Digital rectal examination and the diagnosis of prostate cancer--a study based on 8 years and three screenings within the European Randomized Study of Screening for Prostate Cancer (ERSPC), Rotterdam

Background

Evidence indicates that an abnormal digital rectal examination (DRE) is a risk factor for high-grade prostate cancer (PC).

Objective

To determine whether men with an initially suspicious DRE, a prostate-specific antigen (PSA) level ≥3.0 ng/ml, and a benign prostate biopsy are at higher risk for significant PC at rescreening than men with an initially normal DRE, and whether an adaptation of the rescreening interval is warranted for this group.

Design, Setting, and Participants

Within the European Randomized Study of Screening for Prostate Cancer (ERSPC), Rotterdam, 2218 men underwent biopsy of the prostate (from 1993 to 2000) with a benign result at initial screening. The serum PSA was determined every 4 yr. A PSA level of ≥3.0 ng/ml prompted a DRE and a lateralised sextant biopsy.

Measurements

Number and characteristics of PCs found at repeat screenings and as interval cancers (ICs) were compared between men with or without a suspicious DRE result at initial screening. Multivariate logistic regression analyses were performed to evaluate if an initially suspicious DRE was a significant predictor for detecting cancer at consecutive screenings.

Results and Limitations

After 4 yr, the total number of PCs detected in men with and without an initially suspicious DRE was, respectively, 27 (6%) versus 103 (6%) (p = 0.99). After 8 yr these numbers increased, respectively, to,45 (10%) versus 167 (10%) (p = 0.88). The proportion of clinically significant PCs was 2% and 3%, respectively, for the group with initially normal and abnormal DRE after 8 yr. Having a suspicious DRE result at initial screening was not a significant predictor for detecting PC after 4 yr [odds ratio (OR) = 1.15, p = 0.59) or 8 yr (OR = 1.41, p = 0.43)]. A limitation of this study is the relatively short follow-up of 8 yr.

Conclusions

During a follow-up of 8 yr after initial cancer-negative biopsy, an initially suspicious DRE did not influence the chance for detection of cancer or significant cancer at later screens. An adaptation of the rescreening interval on the basis of the initial DRE-outcome is not warranted in future population-based screening for prostate cancer.     

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.     

Elevated serum prostate specific antigen levels in conjunction with an initial prostatic biopsy negative for carcinoma: who should undergo a repeat biopsy?

OBJECTIVE: To determine the outcome of repeated prostatic biopsies in men attending with suspected prostate cancer but an initial negative biopsy. PATIENTS AND METHODS: Patients who had undergone two or more transrectal ultrasonography (TRUS)-guided prostate biopsies were identified from the Hospital Information Support System database. Indications for TRUS were a raised prostate-specific antigen (PSA) level (>4.0 ng/mL), with or without an abnormal digital rectal examination (DRE). Sextant prostate biopsies plus biopsies of any suspicious hypoechoic area or area of DRE abnormality were obtained for histology. Forty-eight patients underwent repeat TRUS-guided prostatic biopsies (mean age 67.5, sd 7. 25, range 53-82 years). RESULTS: The mean (sd, median, range) PSA level was 16.9 (13.5, 11.6, 5.2-61.8) ng/mL. Fifteen patients (31%) had carcinoma on repeat biopsy, 11 after the second and four after a third biopsy. The positive repeat biopsy rate was 24% where the PSA level was 4.0-9.9 ng/mL, 33% if the level was 10.0-19.9 ng/mL and 39% if it was >/=20.0 ng/mL. There was no significant difference in age or initial PSA concentration between those men with positive and those with negative repeat biopsies. However, patients with cancer had significantly higher PSA levels before repeat biopsy than at first biopsy (P=0.0043) and had greater PSA velocities than had patients with no diagnosis of cancer (P=0.0067). CONCLUSION: Where sufficient clinical suspicion exists, despite an initial negative biopsy, repeat TRUS-guided prostate biopsies should be carried out to exclude carcinoma of the prostate.     

