Results after Four Years of Screening for Prostate Cancer with PSA and MRI.

BACKGROUND: Data on the efficacy and safety of screening for prostate cancer with magnetic resonance imaging (MRI) are needed from studies of follow-up screening. METHODS: In a population-based trial that started in 2015, we invited men who were 50 to 60 years of age to undergo prostate-specific antigen (PSA) screening. Men with a PSA level of 3 ng per milliliter or higher underwent MRI of the prostate. Men were randomly assigned to the systematic biopsy group, in which they underwent systematic biopsy and, if suspicious lesions were found on MRI, targeted biopsy, or the MRI-targeted biopsy group, in which they underwent MRI-targeted biopsy only. At each visit, men were invited for repeat screening 2, 4, or 8 years later, depending on the PSA level. The primary outcome was detection of clinically insignificant (International Society of Urological Pathology [ISUP] grade 1) prostate cancer; detection of clinically significant (ISUP grade ≥2) cancer was a secondary outcome, and detection of clinically advanced or high-risk (metastatic or ISUP grade 4 or 5) cancer was also assessed. RESULTS: After a median follow-up of 3.9 years (approximately 26,000 person-years in each group), prostate cancer had been detected in 185 of the 6575 men (2.8%) in the MRI-targeted biopsy group and 298 of the 6578 men (4.5%) in the systematic biopsy group. The relative risk of detecting clinically insignificant cancer in the MRI-targeted biopsy group as compared with the systematic biopsy group was 0.43 (95% confidence interval [CI], 0.32 to 0.57; P<0.001) and was lower at repeat rounds of screening than in the first round (relative risk, 0.25 vs. 0.49); the relative risk of a diagnosis of clinically significant prostate cancer was 0.84 (95% CI, 0.66 to 1.07). The number of advanced or high-risk cancers detected (by screening or as interval cancer) was 15 in the MRI-targeted biopsy group and 23 in the systematic biopsy group (relative risk, 0.65; 95% CI, 0.34 to 1.24). Five severe adverse events occurred (three in the systematic biopsy group and two in the MRI-targeted biopsy group). CONCLUSIONS: In this trial, omitting biopsy in patients with negative MRI results eliminated more than half of diagnoses of clinically insignificant prostate cancer, and the associated risk of having incurable cancer diagnosed at screening or as interval cancer was very low. (Funded by Karin and Christer Johansson's Foundation and others; GÖTEBORG-2 ISRCTN registry number, ISRCTN94604465.).

Histologically benign PI-RADS 4 and 5 lesions contain cancer-associated epigenetic alterations.

BACKGROUND: The detection rate of clinically significant prostate cancer has improved with the use of multiparametric magnetic resonance imaging (mpMRI). Yet, even with MRI-guided biopsy 15%-35% of high-risk lesions (Prostate Imaging-Reporting and Data System [PI-RADS] 4 and 5) are histologically benign. It is unclear if these false positives are due to diagnostic/sampling errors or pathophysiological alterations. To better understand this, we tested histologically benign PI-RAD 4 and 5 lesions for common malignant epigenetic alterations. MATERIALS AND METHODS: MRI-guided in-bore biopsy samples were collected from 45 patients with PI-RADS 4 (n = 31) or 5 (n = 14) lesions. Patients had a median clinical follow-up of 3.8 years. High-risk mpMRI patients were grouped based on their histology into biopsy positive for tumor (BPT; n = 28) or biopsy negative for tumor (BNT; n = 17). From these biopsy samples, DNA methylation of well-known tumor suppressor genes (APC, GSTP1, and RARß2) was quantified. RESULTS: Similar to previous work we observed high rates of promoter methylation at GSTP1 (92.7%), RARß2 (57.3%), and APC (37.8%) in malignant BPT samples but no methylation in benign TURP chips. Interestingly, similar to the malignant samples the BNT biopsies also had increased methylation at the promoter of GSTP1 (78.8%) and RARß2 (34.6%). However, despite these epigenetic alterations none of these BNT patients developed prostate cancer, and those who underwent repeat mpMRI (n = 8) demonstrated either radiological regression or stability. CONCLUSIONS: Histologically benign PI-RADS 4 and 5 lesions harbor prostate cancer-associated epigenetic alterations.

A Comparison of Image-Guided Targeted Prostate Biopsy Outcomes by PI-RADS® Score and Ethnicity in a Diverse, Multiethnic Population.

