Image-guided multiparametric magnetic resonance imaging-transrectal ultrasound fusion biopsy augmented with a sextant versus an extended template random biopsy: Comparison of cancer detection rates, complication and functional outcomes.

PURPOSE: To compare the efficacy of a novel fusion template "reduced six-core systemic template and multiparametric magnetic resonance imaging/transrectal ultrasound (mpMRI/TRUS) fusion targeted biopsy" (TBx+6c), with mpMRI/TRUS fusion-targeted biopsy and 12-core systematic biopsy template (TBx+12c) in the diagnosis of prostate cancer (PCa). MATERIALS AND METHODS: This is an institutional review board approved single-center observational study involving adult men undergoing fusion-targeted biopsies for the diagnosis of PCa. Patients were sorted into cohorts of TBx+6c or TBx+12c based on the systematic biopsy template used. The study's main objective was to determine the cancer detection rate (CDR) for overall PCa and clinically significant PCa (csPCa) and the secondary objectives were to compare complication rates and functional outcome differences between the cohort. RESULTS: A total of 204 patients met study's inclusion criteria. TBx+6c group had 120 patients, while TBx+12c cohort had 84 patients. The groups had similar baseline characteristics and overall CDR in the TBx+6c cohort was 71.7% versus 79.8%, compared to the TBx+12c (p = 0.18) whereas, the csPCa detection rate in the TBx+6c group was 50.8% versus 54.8% in the TBx+12c group (p = 0.5). TBx+6c cohort had lower overall complication rate of 3% versus 13%, (p = 0.01) and ≥ grade 2 complication rates (1 (1%) vs. 3(4%), p = 0.03) compared to the TBx+12c cohort. There were no differences in IIEF-5 (p = 0.5) or IPSS (p = 0.1) scores at baseline and 2-weeks and 6-weeks post-biopsy. CONCLUSION: TBx+6c cohort, when compared to the TBx+12c cohort, demonstrated comparable diagnostic performance along with similar functional outcomes and lower complication rates. These results suggest the importance of further exploring the clinical implications of adopting a TBx+6c schema for PCa diagnosis in comparison to the widely used TBx+12c schema through a multicenter randomized controlled trial.

Intermediate-term oncological and functional outcomes of salvage cryotherapy for the management of prostate cancer recurrence after primary brachytherapy versus primary cryotherapy: A propensity score-matched analysis.

BACKGROUND: Salvage cryotherapy (SCT) is widely used to treat prostate cancer (PCa) recurrence after radiotherapy (RT). We studied the intermediate oncological and functional outcomes of patients who underwent SCT following cryotherapy (CRYO-SCT) recurrence and compare it to recurrence after brachytherapy (BT-SCT). METHODS: An IRB-approved retrospective cohort study utilizing patient data from the Cryo On-Line Data Registry and the Duke PCa database between 1992 and 2016. Biochemical recurrence (BCR) using Phoenix criteria was the primary endpoint assessed at 2- and 5-years post-SCT. Secondary endpoints assessed functional outcomes including urinary continence, erectile function, and recto-urethral fistula. Association between treatment and biochemical progression-free survival was assessed using inverse probability weighted (IPTW) Cox proportional hazards regression. The differences in the secondary functional outcomes were assessed by Pearson's χ2 test or Fisher's exact test, corrected for IPTW. RESULTS: A total of 194 patients met inclusion criteria. The BCR rate for BT-SCT and CRYO-SCT was 23 (20.4%) and 17 (21%) at 2 years and 30 (26.5%) and 22 (27.2%) at 5 years according to Phoenix criteria. There was no statistical difference in 2 years (hazard ratio [HR] 0.9; 95% confidence interval [CI], 0.5-1.7, p = 0.7) or 5-year BCR (HR: 0.86; 95% CI, 0.5-1.5, p = 0.6) between the groups. The functional outcomes like urinary continence (p = 0.4), erectile function (p = 0.1), and recto-urethral fistula (p = 0.3) were not statistically different. CONCLUSION: CRYO-SCT appears to be well tolerated, with comparable oncological and functional outcomes to patients failing primary BT. The findings also demonstrated that SCT can render a significant number of patients biochemically free of disease after initial CRYO with minimal morbidity. SCT is a viable treatment option to salvage local PCa recurrence following either BT or cryoablation failure.

