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Rate of clinically significant prostate cancer on repeat saturation biopsy after a diagnosis of atypical small acinar proliferation
Abstract
Background
Atypical small acinar proliferation (ASAP) occurs in approximately 5% of prostate biopsies. Approximately 30%–40% of these patients may develop prostate cancer (PCa) within a 5-year period, often not clinically significant. Current guidelines recommend a repeat biopsy within 3–6 months after the initial diagnosis, but it seem not to be the best strategy.
Methods
Objectives—evaluating the natural history of ASAP, stratifying the risk of csPCa after ASAP, identifying predictive factors of PCa after atypical diagnosis. Materials and methods—retrospective single-institutional study on patients undergoing prostate biopsy for suspicious PCa (2005–2016). We evaluated the incidence of overall PCa, intermediate-high risk of PCa and csPCa in case of ASAP, according to D’Amico classification and Epstein modified criteria.
Results
Out of 4.567 patients undergoing prostate biopsy, ASAP was detected in 2.6% of cases. All patients with ASAP underwent repeat saturation biopsy within 6 months and PCa was diagnosed in 34.5%. According to D’Amico classification, 26%, 5.9%, and 2.5% had low, intermediate, and high-risk disease, respectively. According modified Epstein criteria, the incidence of csPCa was 12.6%. LRT showed that the overall probability to develop PCa doubled when PSA density (PSAD) moved from values lower than 0.13 ng/ml/cc to class 0.13–0.30 ng/ml/cc, and it tripled when PSAD was higher than 0.30 ng/ml/cc.
Conclusions
The rate of csPCa in patients with an initial diagnosis of ASAP who had repeat biopsy was 12.6%. The overall PCa rate was 34.5%. Among patient undergoing RP, an upgrading from ncsPCa to csPCa was reported in 35% of cases. PSAD is the only predictive factor directly associated to the risk of developing PCa on repeat biopsy. These findings suggest that immediate repeat biopsy remains the correct strategy in absence of novel predictor factors and non-invasive diagnostic evaluations.
Atypical small acinar proliferation (ASAP) occurs in approximately 5% of prostate biopsies. Approximately 30–40% of patients with ASAP have biopsy detectable prostate cancer (PCa) within 5 years. Current guidelines recommend a repeat biopsy within 3–6 months after the initial diagnosis. The aim of the present study was to examine the association between ASAP and subsequent diagnosis of clinically significant PCa (csPCa). The need for immediate repeat biopsy was also evaluated. We identified 212 patients with an ASAP diagnosis on their first biopsy at our institution between February 2006 and March 2018. Of these patients, 102 (48.1%) had at least one follow-up biopsy. Clinicopathologic features including rates of subsequent PCa and csPCa were assessed. Thirty-five patients subsequently underwent radical prostatectomy (RP). Their pathologic results were reviewed. csPCa was defined as the presence of Gleason score (GS) ≥ 3 + 4 in ≥ 1 biopsy core. Adverse pathology (AP) was defined as high-grade (primary Gleason pattern ≥ 4) or non-organ-confined disease (pT3/N1) after RP. Of 102 patients, 87 (85.3%), 13 (12.7%), and 2 (2.0%) had one, two, and three follow-up biopsies, respectively. Median time from the initial ASAP diagnosis to the 2nd follow-up biopsy and the last follow-up biopsy were 21.9 months (range 1–129 months) and 27.7 months (range 1–129 months), respectively. Of these patients, 46 (45.1%) were subsequently diagnosed with PCa, including 20 (19.6%) with csPCa. Only 2 (2.0%) patients had GS ≥ 8 disease. Five (4.9%) patients had number of positive cores > 3. Of 35 patients who subsequently underwent RP, seven (20%) had AP after RP and 17 (48.6%) showed GS upgrading. Of these 17 patients, the vast majority (16/17, 94.1%) had GS upgrading from 3 + 3 to 3 + 4. 45.1% of patients with an initial diagnosis of ASAP who had repeat prostate biopsy were subsequently diagnosed with PCa and 19.6% were found to have csPCa. Our findings add further evidence that after a diagnosis of ASAP, a repeat biopsy is warranted and that the repeat biopsy should not be postponed.
Introduction:
This study evaluates the clinical benefit of magnetic resonance-transrectal ultrasound (MR-TRUS) fusion biopsy over systematic biopsy between first-time and repeat prostate biopsy patients with prior atypical small acinar proliferation (ASAP).
Materials:
100 patients were enrolled in a single-centre prospective cohort study: 50 for first biopsy, 50 for repeat biopsy with prior ASAP. Multiparameteric magnetic resonance imaging (MP-MRI) and standard 12-core ultrasound biopsy (Std-Bx) were performed on all patients. Targeted biopsy using MRI-TRUS fusion (Fn-Bx) was performed f suspicious lesions were identified on the pre-biopsy MP-MRI. Classification of clinically significant disease was assessed independently for the Std-Bx vs. Fn-Bx cores to compare the two approaches.