PURPOSE: NonHispanic Black (NHB) and Hispanic/Afro-Caribbean men have the highest risk of prostate cancer (PCa) compared to nonHispanic White (NHW) men. However, ethnicity-specific outcomes of targeted fusion biopsy (FB) for the detection of PCa are poorly characterized. We compared the outcomes of FB by Prostate Imaging Reporting and Data System (PI-RADS®) score and race/ethnicity among a diverse population. MATERIALS AND METHODS: We evaluated all men who underwent image-guided FB for suspicious lesions on prostate magnetic resonance imaging (≥PI-RADS 3) over a 2-year period. We examined associations of race/ethnicity and PI-RADS score with risk of PCa or clinically significant PCa (cs-PCa, Gleason Group ≥2) on FB using mixed-effects logistic regression models. RESULTS: A total of 410 men with 658 lesions were analyzed, with 201 (49.0%) identified as NHB and 125 (30.5%) identified as Hispanic. NHB men had a twofold increase in the odds of detecting cs-PCa (OR=2.7, p=0.045), while Hispanic men had similar odds of detecting cs-PCa compared to NHW men. With regard to all PCa, NHB men had a similar increase in the odds of detecting all PCa (OR=2.4, p=0.050), which was borderline statistically significant compared to NHW men on FB. When we excluded men on active surveillance, NHB men had even stronger associations with detection of cs-PCa (OR=3.10, p=0.047) or all PCa (OR=2.77, p=0.032) compared to NHW men. CONCLUSIONS: NHB men have higher odds for overall PCa and cs-PCa on FB compared to NHW men. Further work may clarify differences per PI-RADS score. Clinicians should interpret prostate magnetic resonance imaging lesions with more caution in NHB men.

Optimizing Spatial Biopsy Sampling for the Detection of Prostate Cancer.

PURPOSE: The appropriate number of systematic biopsy cores to retrieve during magnetic resonance imaging (MRI)-targeted prostate biopsy is not well defined. We aimed to demonstrate a biopsy sampling approach that reduces required core count while maintaining diagnostic performance. MATERIALS AND METHODS: We collected data from a cohort of 971 men who underwent MRI-ultrasound fusion targeted biopsy for suspected prostate cancer. A regional targeted biopsy (RTB) was evaluated retrospectively; only cores within 2 cm of the margin of a radiologist-defined region of interest were considered part of the RTB. We compared detection rates for clinically significant prostate cancer (csPCa) and cancer upgrading rate on final whole mount pathology after prostatectomy between RTB, combined, MRI-targeted, and systematic biopsy. RESULTS: A total of 16,459 total cores from 971 men were included in the study data sets, of which 1,535 (9%) contained csPCa. The csPCa detection rates for systematic, MRI-targeted, combined, and RTB were 27.0% (262/971), 38.3% (372/971), 44.8% (435/971), and 44.0% (427/971), respectively. Combined biopsy detected significantly more csPCa than systematic and MRI-targeted biopsy (p <0.001 and p=0.004, respectively) but was similar to RTB (p=0.71), which used on average 3.8 (22%) fewer cores per patient. In 102 patients who underwent prostatectomy, there was no significant difference in upgrading rates between RTB and combined biopsy (p=0.84). CONCLUSIONS: A RTB approach can maintain state-of-the-art detection rates while requiring fewer retrieved cores. This result informs decision making about biopsy site selection and total retrieved core count.

The Risk of Prostate Cancer Progression in Active Surveillance Patients with Bilateral Disease Detected by Combined Magnetic Resonance Imaging-Fusion and Systematic Biopsy.

PURPOSE: We sought to evaluate whether bilateral prostate cancer detected at active surveillance (AS) enrollment is associated with progression to Grade Group (GG) ≥2 and to compare the efficacy of combined targeted biopsy plus systematic biopsy (Cbx) vs systematic biopsy (Sbx) or targeted biopsy alone to detect bilateral disease. MATERIALS AND METHODS: A prospectively maintained database of patients referred to our institution from 2007-2020 was queried. The study cohort included all AS patients with GG1 on confirmatory Cbx and followup of at least 1 year. Cox proportional hazard analysis identified baseline characteristics associated with progression to ≥GG2 at any point throughout followup. RESULTS: Of 579 patients referred, 103 patients had GG1 on Cbx and were included in the study; 49/103 (47.6%) patients progressed to ≥GG2, with 30/72 (41.7%) patients with unilateral disease progressing and 19/31 (61.3%) patients with bilateral disease progressing. Median time to progression was 68 months vs 52 months for unilateral and bilateral disease, respectively (p=0.006). Both prostate specific antigen density (HR 1.72, p=0.005) and presence of bilateral disease (HR 2.21, p=0.012) on confirmatory biopsy were associated with AS progression. At time of progression, GG and risk group were significantly higher in patients with bilateral versus unilateral disease. Cbx detected 16% more patients with bilateral disease than Sbx alone. CONCLUSIONS: Bilateral disease and prostate specific antigen density at confirmatory Cbx conferred greater risk of earlier AS progression. Cbx was superior to Sbx for identifying bilateral disease. AS risk-stratification protocols may benefit from including presence of bilateral disease and should use Cbx to detect bilateral disease.