Predictors of subsequent prostate cancer in men with a prostate specific antigen of 2.6 to 4.0 ng/ml and an initially negative biopsy

PURPOSE: Almost 75% of men with a prostate specific antigen (PSA) of 2.6 to 4.0 ng/ml have no evidence of prostate cancer on biopsy. Deciding whether and when to repeat the biopsy is challenging. We determined if patient specific variables might identify men at increased risk for the subsequent detection of prostate cancer. MATERIALS AND METHODS: We analyzed the records of 24,893 men from a community based prostate cancer screening study. Our study group consisted of 1,202 men with PSA 2.6 to 4.0 ng/ml and a previously negative prostate biopsy. Patient specific variables were analyzed for their value in predicting a future diagnosis of prostate cancer. RESULTS: Of 1,011 men with adequate followup 136 (13.5%) were subsequently diagnosed with prostate cancer. Mean followup +/- SD in men without prostate cancer was 72 +/- 36 months. Prostate cancer was subsequently diagnosed in 35% of men with high grade prostatic intraepithelial neoplasia (HGPIN) on initial biopsy (p <0.0001), in 18% with abnormal or suspicious digital rectal examination (DRE) (p = 0.02) and 16% with an annual PSA velocity of 0 ng/ml (p = 0.002). Multivariate analysis identified HGPIN, initial PSA 3.6 to 4.0 ng/ml, abnormal DRE, family history of prostate cancer and annual PSA velocity 0 ng/ml as predictors of prostate cancer. CONCLUSIONS: Men with a PSA of 2.6 to 4.0 ng/ml and negative biopsy should be advised to undergo repeat biopsy if they have HGPIN, initial PSA 3.6 to 4.0 ng/ml, abnormal DRE, a family history of prostate cancer or a PSA velocity of 0 ng/ml or greater.     

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.     

Repeating the measurement of prostate-specific antigen in symptomatic men can avoid unnecessary prostatic biopsy

OBJECTIVES: To report the 2-year clinical and biochemical follow-up of symptomatic men who had a high prostate-specific-antigen (PSA) level, for whom our policy has been to avoid biopsy in those with a normal repeat PSA, as minimizing negative prostate biopsies is an important goal in managing men with a high PSA, where the decision for biopsy based on one high value may be inappropriate. PATIENTS AND METHODS: In all, 101 men (median age 72 years, range 47-85) referred to a urology department over 1 year with a PSA level above the age-specific reference range (but < 50 ng/mL) had a repeat PSA measurement. Those with a normal PSA and a normal digital rectal examination (DRE) were not biopsied. Their follow-up included a symptom review, DRE and PSA measurements. RESULTS: Of the 101 men, 67% presented with LUTS, 11% with symptoms of urinary infection, 8% with haematuria and 9% for screening. In 35 patients the repeat PSA level was normal; in three of these 35 prostate cancer was diagnosed after biopsy because of an abnormal DRE, three were lost to follow-up and one died from unrelated causes. Thus 28 patients were available for review at 2 years. In 23 (82%) the PSA remained within the normal range. In 66 of the 101 men the repeat PSA was abnormal. Cancer was diagnosed in 28 and the remaining 36 with no cancer were managed by PSA review; 30 were reviewed at 2 years and in half of them the PSA level returned to normal. CONCLUSIONS: In symptomatic men referred with a raised PSA level and who have a normal DRE and normal repeat PSA, prostatic biopsy can be safely avoided.     

ROLE OF PROSTATE-SPECIFIC ANTIGEN AND DIGITAL RECTAL EXAMINATION IN THE DETECTION OF PROSTATE CANCER

Prostate-specific antigen (PSA) is a kallikrein-like serine protease that is secreted exclusively by the epithelial cells of all types of prostatic tissue, benign and malignant. Its serum concentration is raised in men with prostatic disease including cancer. We have evaluated its usefulness in the diagnosis of prostate cancer by measuring serum PSA concentrations in 260 men aged 50 years or over. All had abnormalities at digital rectal examination (DRE) involving suspected cancer, signs and symptoms of benign prostatic hyperplasia and equivocal findings on DRE, and miscellaneous other conditions, including hematospermia, chronic prostatitis and microscopic hematuria. Transrectal prostatic needle biopsies were performed in the men with abnormal findings on DRE or elevated serum PSA (above 4ng/ml). Serum PSA ranged from 4.0 to 9.9ng/ml in 14 (5%) of the 260 men. Four of the men in this group (31%) who underwent prostatic biopsy had prostate cancer. Serum PSA levels greater than or equal to 10.0 ng/ml were found in 8 (3%) of the 260 men. 5 of these 8 (63%) who underwent prostatic biopsy had cancer. If DRE alone had been used to screen the men having biopsies, 4 of the 10 cancers (40%) would have been missed. If PSA alone had been used to screen these men, only 1 of the 10 cancers would have been missed. Serum PSA measurement was more reliable than DRE for detecting prostate cancer. Since these two methods do not always detect the same malignant tumor, the combined use of DRE and PSA testing affords a more complete evaluation of the prostate gland for malignant involvement.     

