Prostate cancer detection with office based saturation biopsy in a repeat biopsy population

PURPOSE: Patients at increased risk for prostate cancer with previously negative biopsies pose a diagnostic challenge. We have previously demonstrated that extensive saturation biopsy can be performed in an office setting. We now report the diagnostic yield of office saturation biopsy in patients at increased risk for prostate cancer and at least 1 negative prior biopsy. MATERIALS AND METHODS: We performed saturation prostate biopsy with local anesthesia in the office in 116 patients with at least 1 prior negative biopsy and with certain risk factors, namely persistently elevated prostate specific antigen, abnormal digital rectal examination, or prior atypia or PIN on prior biopsy. RESULTS: A total of 34 cancers were detected for an overall diagnostic yield of 29%. A 64% detection rate was noted when a patient had undergone a single prior sextant biopsy. Subgroup analysis revealed a cancer detection rate of 41% when only prior sextant biopsies were performed, and a 24% detection rate when 10 or more cores were taken on prior biopsy. The detection rate was 33% when only 1 prior biopsy was taken and it was 24% when 2 or more prior biopsies were performed. CONCLUSIONS: Saturation biopsy can be performed safely and effectively in the office with a significant diagnostic yield even in patients with previous extended biopsy schemes. We believe that it should be the next diagnostic step after an initial negative biopsy in patients in whom the diagnosis of prostate cancer is strongly suspected.     

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.     

Effects of systematic 12-core biopsy on the performance of percent free prostate specific antigen for prostate cancer detection

PURPOSE: The performance characteristics of percent free (f) prostate specific antigen (PSA) for differentiating between benign prostatic hyperplasia and prostate cancer were originally established using primarily sextant biopsy. We determined whether the addition of 6 laterally directed cores to the traditional sextant prostate biopsy affects the performance of percent fPSA. MATERIALS AND METHODS: We retrospectively evaluated a cohort of 350 consecutive biopsies in men with negative digital rectal examinations and PSA between 4 and 10 ng/ml who underwent systematic 12 core biopsy (S12C) biopsy at Scott Department of Urology between March 1999 and January 2003. The effects of 6 additional, laterally directed biopsies on the sensitivity, specificity and area under the ROC curve for percent fPSA was evaluated in the 277 men in whom percent fPSA was measured. RESULTS: Cancers detected exclusively in the 6 laterally directed cores were associated with percent fPSA values similar to those in patients with a benign S12C biopsy. This resulted in a modest and yet predictable decrease in the sensitivity of percent fPSA at each biopsy threshold value without affecting specificity. There was a nonstatistically significant decrease in the area under the ROC curve with the addition of 6 laterally directed cores to sextant biopsy (medial sextant cores 0.66 vs S12C 0.60). CONCLUSIONS: The 12 core biopsy strategies have a higher cancer detection rate than sextant biopsies and they are gaining widespread acceptance. The addition of 6 laterally directed cores to traditional sextant biopsy may result in a modest decrease in the sensitivity of percent fPSA at each selected biopsy threshold without affecting specificity.     

Saturation technique does not improve cancer detection as an initial prostate biopsy strategy

PURPOSE: We reported on the results of a sequential cohort study comparing office based saturation prostate biopsy to traditional 10-core sampling as an initial biopsy. MATERIALS AND METHODS: Based on improved cancer detection of office based saturation prostate biopsy repeat biopsy, we adopted the technique as an initial biopsy strategy to improve cancer detection. Two surgeons performed 24-core saturation prostate biopsies in 139 patients undergoing initial biopsy under periprostatic local anesthesia. Indication for biopsy was an increased PSA of 2.5 ng/dl or greater in all patients. Results were compared to those of 87 patients who had previously undergone 10-core initial biopsies. RESULTS: Cancer was detected in 62 of 139 patients (44.6%) who underwent saturation biopsy and in 45 of 87 patients (51.7%) who underwent 10-core biopsy (p >0.9). Breakdown by PSA level failed to show benefit to the saturation technique for any degree PSA increase. Men with PSA 2.5 to 9.9 ng/dl were found to have cancer in 53 of 122 (43.4%) saturation biopsies and 26 of 58 (44.8%) 10-core biopsies. Complications included 3 cases of prostatitis in each group. Rectal bleeding was troublesome enough to require evaluation only in 3 men in the saturation group and 1 in the 10-core group. CONCLUSIONS: Although saturation prostate biopsy improves cancer detection in men with suspicion of cancer following a negative biopsy, it does not appear to offer benefit as an initial biopsy technique. These findings suggest that further efforts at extended biopsy strategies beyond 10 to 12 cores are not appropriate as an initial biopsy strategy.     