Freehand versus Grid-Based Transperineal Prostate Biopsy: A Comparison of Anatomical Region Yield and Complications.

PURPOSE: The freehand (FH) technique of transperineal prostate biopsy using commercialized needle access systems facilitates a reduction in anesthesia requirements from general to local or local/sedation. We sought to compare the efficacy and complication rates of the FH method with those of the standard grid-based (GB) method. MATERIALS AND METHODS: The GB method was performed from 2014 to 2018, and the updated FH technique was performed from 2018 to 2020, yielding comparative cohorts of 174 and 304, respectively. RESULTS: The FH and GB techniques demonstrated equivalent yields of ≥Gleason grade group (GGG)-2 prostate cancer (PCa). The FH group had a significantly higher mean number of cores with ≥GGG-2 PCa involvement (p=0.011) but a significantly lower mean number of biopsy samples (p <0.01). The urinary retention rate of the GB group (10%) was significantly higher than that of the FH group (1%; p <0.01). The rates of ≥GGG-2 PCa involvement in the anterior (GB, 31%) and anteromedial (FH, 22%) sectors were higher than those in other sectors (range, 0%-9%). For multiparametric magnetic resonance imaging, the rate of ≥GGG-2 PCa detection in the anteromedial prostate (23%) was nearly half that in other locations (range, 38%-55%). CONCLUSIONS: Compared with GB transperineal biopsy, FH transperineal biopsy demonstrates an equivalent cancer yield with no risk of sepsis, a significantly reduced risk of urinary retention, and reduced anesthesia needs. The higher number of cores with ≥GGG-2 PCa involvement in the FH group suggests that FH transperineal biopsy can sample the prostate better than GB-transperineal biopsy can.

The Clinical Significance of Multiple Negative Surveillance Prostate Biopsies for Men on Active Surveillance-Does Cancer Vanish or Simply Hide?

PURPOSE: Men with low risk prostate cancer on active surveillance undergo multiple biopsies over time. The long-term clinical significance of consecutively negative biopsies is not known. MATERIALS AND METHODS: Men with low risk prostate cancer prospectively enrolled in an active surveillance database with at least 4 biopsies were included in the study. Exposure variables were 0, 1 or 2 consecutively negative biopsies after diagnosis. Other variables included age, prostate specific antigen, prostate specific antigen density, Gleason grade group, percent positive cores and magnetic resonance imaging findings. Outcome variables were the detection of any cancer at fourth biopsy and active treatment. RESULTS: A total of 514 men were included, with 112 (22%) men having 1 negative biopsy and 78 (15%) with 2 consecutively negative biopsies. Median prostate specific antigen density was lower for men with 1 negative biopsy (0.11) and consecutively negative biopsies (0.10) compared to men who never had a negative biopsy (0.13, p <0.01). On univariable logistic regression higher prostate specific antigen density (OR 1.68, 95% CI 1.16-2.45) and suspicious magnetic resonance imaging lesions (OR 2.00, 95% CI 1.16-3.42) were associated with a higher likelihood of detecting cancer on fourth biopsy. On multivariable logistic regression 1 negative biopsy (OR 0.22, 95% CI 0.12-0.41) and consecutively negative biopsies (OR 0.12, 95% CI 0.06-0.24) were associated with a lower likelihood of detecting cancer at outcome biopsy. Unadjusted 10-year treatment-free survival was highest for patients with consecutively negative biopsies (84%) and 1 negative biopsy (74%) than those who had none (66%) (log rank p=0.02). CONCLUSIONS: Consecutively negative surveillance biopsies are correlated with favorable clinical risk factors and independently associated with subsequent negative biopsy and lower risk of active treatment.

Is PSA density of the peripheral zone as a useful predictor for prostate cancer in patients with gray zone PSA levels?

BACKGROUND: Serum prostate-specific antigen (PSA) is widely used in screening tests for prostate cancer. As the low specificity of PSA results in unnecessary and invasive prostate biopsies, we evaluated the clinical significance of various PSAs and PSA density (PSAD) related to peripheral zones in patients with gray zone PSA level (4-10 ng/mL). METHODS: A total of 1300 patients underwent transrectal ultrasonography-guided prostate biopsy from 2014 to 2019. Among them, 545 patients in the gray zone were divided into the prostate cancer diagnosis group and the non-prostate cancer diagnosis group, and PSA, relative extra transitional zone PSA (RETzPSA), estimated post holmium laser enucleation of the prostate PSA (EPHPSA), PSAD, peripheral zone PSA density (PZPSAD) and extra-transitional zone density (ETzD) were compared and analyzed using receiver-operating characteristics (ROC) analysis after 1:1 matching using propensity score. RESULTS: Area under the ROC curve values of PSA, EPHPSA, RETzPSA, PSA density, ETzD, and PZPSAD were 0.553 (95% CI: 0.495-0.610), 0.611 (95% CI: 0.554-0.666), 0.673 (95% CI: 0.617-0.725), 0.745 (95% CI: 0.693-0.793), 0.731 (95% CI: 0.677-0.780) and 0.677 (95% CI: 0.611-0.719), respectively. PSAD had 67.11% sensitivity, 71.71% specificity, and 70.34% positive predictive rate at 0.18 ng/mL/cc. ETzD had 69.08% sensitivity, 64.47% specificity, and 66.04% positive predictive rate at 0.04 ng/mL/cc. When the cut-off value of PSAD was increased to 0.18 ng/mL/cc, the best results were obtained with an odds ratio of 5.171 (95% CI: 3.171-8.432), followed by ETzD with 4.054 (95% CI: 2.513-6.540). CONCLUSIONS: These results suggested that volume-adjusted parameters (ETzD and PSAD) might be more sensitive and accurate than various PSA in gray zone patients who required prostate biopsy to reduce unnecessary biopsy.

