Can MRI Help Inform Which Men With a History of Multifocal High-Grade Prostatic Intraepithelial Neoplasia or Atypical Small Acinar Proliferation Remain at an Elevated Risk for Clinically Significant Prostate Cancer?

PURPOSE: We investigated the association of MRI findings in men with a previous diagnosis of atypical small acinar proliferation (ASAP) or multifocal high-grade intraepithelial neoplasia (HGPIN) with pathologic findings on repeat biopsy. MATERIALS AND METHODS: We retrospectively reviewed patients with ASAP/multifocal HGPIN undergoing a repeat biopsy in the Michigan Urological Surgery Improvement Collaborative registry. We included men with and without an MRI after the index biopsy demonstrating ASAP/multifocal HGPIN but before the repeat biopsy. Men with an MRI prior to the index biopsy were excluded. We compared the proportion of men with ≥ GG2 CaP (Grade Group 2 prostate cancer) on repeat biopsy among the following groups with the χ2 test: no MRI, PIRADS (Prostate Imaging-Reporting and Data System) ≥ 4, and PIRADS ≤ 3. Multivariable models were used to estimate the adjusted association between MRI findings and ≥ GG2 CaP on repeat biopsy. RESULTS: Among the 207 men with a previous diagnosis of ASAP/multifocal HGPIN that underwent a repeat biopsy, men with a PIRADS ≥ 4 lesion had a higher proportion of ≥ GG2 CaP (56%) compared with men without an MRI (12%, P < .001). A lower proportion of men with PIRADS ≤ 3 lesions had ≥ GG2 CaP (3.0%) compared with men without an MRI (12%, P = .13). In the adjusted model, men with a PIRADS 4 to 5 lesion had higher odds (OR: 11.4, P < .001) of ≥ GG2 CaP on repeat biopsy. CONCLUSIONS: MRI is a valuable diagnostic tool to triage which men with a history of ASAP or multifocal HGPIN on initial biopsy should undergo or avoid repeat biopsy without missing clinically significant CaP.

Multiparametric MR can identify high grade prostatic intraepithelial neoplasia (HGPIN) lesions and predict future detection of prostate cancer in men with a negative initial prostate biopsy.

PURPOSE: This study aims to determine the pre-biopsy diffusion-weighted imaging (DWI) and magnetic resonance spectroscopic imaging (MRSI) characteristics of patients with high-grade prostatic intraepithelial neoplasia (HGPIN) and perform follow-up studies in these patients to assess the clinical implications. MATERIALS AND METHODS: One hundred sixteen men with prostate specific antigen between 4 and 10ng/ml underwent pre-biopsy MR examinations. Nine of them had HGPIN lesions without concomitant prostate cancer (PCa) on biopsy. Apparent diffusion coefficient (ADC) and metabolite ratio [Citrate/(Choline+Creatine)] were calculated and these 9 patients were followed to determine the clinical outcomes. RESULTS: Mean ADC for HGPIN foci was 1.01±0.16×10(-3)mm(2)/s while for the normal peripheral zone it was 1.69±0.25×10(-3)mm(2)/s (p<0.005). Mean metabolite ratio for voxels in the HGPIN region of initial biopsy was 0.24±0.16 while for the normal peripheral zone the value was 2.66±1.57 (p<0.005). Four of 5 patients who were available for follow-up were detected to have prostate cancer on repeat biopsy. No significant change in metabolite ratio and PSA was observed while ADC showed further reduction on follow-up. CONCLUSION: HGPIN foci have ADC and metabolite ratio values similar to adenocarcinoma prostate, indicating that such patients have a high likelihood of developing cancer. DWI may help identify such men who may be candidates for close follow-up.

Utility of Histoscanning™ prior to prostate biopsy for the diagnosis of prostate adenocarcinoma.

