Interaction of patient age and high-grade prostate cancer on targeted biopsies of MRI suspicious lesions.

OBJECTIVES: To evaluate the interaction of patient age and Prostate Imaging-Reporting and Data System (PI-RADS) score in determining the grade of prostate cancer (PCa) identified on magnetic resonance imaging (MRI)-targeted biopsy in older men. PATIENTS AND METHODS: From a prospectively accrued Institutional Review Board-approved comparative study of MRI-targeted and systematic biopsy between June 2012 and December 2022, men with at least one PI-RADS ≥3 lesion on pre-biopsy MRI and no prior history of PCa were selected. Ordinal and binomial logistic regression analyses were performed. RESULTS: A total of 2677 men met study criteria. The highest PI-RADS score was 3 in 1220 men (46%), 4 in 950 men (36%), and 5 in 507 men (19%). The median (interquartile range [IQR]) patient age was 66.7 (60.8-71.8) years, median (IQR) prostate-specific antigen (PSA) level was 6.1 (4.6-9.0) ng/mL, median (IQR) prostate volume was 48 (34-68) mL, and median (IQR) PSA density was 0.13 (0.08-0.20) ng/mL/mL. Clinically significant (cs)PCa and high-risk PCa were identified on targeted biopsy in 1264 (47%) and 321 (12%) men, respectively. Prevalence of csPCa and high-risk PCa were significantly higher in the older age groups. On multivariable analyses, patient age was significantly associated with csPCa but not high-risk PCa; PI-RADS score and the interaction of age and PI-RADS score were significantly associated with high-risk PCa but not csPCa. CONCLUSION: In our cohort, the substantial rate of high-risk PCa on MRI-ultrasound fusion targeted biopsies in older men, and its significant association with MRI findings, supports the value of pre-biopsy MRI to localise disease that could cause cancer mortality even in older men.

Prostate magnetic resonance imaging-targeted biopsy global grade correlates better than highest grade with prostatectomy grade.

BACKGROUND: Magnetic resonance imaging (MRI)-targeted prostate biopsy has become an increasingly common method of diagnosing prostate cancer. A previous study from our institution demonstrated that the biopsy global Grade Group (gGG, aggregate GG of all positive cores) and highest Grade Group (hGG in any core) both show substantial concordance with the Grade Group at radical prostatectomy (RPGG) while the discordance predominantly consists of upgrading in gGG and downgrading in hGG. We performed a larger cohort study focused on biopsy cases in which gGG and hGG differ, to determine their relative concordance with RPGG. METHODS: We conducted a retrospective review of radical prostatectomy specimens with prior MRI-targeted biopsies from our institution between 2016 and 2020. Separate gGG and hGG were assigned to each MRI-targeted lesion. Targeted lesions with different gGG versus hGG were segregated from those with identical gGG and hGG. The concordance of biopsy GG with RPGG was evaluated using κ coefficient analysis. RESULTS: Of the 489 lesions with MRI-targeted biopsies, 82 (17%) differed in gGG versus hGG. The gGG of 46 (56%), 33 (40%), and 3 (4%) lesions were unchanged, upgraded, and downgraded at radical prostatectomy, respectively (κ= 0.302, weighted κ = 0.334). The hGG of 24 (29%), 9 (11%), and 49 (60%) lesions were unchanged, upgraded, and downgraded at radical prostatectomy, respectively (κ = 0.040, weighted κ = 0.198). When stratified by the biopsy GG, gGG showed the highest concordance in GG2 (61%) and GG3 (54%) lesions. The hGG resulted in substantial downgrading (60%) with less optimal concordance regardless of the biopsy GG. Neither the prebiopsy prostate specific antigen level nor the PI-RADS score was predictive of upgrading of gGG. CONCLUSIONS: When gGG and hGG differ, gGG method more accurately predicts the RPGG than hGG, particularly in GG2 and GG3 lesions which comprised the majority of targeted lesions.

Single-cell analysis of localized prostate cancer patients links high Gleason score with an immunosuppressive profile.