High-Risk Lesions Detected by MRI-Guided Core Biopsy: Upgrade Rates at Surgical Excision and Implications for Management.

OBJECTIVE. The purpose of our study was to evaluate the upgrade rates of high-risk lesions (HRLs) diagnosed by MRI-guided core biopsy and to assess which clinical and imaging characteristics are predictive of upgrade to malignancy. MATERIALS AND METHODS. A retrospective review was performed of all women who presented to an academic breast radiology center for MRI-guided biopsy between January 1, 2015, and November 30, 2018. Histopathologic results from each biopsy were extracted. HRLs-that is, atypical ductal hyperplasia (ADH), lobular carcinoma in situ (LCIS), atypical lobular hyperplasia (ALH), radial scar, papilloma, flat epithelial atypia (FEA), benign vascular lesion (BVL), and mucocelelike lesion-were included for analysis. Clinical history, imaging characteristics, surgical outcome, and follow-up data were recorded. Radiologic-pathologic correlation was performed. RESULTS. Of 810 MRI-guided biopsies, 189 cases (23.3%) met the inclusion criteria for HRLs. Of the 189 HRLs, 30 cases were excluded for the following reasons: 15 cases were lost to follow-up, six cases were in patients who received neoadjuvant chemotherapy after biopsy, two lesions that were not excised had less than 2 years of imaging follow-up, and seven lesions had radiologic-pathologic discordance at retrospective review. Of the 159 HRLs in our study cohort, 13 (8.2%) were upgraded to carcinoma. Surgical upgrade rates were high for ADH (22.5%, 9/40) and FEA (33.3%, 1/3); moderate for LCIS (6.3%, 3/48); and low for ALH (0.0%, 0/11), radial scar (0.0%, 0/28), papilloma (0.0%, 0/26), and BVL (0.0%, 0/3). Of the upgraded lesions, 69.2% (9/13) were upgraded to ductal carcinoma in situ (DCIS) or well-differentiated carcinoma. ADH lesions were significantly more likely to be upgraded than non-ADH lesions (p = .005). CONCLUSION. ADH diagnosed by MRI-guided core biopsy warrants surgical excision. The other HRLs, however, may be candidates for imaging follow-up rather than excision, especially after meticulous radiologic-pathologic correlation.

Outcomes of transjugular liver biopsies for liver transplant recipients with bicaval and piggyback hepatic vein anastomoses.

BACKGROUND: Liver transplant hepatic venous anastomoses are usually created using "bicaval" or "piggyback" techniques, which may result in unfavorable angulation between the inferior vena cava and hepatic veins, and makes hepatic vein catheterization and tissue sampling during transjugular liver biopsy (TLB) technically challenging. PURPOSE: To compare the technical successes and complications of TLBs for recipients of liver transplants with bicaval and piggyback hepatic vein anastomoses. MATERIAL AND METHODS: Information on type of hepatic vein surgical anastomosis was available for 190 adult patients in whom 306 consecutive TLBs were performed during 2009-2017: 158 with bicaval and 148 with piggyback anastomoses. The primary outcome of procedural success was defined as obtaining a tissue sample sufficient to make a pathologic diagnosis. RESULTS: A technical success rate of 97% with adequate liver tissue for diagnosis was similar between the anastomotic groups (P = 0.50). TLB was unsuccessful in 3% of patients with piggyback anastomoses due to unfavorable hepatic venous anatomy whereas biopsy was successful in all patients with bicaval anastomoses (P = 0.02). Fluoroscopy times were not significantly different (12.1 vs. 13.9 min, P = 0.08). Rates of major complication were similar between the two groups (3% vs. 3%, P > 0.99). CONCLUSION: TLB is safe and effective for liver transplant patients regardless of the type of hepatic vein anastomosis. While failure to catheterize or advance the stiffened biopsy cannula into the hepatic vein is more likely to occur in patients with piggyback anastomoses, this is a rare occurrence.