Results:
Adenocarcinoma was detected in 49/100 patients (26 first biopsy, 23 ASAP biopsy), with 25 having significant disease (17 first, 8 ASAP). Fn-Bx demonstrated significantly higher per-core cancer detection rates, cancer involvement, and Gleason scores for first-time and ASAP patients. However, Fn-Bx was significantly more likely to detect significant cancer missed on Std-Bx for ASAP patients than first-time biopsy patients. The addition of Fn-Bx to Std-Bx for ASAP patients had a 166.7% relative risk reduction for missing Gleason ≥ 3 + 4 disease (number needed to image with MP-MRI=10 patients) compared to 6.3% for first biopsy (number to image=50 patients). Negative predictive value of MP-MRI for negative biopsy was 79% for first-time and 100% for ASAP patients, with median followup of 32.1 ± 15.5 months.
Conclusions:
MR-TRUS Fn-Bx has a greater clinical impact for repeat biopsy patients with prior ASAP than biopsy-naïve patients by detecting more significant cancers that are missed on Std-Bx.
Objective:
To assess the value of the Prostate Imaging Reporting and Data System (PI-RADS) scoring system, for prostate multi-parametric magnetic resonance imaging (mpMRI) to detect prostate cancer, and classical parameters, such as prostate specific antigen (PSA), prostate volume and PSA density, for predicting biopsy outcome in biopsy naïve patients who have suspected prostate cancer (PCa).
Patients and methods:
Patients who underwent mpMRI at our hospital, and who had their first prostate biopsy between July 2010 and April 2014, were analysed retrospectively. The prostate biopsies were performed transperineally under transrectal ultrasound guidance. Fourteen cores were biopsied as a systemic biopsy in all patients. Two cognitive fusion-targeted biopsy cores were added for each lesion in patients who had suspicious or equivocal lesions on mpMRI. The PI-RADS scoring system ver. 2.0 (PI-RADS v2) was used to describe the MRI findings. Univariate and multivariate analyses were performed to determine significant predictors of PCa and clinically significant PCa.
Results:
In total, 288 patients were analysed. Median patient age, PSA, prostate volume and PSA density were 69, 7.5 ng/mL, 28.7 cm3 and 0.26 ng/mL/cm3, respectively. The biopsy results were benign, clinically insignificant and clinically significant PCa in 129 (45%), 18 (6%) and 141 (49%) patients, respectively. The multivariate analysis revealed that PI-RADS v2 score and PSA density were independent predictors for PCa and clinically significant PCa. When PI-RADS v2 score and PSA density were combined, PI-RADS v2 score > 4 and PSA density > 0.15, or PI-RADS v2 score 3 and PSA density > 0.30, was associated with the highest clinically significant PCa detection rates (76-97%) on the first biopsy. Of the patients in this group with negative biopsy results, 22% were subsequently diagnosed as PCa. In contrast, PI-RADS v2 score < 3 and PSA density < 0.15 yielded no clinically significant PCa and no additional detection of PCa on further biopsies.
Conclusions:
A combination of PI-RADS v2 score and PSA density can help in the decision-making process before prostate biopsy and the follow-up strategy in biopsy naïve patients. Patients with PI-RADS v2 score < 3 and PSA density < 0.15 may avoid unnecessary biopsies. This article is protected by copyright. All rights reserved.
Purpose: Atypical small acinar proliferation (ASAP) denotes the presence of suspicious glands with insufficient cytological architecture for a definitive prostate cancer diagnosis. We evaluated the subsequent prostate cancer detection rate of rebiopsy in patients with an initial diagnosis of ASAP. Materials and Methods: Between January 2003 and December 2006, 1,416 men with suspected prostate cancer underwent a transrectal ultrasound-guided prostate biopsy, and 214 (15.1%) were diagnosed as having ASAP. Ninety-five of the 215 patients underwent at least one more biopsy. We evaluated the cancer detection rates after rebiopsy. Results: In men with ASAP, 36 patients (37.9%) had prostate cancer. The cancer detection rates of the 1st, 2nd, and 3rd rebiopsies were 30.5%, 23.8%, and 40%, respectively. Mean patient age and prostate-specific antigen did not differ significantly between the prostate cancer and noncancer groups after rebiopsy. Prostate volume, however, was significantly smaller in the cancer group (p<0.05). Conclusions: Our results showed a detection rate for prostate cancer of 37.9% after an initial diagnosis of ASAP, which indicates that an initial diagnosis of ASAP mandates rebiopsy.
In clinical practice, atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN) are two common findings on prostate biopsies. Knowing the frequency of a prostate cancer diagnosis on repeat biopsies would aid primary treating physicians regarding their decisions in suspicious cases.
One hundred forty-three patients in whom biopsies revealed ASAP or HGPIN or both were enrolled in the present study; prostate cancer was not reported in the biopsy specimens and at least one repeat biopsy was performed. Age, digital rectal examination findings, prostate volumes, and free and total prostate-specific antigen (PSA) levels and the biopsy results of the patients were recorded.
Of the 97 patients with ASAP on the first set of biopsies, prostate cancer was diagnosed in the second and third biopsies of 32 and 6 patients, respectively. Prostate cancer was not detected in the second or third biopsies of the 40 patients with HGPIN in the first biopsy. Of the 6 patients with ASAP+HGPIN in the first biopsy, prostate cancer was detected in 3 patients in the second biopsy and in 1 patient in the third biopsy.