Patient-reported functional outcomes and oncological control after primary focal cryotherapy for clinically significant prostate cancer: A Phase II mandatory biopsy-monitored study.

INTRODUCTION: We report herein the impact of focal therapy (FT) on multi-domain functional outcomes in a Phase II prospective clinical trial (NCT04138914) in focal cryotherapy for clinically significant prostate cancer (csPCa). METHODS: The primary outcome was the detection of a ≥5 point deterioration in any of the four main expanded prostate index composite (EPIC) functional domains. Pretreatment multiparametric magnetic resonance imaging (mpMRI) and transperineal targeted and systematic saturation biopsy were used to select patients with prostate-specific antigen (PSA)≤20 ng/mL, Gleason grade group (GG) ≤4, mpMRI lesion volume ≤ 3 mL (for a single lesion) or ≤1.5 mL (where two lesions were present). Focal cryotherapy was performed with a minimum 5 mm margin around each target lesion. EPIC scores were obtained at baseline and posttreatment at 1, 3, 6, and 12 months. Mandatory repeat mpMRI and prostate biopsy were performed at 12 months to determine the infield and outfield recurrence. RESULTS: Twenty-eight patients were recruited. The mean age was 68 years, with PSA of 7.3 ng/mL and PSA density of 0.19 ng/mL2 . No Clavien-Dindo ≥3 complications occurred. Transient worsening of EPIC urinary (mean diff 16.0, p < 0.001, 95% confidence interval [CI]: 8.8-23.6) and sexual function scores (mean diff 11.0, p:0.005, 95% CI: 4.0-17.7) were observed at 1-month posttreatment, with recovery by Month 3. A subgroup who had ablation extending to the neurovascular bundle had a trend to delayed recovery of sexual function to Month 6. At 12-month repeat mpMRI and biopsy, 22 patients (78.6%) had no detectable csPCa. Of the six patients (21.4%) who had csPCa recurrences, four were GG2, one GG3, and one GG4. Four patients underwent repeat FT, one underwent radical prostatectomy, while the remaining one patient with low-volume GG2 cancer opted for active surveillance. CONCLUSION: FT using cryotherapy was associated with a transient deterioration of urinary and sexual function with resolution at 3 months posttreatment and with reasonable early efficacy in well-selected csPCa patients.

Clinical utility of multiple secondary combined tests in prostate cancer screening.

INTRODUCTION: The clinical utility of concurrent Prostate Health Index (PHI) and ExosomeDx Prostate Intelliscore (EPI) testing is unclear. We sought to examine the performance of combined PHI and EPI testing on men undergoing elevated PSA work up. MATERIALS AND METHODS: Patients who received both EPI and PHI testing were identified from an institutional database of men referred to urology for an elevated total PSA. Cut points of EPI > 15.6 and PHI ≥ 36 were used to denote a positive test. Patients were placed into one of four groups determined by combination of EPI and PHI results. Demographic variables and biopsy recommendations were compared between groups. The concordance of test positivity between EPI and PHI was compared by Cohen's kappa. Demographic variables and secondary testing results were compared between patients' compliant and non-compliant with prostate biopsy recommendation. Biopsy pathology was compared between groups. RESULTS: A total of 162 patients had both EPI and PHI testing. Median age was 65 years, with a median PSA of 6.64 ng/mL. Age (p = 0.001), PSA (< 0.001) and biopsy recommendation (< 0.001) differed between combined secondary screening test result groups. Seventy-five percent of patients with both a positive EPI and PHI were found to have prostate cancer, with 54.2% being ≥ Gleason 7. Cohen's kappa was 0.19, indicating poor concordance. The AUC of EPI and PHI for clinically significant cancer was 0.563 (95% CI: 0.4331-0.6923) and 0.685 (95% CI: 0.569-0.8) (p = 0.147). CONCLUSIONS: Concurrently positive EPI and PHI indicate increased prostate cancer risk, with combined usage potentially influencing biopsy recommendation and compliance.