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.     

Value of Systematic Transition Zone Biopsy in the Detection of Prostate Cancer

Background:
We evaluated routine transition zone biopsies for the detection of prostate cancer.
Methods:
Systematic sextant transrectal biopsies, including 2 systematic transition zone biopsies (sextant biopsy group), were performed on 196 consecutive patients. Biopsies were based on indications from digital rectal examination and/or a serum PSA level greater than 4.0 ng/ml. During the same period, 21 patients with persistently elevated PSA levels and earlier negative systematic biopsies also had the sextant biopsy (re-biopsy group). The sextant biopsy group was compared with 1 24 cases in our previous cancer detection program who had systematic quadrant biopsies targeted to the peripheral zone (quadrant biopsy group).
Results:
Between the sextant and quadrant biopsy groups, the difference in rate of cancer detection was not significant statistically. Of the sextant biopsy group, 64 (33%) demonstrated malignancy, including 9 (4.6%) with cancer found exclusively in the peripheral zone and 55 (28%) both in the peripheral and transition zones. No cancer was found exclusively in the transition zone. Of the re-biopsy group, all 4 cancers (19%) were detected in the transition zone, 2 of them exclusively in the transition zone.
Conclusion:
Routine transition zone biopsies did not increase the detection rate of prostate cancer. Systematic transition zone biopsies proved useful to the patients with persistently elevated PSA values and negative results in previous systematic peripheral zone biopsies.     

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.     

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

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

Transrectal ultrasound guided biopsy of the prostate: random sextant versus biopsies of sono-morphologically suspicious lesions

Transrectal ultrasound (TRUS) guided multiple systematic random biopsies are presently the method of choice for determining the presence or absence of prostate cancer. TRUS image information is only used to guide the biopsy needle into the prostate, but not to localize and target cancerous lesions. Our aim in this study was to evaluated the possible predictive value of tumor suspicious endosonographic lesions of the prostate for prostate biopsies. We prospectively compared six systematic biopsies with lesion guided biopsies in a consecutive series of 217 patients. All patients had a prostate specific antigen (PSA) level of >4 ng/ml without a history of prostate disease. In a subgroup of 145 men with sonomorphologic lesions suggestive for prostate cancer (hypoechoic areas or asymmetries predominantly in the peripheral zone), lesion-guided biopsies were taken in addition to the systematic biopsies. We evaluated the number of tumors which were diagnosed or missed by both of the biopsy strategies. Of the 217 evaluated patients, 64 (29%) had histology confirmed cancer. Four patients with negative sextant biopsies had a positive TRUS guided biopsy. Out of 145 patients with a normal TRUS, three were cancer positive by sextant biopsy. A total of 1,387 individual biopsy cores were evaluated. Of the 1,304 systematic biopsy cores, 182 (14%) were positive and 1,122 (86%) negative. Of the 329 TRUS lesion guided biopsy cores 139 (42%) were positive and 190 (58%) negative. Patients with tumor suggestive TRUS lesions have a considerably higher risk of being diagnosed with prostate cancer compared to patients without such lesions. Both systematic sextant and TRUS lesion guided biopsies missed detectable prostate cancer in a minority of patients. Taking the endosonographic morphology of the prostate gland into consideration for biopsy strategies may improve the quality of the biopsy and avoid unnecessary invasive procedures in selected cases.     

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.     

Use of 2.6 ng/ml prostate specific antigen prompt for biopsy in men older than 60 years

PURPOSE: Since the United States Food and Drug Administration approved the prostate specific antigen (PSA) blood test as an aid to early prostate cancer detection, using a cutoff of 4.0 ng/ml in 1994, this cutoff has been widely adopted to recommend prostate biopsy. There has been recent investigation into lowering the PSA prompt for biopsy, especially in men younger than 60 years. We determined how a lower cutoff would perform in men older than 60 years. MATERIALS AND METHODS: From a prostate cancer screening study we studied 782 consecutive men who underwent prostate biopsy for PSA greater than 2.5 ng/ml or suspicious digital rectal examination. Biopsy results were evaluated as a function of patient age. RESULTS: Clinical and pathological characteristics of cancers detected in the PSA range 2.6 to 4.0 ng/ml were similar regardless of patient age. Overall PSA between 2.6 and 4.0 ng/ml was associated with a cancer detection rate of 16.2% using a sextant biopsy technique. PSA velocity was similar in men with prostate cancer in all age groups. CONCLUSIONS: More than 15% of men with PSA 2.6 to 4.0 ng/ml who are 40 years or older have prostate cancer detected with sextant needle biopsies. PSA velocity, tumor stage, Gleason grade and tumor volume were similar in all age groups.     