The diagnosis of ASAP is a strong risk factor for prostate cancer. A repeat biopsy should be performed for the entire prostate subsequent to the diagnosis of ASAP. In patients with HGPIN according to the biopsy result, the clinical decision should be based on other parameters, such as PSA values and rectal examination, and a repeat biopsy should be avoided if the initial biopsy was performed with multiple sampling.
Cancer detection has been reported in up to 27% of patients when lowering the PSA cutoff to 2.5 ng/mL. Although this practice could increase the number of biopsies performed, it also could lead to more frequent detection of significant prostate cancers at an organ-confined stage and/or a less aggressive state. This study describes the incidence of malignancy and tumor characteristics in extended prostate biopsies with PSA <or= 4 ng/mL.
Prostate biopsies from 1081 patients where examined, 275 (25.4%) patients had PSA level <or= 4 ng/mL.
Cancer was diagnosed in 32.0% and 35.7% of patients with PSA <or= 4 ng/mL and >4 ng/mL, respectively (p=0.906). The median Gleason score was 7 independent of PSA > or <or= 4 ng/mL (p=0.078). The median number of cores positive for tumor was 4 and 3, respectively, for PSA >4 ng/mL and PSA <or= 4 ng/mL (p=0.627). There was a difference in the total percent of tumors involving all cores, 11% and 7% for PSA > or <or= 4 ng/mL (p=0.042). Fifty-six patients underwent radical prostatectomy, 12 had PSA <or= 4 ng/mL. In both groups, a diagnosis of cancer was accurate with no differences in Gleason score, tumor volume or staging for both groups.
When PSA is below 4 ng/mL, cancer is detected in a proportion equal to the proportion diagnosed with a PSA >4 ng/mL, and tumor characteristics are similar between the two groups. Only clinically significant tumors were diagnosed following radical prostatectomy.
Objective:
To assess the incidence of clinically significant and insignificant prostate cancer after an initial biopsy that revealed either atypical small acinar proliferation (ASAP), high-grade prostatic intraepithelial neoplasia (HGPIN), or benign tissue.
Materials and methods:
We retrospectively identified patients diagnosed with ASAP, HGPIN, or benign tissue who had a repeat prostate biopsy within 1 year of diagnosis during 1987-2015. We compared the incidence of any prostate cancer and clinically significant prostate cancer (based on Gleason score, prostate-specific antigen (PSA), number of positive cores, and core volume) for each diagnostic group.
Results:
A total of 17,016 biopsies were performed in 12,817 patients during 1987-2015. Among the 615 patients who had a repeat biopsy within 1 year of their first, 261 (42.4%), 208 (33.8%), and 146 (23.8%) had ASAP, HGPIN, or benign tissue on the initial biopsy, respectively. The second biopsy demonstrated significant differences in prostate cancer detection rates between these 3 groups (34.1%, 20.2%, and 15.8%, respectively; P <.001), with cancer detected significantly more often in the ASAP group relative to other groups (P <.001 vs benign and P = .001 vs HGPIN). The rates of clinically significant prostate cancer did not differ between groups (8.0%, 6.7%, and 4.1%, respectively, P = .31).
Conclusion:
On repeat biopsy, rates of clinically significant prostate cancer did not differ between patients initially diagnosed with ASAP, HGPIN, or benign tissue. Elevated rates of prostate cancer after a diagnosis of ASAP appear to be largely due to differences in the rate of clinically insignificant disease.
Background:
Atypical small acinar proliferation (ASAP) occurs in approximately 5% of prostate biopsies. Approximately 30-40% of patients with ASAP may develop prostate cancer (PCa) within a 5-year period. Current guidelines recommend a repeat biopsy within 3-6 months after the initial diagnosis. Our objective was to examine the association between ASAP and subsequent diagnosis of high-grade PCa and to evaluate the need for immediate repeat biopsy.
Methods:
A retrospective multi-institutional review identified 264 patients who underwent prostate biopsy from 2000 to 2013 (Brown), 2008 to 2013 (University of Massachusetts) and 1994 to 2005 (Mayo) and were diagnosed with ASAP. Patients underwent transrectal ultrasound-guided biopsies for elevated PSA and/or abnormal digital rectal exam. Clinicopathologic features were assessed, including rates of subsequent PCa detection of any high-grade (Gleason 7-10) PCa. Comparison was made between those with subsequent PCa on repeat biopsy and those with benign repeat pathology.
Results:
All 264 patients included underwent repeat biopsy with a median follow-up of 5.4 years (interquartile range: 4.6, 6.7). Of these patients, 89 (34%) were subsequently diagnosed with PCa including 21 (8%) with high-grade PCa. Pre-biopsy PSA was higher among patients subsequently diagnosed with (6.7 vs 5.8, P<0.001). Of those diagnosed with subsequent PCa, 69/89 (78%) had less than or equal to Gleason 3+3 disease and only 15/89 (17%) had Gleason 7 and 6/89 (6%) revealed Gleason ⩾8-10. Radical prostatectomy was performed on 36/89 (40%) patients. Surgical pathology revealed 11 patients ⩾Gleason 8-10 PCa.
Conclusions:
Although 34% of patients with an initial diagnosis of ASAP who had repeat biopsy were subsequently diagnosed with PCa only, only 22% (8% of the total cohort) were found to have high-grade disease. Higher PSA was associated with increased risk of identifying PCa on repeat biopsy. These findings suggest that immediate repeat biopsy may be omitted in the majority of men with ASAP.