BACKGROUND: Evading immune surveillance is a hallmark for the development of multiple cancer types. Whether immune evasion contributes to the pathogenesis of high-grade prostate cancer (HGPCa) remains an area of active inquiry. METHODS: Through single-cell RNA sequencing and multicolor flow cytometry of freshly isolated prostatectomy specimens and matched peripheral blood, we aimed to characterize the tumor immune microenvironment (TME) of localized prostate cancer (PCa), including HGPCa and low-grade prostate cancer (LGPCa). RESULTS: HGPCa are highly infiltrated by exhausted CD8+ T cells, myeloid cells, and regulatory T cells (TRegs). These HGPCa-infiltrating CD8+ T cells expressed high levels of exhaustion markers including TIM3, TOX, TCF7, PD-1, CTLA4, TIGIT, and CXCL13. By contrast, a high ratio of activated CD8+  effector T cells relative to TRegs and myeloid cells infiltrate the TME of LGPCa. HGPCa CD8+  tumor-infiltrating lymphocytes (TILs) expressed more androgen receptor and prostate-specific membran antigen yet less prostate-specific antigen than the LGPCa CD8+  TILs. The PCa TME was infiltrated by macrophages but these did not clearly cluster by M1 and M2 markers. CONCLUSIONS: Our study reveals a suppressive TME with high levels of CD8+ T cell exhaustion in localized PCa, a finding enriched in HGPCa relative to LGPCa. These studies suggest a possible link between the clinical-pathologic risk of PCa and the associated TME. Our results have implications for our understanding of the immunologic mechanisms of PCa pathogenesis and the implementation of immunotherapy for localized PCa.

Copolymerization of single-cell nucleic acids into balls of acrylamide gel.

We show the use of 5'-Acrydite oligonucleotides to copolymerize single-cell DNA or RNA into balls of acrylamide gel (BAGs). Combining this step with split-and-pool techniques for creating barcodes yields a method with advantages in cost and scalability, depth of coverage, ease of operation, minimal cross-contamination, and efficient use of samples. We perform DNA copy number profiling on mixtures of cell lines, nuclei from frozen prostate tumors, and biopsy washes. As applied to RNA, the method has high capture efficiency of transcripts and sufficient consistency to clearly distinguish the expression patterns of cell lines and individual nuclei from neurons dissected from the mouse brain. By using varietal tags (UMIs) to achieve sequence error correction, we show extremely low levels of cross-contamination by tracking source-specific SNVs. The method is readily modifiable, and we will discuss its adaptability and diverse applications.

Biopsy Assessment of Oncologic Control 3 Years Following Primary Partial Gland Cryoablation: A Prospective Cohort Study of Men With Intermediate-risk Prostate Cancer.

PURPOSE: We evaluated 3-year oncologic outcomes following primary partial gland cryoablation. MATERIALS AND METHODS: Men with unilateral intermediate-risk prostate cancer undergoing primary partial gland cryoablation since March 2017 enrolled in a prospective outcome registry. The postablation protocol for all men included surveillance prostate biopsy at 2 years postablation and reflex prostate biopsy for cases with high suspicion of recurrence (eg, progressive rise in PSA). Recurrence of clinically significant prostate cancer was defined as any Gleason grade group ≥2 disease on postablation biopsy. Freedom from failure represented no whole gland salvage treatment, metastatic prostate cancer, or prostate cancer mortality. Freedom from recurrence and freedom from failure were characterized using nonparametric maximum likelihood estimators. RESULTS: A total of 132 men had at least 24 months of follow-up data. Biopsies identified clinically significant prostate cancer in 12 men. At 36 months, model-estimated rates of freedom from recurrence of in-field, out-of-field, and overall clinically significant cancer were 97% (95% CI: 92-100), 87% (95% CI: 80-94), and 86% (95% CI: 78-93), respectively. The model-estimated proportion with freedom from failure at 36 months was 97% (95% CI: 93-100). CONCLUSIONS: The low in-field cancer detection rate at 3 years indicates successful ablation of localized cancers. Conversely, our observed out-of-field detection rate highlights the need for continued surveillance following partial gland cryoablation. Many of these recurrences exhibited very low volume of clinically significant disease below the detection threshold of multiparametric MRI, suggesting a limited role for multiparametric MRI in detecting clinically significant recurrences at 2 years. These findings emphasize the need for long-term surveillance and identification of predictors of clinically significant prostate cancer recurrences to guide biopsy timing.