The role of the digital rectal examination in subsequent screening visits in the European randomized study of screening for prostate cancer (ERSPC), Rotterdam

BACKGROUND: The value of digital rectal examination (DRE) as a screening test for prostate cancer (PC) is controversial in the current prostate-specific antigen (PSA) era. OBJECTIVES: To determine (1) the additional value of a suspicious DRE for the detection of PC in men with an elevated PSA level in subsequent screenings and (2) the tumour characteristics of PCs detected in men with a suspicious DRE. DESIGN, SETTING, PARTICIPANTS: Within the screening study, from 1997-2006 men aged 55-75 years were invited for an every 4-yr PSA determination. A PSA level >/=3.0ng/ml prompted a DRE and a transrectal ultrasound (TRUS)-guided, lateralized sextant biopsy. Throughout the three screenings of the ERSPC, Rotterdam, 5040 biopsy sessions were evaluated. MEASUREMENTS: We determined the positive predictive values (PPVs) of a suspicious DRE and normal DRE, which entailed, respectively, the proportion of PCs detected in men with a suspicious DRE or normal DRE divided by, respectively, all biopsied men with a suspicious DRE or normal DRE. RESULTS AND LIMITATIONS: At initial screening, the PPV of a suspicious DRE, in conjunction with an elevated PSA level, to detect PC was 48.6% compared to 22.4% for men with a normal DRE. Both PPVs decreased in consecutive screens: respectively, 29.9% versus 17.1% (screen 2) and 21.2% versus 18.2% (screen 3). Respectively, 71.0% (p<0.001), 68.8% (p<0.001), and 85.7% (p=0.002) of all PCs with a Gleason score >7 were detected in men with a suspicious DRE at screens 1, 2, and 3. A limitation is that only biopsied men were evaluated. CONCLUSIONS: At initial and subsequent screenings, the chance of having cancer at biopsy was higher in men with a suspicious DRE compared to men with a normal DRE (to a lesser extent in subsequent screenings), and the combination of a PSA level >/=3.0ng/ml with a suspicious DRE resulted in detecting significantly more PCs with Gleason score >7. DRE may be useful in more selective screening procedures to decrease unnecessary biopsies and overdiagnosis.     

Anterior apical biopsy: Is it useful for prostate cancer detection?

Objectives: To evaluate the utility of a 12‐core prostate biopsy protocol including apical anterior peripheral zone (AAPZ) cores. Methods: Between February 2002 and October 2006, 10‐core and 12‐core initial transrectal prostate biopsies were performed on 164 and 549 men, respectively. Two AAPZ‐directed biopsies were included in the 12‐core biopsy. During the same period, 12‐core repeat biopsies including six AAPZ sites were performed on 118 men. Results: Cancer was found in 66 cases (40.2%) in the 10‐core biopsy group and in 252 (45.9%) in the 12‐core biopsy group. In this latter group, 13 (5.2%) of the 252 men with positive biopsy had cancer exclusively in the AAPZ cores. When the cancer detection rate at initial biopsy in AAPZ alone was compared according to the digital rectal examination (DRE) findings, it was significantly higher in men with normal rather than abnormal DRE: 12/250 (3.4%) vs 1/185 (0.5%) (P < 0.01). In repeat 12‐core biopsies, cancer was detected in 25 (21.2%) men and 9 of them (36.0%) had cancer exclusively in the AAPZ cores. The cancer detection rate from AAPZ sites was significantly higher in repeat biopsy than that in initial biopsy (P < 0.01). Conclusions: Addition of the AAPZ site‐directed biopsy had greater utility in men with normal DRE and particularly in patients with a prior negative biopsy.     

Are prostatic biopsies necessary in men aged > or =80 years?