Combined ARFI and Shear Wave Imaging of Prostate Cancer: Optimizing Beam Sequences and Parameter Reconstruction Approaches.

This study demonstrates the implementation of a shear wave reconstruction algorithm that enables concurrent acoustic radiation force impulse (ARFI) imaging and shear wave elasticity imaging (SWEI) of prostate cancer and zonal anatomy. The combined ARFI/SWEI sequence uses closely spaced push beams across the lateral field of view and simultaneously tracks both on-axis (within the region of excitation) and off-axis (laterally offset from the excitation) after each push beam. Using a large number of push beams across the lateral field of view enables the collection of higher signal-to-noise ratio (SNR) shear wave data to reconstruct the SWEI volume than is typically acquired. The shear wave arrival times were determined with cross-correlation of shear wave velocity signals in two dimensions after 3-D directional filtering to remove reflection artifacts. To combine data from serially interrogated lateral push locations, arrival times from different pushes were aligned by estimating the shear wave propagation time between push locations. Shear wave data acquired in an elasticity lesion phantom and reconstructed using this algorithm demonstrate benefits to contrast-to-noise ratio (CNR) with increased push beam density and 3-D directional filtering. Increasing the push beam spacing from 0.3 to 11.6 mm (typical for commercial SWEI systems) resulted in a 53% decrease in CNR. In human in vivo data, this imaging approach enabled high CNR (1.61-1.86) imaging of histologically-confirmed prostate cancer. The in vivo images had improved spatial resolution and CNR and fewer reflection artifacts as a result of the high push beam density, the high shear wave SNR, the use of multidimensional directional filtering, and the combination of shear wave data from different push beams.

Are higher pre-diagnosis follicle stimulating hormone levels associated with long-term prostate cancer risk?

BACKGROUND: Follicle stimulating hormone (FSH) is a pituitary hormone that helps regulate testosterone homeostasis. Although it is generally accepted that FSH levels increase with LHRH-agonist therapy for prostate cancer (PC), the specific impact of FSH levels on risk of PC diagnosis is largely unknown. The objective of this study was to perform a population-level analysis to assess the association between FSH levels and PC diagnosis. METHODS: All men (n = 386,018) who had a pre-PC diagnosis FSH level and complete data were identified within the Veterans Affairs Health System between 1999 and 2018. The association between FSH level and time from FSH test to PC diagnosis was tested using stratified Cox proportional hazards models. Multivariable models were adjusted for age, year, race, body mass index, and Charlson comorbidity index. Due to nonproportional hazards over time, time to PC was modeled separately: ≤4 years after an FSH test and >4 years following an FSH test. RESULTS: Median age at first FSH level was 64 years (interquartile range [IQR]: 54-72), median year of FSH was 2010 (IQR: 2005-2014), and 70% of the cohort was white. Median follow-up was 76 months (IQR: 38-126) during which 17,519 men (4.5%) were diagnosed with PC. On multivariable analysis, in the first 4 years after FSH test, there was no association between FSH and time to PC diagnosis. Starting from 4 years after FSH test, on multivariable analysis, a higher FSH level was associated with lower risk of PC with continuous modeling, but found no association with log continuous and categorical modeling. CONCLUSIONS: In this population-level study among male veterans receiving an FSH test for an unknown clinical indication, associations between FSH levels and PC risk were inconsistent and likely driven by selection bias and confounding variables. Future studies should consider different study designs.

Oncological and functional outcomes of men undergoing primary whole gland cryoablation of the prostate: A 20-year experience.