Axumin (18F-Fluciclovine) PET imaging in men exhibiting no clinically significant cancer on initial negative biopsy of PI-RADS 4 and 5 regions of interest.

PURPOSE: The objective of the study was to determine whether Axumin (18F-Fluciclovine) PET/MRI informs the decision to perform an early repeat biopsy of PI-RADS 4/5 region of interest (ROI) exhibiting no clinically significant prostate cancer (csPCa) on initial biopsy. METHODS: This prospective study enrolled men with at least one PI-RADS 4/5 ROI on multi-parametric MRI and no csPCa on prior biopsy defined as Gleason grade group (GGG) > 1. All men underwent an Axumin PET/MRI and only-persistent PI-RADS > 2 ROI were advised to undergo a repeat biopsy. A PET cancer suspicion score (PETCSS) was internally developed to stratify PET avid lesions according to their suspicion of harboring csPCa. The sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of the PETCSS for predicting csPCa were assessed. Relative risk was calculated to analyze the association of baseline variables with csPCa on repeat biopsy. RESULTS: Thirty-eight ROI on 36 enrolled men were analyzed. Fourteen (36.8%) were downgraded to PI-RADS 1/2 and were not subjected to repeat biopsy. Thirteen (92.9%) of these downgraded scans also exhibited low-risk PETCSS. Overall, 18/22 (81.2%) subjects underwent a repeat per protocol biopsy. Of the 20 ROI subjected to repeat biopsy, eight (40%) were found to harbour csPCa. The sensitivity, specificity, PPV and NPV of the PETCSS were 50, 50, 40, and 60%, respectively. No predictor of csPCa was found in the risk analysis. CONCLUSION: Our pilot study showed that both MRI and PET sequences have limited performance for identifying those persistently suspicious PI-RADS 4/5 ROI that are found to harbor csPCa on repeat biopsy.

Early functional outcomes following partial gland cryo-ablation.

INTRODUCTION: Given the increasing interest in partial gland cryo-ablation as a treatment modality and the lack of data surrounding urinary and sexual outcomes after the procedure, the goal of this analysis was to assess functional outcomes following partial gland cryo-ablation (PGCA) stratified according to baseline severity of lower urinary tract symptoms (LUTS) and erectile function (EF). A secondary goal was to also determine if there were any clinical factors associated with significant change in LUTS and EF. MATERIALS AND METHODS: Since 3/2017, all men undergoing primary PGCA were offered enrollment into an IRB-approved prospective outcomes registry. Men were given International Prostate Symptom Score (IPSS) and Sexual Health Inventory for Men (SHIM) surveys prior to and 6 months post treatment. Differences in IPSS and SHIM scores are described, and factors associated with clinically significant change were assessed using univariate and multivariate analysis. RESULTS: A total of 100 men completed 6 month follow up. The mean IPSS for the overall cohort decreased 2.1 units (p > 0.05). The mean changes in IPSS for men with baseline mild, moderate, and severe LUTS were 0.9 (p = 0.06), -4.2 (p = 0.001), and -11.1(p = 0.001) units, respectively. The mean changes in the SHIM score for all men were - 5.1 units (p = 0.001). The mean changes in SHIM score for baseline none, mild/mild-to-moderate, moderate-severe ED were -7.6 (p = 0.001), -6.5 (p = 0.001) and -1.1 units (p = 0.27), respectively. No variables of interest were significantly associated with changes in IPSS or SHIM scores. CONCLUSION: Stratifying functional outcomes according to baseline IPSS and SHIM is imperative to assess the true impact of PGCA on functional outcomes.

Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice.