OBJECTIVE: To examine whether prostatic biopsies are necessary in all men aged > or =80 years, as men found to have prostate cancer are frequently treated with a 'watch and wait' policy or with hormonal withdrawal alone, and biopsies are associated with a small but significant complication rate. PATIENTS AND METHODS: The findings on a digital rectal examination (DRE), the prostate-specific antigen (PSA) level, the biopsy and staging bone scan results for all men aged > or = 80 years who had prostatic biopsies over a 3-year period were reviewed, together with those in a group of men aged <80 years for comparison. All biopsy samples had been examined in one of three histopathology units, and 33 consultant urological surgeons contributed. RESULTS: In all, 210 biopsies from 205 men aged > or = 80 years were identified, of whom 163 (79%) had biopsy-confirmed prostate cancer. All 29 men with a PSA level of > or = 100 ng/mL, 98% of 47 with > or = 50 ng/mL, 97% of 76 with > or = 30 ng/mL and 92% of 101 with > or = 20 ng/mL had biopsy cores containing cancer; 63% of men with a PSA level of <20 ng/mL had cancer on biopsy. In men with cancer and a PSA level of > or = 30 ng/mL, 92% had Gleason grade > or = 7 and 93% were treated with hormonal withdrawal alone. In all men with cancer the DRE was abnormal in 91%, the mean number of positive cores was 59% and the bone scan was positive in 18%. The DRE was abnormal in 77% of men with benign biopsies. CONCLUSIONS: In men aged > or = 80 years with a PSA level of > or = 30 ng/mL, at least 97% had prostate cancer, >90% of whom had high-grade disease, and nearly all with cancer received active pharmacological treatment. In the vast majority of these men prostate biopsies did not alter their cancer management. The value of prostatic biopsy in this age group, with a PSA level of > or = 30 ng/mL, is questionable.     

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.     

Repeat prostate biopsy in the prostate, lung, colorectal and ovarian cancer screening trial

OBJECTIVE: To determine patterns of repeat prostate biopsy in a cohort of men undergoing prostate cancer screening who have a negative initial biopsy. SUBJECTS AND METHODS: The Prostate, Colorectal, Lung, and Ovarian (PLCO) cancer screening trial is an ongoing study the prostate component of which consists of six annual screens with measurements of prostate-specific antigen (PSA) level and a digital rectal examination (DRE). The diagnostic follow-up of positive screening results is done by the subject's healthcare provider outside the purview of the PLCO. We analysed the experience of repeat biopsy in men in the PLCO with an initial negative biopsy. Men were divided by indication for initial biopsy into those with suspicious PSA levels and those with suspicious DRE findings. RESULTS: The probability of having a repeat biopsy within 3 years of initial biopsy was 43% for 1736 men with suspicious PSA levels and 13% for 1025 men with suspicious DRE findings. Rates of third and fourth biopsy after a previous negative biopsy were similar to the initial repeat biopsy rate in PSA-positive men. Most men had a repeat biopsy only after having an additional round of screening. The PSA level and PSA velocity determined after initial biopsy were independent risk factors for a repeat biopsy, both in PSA-positive and DRE-positive men. High-grade prostatic intraepithelial neoplasia was a risk factor for repeat biopsy before any repeat PSA or DRE testing. CONCLUSION: The experience of this cohort should be generally representative of patterns of care for repeat biopsy in men undergoing periodic screening. These data can provide context to the debate over optimum practices for repeat biopsy.     

Impact of immediate TRUS rebiopsy in a patient cohort considering active surveillance for favorable risk prostate cancer

Introduction and ObjectiveActive surveillance (AS) is an option for the management of favorable risk prostate cancer (CaP) in the PSA era. Published studies have reported variable inclusion criteria for cohort selection. Accurate assessment of individual patient risk in AS is dependent not only upon rigorous selection criteria, but also reliability of diagnosis at tissue biopsy. To date, the impact of immediate transrectal ultrasound (TRUS) rebiopsy in confirming candidates for AS has been incompletely defined.MethodsFrom a total of over 567 men, 67 met criteria for AS (Gleason <7, PSA <10, PSAD <0.15, <3 cores with <50% involvement of any 1 core). Fifty-two men agreed to a 12-core TRUS rebiopsy within 6 months of first diagnosis performed in clinic. Statistical analysis was performed using Wilcoxon signed rank test and logistic regression to determine predictors of rebiopsy characteristics, histopathologic outcomes, and impact on treatment choice.ResultsMean cohort age was 63.9 years (range 56–72 years), PSA 5.9 ng/ml (4.1–10), and PSA density 0.12 ng/ml/cc at initial biopsy. Tumor involved 1.1 cores and 3.2% (range 1%–5%) of the total tissue. Average time to rebiopsy was 2.7 months. Notably, 29 of 52 men (56%) demonstrated no evidence of CaP on repeat biopsy; 14 of 23 men with a positive repeat biopsy showed either an increase in cancer volume (2.8% mean increase) and 9 (18%) were upgraded to Gleason pattern 3+4 = 7. Rebiopsy demonstrated 9 (17%) patients exceeded AS criteria. Nine patients chose curative surgical intervention (radical prostatectomy) based on increased cancer volume or grade (4) or an elective desire for treatment (5). All had organ confined disease with negative margins on final pathologic analysis. Statistical review revealed that initial Gleason score, PSA density, and number of positive cores at first biopsy were not predictive of men with higher volume/grade on re-biopsy.ConclusionsImmediate TRUS repeat biopsy after diagnosis frequently fails to redemonstrate prostate cancer confirming the favorable-risk nature of disease burden in this group being considered for AS. A subset of patients are upgraded (17%) leading to reconsideration of AS. We conclude this clinic-based approach provides valuable additional information to discriminate appropriate AS candidates.     