OBJECTIVES: HistoScanning™ (HS) is a method of ecographic diagnosis of prostate cancer. We analyze the effectiveness of the HS realization prior to the biopsies for the prostate adenocarcinoma diagnosis. MATERIAL AND METHODS: From August to October 2012 we have carried out a study with HS prior to the biopsies in 32 patients. In all cases sextants transrectal biopsies have been realized (two cores in each sextant) in the periphery zone. In those sextants in which there were suspicious areas with HS, the biopsies were addressed to those areas. Transperineal biopsies were added to those zones placed in the half-front or apical prostatic zone. The medium age was 63.7 years (range 40-82) with a medium PSA of 8.0 ng/ml (range 3.5-36.2) and a medium prostatic volume of 46.6cc (range 18.2-103.2). In eight cases it was the first biopsy, in 14 cases they were repetition biopsies and 10 patients had a previous diagnosis of prostate adenocarcinoma (8 in a program of active surveillance and 2 T1a in RTU of previous prostate). RESULTS: In the 32 patients a medium of 7,5 zones were biopsied (range 6-9) with a total of 239 zones studied. There were identified a medium of 3.2 zones with suspicious areas (ZS) with HS (range 2-5) with a total of 103 ZS. In 72 zones of 25 patients it was found adenocarcinoma or PIN (2 PIN, 11 score Gleason 6, 7 score Gleason 7, 3 score Gleason 8 and 2 score Gleason 9). There were 35 positive false zones in 20 patients (11 normal parenquima and 9 chronic inflammation). Negative falses were produced in 5 zones in 5 patients (2PIN, 2 score Gleason 6 and 1 score Gleason 7) although in all 5 cases adenocarcinoma was encountered (o discovered) in other zones. The HS presented a sensibility of a 93.5% with a specificity of 79.5%. The positive predictive value was of the 67.35% with a negative predictive value of 96.5%. CONCLUSIONS: In spite of being a selected serie, with a high rate of patients with adenocarcinoma, the exploration with HS has presented a great sensibility and a high negative predictive value. These data, although they must be confirmed in less selected series, state that the prior exploration with HS can help as in the diagnostic in the biopsies as in the follow-up of programs of active surveillance.

In situ and intraductal epithelial proliferations of prostate: definitions and treatment implications. Part 2: intraductal carcinoma and ductal adenocarcinoma of prostate.

• High-grade prostatic intraepithelial neoplasia (HGPIN) is an intracellular proliferation of ductal epithelial cells. On its own, the presence of HGPIN does not warrant active intervention. • In contrast, intraductal carcinoma of prostate and prostatic ductal adenocarcinoma of prostate are markers of aggressive prostatic adenocarcinoma. • The presence of even small foci of these tumours on biopsy warrants immediate intervention, even in the absence of demonstrable invasive disease. • This second part of the review of in situ epithelial proliferations of the prostate looks at these conditions in more detail.

Annotating MYC status with 89Zr-transferrin imaging.

A noninvasive technology that quantitatively measures the activity of oncogenic signaling pathways could have a broad impact on cancer diagnosis and treatment with targeted therapies. Here we describe the development of (89)Zr-desferrioxamine-labeled transferrin ((89)Zr-transferrin), a new positron emission tomography (PET) radiotracer that binds the transferrin receptor 1 (TFRC, CD71) with high avidity. The use of (89)Zr-transferrin produces high-contrast PET images that quantitatively reflect treatment-induced changes in MYC-regulated TFRC expression in a MYC-driven prostate cancer xenograft model. Moreover, (89)Zr-transferrin imaging can detect the in situ development of prostate cancer in a transgenic MYC prostate cancer model, as well as in prostatic intraepithelial neoplasia (PIN) before histological or anatomic evidence of invasive cancer. These preclinical data establish (89)Zr-transferrin as a sensitive tool for noninvasive measurement of oncogene-driven TFRC expression in prostate and potentially other cancers, with prospective near-term clinical application.

[Prostate biopsy: Diagnostic responsibility and recent changes]. / Biopsia prostática: responsabilidad diagnóstica y cambios recientes.