Limited information is known about the clinical significance of cancers diagnosed upon repeat biopsy for the indication of atypical small acinar proliferation (ASAP). With increasing concern regarding overdiagnosis and overtreatment of prostate cancer, and the reported rise in infectious complications related to prostate biopsy, we examined the outcomes of patients rebiopsied for a diagnosis of ASAP.
Clinical, pathologic and outcomes data of patients diagnosed with ASAP on prostate biopsy at our institutions between 2000 and 2010 were abstracted through chart review. Statistical analyses included Fisher's exact and the two-sample Wilcoxon rank sum tests. Logistic regression evaluated risk factors for the probability of cancer following a diagnosis of ASAP.
A total of 349 patients met the inclusion criteria with median follow-up of 4.4 years. Median age was 65.3 years with a median PSA of 5.3 ng ml(-1). Of men diagnosed with ASAP, 250/349 (71.6%) had a repeat biopsy within 1 year with 94/246 (38.2%) demonstrating prostate cancer; only 26/245 (10.6%) had ⩾Gleason 7 disease. Of men diagnosed with ASAP, 284/349 (81.4%) underwent biopsy at some time during follow-up. Prostate cancer was diagnosed in 132/279 (47.3%) of these men, 48/278 (17.3%) with ⩾Gleason 7 disease. Multivariate analyses suggested that older age, no previous biopsy and PSA density were predictive of cancer on repeat biopsy within 1 year from ASAP. Univariate analysis revealed PSA density was associated with the presence of ⩾Gleason 7 disease at 1 year and any time after a diagnosis of ASAP.
The overall rate of intermediate- and high-grade prostate cancer found on repeat biopsy for ASAP is low. Further investigation into ways to further risk stratify these men may be warranted. However, until such tests become available, repeat biopsy of men diagnosed with ASAP remains prudent.Prostate Cancer and Prostatic Disease advance online publication, 21 April 2015; doi:10.1038/pcan.2015.14.
Context.— Interstitial radiation (implant) therapy is used to treat clinically
localized adenocarcinoma of the prostate, but how it compares with other treatments
is not known.Objective.— To estimate control of prostate-specific antigen (PSA) after radical
prostatectomy (RP), external beam radiation (RT), or implant with or without
neoadjuvant androgen deprivation therapy in patients with clinically localized
prostate cancer.Design.— Retrospective cohort study of outcome data compared using Cox regression
multivariable analyses.Setting and Patients.— A total of 1872 men treated between January 1989 and October 1997 with
an RP (n=888) or implant with or without neoadjuvant androgen deprivation
therapy (n=218) at the Hospital of the University of Pennsylvania, Philadelphia,
or RT (n=766) at the Joint Center for Radiation Therapy, Boston, Mass, were
enrolled.Main Outcome Measure.— Actuarial freedom from PSA failure (defined as PSA outcome).Results.— The relative risk (RR) of PSA failure in low-risk patients (stage T1c,
T2a and PSA level ≤10 ng/mL and Gleason score ≤6) treated using RT,
implant plus androgen deprivation therapy, or implant therapy was 1.1 (95%
confidence interval [CI], 0.5-2.7), 0.5 (95% CI, 0.1-1.9), and 1.1 (95% CI,
0.3-3.6), respectively, compared with those patients treated with RP. The
RRs of PSA failure in the intermediate-risk patients (stage T2b or Gleason
score of 7 or PSA level >10 and ≤20 ng/mL) and high-risk patients (stage
T2c or PSA level >20 ng/mL or Gleason score ≥8) treated with implant compared
with RP were 3.1 (95% CI, 1.5-6.1) and 3.0 (95% CI, 1.8-5.0), respectively.
The addition of androgen deprivation to implant therapy did not improve PSA
outcome in high-risk patients but resulted in a PSA outcome that was not statistically
different compared with the results obtained using RP or RT in intermediate-risk
patients. These results were unchanged when patients were stratified using
the traditional rankings of biopsy Gleason scores of 2 through 4 vs 5 through
6 vs 7 vs 8 through 10.Conclusions.— Low-risk patients had estimates of 5-year PSA outcome after treatment
with RP, RT, or implant with or without neoadjuvant androgen deprivation that
were not statistically different, whereas intermediate- and high-risk patients
treated with RP or RT did better then those treated by implant. Prospective
randomized trials are needed to verify these findings.
Purpose:
Men diagnosed with atypical small acinar proliferation are counseled to undergo early rebiopsy because the risk of prostate cancer is high. However, random rebiopsies may not resample areas of concern. Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy offers an opportunity to accurately target and later retarget specific areas in the prostate. We describe the ability of magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy to detect prostate cancer in areas with an initial diagnosis of atypical small acinar proliferation.
Materials and methods:
Multiparametric magnetic resonance imaging of the prostate and magnetic resonance imaging/transrectal ultrasound fusion guided biopsy were performed in 1,028 patients from March 2007 to February 2014. Of the men 20 met the stringent study inclusion criteria, which were no prostate cancer history, index biopsy showing at least 1 core of atypical small acinar proliferation with benign glands in all remaining cores and fusion targeted rebiopsy with at least 1 targeted core directly resampling an area of the prostate that previously contained atypical small acinar proliferation.