Electronic-cigarettes (E-cigs) are marketed as a safe alternative to tobacco to deliver the stimulant nicotine, and their use is gaining in popularity, particularly among the younger population. We recently showed that mice exposed to short-term (12 wk) E-cig smoke (ECS) sustained extensive DNA damage in lungs, heart, and bladder mucosa and diminished DNA repair in lungs. Nicotine and its nitrosation product, nicotine-derived nitrosamine ketone, cause the same deleterious effects in human lung epithelial and bladder urothelial cells. These findings raise the possibility that ECS is a lung and bladder carcinogen in addition to nicotine. Given the fact that E-cig use has become popular in the past decade, epidemiological data on the relationship between ECS and human cancer may not be known for a decade to come. In this study, the carcinogenicity of ECS was tested in mice. We found that mice exposed to ECS for 54 wk developed lung adenocarcinomas (9 of 40 mice, 22.5%) and bladder urothelial hyperplasia (23 of 40 mice, 57.5%). These lesions were extremely rare in mice exposed to vehicle control or filtered air. Current observations that ECS induces lung adenocarcinomas and bladder urothelial hyperplasia, combined with our previous findings that ECS induces DNA damage in the lungs and bladder and inhibits DNA repair in lung tissues, implicate ECS as a lung and potential bladder carcinogen in mice. While it is well established that tobacco smoke poses a huge threat to human health, whether ECS poses any threat to humans is not yet known and warrants careful investigation.

Interaction between race and prostate cancer treatment benefit in the Veterans Health Administration.

BACKGROUND: Studies have demonstrated that Black men may undergo definitive prostate cancer (CaP) treatment less often than men of other races, but it is unclear whether they are avoiding overtreatment of low-risk disease or experiencing a reduction in appropriate care. The authors' aim was to assess the role of race as it relates to treatment benefit in access to CaP treatment in a single-payer population. METHODS: The authors used the Veterans Health Administration (VHA) Corporate Data Warehouse to perform a retrospective cohort study of veterans diagnosed with low- or intermediate-risk CaP between 2011 and 2017. RESULTS: The authors identified 35,427 men with incident low- or intermediate-risk CaP. When they controlled for covariates, Black men had 1.05 times the odds of receiving treatment in comparison with non-Black men (P < .001), and high-treatment-benefit men had 1.4 times the odds of receiving treatment in comparison with those in the low-treatment-benefit group (P < .001). The interaction of race and treatment benefit was significant, with Black men in the high-treatment-benefit category less likely to receive treatment than non-Black men in the same treatment category (odds ratio, 0.89; P < .001). CONCLUSIONS: Although race does appear to influence the receipt of definitive treatment in the VHA, this relationship varies in the context of the patient's treatment benefit, with Black men receiving less definitive treatment in high-benefit situations. The influence of patient race at high treatment benefit levels invites further investigation into the driving forces behind this persistent disparity in this consequential group.

Application of the PRECISION Trial Biopsy Strategy to a Contemporary Magnetic Resonance Imaging-Targeted Biopsy Cohort-How Many Clinically Significant Prostate Cancers are Missed?

PURPOSE: To demonstrate the generalizability of PRECISION findings and apply the PRECISION biopsy strategy to a contemporary cohort to characterize cancers missed by employing this strategy. MATERIALS AND METHODS: A total of 629 men biopsied between February 2015 and September 2018 met PRECISION inclusion criteria. Men with PI-RADS™ 1-2 magnetic resonance imaging were only biopsied if high clinical suspicion for cancer. Missed cancers were defined as prostate cancer identified uniquely on systematic biopsy in men with PI-RADS 3-5 magnetic resonance imaging, or on either systematic biopsy or magnetic resonance imaging-targeted prostate biopsy in men with PI-RADS 1-2 magnetic resonance imaging. Outcomes included 1) clinically significant prostate cancer, Gleason grade group 2 or greater, detection rate, 2) missed clinically significant prostate cancer rate upon application of PRECISION biopsy strategy, 3) Gleason grade group distribution, core size, spatial orientation and oncologic risk among missed cancers. RESULTS: Application of the PRECISION biopsy strategy to the study cohort resulted in avoidance of biopsy in 28%, similar magnetic resonance imaging-targeted prostate biopsy detection rate to PRECISION, reduction of Gleason grade group 1 detection rate by 60% and reduction of clinically significant prostate cancer detection rate by 19%. Missed clinically significant prostate cancers were often smaller than 6 mm (54.5%), Gleason grade group 2 (67.3%) and low risk by clinical nomogram (74.6%). Gleason grade group 1 cancers identified uniquely on systematic biopsy were often contralateral to magnetic resonance imaging target (46.4%), while missed clinically significant prostate cancer was predominantly ipsilateral (81%). Limitations include biopsy of only men with high risk clinical features among PI-RADS 1-2 magnetic resonance imaging, potentially overestimating the clinically significant prostate cancer detection rate. CONCLUSIONS: The study cohort demonstrated generalizability of PRECISION findings. Applying the PRECISION biopsy strategy greatly reduces Gleason grade group 1 detection rate, while missing a small number of clinically significant prostate cancer, typically small volume, low risk, and Gleason grade group 2. Missed clinically significant prostate cancer is predominantly ipsilateral to magnetic resonance imaging target, possibly representing targeting error.