Digital Mammography Stereotactic Biopsy versus Digital Breast Tomosynthesis-guided Biopsy: Differences in Biopsy Targets, Pathologic Results, and Discordance Rates.

Background Digital breast tomosynthesis (DBT)-guided biopsy is increasingly used in practice. It is important to know expected changes in biopsy targets, pathologic results, and discordance rates. Purpose To compare biopsy target types, pathologic results, and discordance rates for 2 years preceding and 2 years following implementation of DBT-guided biopsy. Materials and Methods All 9-gauge vacuum-assisted core biopsies from a single tertiary breast center that used digital mammography (DM) stereotactic guidance from 2013 to 2015 and DBT-guided biopsy from 2015 to 2017 were retrospectively reviewed. All mammographic examinations were performed with DBT. Patient demographics, biopsy target type, pathologic reports, surgical excision specimens when available, breast density, and imaging follow-up results were recorded. Biopsy targets and discordance rates between radiologic and pathologic examinations were compared between the two biopsy groups. Generalized mixed modeling was used to examine results before and after DBT-guided biopsy. Results A total of 1313 women underwent 1405 breast biopsies: 643 by using DM (August 2013 to July 2015) (median age, 56 years; interquartile range, 49-66 years) and 762 by using DBT (August 2015 to July 2017) (median age, 58 years; interquartile range, 50-67 years), (P = .58). Calcifications were the most common biopsy target for both groups, constituting 89.9% (578 of 643) of DM-guided biopsies and 71.1% (542 of 762) of DBT-guided biopsies (P = .03). The rate of architectural distortion biopsies was 2.0% (13 of 643) with DM-guided biopsy and 17.7% (135 of 762) with DBT-guided biopsy (P = .01). Although overall malignancy rate was similar for DM-guided biopsy (27.8% [179 of 643]) and DBT-guided biopsy (24.8% [191 of 762], P = .54), DBT-guided biopsy helped identify a similar percentage of invasive malignancies (37.4% [72 of 191] vs 29.0% [52 of 179] at DM P = .35), but more radial sclerosing lesions (8.3% [95% confidence interval {CI}: 6.0, 10.0] vs 1.7% [95% CI: 1.0, 3.1]) (P = .01). The discordance rate was 1.4% (95% CI: 1.0, 2.7) with DM-guided biopsy and 4.5% (95% CI: 3.2, 6.3) with DBT-guided biopsy (P = .01). Of the 34 discordant DBT-guided biopsies, 30 were architectural distortions. Conclusion With the transition to digital breast tomosynthesis-guided biopsy, more architectural distortions were biopsied, more radial sclerosing lesions were identified, and more discordance existed in radiologic and pathologic examinations, with a similar percentage of carcinomas diagnosed. © RSNA, 2020 Online supplemental material is available for this article.

Minimum Magnetic Resonance Imaging-Ultrasound Fusion Targeted Biopsy Cores Needed for Prostate Cancer Detection: Multivariable Retrospective, Lesion Based Analyses of Patients Treated with Radical Prostatectomy.

PURPOSE: We analyzed the number of multiparametric magnetic resonance imaging targeted biopsy cores per lesion needed to detect prostate cancer in patients treated with radical prostatectomy. MATERIALS AND METHODS: Analyses focused on targeted biopsy of magnetic resonance imaging lesions suspicious for prostate cancer with a PI-RADS® (Prostate Imaging Reporting and Data System) score of 3 or greater and consecutive radical prostatectomy. Descriptive statistics included the frequency/proportion and IQR. Multivariable logistic regression analyses on the per lesion level were used to predict the number of targeted biopsies with prostate cancer. RESULTS: In the total cohort of 771 radical prostatectomy cases 437 (57%) and 334 (43%) were systematic transrectal ultrasound guided biopsy naïve or had 1 or more prior negative systematic transrectal ultrasound guided biopsies, respectively. A maximum PI-RADS score of 3, 4 and 5 was present in 67 (8.7%), 567 (74%) and 137 patients (18%), respectively. A total of 1,459 multiparametric magnetic resonance imaging lesions suspicious for prostate cancer were identified for analysis. Prostate cancer was detected based on an initial, second, third, or fourth or greater targeted biopsy in 79%, 92%, 98% and 100% of cases, respectively. The rate of prostate cancer detection on the first targeted biopsy core increased with higher PI-RADS scores of 3, 4 and 5 (67%, 79% and 87%, respectively). The number of prior negative systematic transrectal ultrasound guided biopsies and pathological tumor stage emerged as independent predictors on multivariate analysis, addressing the need for 2 or more targeted biopsy cores to detect clinically significant prostate cancer. CONCLUSIONS: Radical prostatectomy based analyses demonstrated that most cancers could be detected by 2 targeted biopsies only while in a minority of cases 3 or more targeted biopsies were necessary. Such findings might indicate that the targeted biopsy procedure and the related technology have improved, especially in patients with intermediate/high risk prostate cancer.

