significant. This free-to-total ratio range may be helpful for identifying prostate cancer. The "window of opportunity" for detection of curable cancer may change in populations with higher life expectancy towards lower PSA. Lack of specificity and characterization of tumor aggressiveness remains an unsolved issue for PSA.     

Extended sector biopsy for detection of carcinoma of the prostate

Purpose: To determine whether an extended sector biopsy of the prostate will increase the detection of prostate cancer, without causing an increase in morbidity. Materials and Methods: A total of 74 men with a mean age of 62.3 years (46-98 years) who either had an elevated PSA or an abnormal digital rectal exam underwent a transrectal ultrasound guided needle biopsy. Beginning on 7/1/98, an extended sector biopsy technique was performed on 74 patients by one urologist (RRB). Each transrectal ultrasound guided needle biopsy included 12 total cores (normal sextant biopsy, 2 in each peripheral zone, and 2 in the transition zone). We retrospectively reviewed the biopsy results for the location of cancer. PSA data and morbidity of the procedures were reviewed. Results: Of 74 total patients, 40 (54.1%) were positive for adenocarcinoma of the prostate. There were 10 positive results detected only in the additional zones. If one looks at the total number of cancers detected (40), then 10/40 (25%) of the cancers detected were found in the additional regions only or in 13.5% of all patients biopsied. Of the 10 patients with sector only prostate cancer, 8 were detected in the peripheral zone, 1 in the transition zone and 1 in both zones. All 10 patients had a Gleason pattern score 3+3=6 or 4+3=7. There were no atypical or PIN cores found in the sector zones only. PSA ranged from 1.2-142 (median 6.0 ng/ml). The median PSA was 6.2 ng/ml in all patients found to have cancer, and 6.0 ng/ml in the cancers detected only in the additional zones. There was 1 (1.4%) complication of urinary retention and fever. Conclusion: Our study suggests that an extensive sector biopsy may increase the detection of prostate cancer by 13.5% over a routine sextant biopsy, without demonstrable serious morbidity.     

经直肠超声引导13点前列腺系统穿刺活检术160例报告

目的　探讨经直肠超声引导 13点前列腺系统穿刺活检术诊断前列腺癌的临床价值。　方法　对 160例直肠指诊阳性和 (或 )PSA >4ng/ml的患者行经直肠超声引导 13点前列腺系统穿刺活检术。即在标准的经直肠超声引导 6点前列腺系统穿刺活检术同时 ,增加前列腺中间部位及前列腺两侧旁正中线远侧的穿刺点数 ,共穿刺活检 13点。将增加的 7点活检部位病理结果与标准的 6点前列腺系统穿刺活检术进行比较。　结果　 160例患者中确诊为前列腺癌者 5 6例 ( 3 5 % )。 5 6例患者如按 6点穿刺方法 ,将有 12例患者漏诊 ,占 2 1%。 160例患者均未出现严重并发症。　结论　经直肠超声引导 13点前列腺系统穿刺活检术可明显提高前列腺癌的临床检出率     

Can Free and Total Prostate Specific Antigen and Prostatic Volume Distinguish Between Men With Negative and Positive Systematic Ultrasound Guided Prostate Biopsies?

Purpose

We evaluated the role of free and total serum prostate specific antigen (PSA) and prostate volume in discriminating between men with negative and positive transrectal ultrasound guided biopsies.

Materials and Methods

A total of 104 consecutive men with a positive biopsy and at least 3 mm. of prostate cancer was compared to 110 consecutive men with a negative biopsy. Prostate volume was determined by transrectal ultrasound. Total PSA was determined by the Tosoh AIA-600† PSA assay and free PSA was measured by the PSA II Dianon‡ assay. We determined the free-to-total PSA ratio, free and total PSA densities, and the relationship of free PSA and free-to-total PSA ratio to prostate volume.

Results

Using a 23% cutoff value of free-to-total PSA, only 22.7% of biopsies were preventable in patients with a negative biopsy but 9.6% of the cancers were missed. At a total PSA of 4 to 10 ng./ml. 44.4% of the biopsy negative cases were correctly identified while missing 9.1% of the cancers if a 20% free PSA cutoff is used. For total PSA more than 10 ng./ml. an 18% free PSA cutoff properly identified 30.2% of the biopsy negative cases while missing 9.3% of the cancers. Percent free PSA is a better discriminant than prostate volume for total PSA more than 4 ng./ml. and the combination was not helpful. Free PSA density was identical in patients with negative and positive biopsies. There was no relationship between free PSA or free-to-total PSA ratio levels and prostate volume.