Increasing prostate biopsy cores based on volume vs the sextant biopsy: a prospective randomized controlled clinical study on cancer detection rates and morbidity

OBJECTIVE: To determine if a volume-adjusted increase in the number of biopsy cores could detect more prostate cancers than the standard sextant biopsy alone, without increasing morbidity, and to determine its applicability in Malaysian patients, as a standard sextant biopsy misses 20-25% of prostate malignancies. PATIENTS AND METHODS: In a prospective randomized study of patients undergoing transrectal ultrasonography (TRUS)-guided biopsy for a prostate-specific antigen (PSA) level of 4-20 ng/mL without abnormal digital rectal examination (DRE), the men were divided into five main groups (A-E) with prostate volumes of <20, 20-40, 40-60, 60-80 and >80 mL, respectively. Patients in groups B-E were randomized into sextant (B1 to E1) and increased biopsy-core subgroups, i.e. B2 (eight cores), C2 (10 cores), D2 (12 cores) and E2 (14 cores). The morbidity profile was also evaluated during and after TRUS biopsy, assessing a pain score, rectal bleeding, haematuria, haemospermia and development of fever. In all, 132 patients were recruited (mean age 67.8 years; mean PSA 9.41 ng/mL). RESULTS: The overall cancer detection rate was 24% (32 men). Taking more cores detected 65.5% of cancers, and the sextant biopsy 34.5% (P = 0.0025), but did not increase the overall morbidity. CONCLUSIONS: The volume-adjusted, increased-core regimen significantly increased the positive biopsy rate of TRUS-guided prostate biopsies with no added morbidity.     

High detection rate of significant prostate tumours in anterior zones using transperineal ultrasound-guided template saturation biopsy

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Men with persistent suspicion for prostate cancer after previous negative standard transrectal biopsy series are offered saturation biopsy either transrectally or transperineally to increase cancer detection rate. A high‐risk group of men with at least two previous negative transrectal biopsies underwent transperineal template‐guided saturation biopsy. Prostate cancer was detected in 26%, predominantly in the anterior zones. PSA velocity or doubling time were the most powerful factors to predict cancer.

OBJECTIVE

• ? To evaluate the detection rate and the regional location of prostate cancer in men undergoing transperineal template‐guided saturation biopsy (TTSB).

PATIENTS AND METHODS

• ? In all, 92 consecutive men with at least two previous negative transrectal biopsy series who underwent a multiple‐core prostate TTSB at our centre were included in the study.
• ? Univariable and multivariable logistic regression analyses were used to address the relationship between parameters before TTSB and prostate cancer‐detection rate.
• ? Covariates consisted of age at biopsy, free and total prostate‐specific antigen (PSA), prostate volume, digital rectal examination findings, histological findings on previous biopsy, PSA velocity (PSAV), PSA‐doubling time (PSADT) and the number of previous negative biopsy sets.

RESULTS

• ? Prostate cancer was diagnosed in 26% of the men.
• ? A median of 30 cores was taken by TTSB.
• ? Adenocarcinoma in >2 cores was detected in 58.5% and Gleason score ≥7 was detected in 46% of the diagnosed men.
• ? Most of the tumours (83.3%) were found in the anterior zones of the gland, with a significantly higher number of positive cores vs the posterior zones (mean 4.9 vs 1.5, P= 0.015).
• ? PSADT and PSAV were the only independent predictors of prostate cancer detection at multivariate analyses with odds ratios of 0.71 (P= 0.014) and 1.58 (P= 0.025), respectively.

CONCLUSIONS

• ? TTSB has a high prostate cancer‐detection rate, especially in the anterior zones.
• ? Men after at least two previous negative transrectal biopsy series and persistent suspicion of prostate cancer, as evidenced by rapid PSA dynamics, should be offered TTSB.