Digital rectal examination as a prostate cancer-screening method in a country with a low incidence of prostate cancer

The objective of this study was to evaluate the value of using digital rectal examination (DRE) for prostate cancer diagnosis in an Asian population. Patients with serum prostate-specific antigen (PSA) levels ranging from 2.5 to 19.9 ng/ml underwent transrectal ultrasonography-guided prostate biopsies. Patients were divided into two groups: the normal DRE group (n=721) and the abnormal DRE group (n=192). The cancer detection rate was higher in the abnormal DRE group (47.4%) than in the normal DRE group (23.0%) (P<0.001). However, the detection rates in these two groups were not significantly different in men 45-59 years old as well as in men with low PSA levels (2.5-3.9 ng/ml). In all subjects, the areas under the receiver operating characteristic curves for positive biopsies were 60.0% (95% confidence interval (CI), 55.7-64.3%, P<0.001). However, in the subgroup analysis, the predictive power of the DRE was not significant in men 45-59 years old. In addition, DREs of patients with low PSA levels had no discriminative ability. The pathological features of the prostate biopsies were not significantly different between the two groups in subjects 45-59 years old and in subjects with PSA levels from 2.5 to 3.9 ng/ml. Our data indicate that DREs increase the probability of cancer detection. However, our findings also raise the question, 'Are DREs really useful for cancer detection in younger men and men with low PSA levels in the Asian population?'     

Screening for prostate cancer without digital rectal examination and transrectal ultrasound: results after four years in the European Randomized Study of Screening for Prostate Cancer (ERSPC), Rotterdam

BACKGROUND: Omission of DRE/TRUS as biopsy indication results in fewer unnecessary biopsies, but may increase the risk of missing potentially aggressive prostate cancers (PCs). In 1997, the biopsy indication within the ERSPC was changed from a PSA cut-off of 4.0 ng/ml and/or abnormal DRE/TRUS (group-1) to solely a PSA cut-off of 3.0 ng/ml (group-2). We estimated the effect of omitting DRE/TRUS by comparing the results of a re-screening 4 years after initial screening to the original policy. METHODS: We compared rate and characteristics of detected PCs in the second round in men initially screened in group-1 (N=5,957) or group-2 (N=8,044). Additionally, we compared the rate of interval cancers (ICs) after screening with and without DRE/TRUS. RESULTS: There was no significant difference in second round cancer-detection-rates (group-1, 3.0%; group-2, 2.7%), positive-predictive-values (group-1, 23.9%; group-2, 26.3%), and number of poorly-differentiated tumors (group-1, 2.6%; group-2, 3.8%). Most PCs were clinically confined to the prostate. Eleven ICs were detected in each group (0.18 and 0.14%). CONCLUSIONS: Omitting DRE/TRUS did not result in an increased IC- or PC-detection. However, considering the natural history of PC, the 4-year follow-up may be too short to draw a definitive conclusion.     