Conclusions

Use of a single discriminant criterion of free-to-total PSA ratio in the practical clinical setting of distinguishing negative and positive biopsies appears useful in patients with a total PSA of 4 to 10 ng./ml. Since free PSA is unrelated to prostate volume in biopsy negative and positive cases the physiological basis of free PSA is an enigma.     

Does transrectal ultrasound guided eight‐core prostate biopsy improve cancer detection rates in patients with prostate‐specific antigen levels of 4.1–10 ng/mL?

BACKGROUND: To investigate retrospectively whether the eight-core biopsy method improves the prostate cancer detection rate when compared with the standard sextant biopsy method in patients with prostate specific antigen (PSA) levels of 4.1-10 ng/mL. MATERIAL AND METHODS: Of 437 patients whose PSA levels ranged from 4.1 to 10 ng/mL, 237 underwent a transrectal ultrasound guided sextant biopsy (sextant group), and 200 underwent an eight-core biopsy (eight-core group). Eight core samples were obtained from each of the far lateral regions in addition to the standard sextant biopsy cores. None of the patients had a previous history of prostate biopsy. RESULTS: Of the 237 patients in the sextant group, prostate cancer was detected in 47 patients (19.8%) and in 50 of the 200 patients in the eight- core group (25.0%). The rates of detection in the two methods were not statistically significant. However, in patients whose PSA density was less than 0.1 ng/mL per cc, the cancer detection rates in the sextant group and the eight-core group were 4.5% and 18.8%, respectively (P = 0.046). The morbidity and complications of the eight-core biopsy method were not notable. CONCLUSIONS: Only in patients with PSA levels of 4.1-10 ng/mL and density of less than 0.1 ng/mL per cc was the eight-core biopsy method an improvement on the sextant biopsy method in terms of prostate cancer detection rate. Accordingly, a number of cores greater than eight will be required to improve the cancer detection rates in patients with PSA levels of 4.1-10 ng/mL and PSA densities of more than 0.1 ng/mL per cc.     

Difference of cancer core distribution between first and repeat biopsy: In patients diagnosed by extensive transperineal ultrasound guided template prostate biopsy

BACKGROUND: We performed extensive transperineal ultrasound guided template prostate biopsy and evaluated cancer core distribution. METHODS: From August 2000 to May 2002, 113 men with prostate specific antigen levels between 4.0 and 10.0 ng/ml underwent template biopsy. Eighty-six had no previous biopsy (first group) and 27 had previous transrectal sextant biopsies (repeat group). A mean of 18.4 biopsy cores were taken. We defined the region over 2 cm from the rectal face of the prostate as the anterior region and the other as the posterior. RESULTS: Cancer was detected in 49 of 113 (43%) men. Forty-two were in the first group and seven in the repeat group. In the first group, the cancer core rate (cancer core number/biopsy core number) in the anterior region (7.0%) had no difference from that in the posterior region (8.6%) (P = 0.7111). But in the repeat group, the cancer core rate in the anterior region (4.6%) was higher than in the posterior (1.5%) (P < 0.0001). CONCLUSIONS: These results suggest that transrectal sextant biopsies miss more cancers in the anterior region than in the posterior. We believe template technique has an advantage to be able to detect cancer equally in the anterior and posterior.     

Predictors of prostate cancer on repeat transrectal ultrasound-guided systematic prostate biopsy

BACKGROUND: We analyzed the outcome of repeated transrectal ultrasound (TRUS)-guided systematic prostate biopsy in Japanese men whose clinical findings were suspected of prostate cancer after previous negative biopsies. METHODS: Between January 1993 and March 2002, 1045 patients underwent TRUS-guided prostate biopsy. Among them, 104 patients underwent repeat biopsy due to indications of persistent elevated serum prostate-specific antigen (PSA), abnormal digital rectal examination (DRE) or TRUS, increased PSA velocity, and/or previous suspicious biopsy findings. Several clinicopathological factors were evaluated for their ability to predict the detection of prostate cancer on repeat biopsy. RESULTS: Prostate cancer was detected in 22 of 104 patients (21.2%) who underwent repeat biopsies. PSA concentration and PSA density at both the initial and repeat biopsies, and PSA velocity in men with positive repeat biopsy were significantly greater than those in men with negative repeat biopsy. The incidence of abnormal findings in DRE and TRUS at initial biopsy in men with positive repeat biopsy was also significantly higher than that in men with negative repeat biopsy. However, neither the presence of prostatic intraepithelial neoplasia nor number of biopsy cores at initial biopsy had a significant association with the results of the repeat biopsy. Furthermore, multivariate analysis revealed that PSA and PSA density at both the initial and repeat biopsies, PSA velocity, and DRE and TRUS findings at initial biopsy were independent predictors of malignant disease on repeat biopsy. CONCLUSION: Despite an initial negative biopsy, repeat TRUS-guided biopsy should be carried out to exclude prostate cancer in cases of suspicious clinical findings, such as elevated PSA or PSA-related parameters, or abnormal findings of DRE or TRUS.     