In this bibliographic review we reexamine the different features in relation to indication, performance and interpretation of prostatic biopsy (PB). The main objective is to place methodological features involving PB in the current scientific scenario, establishing the correlation between the most relevant and analyzing the historic evolution this procedure has followed, particularly over the last two decades. Prostate biopsy has evolved to be a regular element in urologists` daily practice and its learning process has been simplified to the point it can be approached with adequacy during the first years of residency in Urology. This privileged position PB enjoys in daily practice and the performance obtained from it would have not been a reality without optimization of transrectal ultrasound or local anesthesia techniques, yet reviled in some forums, the real responsible of such success. The consensus reached in the various scientific associations, the clinical guidelines of which are widely consulted worldwide, is the best to support the current state of the art, being the starting point for the addition of new improvements to PB.

Contrast-enhanced colour Doppler-targeted vs a 10-core systematic repeat biopsy strategy in patients with previous high-grade prostatic intraepithelial neoplasia.

OBJECTIVE: To compare the results of contrast-enhanced colour Doppler (CECD)-targeted prostate biopsy with a systematic 10-core grey-scale biopsy scheme in patients initially diagnosed with high-grade prostatic intraepithelial neoplasia (HGPIN), as although HGPIN is thought to be a precursor to invasive adenocarcinoma, its diagnosis is no longer considered an indication for repeat prostate biopsy and patients should be followed by prostate-specific antigen levels and a digital rectal examination. PATIENTS AND METHODS: In all, 104 patients (aged 45-78 years) diagnosed with HGPIN on initial prostate needle biopsy were referred for a repeat biopsy within 6 months. Two independent examiners evaluated each patient; one used CECD-targeted biopsy (up to five cores) into hypervascular regions in the peripheral zone only, and subsequently the second took a systematic 10-core grey-scale biopsy. Cancer detection rates of both techniques were compared. RESULTS: Overall, 26 of the 104 men (25%) had prostate cancer in the repeated biopsy. Using the CECD technique cancer was detected in 21% (22 of 104). The positive re-biopsy rate using the systematic technique was 9.6% (10 of 104; P < 0.001). The total incidence of HGPIN with no evidence of tumour on re-biopsy was 8.7% (nine of 104). The Gleason score in all 22 cancers detected with the CECD technique varied between 6 and 8. The systematic technique detected cancers with Gleason scores of 6 or 7. There were no adverse events or complications. CONCLUSION: CECD increased the detection rate of prostate cancer, and using fewer biopsy cores than the systematic biopsy technique in patients previously diagnosed with HGPIN.

The clinical and pathological history of prostate cancer progression in men with a prior history of high grade prostatic intraepithelial neoplasia.

OBJECTIVES: The natural history of high grade prostatic intraepithelial neoplasia (HGPIN) is incompletely understood limiting evidence based recommendations regarding screening and repeat biopsy intervals. Our objective was to evaluate the natural history of HGPIN to better assess the time frame to disease progression and the pathological findings at the time of progression to cancer. METHODS AND MATERIALS: We retrospectively reviewed 74 consecutive patients with an initial diagnosis of HGPIN. The number and timing of all biopsies leading to the diagnosis of cancer were assessed. Clinical and pathological features of those patients with eventual disease progression were evaluated. RESULTS: The mean number of biopsies performed before subsequent cancer diagnosis was 5 (range: 3-13). The mean time to the diagnosis of cancer was 29 months (range: 7-83). Men with a history of HGPIN had lower percent positive biopsies at the time of cancer diagnosis (p < 0.001) and smaller volume tumors on final pathology (p = 0.041) compared to men without a history of HGPIN. CONCLUSIONS: Patients with an initial diagnosis of HGPIN on transrectal ultrasound (TRUS) guided biopsy progressed to cancer at a mean of 29 months. The vast majority of patients that progressed to prostate cancer had low volume disease at the time of diagnosis and definitive treatment. Our data indicate the importance of re-evaluation in HGPIN patients and suggest a trend toward low volume disease in carefully followed patients. Prospective data is warranted to adequately define an evidence based biopsy regimen in men with HGPIN.

Biopsy standards for detection of prostate cancer.