Community‐based prostate cancer screening in Japan: Predicting factors for positive repeat biopsy

Objectives: To assess possible predictors in determining criteria for repeat biopsy in a prostate cancer screening population. Methods: A total of 50 207 men over 55 years‐of‐age have participated in a prostate cancer screening program in Otokuni, Kyoto, Japan for 12 years. Transperineal systematic biopsy was carried out in case of positive digital rectal examination (DRE) or positive transrectal ultrasonography (TRUS) or a prostate‐specific antigen (PSA) value greater than 10.0 ng/mL. For those with a PSA level from 4.1 to 10.0 ng/mL, and negative DRE and TRUS findings, biopsy was indicated only when PSA density (PSAD) was greater than 0.15. The same indication was applied for the repeat biopsy. Results: A repeat biopsy after an interval of more than 2 years was carried out in 140 patients and was positive in 50 (36%) patients. The PSA value at the diagnosis of cancer declined from the initial value in six (12%) patients. On multivariate logistic regression analysis, PSA velocity (PSAV) as well as PSAD and DRE findings at latest screening were independent predictors for positive repeat‐biopsy outcome. The odds ratio (95% confidence intervals) of PSAV >0.48, latest PSAD >0.33 and positive latest DRE were 4.17 (1.05–18.5), 4.15 (1.31–14.0), and 3.62 (1.06–13.2), respectively. A combination of three variables defined as positive if any of these were positive, reduced 31% of unnecessary biopsies while missing 8% of low volume, low grade cancers. Conclusions: A combination of latest PSAD, PSAV and positive DRE at latest screening might help to reduce unnecessary repeat biopsies in high‐risk patients with an initial negative biopsy.     

Prostate biopsy following a positive screen in the prostate, lung, colorectal and ovarian cancer screening trial

PURPOSE: The benefit of prostate specific antigen (PSA) and digital rectal examination (DRE) screening for prostate cancer is under evaluation in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Followup of positive screens in PLCO is done by subject personal physicians and it is outside of trial control. We describe the pattern of prostate biopsy in men with positive screens in PLCO. MATERIALS AND METHODS: We examined all men with positive baseline PSA or DRE screens and men with positive post-baseline screens occurring by December 2000. RESULTS: Of 2,717 men with positive PSA (greater than 4 ng/ml) at baseline 41% and 64% underwent biopsy within 1 and 3 years, respectively. A screening PSA of 7 to 10 and greater than 10 ng/ml at baseline was associated with significantly higher biopsy rates (HR 1.9 and 2.6, respectively) compared to PSA 4 to 7 ng/ml. The 1,793 in men whom the first positive PSA was after baseline had a lower overall biopsy rate (50% within 3 years). Furthermore, PSA above 7 ng/ml were not associated with higher biopsy rates in this group. The 4,449 men with positive DRE screens and negative PSA had a 3-year biopsy rate of 27%. Men with positive DRE at diagnostic followup had a biopsy rate of around 90%. However, few men, even of those with positive DRE screens, had positive diagnostic DREs. CONCLUSIONS:: These biopsy rates following positive PSA and DRE screens are likely to be representative of national rates. These results suggest that PLCO is evaluating the effects of screening in a contemporary and robust manner.     

The value of endorectal MRI in the early diagnosis of prostate cancer

OBJECTIVE: Assess the value of endorectal MR imaging (EMRI) in the early diagnosis of prostate cancer (PCa) and compare this test to prostate specific antigen (PSA) and digital rectal examination (DRE) in the prediction of negative biopsies. MATERIAL AND METHODS: 92 patients with elevated PSA (>4 ng/ml) and/or abnormal DRE were studied. All patients underwent an EMRI previous to transrectal ultrasound guided needle sextant biopsies (3 cores in each peripheral zone), and were followed up. We performed a total of 184 biopsies: 92 patients underwent 1 biopsy; out of them, 61 patients underwent 2 biopsies, 27 patients 3 biopsies, 3 patients 4 biopsies and 1 patient 5 biopsies. 67 patients had a final negative biopsy and 25 had a final positive biopsy. Mean PSA was 10.44 ng/ml, and the mean % fPSA/tPSA was 0.20. Uni- and multivariate analysis and ROC curves were used to compare the accuracy of the different tests. The probability of positive biopsy with each technique was also assessed. RESULTS: EMRI had a high negative predictive value (91.07%) and the highest accuracy (77%) of all tests, higher than PSA (62%). Mean PSA was not statistically different in patients with negative biopsies (9.44 ng/ml) and positive biopsies (11.8 ng/ml) (p=0.064). The association of EMRI-DRE-PSA had the highest accuracy (83%) significantly higher than DRE-PSA (70%). The probability of positive biopsy in patients with negative DRE and EMRI, and PSA values between 5 and 15 ng/ml was 5-10% at first and second biopsies, but decreased progressively on subsequent biopsies (<8% at third biopsy, <5% at fourth biopsy and <3% at fifth biopsy). CONCLUSION: In patients with elevated PSA and/or abnormal DRE with two previous negative biopsies, an EMRI is a useful test to rule out PCa, when negative, and avoid subsequent biopsies, as they have a low chance of positive biopsy.     