Insulin-like growth factor-1 and insulin-like growth factor binding protein-3 for prostate cancer detection in patients undergoing prostate biopsy

PURPOSE: Laboratory and epidemiological studies suggest that high circulating insulin-like growth factor (IGF)-1 and low IGF binding protein-3 are associated with increased prostate cancer risk. However, the usefulness of serum IGF-1 or IGF binding protein-3 for predicting pathology results in men undergoing prostate biopsy is unclear. We examined the relationships of serum IGF-1, IGF binding protein-3 and the results of prostate biopsy. MATERIALS AND METHODS: A total of 652 consecutive patients with elevated serum prostate specific antigen (PSA) or abnormal digital rectal examination who were referred for transrectal ultrasound sextant prostate needle biopsy underwent blood sampling before biopsy. PSA, free PSA, IGF-1 and IGF binding protein-3 were measured. There were 244 men (37.4%) with cancer and 408 controls with benign conditions. RESULTS: Mean IGF-1 plus or minus SD in the cancer and control groups was 176.1 +/- 58.3 and 178.7 +/- 54.7 ng./ml., respectively (p = 0.57). Mean IGF binding protein-3 in the cancer and control groups was 2,724 +/- 647 and 2,673 +/- 589 ng./ml., respectively (p = 0.3). Adjustment for age and PSA showed significantly lower IGF-1 in cancer cases, while IGF binding protein-3 was not significant. ROC values were significantly higher for free-to-total PSA and PSA than for crude and age adjusted IGF-1 and IGF binding protein-3. CONCLUSIONS: Our data indicate that serum IGF-1 or IGF binding protein-3 does not predict the results of prostate biopsy in men with elevated PSA or abnormal digital rectal examination. This finding implies that while there is evidence that the IGF-1 level is a risk factor for prostate cancer, neither IGF-1 nor IGF binding protein-3 can be used as a tumor marker for this disease.     

Follow-up of men with elevated prostate-specific antigen and one set of benign biopsies at prostate cancer screening

OBJECTIVE: To study the follow-up of men with elevated prostate-specific antigen (PSA) (>3 ng/ml) after one benign set of sextant biopsies. From the G?teborg branch of the European Randomised Study of Screening for Prostate Cancer (ERSPC). METHOD: 456 men with one set of benign sextant biopsies were followed every second year for 4 years with PSA determinations. In cases of elevated PSA, transrectal ultrasound (TRUS) guided sextant biopsies were suggested. Digital rectal examination (DRE), prostate volume, PSA, PSA density (PSAD) and the ratio between free and total PSA (PSA F/T) were recorded. RESULTS: Complete data were available for 322 men. 3 groups were identified. In 84/322 (26%) men cancer was found ("cancer" group). 182/322 (56%) had benign biopsies ("benign" group) and 56/322 (17%) had normalised PSA ("normalised PSA" group). Median prostate volumes were 36, 46, and 33 cc respectively in the three groups. DRE and/or TRUS were abnormal in only 30% of the men in all groups. Cancer was not found in any prostate >70 cc volume. In prostates of <20 cc either cancer was found or PSA was normalised. The "normalised PSA" group had initial PSA, PSAD and PSA F/T similar to cancer, normalising during follow-up. CONCLUSIONS: Patients with one negative sextant biopsy still have a high likelihood of cancer, especially men with persistently elevated PSA and small prostates (<20 cc) while the majority of men with large prostates (>70 cc) have PSA elevation due to benign prostate hyperplasia (BPH) and not to cancer.     