     

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.     

Repeat prostate biopsy: who,how and when?. a review

Urologists are frequently faced with the dilemma of treating a patient with a high index of suspicion of prostate cancer (PCa), but an initial set of negative biopsies. In this review, we evaluated the current knowledge on repeat prostate biopsies, focusing on when to perform them and in which patients, how many samples to take, where to direct the biopsies and what morbidity should be expected. We focussed on the available literature and the multicenter European Prostate Cancer Detection (EPCD) study. The EPCD study included 1051 men with a total PSA from 4 to 10 ng/ml who underwent a transrectal ultrasound (TRUS) guided sextant biopsy and a repeat biopsy in case of a negative initial biopsy. Most studies support that increasing the number of biopsy cores as compared to the sextant technique and improving prostate peripheral zone (PZ) sampling result in a significant improvement in the detection of prostate cancer without increase in morbidity or effects on quality of life. Re-biopsy can be performed 6 weeks later with no significant difference in pain or morbidity. At least 10% of patients with negative sextant prostatic biopsy results in the EPCD study were diagnosed with PCa on repeat biopsy, percent free PSA and PSA density of the transition zone being the most accurate predictors. Despite differences in location (more apico-dorsal) and multifocality, pathological and biochemical features of cancers detected on initial and repeat biopsy were similar, suggesting similar biological behavior and thus advocating for a repeat prostate biopsy in case of a negative finding on initial biopsy. Indications and ideal number of biopsy cores to take when repeating biopsies in patients who already underwent extensive biopsy protocols on the first biopsy remains to be determined.     

Prostate cancer detection at low prostate specific antigen

PURPOSE: At low prostate specific antigen (PSA) the indication for prostate biopsy is usually an abnormal digital rectal examination. We evaluate the diagnostic value of PSA, digital rectal examination, transrectal ultrasonography and tumor characteristics at low PSA (0 to 4.0 ng./ml.). We confirm and add to recent evidence that digital rectal examination has a low predictive value and that many significant cancers at this PSA range may be missed. MATERIALS AND METHODS: From 1994 to 1997 a total of 10,523 participants 54 to 74 years old were randomized to screening in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer. Of the participants 9,211 (87.5%) had PSA less than 4.0 ng./ml., and underwent digital rectal examination and transrectal ultrasonography. Expected rates of prostate cancer detection were calculated using logistic regression analysis. Radical prostatectomy was performed in about half of the 478 men diagnosed with prostate cancer. Tumors were characterized by pT category, Gleason score and cancer volume in 166 processed radical prostatectomy specimens. In 50 of these cases PSA was 0 to 4.0 ng./ml. RESULTS: The positive predictive value of digital rectal examination and transrectal ultrasonography at PSA 0 to 4.0 ng./ml. was only 9.7%. Positive predictive value strongly depended on PSA. Sensitivity was calculated by using estimates of the prevalence of sextant biopsy detectable prostate cancers. Of 760 detectable cancers 478 (67%) were diagnosed irrespective of PSA in men screened with digital rectal examination, transrectal ultrasonography and PSA. Only 127 of 348 detectable prostate cancers (36.5%) were actually diagnosed in men with PSA 2 to 4 mg./ml. The importance of these missed cancers was evaluated with parameters of tumor aggressiveness within PSA ranges. CONCLUSIONS: Approximately half of the tumors missed with PSA 0 to 4 ng./ml. had aggressive characteristics (Gleason score 7 or greater, Gleason 4-5 components) and were organ confined. These tumors should be diagnosed and treated according to the present understanding of their natural history. More sensitive and selective screening strategies are needed. Presently a wrong "window of opportunity" is used for early detection of prostate cancer.     