BACKGROUND: This study reports the oncological and functional outcomes in men with localized prostate cancer (Pca) who were treated with primary whole gland cryoablation (WGC) of the prostate. METHODS: The authors retrospectively reviewed their prospectively collected cryosurgery database between January 2002 and September 2019 for men who were treated with WGC of the prostate at a tertiary referral center. Primary outcome includes biochemical recurrence-free survival (BRFS). Secondary outcomes include failure-free survival (FFS), metastasis-free survival (MFS) and adverse events. RESULTS: A total of 260 men were included in the study. Men having had prior treatment for Pca were excluded. Median follow-up was 107 months (interquartile range [IQR], 68.3-132.5 months). BRFS, FFS, and MFS at 10 years were 84%, 66%, and 96%, respectively. High risk D'Amico classification was associated with a lower BRFS and FFS on multivariable analysis. No patient had any Pca-related death during follow-up. American Urological Association symptoms score and bother index were unchanged following cryoablation. Median International Index of Erectile Function score precryoablation and post-cryoablation was 7 (IQR, 3-11) and 1 (IQR, 1-5), respectively. Stress urinary incontinence, defined as requiring any protective pads only occurred in five patients (2%). No patient developed a fistula. Grade > 2 Clavien-Dindo adverse events occurred in six (2.3%) patients. CONCLUSION: WGC of the prostate can achieve excellent oncological and functional outcomes in men with localized Pca at the 10-year mark. Primary WGC may be a good option for men who desire to preserve urinary continence and have an excellent oncologic outcome. LAY SUMMARY: Primary whole gland cryoablation is an alternative treatment option to radical prostatectomy and radiotherapy for men with organ-confined prostate cancer. Patients had excellent cancer outcomes 1 years after whole gland cryoablation, and patients with PSA nadir 0.1 ng/ml or lower after treatment were less likely to have disease recurrence.

Assessment after focal therapy: what is the latest?

PURPOSE OF REVIEW: To review assessment after focal therapy (FT) in the context of developments from the past two years. RECENT FINDINGS: With a paucity of high-quality studies, recent findings are primarily reliant on results from institutional-based cohorts and reports of expert consensus. Notably, oncologic treatment failure should be further stratified into recurrence in the in-field or out-of-field ablation zone, and both regions should be surveilled postoperatively. Monitoring primarily consists of periodic evaluations of prostate-specific antigen (PSA) testing and magnetic resonance imaging, with histologic sampling needed to confirm suspicion of recurrence. Recent investigations into PSA derivatives, contrast-enhanced ultrasound, and prostate-specific membrane antigen imaging have shown preliminary promise. Although postablation functional outcomes are generally accepted to be excellent, they are limited by the wide range of patient-reported measures, variability in individual practice, and low questionnaire completion rates. SUMMARY: There is still a need for high-level, long-term data to inform exact standardized protocols to manage patients after FT. A multifaceted approach is required to surveil patients and identify those at risk of recurrence. Embracing shared responsibility between the patient and clinician to fastidiously monitor the infield and out-of-field ablation zones postoperatively is critical to maximize oncologic outcomes.

Available evidence on HIFU for focal treatment of prostate cancer: a systematic review.

PURPOSE: Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa. MATERIAL AND METHODS: We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included. RESULTS: Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade. CONCLUSIONS: This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.

Safety of concomitant therapy with radium-223 and abiraterone or enzalutamide in a real-world population.