A Multicenter Study of the Clinical Utility of Nontargeted Systematic Transperineal Prostate Biopsies in Patients Undergoing Pre-Biopsy Multiparametric Magnetic Resonance Imaging.

PURPOSE: The added value of nontargeted systematic prostate biopsies when performed alongside magnetic resonance imaging targeted biopsies in men referred with a suspicion of prostate cancer is unclear. We aimed to determine the clinical utility of transperineal nontargeted systematic prostate biopsies, when performed alongside targeted systematic prostate biopsies, using pre-biopsy multiparametric magnetic resonance imaging. MATERIALS AND METHODS: Consecutive patients referred with a suspicion of prostate cancer (April 2017 to October 2019) underwent pre-biopsy multiparametric magnetic resonance imaging. A transperineal biopsy was advised if multiparametric magnetic resonance imaging PI-RADS® (v.2.0) score was 4 or 5, and score 3 required a prostate specific antigen density 0.12 ng/ml or greater. Primary threshold for clinically significant prostate cancer was defined as any Gleason 3+4 or greater. Multivariable logistic regression analysis identified pre-biopsy predictors of clinically significant prostate cancer in nontargeted systematic prostate biopsies, regardless of targeted pathology (p <0.05, R, version 3.5.1). RESULTS: A total of 1,719 men underwent a pre-biopsy multiparametric magnetic resonance imaging, with 679 (39.5%) proceeding to combined targeted systematic prostate biopsies and nontargeted systematic prostate biopsies. In these men clinically significant prostate cancer was detected in 333 (49%) and 139 (20.5%) with targeted systematic prostate biopsies and nontargeted systematic prostate biopsies, respectively. In those men with clinically significant prostate cancer in targeted systematic prostate biopsies, clinically significant prostate cancer was also present in nontargeted systematic prostate biopsies in 117 (17.2%); Gleason 3+3 was present in 50 (7.4%). In 287 men without any cancer in the targeted systematic prostate biopsies, 13 (1.9%) had clinically significant prostate cancer in nontargeted systematic prostate biopsies. In addition 18/679 (2.7%) had Gleason 3+3 disease and no Gleason greater than 4+3 was detected. Predictors associated with clinically significant prostate cancer in nontargeted systematic prostate biopsies were prostate specific antigen 5 ng/ml or greater (OR 2.05, 95% CI 1.13-3.73, p=0.02), PI-RADS score 5 (OR 2.26, 95% CI 1.51-3.38, p <0.001) and prostate volume less than 50 cc (OR 2.47, 95% CI 1.57-3.87, p <0.001). CONCLUSIONS: Detection of clinically significant prostate cancer in exclusively nontargeted transperineal systematic biopsies in a pre-biopsy multiparametric magnetic resonance imaging pathway was low (1.9%).

The Long-Term Risks of Metastases in Men on Active Surveillance for Early Stage Prostate Cancer.

PURPOSE: We assessd the long-term outcomes from a large prospective cohort of men diagnosed with prostate cancer managed with active surveillance and determined the clinical prognostic factors that may predict the risk of metastases. MATERIALS AND METHODS: We retrospectively reviewed data of men enrolled on active surveillance at our institution between 1990 and 2018 with low or intermediate risk disease (stage cT1-2, prostate specific antigen less than 20 ng/ml, and biopsy Grade Group [GG]1-2). Patients were classified into 3 groups by diagnostic GG and prostate specific antigen density. Primary outcome was metastatic prostate cancer detected on imaging or at prostatectomy. In addition, upgrade at surveillance biopsy, active treatment, and overall and prostate cancer specific survival outcomes were assessed. Cox proportional hazards regression models were used. RESULTS: A total of 1,450 men met the inclusion criteria. Median followup was 77 months (IQR 49-114). The 7-year metastasis-free survival rate was 99%. Metastases developed in 15 men at a median of 62 months (IQR 29-104), of which 69% were confined to lymph nodes. Men with GG2 had a lower metastasis-free survival rate compared to those with GG1 disease. GG2, prostate specific antigen velocity and PI-RADS® 4-5 lesions on multiparametric magnetic resonance imaging were associated with a higher risk of metastases. The 7-year prostate cancer specific survival was greater than 99%. CONCLUSIONS: Active surveillance seems to preserve favorable long-term prognosis, as metastases and prostate cancer specific death are rare. However, the higher risk of metastases associated with higher Gleason grade, prostate specific antigen velocity, and characteristics on multiparametric magnetic resonance imaging should be considered when selecting and counseling patients for active surveillance.

Hemigland Cryoablation of Clinically Significant Prostate Cancer: Intermediate-Term Followup via Magnetic Resonance Imaging Guided Biopsy.