Prostate specific antigen based biennial screening is sufficient to detect almost all prostate cancers while still curable

PURPOSE: We evaluated whether biennial screening with prostate specific antigen (PSA) only is sufficient to detect prostate cancer while still curable. MATERIALS AND METHODS: In G?teborg, Sweden 9,972 men 50 to 65 years old were randomized to PSA screening. During 1995 and 1996 these men were invited for a first PSA screening and invited during 1997 and 1998 for a second screening. The screening procedure included PSA measurement in all men and in those with a PSA of 3 ng./ml. or greater also it included digital rectal examination, transrectal ultrasound and sextant biopsies. RESULTS: In the first screening 5,854 men participated and 145 cancers were detected. In the second screening 5,267 men participated and 111 cancers were detected. Only 9 interval cancers were diagnosed. In the second screening 102 cancers (92%) were associated with PSA less than 10 ng./ml. Of 465 men with increased PSA and who underwent biopsy with a benign outcome in the first screening 50 had cancer at the second screening. Of 241 men in whom PSA increased between screenings 1 and 2 cancer was detected in 46. None of the 2,950 men with an initial PSA of less than 1 ng./ml. had a PSA of greater than 3 ng./ml. or interval cancer. CONCLUSIONS: In men with a PSA of less than 2 ng./ml. it seems safe to offer repeat screening after 2 years with PSA only. Men with a PSA of 2 to 3 ng./ml. or a value of greater than 3 ng./ml. with negative biopsy may be better served by a shorter screening interval. Thus, different screening intervals are implied depending on baseline PSA.     

Serial biopsy results in prostate cancer screening study

PURPOSE: We evaluated prostate biopsy results in men with elevated prostate specific antigen (PSA) levels and/or suspicious digital rectal examination whose initial biopsies did not reveal cancer. MATERIALS AND METHODS: A total of 2,526 volunteers 40 years old or older underwent 1 or more prostate biopsies for serum PSA concentrations greater than 4.0 ng./ml. (before May 1995) or greater than 2.5 ng./ml. (after May 1995), or digital rectal examination suspicious of cancer. We evaluated compliance with the biopsy recommendation and the cancer detection rate with regard to digital rectal examination results and increasing PSA levels. RESULTS: Of the men who underwent up to 10 biopsy procedures the serial cancer detection rates were 29%, 17%, 14%, 11%, 9% and 7%, respectively, on biopsy procedures 1 through 6. No significant difference in the yield of cancer on serial biopsies was observed between the groups using the greater than 4.0 ng./ml. and greater than 2.5 ng./ml. cutoff. There was a trend for more cancers detected through serial screening to be organ confined compared with those detected on initial screening (78% versus 69%, p = 0.05). Also, more cancers detected using the greater than 2.5 ng./ml. cutoff were organ confined (80% versus 66%, p = 0.004). Only approximately 1% of the cancers fulfilled the published criteria for clinically insignificant tumors. CONCLUSIONS: Nearly a quarter of prostate cancers detected in this screening study were missed by the initial biopsy. Of the 962 prostate cancers detected 77% were detected with 1, 91% with 2, 97% with 3 and 99% with 4 biopsy procedures. Serial biopsies detect more organ confined cancers without over detecting clinically unimportant tumors. Future studies are needed to determine whether obtaining more biopsy cores initially would provide earlier prostate cancer detection and avoid unnecessary repeat biopsies.     

Prostate cancer screening with prostate specific antigen in spinal cord injured men

PURPOSE: As the spinal cord injured population ages, prostate cancer becomes a more significant cause of potential mortality. Consequently due to various bladder management techniques the validity of standard prostate specific antigen (PSA) screening values in this population must be evaluated. We compared screening PSA values in a large population of spinal cord injured patients with those in age matched, nonspinal cord injured men. MATERIALS AND METHODS: Screening PSA values were obtained using the AxSYM assay (Abbott Laboratories, Abbott Park, Illinois) in 366 spinal cord injured men 40 to 79 years old. In those with PSA elevated to greater than 4 ng./ml. who consented to further evaluation standard sextant needle biopsy of the prostate were performed under transrectal ultrasound guidance. Data were compared with data on 371 randomly selected, age matched controls from the Baylor College of Medicine community screening program database of more than 19,000 patient-tests. Analysis was performed with the unpaired Student t test. RESULTS: When we divided patients 40 to 80 years old into 4 age groups by decade and compared them with normal controls by decade, there was no statistically significant difference in mean PSA in the 2 groups. Of 18 spinal cord injured patients with PSA greater than 4 ng./ml. 12 underwent transrectal ultrasound guided needle biopsy of the prostate and 6 refused further evaluation. Five of these biopsies (1.3% overall) were positive and 7 were negative for adenocarcinoma. CONCLUSIONS: As in healthy men, PSA and digital rectal examination can be performed in spinal cord injured men to screen for prostate cancer. None of the various bladder management techniques in these cases seemed to affect screening results.     

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.