BACKGROUND: Real-world utilization and outcomes of combination therapy for men with metastatic castrate-resistant prostate cancer (mCRPC) are largely unknown. We evaluated the overall survival (OS) and skeletal-related events (SREs) among men who received radium-223 with or without concomitant abiraterone or enzalutamide in the Veterans Affairs (VA) Health System. METHODS: We reviewed charts of all mCRPC patients who received radium-223 in the VA from January 2013 to September 2017. We used Cox models to test the association between concomitant therapy versus radium-223 alone on OS and SRE. Sensitivity analyses were performed for concomitant use of denosumab/bisphosphonates. RESULTS: Three hundred and eighteen patients treated with radium-223 were identified; 116/318 (37%) received concomitant abiraterone/enzalutamide. Two hundred and seventy-seven (87%) patients died during follow-up. Patients who received concomitant therapy were younger at radium-223 initiation (median age 68 vs. 70, p = .027) and had a longer follow-up (median 29.5 vs. 17.9 months, p = .030). There was no OS benefit for those on concomitant therapy (hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.67-1.12, p = .28). There was a trend for an increased SRE risk for patients on concomitant therapy (HR: 1.87, 95% CI: 0.96-3.61, p = .066), but this was not significant. When analyses were limited to men using bone heath agents, similar results were seen for OS (HR: 0.86, 95% CI 0.64-1.15, p = .30) and SRE (HR: 2.36, 95% CI: 0.94-5.94, p = .068). CONCLUSIONS: Despite the common use of concomitant therapy in this real-world study, there was no difference in OS among mCRPC patients. A nonsignificant increased SRE risk was observed. Further work needs to evaluate the optimal sequence, timing, and safety of combination therapies.

Implementation and Impact of a Risk-Stratified Prostate Cancer Screening Algorithm as a Clinical Decision Support Tool in a Primary Care Network.

BACKGROUND: Implementation methods of risk-stratified cancer screening guidance throughout a health care system remains understudied. OBJECTIVE: Conduct a preliminary analysis of the implementation of a risk-stratified prostate cancer screening algorithm in a single health care system. DESIGN: Comparison of men seen pre-implementation (2/1/2016-2/1/2017) vs. post-implementation (2/2/2017-2/21/2018). PARTICIPANTS: Men, aged 40-75 years, without a history of prostate cancer, who were seen by a primary care provider. INTERVENTIONS: The algorithm was integrated into two components in the electronic health record (EHR): in Health Maintenance as a personalized screening reminder and in tailored messages to providers that accompanied prostate-specific antigen (PSA) results. MAIN MEASURES: Primary outcomes: percent of men who met screening algorithm criteria; percent of men with a PSA result. Logistic repeated measures mixed models were used to test for differences in the proportion of individuals that met screening criteria in the pre- and post-implementation periods with age, race, family history, and PSA level included as covariates. KEY RESULTS: During the pre- and post-implementation periods, 49,053 and 49,980 men, respectively, were seen across 26 clinics (20.6% African American). The proportion of men who met screening algorithm criteria increased from 49.3% (pre-implementation) to 68.0% (post-implementation) (p < 0.001); this increase was observed across all races, age groups, and primary care clinics. Importantly, the percent of men who had a PSA did not change: 55.3% pre-implementation, 55.0% post-implementation. The adjusted odds of meeting algorithm-based screening was 6.5-times higher in the post-implementation period than in the pre-implementation period (95% confidence interval, 5.97 to 7.05). CONCLUSIONS: In this preliminary analysis, following implementation of an EHR-based algorithm, we observed a rapid change in practice with an increase in screening in higher-risk groups balanced with a decrease in screening in low-risk groups. Future efforts will evaluate costs and downstream outcomes of this strategy.

Current state of image-guided focal therapy for prostate cancer.

PURPOSE: To review the current evidence regarding protocols and outcomes of image-guided focal therapy (FT) for prostate cancer (PCa). METHODS: A literature search of the latest published studies assessing primary FT for PCa was carried out in Medline and Cochrane library databases followed by a critical review. FT modalities, follow-up strategies, and oncological and toxicity outcomes were summarized and discussed in this review. RESULTS: Twenty-four studies with six different sources of energy met the inclusion criteria. A heterogeneity of patient selection, energy sources, treatment templates, and definitions of failure was found among the studies. While a third of patients may be found to have additional cancer burden over 3-5 years following FT, most patients will remain free of a radical procedure. The vast majority of patients maintain urinary continence and good erectile function after FT. Acute urinary retention is the most common complication, whilst severe complications remain rare. CONCLUSION: An increasing number of prospective studies with longer follow-up have been recently published. Acceptable cancer control and low treatment toxicity after FT have been consistently reported. Follow-up imaging and routine biopsy must be encouraged post-FT. While there is no reliable PSA threshold to predict failure after FT, reporting post-FT positive biopsies and retreatment rates appear to be standard when assessing treatment efficacy.