MRI predicts prostatic urethral involvement in men undergoing radical prostatectomy: implications for cryo-ablation of localized prostate cancer.

PURPOSE: To determine whether multi-parametric magnetic resonance imaging (mpMRI) can reliably predict proximity of prostate cancer to the prostatic urethra in a contemporary series of men undergoing radical prostatectomy (RP) at two academic centers. METHODS: Clinical characteristics of consecutive men undergoing pre-operative mpMRI prior to RP and whole-mount axial serial step-sectioned pathology examination at two academic centers between Jun 2016 and Oct 2018 were analyzed retrospectively. Every tumor was characterized by its pathologic minimum distance to the prostatic urethral lumen (pMDUL). Only the cancer closest to the urethra represented the prostatic urethral index lesion. The radiologic minimum distance of the index lesion to the prostatic urethral lumen was measured and noted as ≤ 5 mm versus > 5 mm. The sensitivity, specificity, positive and negative predicting values (PPV and NPV) and area under the receivers operating characteristics curve (AUC) were calculated for performance of mpMRI for predicting pMDUL ≤ 5 mm. RESULTS: Of the 163 surgical specimens examined, 112 (69%) exhibited a pMDUL ≤ 5 mm. These men had significantly higher grade group (GG) and advanced pathological and clinical stage. The rates of high PI-RADS score and presence of gross extracapsular extension were also significantly greater for the group with pMDUL ≤ 5 mm. The AUC, sensitivity, specificity, PPV, and NPV were 0.641, 51.8, 76.5, 82.9, and 42.4%, respectively, for mpMRI to predict pMDUL < 5 mm. CONCLUSIONS: Nearly 70% of men undergoing RP present with tumor within 5 mm of the prostatic urethra. These tumors present higher risk characteristics, and mpMRI exhibited moderate performance and high PPV in their pre-operative detection. Physicians performing partial gland ablation should take these results into consideration during treatment selection and planning.

E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells.

E-cigarette smoke delivers stimulant nicotine as aerosol without tobacco or the burning process. It contains neither carcinogenic incomplete combustion byproducts nor tobacco nitrosamines, the nicotine nitrosation products. E-cigarettes are promoted as safe and have gained significant popularity. In this study, instead of detecting nitrosamines, we directly measured DNA damage induced by nitrosamines in different organs of E-cigarette smoke-exposed mice. We found mutagenic O6-methyldeoxyguanosines and γ-hydroxy-1,N2 -propano-deoxyguanosines in the lung, bladder, and heart. DNA-repair activity and repair proteins XPC and OGG1/2 are significantly reduced in the lung. We found that nicotine and its metabolite, nicotine-derived nitrosamine ketone, can induce the same effects and enhance mutational susceptibility and tumorigenic transformation of cultured human bronchial epithelial and urothelial cells. These results indicate that nicotine nitrosation occurs in vivo in mice and that E-cigarette smoke is carcinogenic to the murine lung and bladder and harmful to the murine heart. It is therefore possible that E-cigarette smoke may contribute to lung and bladder cancer, as well as heart disease, in humans.

Aldehydes are the predominant forces inducing DNA damage and inhibiting DNA repair in tobacco smoke carcinogenesis.