The widespread use of measurement of prostate-specific antigen for prostate cancer screening has led to a dramatic increase in the number of transrectal biopsies. Although transrectal ultrasound-guided prostate biopsy is the gold standard in the diagnosis of prostate cancer, the strategies for initial and repeat biopsies remain controversial. Over the past decade numerous biopsy protocols have been developed. Several protocols have been established that increase the number of cores by combining sextant and lateral biopsies to increase the cancer detection rate. We review the current methods of prostate biopsies, the indication to perform an initial and repeat biopsy, the impact of prostate volume on the number of cores taken, and the morbidity of the procedure.

Controversies in transrectal ultrasonography and prostate biopsy.

Transrectal ultrasound-guided biopsy of the prostate is the gold standard for the detection of prostate cancer. In its current form, transrectal gray-scale ultrasound is unable to differentiate malignant prostate tissue from benign tissue. The general indications for performing a sonographic guided biopsy of the prostate are an abnormal digital rectal examination or an abnormal prostate-specific antigen (PSA). Several controversial areas remain: the ideal number of biopsy cores, the use of PSA velocity, free PSA, PSA density, age- and race-adjusted PSA, the use of local anesthetics, and the overall best patient preparation methods, including such topics as routine antibiotic prophylaxis or bowel enemas, remain unsettled. There are also unanswered questions regarding repeat biopsy and protocols for managing patients with a diagnosis of high-grade intraepithelial neoplasia. This article will explore some of the current controversies and review the pertinent literature.

[Prognostic significance of PIN and Atypical Small Acinar Proliferation on transrectal ultrasound-guided prostate biopsy]. / Significación pronóstica del PIN y la atípia glandular focal en la Biopsia Transrectal Ecodirigida de Próstata.

OBJECTIVE: To review the incidence of PIN and Atypical Small Acinar Proliferation (ASAP) on first biopsy, the risk to find cancer on following biopsies and what is the importance given to this findings, analizing how frequently and how long after the initial finding this patients are rebiopsied. METHOD: We selected 6000 patients who underwent TRUS biopsy between 1994 and 2002. Patients with prior cancer diagnosis were not included. 861 of them underwent more than one biopsy, adding up to a total of 7127 biopsies. A descriptive study has been done including percentages and percentiles for qualitative variables, mean and median for continuous variables. RESULTS: Incidence of cancer on the first biopsy was 39,1%. PIN and ASAP are stable or slightly increase from 2 and 2,1% respectively on the first biopsy to more than 6% on the fourth and fifth ones. Mean time between biopsies when ASAP or PIN are the initial findings is 180 +/- 221,6 and 264 +/- 213,8 days respectively. Just 42 and 40% of patients with prior PIN or ASAP diagnose are rebiopsied. On subsequent biopsies 45 and 40% of cancers were respectively found. CONCLUSIONS: Presence of PIN or ASAP implies a higher cancer risk on subsequent biopsies; in spite of that, less than half of them are biopsied again. Performing two more biopsies or an amplified biopsy can find most of the tumors associated.

Prostatic intraepithelial neoplasia: a risk factor for prostate cancer.

Prostatic Intraepithelial Neoplasia (PIN) is an increasingly common finding at ultrasound guided prostate biopsy, with the high grade form (HGPIN) thought to be "precancerous". With the more widespread use of extended biopsy protocols, taking sometimes up to 14 cores or more, the incidence of HGPIN can be up to 25%. Histologically, it has many features in common with cancer of the prostate and has been shown to be both associated with cancer at the time of its finding and predictive for the development of prostate cancer in the future. Basic science research has demonstrated genes common specifically to both prostate cancer and HGPIN and immunostaining studies of microvessel density may help to differentiate HGPIN from lower risk PIN. There are no active treatments for HGPIN although there are trials to assess the effectiveness of hormonal therapy and nutritional supplements. Currently most urologists recommend that patients should be followed at 6 monthly intervals with regular PSA and repeat biopsies as indicated.

Transrectal sonographic features of prostatic intraepithelial neoplasia: correlation with pathologic findings.