PURPOSE: Contemporary biopsy methods were used to determine the success rate of hemigland cryoablation as a primary treatment for prostate cancer. Previous studies, often including men at low risk, have used magnetic resonance imaging guided biopsy to a variable extent. Here, we uniformly used the new diagnostic modality to study all men, each with clinically significant cancer, at baseline and at short and intermediate-term followup. MATERIALS AND METHODS: In an open label trial (NCT03503643) 61 men with unilateral cancer (all clinically significant, ie Grade Group 2 or greater) underwent primary hemigland cryoablation. Subjects were 80% Caucasian, average age 69 years, prostate specific antigen 6.6 ng/ml and prostate volume 38 cc. Biopsy was performed using magnetic resonance imaging/ultrasound fusion prior to treatment and at the followup intervals of near-term (6 months, in 61) and intermediate-term (18 months, in 27). All utilities of fusion biopsy, ie targeting of magnetic resonance imaging visible lesions, template systematic sampling, and in followup, tracking of prior positive sites, were used throughout the study to detect clinically significant cancer, the primary end point. RESULTS: Following treatment 82% of men (50 of 61) had no biopsy detectable clinically significant prostate cancer at 6-month near-term followup and 82% of men (22 of 27) reaching the 18-month intermediate-term remained biopsy negative. Combination of the 3 sampling methods provided maximal cancer detection. During followup a new focus of cancer was found in the contralateral prostate in only 1 of 27 men. No adverse events above Clavien-Dindo grade 2 were encountered. CONCLUSIONS: Hemigland cryoablation, when rigorously evaluated by all utilities of magnetic resonance imaging guided biopsy, appears to eliminate clinically significant cancer in 82% of men, a success rate that endures for at least 18 months.

Risk of Prostate Cancer after a Negative Magnetic Resonance Imaging Guided Biopsy.

PURPOSE: Magnetic resonance imaging guided biopsy which reveals no cancer may impart reassurance beyond that offered by ultrasound guided biopsy. However, followup of men after a negative magnetic resonance imaging guided biopsy has been mostly by prostate specific antigen testing and reports of followup tissue confirmation are few. We investigated the incidence of clinically significant prostate cancer in such men who, because of persistent cancer suspicion, subsequently underwent a repeat magnetic resonance imaging guided biopsy. MATERIALS AND METHODS: Subjects were all men with a negative initial magnetic resonance imaging guided biopsy who underwent at least 1 further magnetic resonance imaging guided biopsy due to continued clinical suspicion of clinically significant prostate cancer (September 2009 to July 2019). Biopsies were magnetic resonance imaging-ultrasound fusion with targeted and systematic cores. Regions of interest from initial magnetic resonance imaging and any new regions of interest at followup magnetic resonance imaging guided biopsy were targeted. The primary end point was detection of clinically significant prostate cancer (Gleason Grade Group 2 or greater). RESULTS: Of 2,716 men 733 had a negative initial magnetic resonance imaging guided biopsy. Study subjects were 73/733 who underwent followup magnetic resonance imaging guided biopsy. Median (IQR) age and prostate specific antigen density were 64 years (59-67) and 0.12 ng/ml/cc (0.08-0.17), respectively. Baseline PI-RADS® scores were 3 or greater in 74%. At followup magnetic resonance imaging guided biopsy (median 2.4 years, IQR 1.3-3.6), 17/73 (23%) were diagnosed with clinically significant prostate cancer. When followup magnetic resonance imaging revealed a lesion (PI-RADS 3 or greater), clinically significant prostate cancer was found in 17/53 (32%). When followup magnetic resonance imaging was negative (PI-RADS less than 3), cancer was not found (0/20) (p <0.01). Overall 54% of men with PI-RADS 5 at followup magnetic resonance imaging guided biopsy were found to have clinically significant prostate cancer. CONCLUSIONS: Men with negative magnetic resonance imaging following an initial negative magnetic resonance imaging guided biopsy are unlikely to harbor clinically significant prostate cancer and may avoid repeat biopsy. However, when lesions are seen on followup magnetic resonance imaging, repeat magnetic resonance imaging guided biopsy is warranted.

PI-RADS® Category as a Predictor of Progression to Unfavorable Risk Prostate Cancer in Men on Active Surveillance.