Results:
At index biopsy median age of the 20 patients was 60 years (IQR 57-64) and median prostate specific antigen was 5.92 ng/ml (IQR 3.34-7.48). At fusion targeted rebiopsy at a median of 11.6 months 5 of 20 patients (25%, 95% CI 6.02-43.98) were diagnosed with primary Gleason grade 3, low volume prostate cancer. On fusion rebiopsy cores that directly retargeted areas of previous atypical small acinar proliferation detected the highest tumor burden.
Conclusions:
When magnetic resonance imaging/transrectal ultrasound fusion guided biopsy detects isolated atypical small acinar proliferation on index biopsy, early rebiopsy is unlikely to detect clinically significant prostate cancer. Cores that retarget areas of previous atypical small acinar proliferation are more effective than random rebiopsy cores.
The most recent summary of the European Association of Urology (EAU) guidelines on prostate cancer (PCa) was published in 2011.
To present a summary of the 2013 version of the EAU guidelines on screening, diagnosis, and local treatment with curative intent of clinically organ-confined PCa.
A literature review of the new data emerging from 2011 to 2013 has been performed by the EAU PCa guideline group. The guidelines have been updated, and levels of evidence and grades of recommendation have been added to the text based on a systematic review of the literature, which included a search of online databases and bibliographic reviews.
A full version of the guidelines is available at the EAU office or online (www.uroweb.org). Current evidence is insufficient to warrant widespread population-based screening by prostate-specific antigen (PSA) for PCa. Systematic prostate biopsies under ultrasound guidance and local anesthesia are the preferred diagnostic method. Active surveillance represents a viable option in men with low-risk PCa and a long life expectancy. A biopsy progression indicates the need for active intervention, whereas the role of PSA doubling time is controversial. In men with locally advanced PCa for whom local therapy is not mandatory, watchful waiting (WW) is a treatment alternative to androgen-deprivation therapy (ADT), with equivalent oncologic efficacy. Active treatment is recommended mostly for patients with localized disease and a long life expectancy, with radical prostatectomy (RP) shown to be superior to WW in prospective randomized trials. Nerve-sparing RP is the approach of choice in organ-confined disease, while neoadjuvant ADT provides no improvement in outcome variables. Radiation therapy should be performed with ≥74Gy in low-risk PCa and 78Gy in intermediate- or high-risk PCa. For locally advanced disease, adjuvant ADT for 3 yr results in superior rates for disease-specific and overall survival and is the treatment of choice. Follow-up after local therapy is largely based on PSA and a disease-specific history, with imaging indicated only when symptoms occur.
Knowledge in the field of PCa is rapidly changing. These EAU guidelines on PCa summarize the most recent findings and put them into clinical practice.
A summary is presented of the 2013 EAU guidelines on screening, diagnosis, and local treatment with curative intent of clinically organ-confined prostate cancer (PCa). Screening continues to be done on an individual basis, in consultation with a physician. Diagnosis is by prostate biopsy. Active surveillance is an option in low-risk PCa and watchful waiting is an alternative to androgen-deprivation therapy in locally advanced PCa not requiring immediate local treatment. Radical prostatectomy is the only surgical option. Radiation therapy can be external or delivered by way of prostate implants. Treatment follow-up is based on the PSA level.
A sequence of 0's and 1's is observed and it is suspected that the chance that a particular trial is a 1 depends on the value of one or more independent variables. Tests and estimates for such situations are considered, dealing first with problems in which the independent variable is preassigned and then with independent variables that are functions of the sequence. There is a considerable amount of earlier work, which is reviewed.
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).METHODSA 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 ≥ 1.0 ng/mL or a PSA level ≥ 4.0 ng/mL. Repeat biopsies were obtained within 6 months after initial biopsy.RESULTSOf 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. Cancer 1999;85:145–52. © 1999 American Cancer Society.
We identified information critical for patient treatment on prostate needle biopsies diagnosed with prostatic intraepithelial neoplasia or atypical foci suspicious for carcinoma.
A search was performed using the MEDLINE database and referenced lists of relevant studies to obtain articles addressing the significance of finding PIN or atypical foci suspicious for carcinoma on needle biopsy.