PURPOSE: This study was conducted to evaluate the transrectal sonographic (TRUS) features of prostatic intraepithelial neoplasia (PIN) by comparing the histopathologic results with TRUS findings in patients who had undergone TRUS-guided prostate biopsy. METHODS: From an initial set of 307 patients who underwent TRUS-guided prostate biopsy, TRUS findings for 44 patients whose pathologic results were consistent with PIN were reviewed retrospectively. Among these 44 patients, 12 had only PIN, 20 PIN associated with prostatitis, and 12 PIN associated with prostate cancer foci. After exclusion of the foci that included PIN associated with prostatitis and PIN associated with prostate cancer at the same site, the pathologic results for the core specimens from the 100 PIN foci were correlated with TRUS findings according to their location. The sonographic features sought were hypoechoic areas and regions of heterogeneous echogenicity. RESULTS: Positive TRUS findings were detected in 43% of PIN and 36% of high-grade PIN (HGPIN) focise. For the HGPIN foci with positive TRUS findings, the detected sonographic features were clusters of millimetric hypoechoic foci (CMHF) (53%), hypoechoic areas with well-defined borders (27%), and heterogeneous echogenicity (20%) (not significant). The sensitivity of the presence of CMHF for the diagnosis of HGPIN was only 19%. CONCLUSIONS: TRUS-detected CMHF may indicate HGPIN. Because of the limited sensitivity of this finding, TRUS detection of CMHF does not warrant biopsy, although these lesions warrant close monitoring.

Monofocal and plurifocal high-grade prostatic intraepithelial neoplasia on extended prostate biopsies: factors predicting cancer detection on extended repeat biopsy.

OBJECTIVES: To evaluate factors predicting cancer detection by extended repeat prostate biopsies in patients with an initial, isolated, monofocal or plurifocal, high-grade prostatic intraepithelial neoplasia (HGPIN) diagnosis. METHODS: From 1995 to 2002, after a first set of 10 to 12 systematic biopsy cores, 47 patients with an initial HGPIN diagnosis underwent repeat biopsy using the same technique (mean repeat biopsy cores 11.5) after a median follow-up of 11.4 months (range 3 to 24). RESULTS: Cancer was detected at the second biopsy in 21 patients (44.6%). Cancer detection was significantly greater in patients with plurifocal HGPIN than in those with monofocal HGPIN (70% vs. 10%, respectively; P <0.005) and in patients who underwent repeat biopsy more than 6 months after the first biopsy set (65%) compared with patients who underwent repeat biopsy within 6 months (25%; P <0.01; mean follow-up 15.5 and 3.8 months, respectively). Multivariate analysis showed that prostate-specific antigen, prostate-specific antigen density, digital rectal examination, and transrectal ultrasound findings were not statistically significant predictors of prostate cancer, and HGPIN multifocality and interval between biopsies (more than a 6-month follow-up interval) were independent prognostic factors (odds ratio 4.65 and 2.65, respectively). After radical prostatectomy (14 patients), no statistically significant differences were found in the pathologic stage between patient groups stratified by repeat biopsy interval (within or after 6 months). CONCLUSIONS: After a 10 to 12-core biopsy, patients with initial, isolated monofocal or plurifocal HGPIN diagnoses had an overall cancer detection rate of 45% on repeat extended biopsies. Plurifocal HGPIN on the first biopsy set was the strongest independent predictive factor in cancer detection. A 12 to 18-month interval before repeat biopsy could permit a significantly greater cancer detection rate, with no apparent likelihood of clinical cancer progression.

Optimal combinations for detection of prostate cancer: systematic sextant and laterally directed biopsies versus systematic sextant and color Doppler-targeted biopsies.