An artificial neural network for prostate cancer staging when serum prostate specific antigen is 10 ng./ml. or less

PURPOSE: An artificial neural network was developed to improve the prediction of pathological stage before radical prostatectomy based on variables available at biopsy and clinical parameters. MATERIALS AND METHODS: We used the prospectively accrued European prostate cancer detection data base to train an artificial neural network to predict pathological stage in 200 men with serum prostate specific antigen (PSA) 10 ng./ml. or less who underwent radical prostatectomy. Variables included in the artificial neural network were patient age, serum PSA, free-to-total PSA ratio, PSA velocity, transrectal ultrasound calculated total and transition zone volumes with their associated PSA parameters (transition zone PSA density and PSA density), digital rectal examination and Gleason score on biopsy. Two multilayer perceptron neural networks were trained on the remaining variables. Data on the 200 patients were divided randomly into a training set, a test set and a validation or prospective set. RESULTS: Overall classification accuracy of the artificial neural network was 92.7% and 84.2% for organ confined and advanced prostate cancer staging, respectively. For preoperatively predicting local versus advanced stage the area under the ROC curve for the artificial neural network was significantly larger (0.91) compared with logistic regression analysis (0.83), Gleason score (0.69), PSA density (0.68), prostate transition zone volume (0.63) and serum PSA (0.62) (all p <0.01). CONCLUSIONS: The artificial neural network outperformed logistic regression analysis and correctly predicted pathological stage in more than 90% of the validation patients with serum PSA 10 ng./ml. or less based on clinical, biochemical and biopsy data. In the future artificial neural networks may represent a significant step for improved staging of prostate cancer when counseling patients referred for radical prostatectomy or other curative treatments.     

Transperineal magnetic resonance image guided prostate biopsy

PURPOSE: We report the findings of a transperineal magnetic resonance image (MRI) guided biopsy of the prostate in a man with increasing prostate specific antigen who was not a candidate for a transrectal ultrasound guided biopsy. MATERIALS AND METHODS: Using an open configuration 0.5 Tesla MRI scanner and pelvic coil, a random sextant sample was obtained under real time MRI guidance from the peripheral zone of the prostate gland as well as a single core from each MRI defined lesion. The patient had previously undergone proctocolectomy for ulcerative colitis and, therefore, was not a candidate for transrectal ultrasound guided biopsy. Prior attempts to make the diagnosis of prostate cancer using a transurethral approach were unsuccessful. RESULTS: The random sextant samples contained benign prostatic hyperplasia, whereas Gleason grade 3 + 3 = 6 adenocarcinoma was confirmed in 15% and 25% of the 2 cores obtained from the MRI targeted specimens of 2 defined lesions. The procedure was well tolerated by the patient. CONCLUSIONS: Transperineal MRI guided biopsy is a new technique that may be useful in detecting prostate cancer in men with increasing prostate specific antigen who are not candidates for transrectal ultrasound guided biopsy.     

A comparative analysis of sextant and an extended 11-core multisite directed biopsy strategy

PURPOSE: The 3 tumor locations unsampled by conventional sextant biopsies that have been identified on composite 3-dimensional reconstruction of 180 radical prostatectomy specimens are the anterior transition zone, midline peripheral zone and inferior portions of the anterior horn in the peripheral zone. We evaluated an 11-core multisite directed biopsy scheme incorporating these alternate areas and conventional sextant biopsies in 362 patients from 2 institutions. MATERIALS AND METHODS: Patients without a prior diagnosis of cancer underwent ultrasound guided 11-core biopsies which included conventional sextant and 3 alternate sites. All specimens were separated for specific location identification. Biopsy was performed in 183 patients at MD Anderson Cancer Center (group 1) and in 179 at Toronto General Hospital (group 2). All group 2 and 54% of group 1 patients (98 of 183) had a prior biopsy negative for cancer. RESULTS: Median prostate specific antigen was higher in group 2 than in group 1 patients (11.5 versus 9.5 ng./ml., p = 0.016). Overall a 33% increase (36 of 110 patients) in cancer detection was observed when biopsy technique included the alternate areas (p = 0.0021). The anterior horn was the most frequently positive biopsy site followed by the transition zone and midline sites. The 11-core technique had significantly better cancer detection rates when digital rectal examination and transrectal ultrasound were normal, and in men with serum prostate specific antigen between 4.1 and 10 ng./ml. CONCLUSIONS: Biopsies of the alternate sites suggested by our simulation studies are feasible and reproducible. This new strategy significantly enhanced (p = 0.0075) prostate cancer detection compared to conventional sextant biopsies in men undergoing a repeat procedure.