Clinical, biochemical and pathological features of initial and repeat transrectal ultrasonography prostate biopsy positive patients

BACKGROUND: Using sextant biopsy, 16-41% of prostate cancers were diagnosed on repeat biopsy. The objective of the present study was to compare the differences in the clinical, biochemical and pathological features between patients with positive results on initial and repeat biopsies, with an aim to identify factors that can be used to improve the detection rate of transrectal ultrasound (TRUS) biopsy of the prostate. METHODS: Between February 2000 and April 2001, 222 patients with a mean age of 64 years (range 38-85) underwent TRUS-guided 10-core prostate biopsy for either abnormal prostate specific antigen (PSA) levels (>4 ng/mL) and/or abnormal digital rectal examination (DRE). Of this number, 165 patients underwent their first biopsy, whereas 45 and 12 patients had had one or two previous biopsies, respectively. RESULTS: Prostate cancer detection rates for the initial biopsy group (n = 165), second biopsy group (n = 45) and third biopsy group (n = 12) were 29.7, 23.0 and 41.7%, respectively. Six patients who had a negative first 10-core biopsy underwent a second 10-core biopsy and one patient (16%) was found to have cancer. Apart from total prostate volume, there were no significant statistical differences between the patient age, mean total PSA, PSA density, PSA-transition zone density, DRE and TRUS findings between the initial and repeat biopsy groups of subjects who had cancer. Those who had cancer detected only on repeat biopsies had larger prostate glands (P = 0.041). CONCLUSION: Patients who had cancer detected only on repeat biopsies had bigger prostate glands, supporting the hypothesis that TRUS sextant biopsy as a technique suffers the error of under-sampling in a bigger prostate.     

Adenocarcinoma of the prostate in men younger than 40 years of age: diagnosis and treatment with emphasis on radical prostatectomy findings

Objectives. Prostate cancer is rarely diagnosed in men younger than 40 years of age. It is thought, although not documented, that these tumors behave particularly aggressively.Methods. We studied 87 men younger than 40 years old who underwent prostate needle biopsy and were from three populations: (a) 71 cases (63 benign, 7 cancer) from Dianon Systems; (b) 9 needle biopsies with cancer sent to one of us (J.I.E.) in consultation; and (c) 7 men with cancer who came to Johns Hopkins for consultation.Results. The median age of men with a benign biopsy was 35 years (mean 33.9, range 22 to 39); the median age of men with cancer was 38 years (mean 35.9, range 22 to 39) (P = 0.004). The most common indications for biopsy were abnormal digital rectal examination (DRE) (n = 61); elevated prostate-specific antigen (PSA) (n = 14), and inflammatory symptoms (n = 12). Other reasons cited included hematuria, abnormal ultrasound, pain, ejaculatory problems, obstructive symptoms, and family history of prostate cancer. The median PSA was 2.6 ng/mL (mean 4.8, range 0.3 to 66) for all men, 1.2 ng/mL (mean 3.4, range 0.3 to 19.9) for benign cases, and 4.4 ng/mL (mean 8.7, range 2.1 to 66) for cancer (P = 0.0004). Abnormal DRE was not predictive of cancer. Of the 55 patients whose family history was known, 40 men had no family history of prostate cancer, and of those, only 6 (15%) had cancer. Of the 15 patients with a family history of cancer, 6 (40%) were found to have cancer on biopsy (P = 0.05). Of the 23 patients with cancer, 3 were lost to follow-up, 1 was treated with hormones, and 3 chose watchful waiting. The remaining 16 patients underwent radical prostatectomy and had diverse pathologic findings. Tumor volume ranged from 0.01 to 6.35 cc. Pathologic stage was pT2 in 9 cases and pT3 in 7 cases (2 with positive pelvic lymph nodes). In 14 men, serum PSA values were available: of 4 men with PSA greater than 10 ng/mL, all had Stage pT3, and of 10 men with PSA less than 10 ng/mL, 3 had Stage pT3.Conclusions. Young men who are candidates for radical prostatectomy have potentially curable disease, particularly if PSA at the time of diagnosis is less than 10 ng/mL.