OBJECTIVES: To determine the accuracy of different combinations of biopsies in detecting prostate cancer. The standard sextant protocol for obtaining prostate biopsy underestimates the presence of prostate cancer. Conversely, an increased cancer detection rate has been obtained with additional laterally directed biopsies. The results of the studies dedicated to transrectal color Doppler (CD) sonography have shown that it might detect neoplastic lesions with no corresponding gray-scale abnormality. METHODS: A total of 120 consecutive patients underwent sextant biopsy with additional biopsy cores taken from the lateral peripheral zone (four to six cores, depending on the prostate volume) and CD-guided biopsy. The sensitivity of laterally directed, CD-guided, and different combinations of biopsies was compared. Various patient, clinical, and pathologic factors were compared, and multivariate analysis was performed to assess the strongest predictor of cancer detection. RESULTS: Cancer was detected in 43 (35.8%) of 120 patients. The combination of sextant biopsy with laterally directed cores gained sensitivity to 56.6% compared with 67.4% obtained in the regimen that combined sextant and CD-guided biopsy. The CD regimen detected cancer in 11 additional patients. However, the differences in the detection rates of these combinations were not statistically significant (P = 0.797). The results of multivariate analysis showed that sextant biopsy and laterally directed cores were the strongest predictors of cancer detection (odds ratio 8.356 versus 49.282; 95% confidence interval 1.698 to 41.114 versus 10.508 to 231.130). CONCLUSIONS: The regimen that included sextant and CD-guided biopsy was the most sensitive. However, only standard sextant and laterally directed biopsies were statistically significant predictors of cancer detection on biopsy.

Pain after transrectal ultrasonography-guided prostate biopsy: the advantages of periprostatic local anaesthesia.

OBJECTIVE: To prospectively evaluate the efficacy and safety of periprostatic local anaesthesia (LA) during prostatic biopsy guided by transrectal ultrasonography (TRUS), as 20-65% of men report moderate to severe pain, and there is anecdotal and published evidence that periprostatic anaesthesia improves patients' tolerance. PATIENTS AND METHODS: In all, 157 patients were prospectively recruited and sequentially randomized to receive either LA or no anaesthesia. Sextant biopsies were taken in all men but some had more than six biopsies. All were asked to complete questionnaires immediately after TRUS-guided biopsy and for the subsequent week, giving pain scores and recording any morbidity, including symptoms of infection; analgesic use was also surveyed. RESULTS: Patients given LA had significantly lower pain scores at the time of biopsy than those given no anaesthesia, with median (sd) pain scores of 1.53 (0.7) and 1.95 (0.65) (P < 0.001), respectively. In addition, there was a trend towards less analgesic use by those given LA, although this was not statistically significant. There was no difference in the amount of haematuria, haematochezia or haematospermia, or infection rate, between the groups. The additional cost and time of the procedure was minimal ( pound3.00 and 3 min/per patient, respectively). CONCLUSION: Periprostatic LA infiltration is a quick and simple procedure which significantly improves immediate pain with no added morbidity; we strongly advocate its use to improve patient tolerance of TRUS-guided prostate biopsy.

Imaging and prostate cancer chemoprevention: Current diagnosis and future directions.

Identifying appropriate patients as targets for prostate cancer chemoprevention is a daunting task due to the multiple known and unknown factors contributing to patients' risk profiles. Confirmation of the extent and location of early prostate cancers, as well as prostatic intraepithelial neoplasia (PIN), also requires improved image guidance of biopsy to contain costs. Prostate-specific antigen (PSA) in conjunction with transrectal ultrasound (TRUS) and digital rectal examination (DRE) have been the front-line tests for early prostate cancer. Although advances in MRI continue to improve its accuracy, limited availability and higher costs preclude its widespread use for chemoprevention trials. Improved biopsy risk assessment has been achieved by categorizing TRUS grayscale and vascular findings for each biopsy region. In addition, concomitant suspicious TRUS findings also improved cancer yield per biopsy, as well as the amount and grade of tumor per core. However, TRUS remains operator dependent despite advancements in grayscale and vascular imaging. Additional risk parameters are needed to better localize small disease foci and improve the overall diagnostic performance while containing costs. Future work may improve the specificity of tissue characterization to produce reliable noninvasive biomarkers for monitoring chemoprevention responses of early prostate cancer or PIN.