Variability of the Positive Predictive Value of PI-RADS for Prostate MRI across 26 Centers: Experience of the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel.

Background Prostate MRI is used widely in clinical care for guiding tissue sampling, active surveillance, and staging. The Prostate Imaging Reporting and Data System (PI-RADS) helps provide a standardized probabilistic approach for identifying clinically significant prostate cancer. Despite widespread use, the variability in performance of prostate MRI across practices remains unknown. Purpose To estimate the positive predictive value (PPV) of PI-RADS for the detection of high-grade prostate cancer across imaging centers. Materials and Methods This retrospective cross-sectional study was compliant with the HIPAA. Twenty-six centers with members in the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel submitted data from men with suspected or biopsy-proven untreated prostate cancer. MRI scans were obtained between January 2015 and April 2018. This was followed with targeted biopsy. Only men with at least one MRI lesion assigned a PI-RADS score of 2-5 were included. Outcome was prostate cancer with Gleason score (GS) greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2). A mixed-model logistic regression with institution and individuals as random effects was used to estimate overall PPVs. The variability of observed PPV of PI-RADS across imaging centers was described by using the median and interquartile range. Results The authors evaluated 3449 men (mean age, 65 years ± 8 [standard deviation]) with 5082 lesions. Biopsy results showed 1698 cancers with GS greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2) in 2082 men. Across all centers, the estimated PPV was 35% (95% confidence interval [CI]: 27%, 43%) for a PI-RADS score greater than or equal to 3 and 49% (95% CI: 40%, 58%) for a PI-RADS score greater than or equal to 4. The interquartile ranges of PPV at these same PI-RADS score thresholds were 27%-44% and 27%-48%, respectively. Conclusion The positive predictive value of the Prostate Imaging and Reporting Data System was low and varied widely across centers. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Milot in this issue.

Racial Discrepancies in Overall Survival among Men Treated with 223Radium.

PURPOSE: Several recent studies on metastatic castration resistant prostate cancer demonstrated improved overall survival in black vs white men. 223Radium is Food and Drug Administration approved for metastatic castration resistant prostate cancer based on a survival benefit in the ALSYMPCA (A Phase III Study of Radium-223 Dichloride in Patients with Symptomatic Hormone Refractory Prostate Cancer with Skeletal Metastases) trial, in which 94% of participants were white. We identified a real world population of patients with metastatic castration resistant prostate cancer who received 223radium to compare differences in baseline characteristics and outcomes in black vs nonblack men. MATERIALS AND METHODS: We reviewed the charts of all men who received 223radium in the entire Veterans Affairs system. We compared treatment patterns and baseline characteristics between black and nonblack men. We used Cox models to analyze predictors of time from 223radium start to overall survival and time to skeletal related events. RESULTS: We identified 318 patients treated with 223radium, including 87 (27%) who were black. Median followup after 223radium initiation was 25.3 months (IQR 13.8-37.1). Black men were younger than nonblack men when starting 223radium (median age 67 vs 70 years, p <0.001) and they had higher prostate specific antigen (median 159.9 vs 90.2 ng/ml, p=0.014) and alkaline phosphatase (median 163 vs 135 IU/l, p=0.017). A greater proportion of black men received docetaxel prior to 223radium (77% vs 55%, p <0.001). On multivariable analysis black race was associated with a decreased risk of mortality from the time of 223radium initiation (HR 0.75, 95% CI 0.57-0.99, p=0.045). CONCLUSIONS: Black men had longer overall survival than nonblack men, although they appeared to receive radium later in the disease course. Further studies are required to verify our findings and explore biological differences between black and nonblack men with metastatic castration resistant prostate cancer.