There were certain results concerning PIN. 1) Low grade PIN should not be documented in pathology reports due to poor interobserver reproducibility and a relatively low risk of cancer following re-biopsy. 2) The expected incidence of HGPIN on needle biopsy is between 5% and 8%. 3) Although the diagnosis of HGPIN is subjective, interobserver reproducibility for its diagnosis is fairly high among urological pathologists, and yet only moderate among pathologists without special expertise in prostate pathology. 4) The median risk recorded in the literature for cancer following the diagnosis of HGPIN on needle biopsy is 24.1%, which is not much higher than the risk reported in the literature for repeat biopsy following a benign diagnosis. 5) The majority of publications that compared the risk of cancer in the same study following a needle biopsy diagnosis of HGPIN to the risk of cancer following a benign diagnosis on needle biopsy show no differences between the 2 groups. 6) Clinical and pathological parameters do not help stratify which men with HGPIN are at increased risk for a cancer diagnosis. 7) A major factor contributing to the decreased incidence of cancer following a diagnosis of HGPIN on needle biopsy in the contemporary era is related to increased needle biopsy core sampling, which detects many associated cancers on initial biopsy, such that re-biopsy, even with good sampling, does not detect many additional cancers. 8) It is recommended that men do not need routine repeat needle biopsy within the first year following the diagnosis of HGPIN, while further studies are needed to confirm whether routine repeat biopsies should be performed several years following a HGPIN diagnosis on needle biopsy. There were certain results concerning atypical glands suspicious for carcinoma. 1) An average of 5% of needle biopsy pathology reports are diagnosed as atypical glands suspicious for carcinoma. 2) Cases diagnosed as atypical have the highest likelihood of being changed upon expert review and urologists should consider sending such cases for consultation in an attempt to resolve the diagnosis as definitively benign or malignant before subjecting the patient to repeat biopsy. 3) Ancillary techniques using basal cell markers and AMACR (alpha-methyl-acyl-coenzyme A racemase) can decrease the number of atypical diagnoses, and yet one must use these techniques with caution since there are numerous false-positive and false-negative results. 4) The average risk of cancer following an atypical diagnosis is approximately 40%. 5) Clinical and pathological parameters do not help predict which men with an atypical diagnosis have cancer on repeat biopsy. 6) Repeat biopsy should include increased sampling of the initial atypical site, and adjacent ipsilateral and contralateral sites with routine sampling of all sextant sites. Therefore, it is critical for urologists to submit needle biopsy specimens in a manner in which the sextant location of each core can be determined. 7) All men with an atypical diagnosis need re-biopsy within 3 to 6 months.
It is critical for urologists to distinguish between a diagnosis of HGPIN and that of atypical foci suspicious for cancer on needle biopsy. These 2 entities indicate different risks of carcinoma on re-biopsy and different recommendations for followup.
To report the sensitivity and resistance of Escherichia coli in patients with infectious complications after prostate biopsy in a North American cohort. Increasing antibiotic-resistant E. coli has been observed worldwide.
Data were available for 1446 patients who had undergone transrectal ultrasound-guided prostate biopsy from 2001 to 2010. Of the 1446 patients, 932 were administered 500 mg of ciprofloxacin 1 hour before prostate biopsy and 514 were administered a 3-day course of ciprofloxacin starting 1 day before biopsy plus an enema the night before. The sensitivity and resistance of E. coli were attained through the analysis of the blood and urine cultures of patients with suspected infection.
Of the 1446 patients, 40 (2.77%) developed an infection after biopsy. Of these 40 patients, 31 (2.14%) had a febrile urinary tract infection and 9 (0.62%) were diagnosed with sepsis requiring hospitalization. Of the 40 patients, 20 (50%) had urine cultures positive for E. coli. Of these 20 patients, 11 (55%) had fluoroquinolone-resistant infection and 9 had fluoroquinolone-sensitive E. coli. Of the remaining 20 patients, culture was not obtained for 9, and 5 had negative urine culture findings. Of the 7 patients (78%) with sepsis had blood cultures positive for E. Coli; 4 (57.1%) of which were fluoroquinolone-resistant and 3 were fluoroquinolone-sensitive.
In the present study, a significant risk of fluoroquinolone-resistant E. coli was observed in patients with both febrile urinary tract infection and sepsis after prostate biopsy. Alternative prophylactic antibiotics should be researched further, and postbiopsy infections developing after standard quinolone prophylaxis should be treated with cephalosporins until culture findings are available to guide therapy.
Prostate needle biopsies occasionally contain an atypical small acinar proliferation (ASAP) that is suspicious for but not diagnostic of malignancy. The predictive value of ASAP for cancer has not been studied in a large series.
To determine the reproducibility and clinical significance of ASAP in a large urologic reference laboratory, we retrospectively studied 295 patients with ASAP diagnosed from 1991 to 1995. Each patient had at least one follow-up biopsy. Mean patient age was 68.0 years (range 40 to 89). Numerous clinical and histologic features were assessed to determine their predictive value for malignancy on subsequent biopsy.
Adenocarcinoma was identified on follow-up biopsy in 125 patients (42%), with a median follow-up of 5.7 months (range 0.1 to 43). Gleason score varied from 4 to 9 (mean 6.2). Cumulative detection of 125 cancers was 90% after second biopsy and 99% after third biopsy. Serum prostate-specific antigen, digital rectal examination result, and patient age were not predictive of cancer on follow-up biopsy. Likewise, the number of biopsy cores and histologic findings including number of acini per focus of ASAP, number of foci of ASAP, degree of nuclear and nucleolar enlargement, and presence of luminal pink granular secretions, mucin, or crystalloids were not predictive of cancer. Stratifying our level of suspicion into three categories (favor benign, uncertain, and favor carcinoma) did not differentially predict subsequent cancer (44%, 44%, and 41% of patients, respectively; P = 0.86) nor the percentage of tissue involved by cancer. No clinical or pathologic feature affected the likelihood of subsequent cancer. In 39% of patients, cancer was only contralateral to or in a different sextant site from the initial ASAP site.
The high predictive value of ASAP for subsequent adenocarcinoma warrants repeat biopsy. Sampling should include multiple sites in the prostate.