Improving diagnostic accuracy of prostate carcinoma by systematic random map-biopsy.

Systematic random rectal ultrasound directed map-biopsy of the prostate was performed in 77 RDE (rectal digital examination) positive and 25 RDE negative cases, if applicable. Hypoechoic areas were found in 30% of RDE positive and in 16% of RDE negative cases. The score for carcinoma in the hypoechoic areas was 6.5% in RDE positive and 0% in RDE negative cases, whereas systematic map biopsy detected 62% carcinomas in RDE positive, and 16% carcinomas in RDE negative patients. The probability of positive diagnosis of prostate carcinoma increased in parallel with the number of biopsy samples/case. The importance of systematic map biopsy is emphasized.

Necessity of repeat biopsies in men for suspected prostate cancer.

BACKGROUND: The indications for repeat prostate needle biopsy in men whose initial biopsy results revealed no evidence of cancer are not defined. METHODS: We retrospectively studied 218 consecutive cases of men undergoing prostate biopsies for suspected cancer. Men in whom cancer was found on repeat biopsy were compared with others with regard to age, digital rectal examination, serum prostate-specific antigen (PSA) concentration, prostate volume, PSA density, PSA slope and the frequency of prostatic intraepithelial neoplasia (PIN) on initial prostate biopsy. RESULTS: Of the 114 cancers detected, 99 (87%) were diagnosed on initial biopsy and 15 (131%) were diagnosed on repeat biopsy. Mean PSA concentration and mean PSA density were significantly higher in patients with cancer on initial biopsy than on repeat biopsy (P<0.05), but they were similar among patients with and without cancer on repeat biopsy. The PSA slope showed a more progressive increase in patients with cancer on repeat biopsy than in those patients without cancer at 6 month intervals. Of the 218 patients undergoing prostate biopsy, seven (3.2%)) were identified with high grade PIN but without concurrent prostate cancer. Prostate cancers were detected in two of these seven patients (29%) on repeat biopsy. CONCLUSIONS: Serum PSA levels and PSA density did not provide useful predictive information about the indications of repeat biopsy. We conclude that men with a more progressive increase in PSA levels at 6 months intervals and high grade PIN on prostate needle biopsy should undergo repeat sampling to exclude missed cancer.

Evaluation of prostate needle biopsies in a population-based screening study: the impact of borderline lesions.

BACKGROUND: The finding of isolated high grade prostatic intraepithelial neoplasia (PIN) or borderline lesions (lesions suspicious for malignancy) in prostate needle biopsies warrants repeat biopsies. The reported frequency of these lesions in prostate needle biopsies varies considerably. The authors evaluated the frequency and clinical impact of high grade PIN and borderline lesions in sextant prostate needle biopsies obtained from screened participants in the European Randomized study of Screening for Prostate Cancer (ERSPC). METHODS: A total of 8763 participants in the Rotterdam section of the ERSPC ages 55-75 years were screened systematically for prostate carcinoma. Systematic sextant prostate needle biopsies were prompted by an abnormal digital rectal examination and/or abnormal transrectal ultrasonography findings at serum prostate specific antigen (PSA) levels > or = 1.0 ng/mL or a PSA level > or = 4.0 ng/mL. Repeat biopsies were obtained within 6 months after initial biopsy. RESULTS: Of 1824 biopsied men, 384 (21.1%) were found to have prostate carcinoma on initial biopsy. Twelve participants (0.7%) had isolated high grade PIN and 43 (2.4%) had borderline lesions. Repeat biopsies yielded no carcinoma in 7 participants with initial high grade PIN and 15 tumors (38.5%) in 39 participants with borderline lesions. CONCLUSIONS: In prostate needle biopsies obtained from a screened population, indications for repeat biopsy such as high grade PIN and borderline lesions do not represent large diagnostic subsets. Borderline lesions comprise the most important indication for a repeat biopsy. The low frequency of equivocal biopsy diagnoses in the current study supports the clinical applicability of sextant needle biopsies in population-based screening for prostate carcinoma.