Influence of African American race on the association between preoperative biopsy grade group and adverse histopathologic features of radical prostatectomy.

BACKGROUND: The current study was performed to evaluate the influence of race on the association between biopsy grade group (GrGp) and the risk of detectable prostate-specific antigen (PSA) and adverse histopathological outcomes after radical prostatectomy (RP). METHODS: Data regarding 4073 men (1344 African American men; 33%) who were treated with RP were categorized based on the 5-tiered GrGp system. Logistic regression was used to test the association between biopsy GrGp and PSA nadir (<0.1 ng/mL) after RP as well as adverse pathological features among all patients and stratified by race. RESULTS: Those patients with a higher biopsy GrGp were found to have lower odds of achieving a PSA nadir <0.1 ng/mL after RP on unadjusted and multivariable analysis (both P < .001). On unadjusted and multivariable analysis, higher GrGp was associated with increased odds of each of the adverse pathological features, namely, GrGp ≥3, extraprostatic extension, seminal vesicle invasion, positive surgical resection margin, and positive lymph nodes (all P < .001). Race had no significant interaction with biopsy GrGp in the prediction of PSA nadir after RP (P = .91) or any adverse pathological features (all P > .06) except positive lymph nodes. When the models were stratified by race, the associations between preoperative biopsy GrGp and having a PSA nadir <0.1 ng/mL, high-grade final pathology, or other adverse histopathologic features were similar in both races except as noted for positive lymph nodes. CONCLUSIONS: Higher preoperative biopsy GrGp is associated with increased odds of adverse histopathological findings as well as lower odds of a PSA nadir <0.1 ng/mL after RP. These associations are largely independent of race, suggesting that GrGp is an accurate tool for risk stratification in both black and white men.

Evaluation and Active Treatment versus Active Surveillance of Localized Prostate Cancer in Renal Transplant Patients in the Era of Low and Very Low Risk Prostate Cancer.

PURPOSE: Current trends in renal transplantation, such as improved allograft/recipient survival and expanded organ transplantation eligibility criteria in older recipients, are concomitant with increasingly detected low risk prostate cancer in candidates for or recipients of renal transplantation. We reviewed the evidence regarding prostate cancer screening, diagnosis and management in renal transplant candidates and recipients. We focused on published reports of prostate cancer incidence and diagnosis in patients with end stage renal disease, pretransplant screening recommendations, and recommendations regarding waiting time between treatment and active wait listing after the prostate cancer diagnosis in renal transplant candidates. In addition, we examined the natural history of prostate cancer development after renal transplantation in the setting of standard immunosuppression. MATERIALS AND METHODS: We reviewed the English language literature using search terms including prostate cancer, end stage renal disease, renal transplantation, prostate cancer screening, prostate specific antigen, prostate cancer treatment and active surveillance in various combinations. RESULTS: Prostate cancer screening is still widely done in almost all patients with end stage renal disease before and after transplantation. Active treatment of any patients with prostate cancer and a 5-year waiting period before transplantation can negatively affect the collective pool of participants and the overall survival of patients on dialysis. Several groups have proposed a shorter waiting time to kidney transplantation in patients with low risk prostate cancer. CONCLUSIONS: There are no standardized guidelines for screening and management of prostate cancer before and after transplantation. In the era of low risk prostate cancer end stage renal disease is a significant competing mortality risk factor. The role of active surveillance in these complex cases has yet to be well investigated. Further studies and nomograms are urged to integrate risk stratified screening and treatment protocols before and after renal transplantation.

SPARED Collaboration: Patient Selection for Partial Gland Ablation in Men with Localized Prostate Cancer.