To determine both how the diagnosis of an atypical biopsy influences a urologist's decision to repeat the biopsy and the outcome of rebiopsy.
Of 200 atypical biopsies that we confirmed from outside consultations to the Johns Hopkins Hospital from 1992 to 1993, we were able to retrieve follow-up information for 144 cases. Each atypical biopsy was evaluated for the reason for atypia (atrophic glands, rule out [r/o] adenosis, atypical not otherwise specified [NOS; insufficient cytologic and/or architectural atypia], r/o prostatic intraepithelial neoplasia [PIN], inflammation, crush artifact) and a favored diagnosis (cancerous, benign, and undetermined).
Of the 144 atypical biopsies, 92 were rebiopsied (63.9%). The time from the initial atypical biopsy to rebiopsy ranged from 0.5 months to 3 years (63% less than 6 months; 39% less than 3 months). Rebiopsy revealed carcinoma in 48.9%, benign in 38%, atypical in 8.7%, and PIN in 4.4%. The median prostate-specific antigen (PSA) value was lower in men who did not undergo a repeat biopsy (6 versus 7.8) (rank sum analysis, P = 0.04). No correlation was found between PSA level and results of the rebiopsy. Of the atypical biopsies in which cancer was favored, 61% were cancerous on rebiopsy versus 33% where a benign process was favored. The three reasons for atypical biopsies that seemed to correlate with outcome of rebiopsy were atypical NOS (68% cancer on rebiopsy); inflammation (63% cancer on rebiopsy); and r/o adenosis (36% cancer on rebiopsy).
Although 48.9% of the rebiopsied cases were cancerous, only 63% of men underwent rebiopsy, raising a concern that cancers are being missed in those cases not rebiopsied after an atypical diagnosis. Although there was a trend for serum PSA to correlate with outcome of rebiopsy, this correlation was not significant, and even men with serum PSA less than 4 ng/mL had a 33% risk of cancer on rebiopsy. Although histologic features of the atypical foci may be useful as factors in determining the urgency for rebiopsy, they also were not statistically significant in predicting outcome. Men with atypical diagnoses should undergo rebiopsy regardless of serum PSA levels and regardless of why the lesions were atypical.
We used clinical variables to predict prostate cancer detection on re-biopsy among patients diagnosed with high grade prostatic intraepithelial neoplasia (PIN) or atypia on initial prostate biopsy.
A total of 45 men with atypia and 43 with high grade PIN were eligible for our study. Clinical variables were tested with univariate and multivariate logistic regression to predict who would have cancer on re-biopsy. We also calculated the odds of detecting cancer with various repeat sampling strategies and determined whether the location of initial atypia or high grade PIN is correlated to that of cancer on re-biopsy.
Of the patients in the atypia and high grade PIN groups 51% had cancer on re-biopsy. Cancer was diagnosed significantly earlier in the high grade PIN than in the atypia cohort (average 7.5 versus 22.9 months, respectively, p = 0.005). Multivariate logistic modeling showed that digital rectal examination and patient age were independent predictors of cancer in atypia, whereas no variables were significantly predictive for high grade PIN. Of cancers in the atypia and high grade PIN 65% and 74%, respectively, would have been detected if re-biopsy was focused only at the initial site of disease.
Men with atypia or high grade PIN merit close followup because 50% will have cancer on re-biopsy as will those who are older with an abnormal digital rectal examination. Although re-biopsy should focus primarily on the original site of atypia or high grade PIN, cancer detection significantly increases with the sampling of adjacent sites.
The term atypical small acinar proliferation (ASAP) has been proposed by pathologists to indicate foci of small atypical acini found in prostatic biopsies that have some but not all of the features of adenocarcinoma. We determined the incidence of ASAP at our institution and evaluated the role of immediate radical prostatectomy (RP) in these patients.
From January 2001 to December 2002, 1,327 patients underwent systematic transrectal prostate biopsies because of increased prostate specific antigen (PSA). Of the 1,327 patients 71 (5.3%) had suspicious cytokeratin negative lesions diagnosed as ASAP, as confirmed by a review pathologist. Mean patient age was 62 years and mean PSA was 8.48 ng/ml (range 5.6 to 19.6). Of the 71 patients 25 underwent pelvic bilateral lymphadenectomy and RP with a nerve sparing procedure immediately after the diagnosis of ASAP. A 79-year-old patient underwent transurethral resection of the prostate. A total of 45 patients were followed with PSA determination every 3 months and with prostatic mapping every 6 months (12 to 14 biopsies).
All 25 patients (100%) with ASAP who underwent immediate RP had a final pathological diagnosis of adenocarcinoma, as confirmed by a review pathologist. Pathological stage was pT2a in 9 patients, pT2b in 8, pT2c in 6, pT3a in 1 and pT4 in 1. The Gleason sum was 2 to 6 in 21 patients, 7 in 2 and 8 in 2. One of the 25 patients had positive nodes (pT4N1G3). The pathological diagnosis in patients with transurethral resection was benign prostatic hyperplasia. Nine of the 45 patients who were followed were seen every 3 months for PSA determination because of age (older than 78 years). Of the 45 patients 23 (51.1%) underwent a second set of biopsies, which revealed adenocarcinoma in 6 of 23 (26%), benign prostatic hyperplasia in 6 (26%), ASAP again in 5 (21.7%), atypia in 4 (17.3%) and high grade PIN in 2 (8.6%). Six of 17 patients had a third set of biopsies (a total of 14 cores), including 3 with adenocarcinoma, 1 with ASAP and 2 with high grade PIN. Two of 45 patients (4.4%) did not undergo a second biopsy because of other malignancies. Four of 45 patients (8.8%) are awaiting a third or fourth biopsy. Ten of 45 patients (22.2%) were lost to followup.