PURPOSE: We identified baseline imaging and clinical characteristics of patients that may improve risk stratification among patients being evaluated for active surveillance. MATERIALS AND METHODS: From July 2007 to January 2020 patients referred to our institution for prostate cancer were evaluated and those who remained on active surveillance were identified. Men underwent multiparametric magnetic resonance imaging upon entry into our active surveillance protocol during which baseline demographic and imaging data were documented. Patients were then followed and outcomes, specifically progression to Gleason Grade Group (GG)3 or greater disease, were recorded. RESULTS: Of the men placed on active surveillance 344 had at least 1 PI-RADS score documented. For those with an index lesion PI-RADS category of 5, 33% (17/51) had progression to GG3 or greater on active surveillance with a median time to progression of 31 months. When comparing the progression-free survival times and progression rates in each category, PI-RADS category was found to be associated with progression to GG3 or greater on active surveillance (p <0.01). On univariable analysis factors associated with progression included an index lesion PI-RADS category of 5, prostate specific antigen density and the size of the largest lesion. On multivariable analysis only PI-RADS category of 5 and prostate specific antigen density were associated with progression on active surveillance. CONCLUSIONS: PI-RADS lesion categories at baseline multiparametric magnetic resonance imaging during active surveillance enrollment can be used to predict cancer progression to GG3 or greater on active surveillance. This information, along with other clinical data, can better assist urologists in identifying and managing patients appropriate for active surveillance.

How Many Targeted Biopsy Cores are Needed for Clinically Significant Prostate Cancer Detection during Transperineal Magnetic Resonance Imaging Ultrasound Fusion Biopsy?

PURPOSE: In this study we determined the optimal number of transperineal magnetic resonance imaging ultrasound fusion targeted biopsy cores per lesion needed for the detection of clinically significant prostate cancer. MATERIALS AND METHODS: A total of 101 patients with at least 1 lesion with a PI-RADS® (Prostate Imaging Reporting and Data System) score of 3 or greater were recruited prospectively. At least 4 transperineal magnetic resonance imaging ultrasound fusion targeted biopsy cores per lesion were performed, followed by systematic biopsy. The Kappa test was used to evaluate the consistency of the clinically significant prostate cancer detection rate between different targeted biopsy cores and 4 or more cores, which was regarded as reference standard. RESULTS: In the total cohort of 101 patients 49 (48.5%), 55 (54.5%) and 57 (56.4%) were diagnosed with clinically significant prostate cancer by systematic biopsy, targeted biopsy or targeted biopsy plus systematic biopsy, respectively. As for the total of 161 lesions, the clinically significant prostate cancer detection rate based on 1, 2, 3, or 4 or more targeted biopsy cores was made in 27.3%, 32.9%, 37.3% and 39.1%, respectively. Three cores showed great consistency with 4 or more cores in clinically significant prostate cancer detection rate (Kappa coefficient of 0.961, p <0.001) with a sensitivity of 95.2% (95% CI 85.8-98.8), and only missed 3 lesions harboring clinically significant prostate cancer. Similar results were obtained in cases with PI-RADS 3 or 4 or maximal diameter of less than 1.5 cm. CONCLUSIONS: Three targeted biopsies per lesion were suitable during transperineal magnetic resonance imaging ultrasound fusion biopsy, especially for lesions of PI-RADS 3 or 4, or small lesions (maximal diameter less than 1.5 cm), which may help to tailor targeted prostate biopsy procedures.

Risk Factors for Biopsy Reclassification over Time in Men on Active Surveillance for Early Stage Prostate Cancer.

PURPOSE: Few validated clinical tools currently exist to standardize the frequency of biopsies for men on active surveillance for low risk prostate cancer. We determined predictors of biopsy reclassification at specific time points after enrollment on active surveillance. MATERIALS AND METHODS: We identified men with clinically low risk prostate cancer prospectively enrolled on active surveillance at the University of California, San Francisco between 2000 and 2016. Biopsy reclassification was defined as Gleason Grade Group 2 or greater on subsequent biopsy. Multivariable Cox proportional hazards regression models were used to identify factors associated with risk of biopsy reclassification at first surveillance biopsy and 1 to 3, 3 to 5 and 5 to 10 years after enrollment, adjusting for clinicodemographic factors, PI-RADS® (Prostate Imaging Reporting and Data System) score and genomic testing. RESULTS: A total of 1,031 men were included in the study. On multivariable analysis biopsy reclassification was associated with prostate specific antigen density 0.15 or greater (HR 3.37, 95% CI 1.83-6.21), percentage biopsy cores positive (HR 1.27, 95% CI 1.05-1.54) and high genomic score (HR 2.81, 95% CI 1.21-6.52) at first surveillance biopsy and also at 1 to 3 years, after adjustment. Prostate specific antigen density 0.15 or greater (HR 2.36, 95% CI 1.56-3.56) and prostate specific antigen kinetics (HR 2.19, 95% CI 1.43-3.34) were associated with reclassification at 3 to 5 years. A PI-RADS 4-5 score was not associated with biopsy reclassification at any time point. CONCLUSIONS: High genomic score, prostate specific antigen kinetics and prostate specific antigen density 0.15 or greater were associated with reclassification within 3 years of commencing active surveillance, and prostate specific antigen kinetics and prostate specific antigen density 0.15 or greater remained associated with reclassification at 5 years after diagnosis.