Tobacco smoke (TS) contains numerous cancer-causing agents, with polycyclic aromatic hydrocarbons (PAHs) and nitrosamines being most frequently cited as the major TS human cancer agents. Many lines of evidence seriously question this conclusion. To resolve this issue, we determined DNA adducts induced by the three major TS carcinogens: benzo(a)pyrene (BP), 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanoe (NNK), and aldehydes in humans and mice. In mice, TS induces abundant aldehyde-induced γ-hydroxy-propano-deoxyguanosine (γ-OH-PdG) and α-methyl-γ-OH-PdG adducts in the lung and bladder, but not in the heart and liver. TS does not induce the BP- and NNK-DNA adducts in lung, heart, liver, and bladder. TS also reduces DNA repair activity and the abundance of repair proteins, XPC and OGG1/2, in lung tissues. These TS effects were greatly reduced by diet with polyphenols. We found that γ-OH-PdG and α-methyl-γ-OH-PdG are the major adducts formed in tobacco smokers' buccal cells as well as the normal lung tissues of tobacco-smoking lung cancer patients, but not in lung tissues of nonsmokers. However, the levels of BP- and NNK-DNA adducts are the same in lung tissues of smokers and nonsmokers. We found that while BP and NNK can induce BPDE-dG and O6-methyl-dG adducts in human lung and bladder epithelial cells, these inductions can be inhibited by acrolein. Acrolein also can reduce DNA repair activity and repair proteins. We propose a TS carcinogenesis paradigm. Aldehydes are major TS carcinogens exerting dominant effect: Aldehydes induce mutagenic PdG adducts, impair DNA repair functions, and inhibit many procarcinogens in TS from becoming DNA-damaging agents.

Long-Term Continence Outcomes in Men Undergoing Radical Prostatectomy: A Prospective 15-Year Longitudinal Study.

PURPOSE: We examined the time dependent rates of urinary continence following open retropubic radical prostatectomy. MATERIALS AND METHODS: A total of 1,995 men treated with radical prostatectomy were enrolled in a prospective longitudinal outcomes study. The UCLA-PCI-UFS (UCLA-Prostate Cancer Index-Urinary Function Index) was administered at baseline, and 3, 6, 12, 24, 96, 120 and 180 months after open retropubic radical prostatectomy. Urinary continence was defined by 1 pad or less in 24 hours. Two multiple regression models were constructed to evaluate the association of time since open retropubic radical prostatectomy with the UCLA-PCI-UFI score and urinary continence. RESULTS: The decrease in urinary continence rates between baseline and 15 years (99.6% vs 87.2%, p <0.001), and 2 and 15 years (95.3% vs 87.2%, p = 0.021) were statistically significant. Urinary continence rates were consistently higher in the younger group at all time points. CONCLUSIONS: A significant decrease in urinary continence rates was observed between baseline and 2 years, and between 2 and 15 years in the entire cohort. Urinary continence rates in age matched men in the general population who were followed longitudinally for 15 years were comparable to those in our study population. This suggests that while open retropubic radical prostatectomy causes primarily sphincteric urinary incontinence, it may be protective for subsequent benign prostatic hyperplasia mediated urinary incontinence.

The Institutional Learning Curve of Magnetic Resonance Imaging-Ultrasound Fusion Targeted Prostate Biopsy: Temporal Improvements in Cancer Detection in 4 Years.

PURPOSE: While magnetic resonance imaging-ultrasound fusion targeted biopsy allows for improved detection of clinically significant prostate cancer, a concerning amount of clinically significant disease is still missed. We hypothesized that a number of these misses are due to the learning curve associated with magnetic resonance imaging-ultrasound fusion targeted biopsy. We report the results of repeat magnetic resonance imaging-ultrasound fusion targeted biopsy in men with continued suspicion for cancer and the institutional learning curve in the detection of clinically significant prostate cancer with time. MATERIALS AND METHODS: We analyzed the records of 1,813 prostate biopsies in a prospectively acquired cohort of men who presented for prostate biopsy in a 4-year period. All men were offered prebiopsy magnetic resonance imaging and were assigned a maximum PI-RADS™ (Prostate Imaging Reporting and Data System version 2) score. Biopsy outcomes in men with a suspicious region of interest were compared. The relationship between time and clinically significant prostate cancer detection was analyzed. RESULTS: The clinically significant prostate cancer detection rate increased 26% with time in men with a PI-RADS 4/5 region of interest. On repeat magnetic resonance imaging-ultrasound fusion targeted biopsy in men with continued suspicion for cancer 53% of those with a PI-RADS 4/5 region of interest demonstrated clinically significant discordance from the initial magnetic resonance imaging-ultrasound fusion targeted biopsy compared to only 23% with a PI-RADS 1/2 region of interest. Significantly less clinically significant prostate cancer was missed or under graded in the most recent biopsies compared to the earliest biopsies. CONCLUSIONS: The high upgrade rate on repeat magnetic resonance imaging-ultrasound fusion targeted biopsy and the increasing cancer detection rate with time show the significant learning curve associated with magnetic resonance imaging-ultrasound fusion targeted biopsy. Men with low risk or negative biopsies with a persistent, concerning region of interest should be promptly rebiopsied. Improved targeting accuracy with operator experience can help decrease the number of missed cases of clinically significant prostate cancer.