The results of our study confirm that immediate RP could be the treatment of choice in young patients with ASAP.
To evaluate the clinical and histopathologic factors that may help to predict cancer detection by means of extended repeated prostate needle biopsies in patients with Jumma atypical small acinar proliferation (ASAP) results on initial prostate biopsy.
From 1998 to September 2003, 105 out of 121 (86%) patients with a diagnosis of ASAP after a first set of 10 to 12 systematic biopsies, were rebiopsied using the same technique plus additional biopsies on the ASAP site (mean number of repeat biopsy samples, 12.6). The median time until a second and third biopsy was 7.04 months (95% confidence interval [CI], 5.5-8.5), and 13.3 months (95% CI, 8.8-17.7; 19 patients), respectively. Each histological slide was reviewed blindly by a single experienced pathologist (M.F) who differentiated highly suspicious (ASAPH) and not highly suspicious (ASAPB) lesions for cancer.
On initial biopsy, a concomitant HGPIN was present in 18 patients (17%) with ASAP The overall cancer detection rate in those who underwent two or three sets of biopsies was 39% (41/105); it was 35% (37/105) and 21% (4/19) in second and third biopsies, respectively. The overall cancer detection rate was higher in patients who had ASAP associated with HGPIN (50%) compared with patients who had isolated ASAP (37%) (p = 0.3). Statistical analysis showed that levels of prostate-specific antigen (PSA), PSA density, prostatic volume, digital rectal examination results, transrectal ultrasound findings, time until rebiopsy (less vs. more than 6 months), and histological level of suspicion were not significant predictors of prostate cancer at the time of rebiopsy. In particular, the cancer detection rate was not significantly higher in patients with ASAPH than those with ASAPB (49% vs. 33%, respectively; p = 0.11). In a univariate analysis, the mean prostate volume was statistically different in patients with cancer compared with those without (56.4 +/- 6.3 and 78.9 +/- 5.3 respectively; p = 0.009), but only in the group of patients who had isolated ASAP In these patients, the rate of cancer detection was significantly higher in patients who had a prostatic volume less than 60 mL (56%) than in patients with a prostatic volume greater than or equal to 60 mL (27%) (p = 0.03).
Patients with an initial ASAP diagnosis after extended biopsies had an overall cancer detection rate less than 40% after two sets of extended biopsy. ASAPH lesions did not indicate a significantly higher risk of cancer than ASAPB lesions on repeated extended biopsies. Despite the extended rebiopsy plus the additional biopsies targeted to the ASAP lesion, the detection rate was lower for patients with a larger prostate than those with a smaller prostate.
To evaluate the factors that predict prostate cancer detection by means of 10 to 12 core repeat biopsies in patients with atypical small acinar proliferation (ASAP) results on initial biopsy.
From 1998 to 2004, 110 of 127 patients (87%) with a diagnosis of ASAP were rebiopsied with the same technique plus additional biopsies on the ASAP site (12.6 +/- 1.1 cores [mean +/- standard deviation]). Each histologic slide was reviewed blindly by a single experienced pathologist, who also differentiated highly suspicious (ASAPH) and not highly suspicious (ASAPB) lesions for cancer.
On initial biopsy, a concomitant high-grade prostatic intraepithelial neoplasia (HGPIN) was present in 26 patients (23%) with ASAP. The overall cancer detection rate was significantly higher in patients who had ASAP associated with HGPIN (58%), compared with patients who had isolated ASAP (35%; P = 0.04). The cancer detection rate was not significantly higher in patients with ASAPH than in those with ASAPB (49% versus 33%, respectively; P = 0.11). In the group of patients who had isolated ASAP, the rate of cancer detection was significantly higher in patients who had a prostatic volume less than 50 mL (56%) than in patients with a prostatic volume of 50 mL or more (27%; P = 0.03).
The cancer detection rate was significantly higher in patients with an ASAP associated with HGPIN on initial biopsy than in patients with isolated ASAP. In ASAP patients, the detection rate was lower for patients with a larger prostate than in those with a smaller prostate.
Econometric analysis
- W Greene
Combination of prostate imaging reporting and data system (PI-RADS) score and prostate-specific antigen (PSA) density predicts biopsy outcome in prostate biopsy naïve patients
- S Washino
- T Okochi
- K Saito
EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent-update 2013
- A Heidenreich
- Bastian
- Pj
- J Bellmunt
Prostate cancer detection following diagnosis of atypical small acinar proliferation
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- Wenger
- Hc
- A M Rosen
Atypical small acinar proliferation and high grade prostatic intraepithelial neoplasia: should we be concerned? An observational cohort study with a minimum follow-up of 3 years
- V Srirangam
- Rai
- Bp
- A Abroaf