Multiparametric magnetic resonance imaging identifies significant apical prostate cancers.

OBJECTIVE: To determine if multiparametric (mp) magnetic resonance imaging (MRI) can identify significant apical disease, thereby informing decisions regarding preservation of the membranous urethra. MATERIALS AND METHODS: Men undergoing radical prostatectomy (RP) between January 2012 and June 2016, who underwent a 12-core transrectal ultrasonography-guided systematic biopsy (SB), preoperative 3-Tesla MRI, and sectioning of the prostate specimen with tumour foci mapping, were extracted from a single surgeon's prospective longitudinal outcomes database. Apical SB and mpMRI lesion results were compared with regard to their ability to predict aggressive tumours in the prostatic apex (PA), defined as prostate cancer grade group >1. RESULTS: Of the 100 men who met the eligibility criteria, 43 (43%) exhibited aggressive prostate cancer in the distal 5 mm of the apex. A Likert score >2 in the apical one-third of the prostate was found to be more reliable than any cancer found on apical SB at detecting aggressive cancer in the apex. On multivariate regression analysis, which included Likert score in the apex, age, prostate-specific antigen (PSA) level, prostate size and presence of any cancer on apical biopsy, only Likert score (P = 0.005) and PSA level (P = 0.025) were significant and independent predictors of aggressive cancer in the distal apex. CONCLUSION: The results of the study showed that MRI was superior to SB at identifying aggressive prostate cancer within the distal PA and may be useful for planning the extent of apical preservation during RP.

Aetiology and management of earlier vs later biochemical recurrence after retropubic radical prostatectomy.

OBJECTIVES: To examine the characteristics and management of earlier (within 5 years) vs later (after 5 years) biochemical recurrence (BCR) after radical prostatectomy (RP). MATERIALS AND METHODS: Between October 2000 and October 2009, 1597 men underwent open retropubic RP. BCRs were managed using salvage radiation therapy (SRT), androgen deprivation therapy (ADT) or active surveillance (AS). BCR-free survival was assessed using Kaplan-Meier analysis. Factors predicting earlier or later BCR and BCR after SRT were assessed using logistic regression and Cox proportional hazard models, respectively. RESULTS: The probabilities of developing BCR within 5 years and 10 years were 12.3% (95% confidence interval [CI] 10.7-13.9) and 18.4% (95% CI 16.2-20.6), respectively. On multivariate analysis, prostate-specific antigen doubling time, positive surgical margins and pathological Gleason score significantly differentiated earlier from later BCR. Overall, 74.5, 12.7 and 12.7% of men developing BCR underwent SRT, ADT or AS, respectively. A significantly greater proportion of men in the earlier BCR group underwent SRT (80.8 vs 59%) and ADT (14.6 vs 8.2%), and a significantly greater proportion of men in the later BCR group underwent AS (32.8 vs 4.6%; P<0.001). The response to SRT was independent of time to BCR. On multivariate analysis, clinical stage and pathological stage significantly predicted failure of SRT. CONCLUSIONS: Approximately one third of BCRs occurred between 5 and 10 years after RP. The aetiology and management of BCR was dependent on time to BCR, whereas response to SRT was independent of time to recurrence. Long-term follow-up is mandatory beyond 5 years for all men after RP.