PURPOSE: The SPARED CRN (Study of Prostate Ablation Related Energy Devices Coordinated Registry Network) is a private-public partnership between academic and community urologists, the FDA (U.S. Food and Drug Administration), the Medical Device Epidemiology Network and device manufacturers to examine the safety and effectiveness of technologies for partial gland ablation in men with localized prostate cancer. MATERIALS AND METHODS: We report on a recent workshop at the FDA with thought leaders to discuss a critical framework for partial gland ablation, focusing on patient selection, surgical planning, followup, study design and appropriate comparators in terms of adverse events and cancer control outcomes. We summarize salient points from experts in urology, oncology and epidemiology that were presented and discussed in an open forum. RESULTS: Given the challenges in achieving patient and physician equipoise to perform a randomized trial, as well as an inherent paradigm shift when comparing partial gland ablation (inability to assess prostate specific antigen recurrence) to whole gland treatments, the group focused on objective performance criteria and goals as a platform to guide the creation of single arm studies in the SPARED CRN. CONCLUSIONS: This summit lays the foundation for prospective, multi-center data collection and evaluation of novel medical devices and drug/device combinations for partial gland ablation.

Surveillance after prostate focal therapy.

INTRODUCTION: Long-term outcomes from large cohorts are not yet available upon which to base recommended follow-up protocols after prostate focal therapy. This is an updated summary of a 2015 SIU-ICUD review of the best available current evidence and expert consensus on guidelines for surveillance after prostate focal therapy. METHODS: We performed a systematic search of the PubMed, Cochrane and Embase databases to identify studies where primary prostate focal therapy was performed to treat prostate cancer. RESULTS: Multiparametric magnetic resonance imaging (mpMRI) should be performed at 3-6 months, 12-24 months and at 5 years after focal therapy. Targeted biopsy of the treated zone should be performed at 3-6 months and fusion biopsy of any suspicious lesion seen on mpMRI. Additionally, a systematic biopsy should be performed at 12-24 months and again at 5 years. In histological diagnosis, characteristic changes of each treatment modality should be noted and in indeterminate situations various immunohistochemical molecular markers can be helpful. Small volume 3 + 3 (Prognostic grade group [PGG] 1) or very small volume (< 0.2 cc or < 7 mm diameter) 3 + 4 (PGG 2) are acceptable in the treated zone at longitudinal follow-up. Significant volumes of 3 + 4 (PGG 2) or more within the treated zone should be treated. Any clinically significant cancer subsequently arising within the non-treated zone should be treated and handled in the same way as any de novo prostate cancer. Patients should be counseled regarding whole-gland and focal approaches to treating these new foci where appropriate. One or two well-delineated foci of significant cancer can be ablated to keep the patient in the 'active surveillance pool'. More extensive disease should be treated with traditional whole-gland techniques. CONCLUSION: Focal therapy remains a nascent field largely comprising single center cohorts with little long-term data. Our current post-focal therapy surveillance consensus recommendations represent the synthesis of the best available evidence as well as expert opinion. Further work is necessary to define the most oncologically safe and cost-effective way of following patients after focal therapy.

Anterior gland focal cryoablation: proof-of-concept primary prostate cancer treatment in select men with localized anterior cancers detected by multi-parametric magnetic resonance imaging.

BACKGROUND: Due to their location away from the nerve bundles, anterior prostate cancers (APC) represent a rational target for image-guided cryoablation. This report describes the feasibility and short-term outcomes of anterior focal cryosurgery. METHODS: A retrospective review between 2012 and 2016 of patients with clinically localized APC treated with anterior gland cryoablation was performed. Descriptive statistics were used to report: age, PSA, prostate volume, prostate cancer grade group (PGG), median time to follow-up, and changes in functional status measured with the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF-5) score. RESULTS: A total of 17 patients underwent anterior focal cryoablation with a median follow-up of 15 months. Median age and PSA at diagnosis were 67 years and 8.7 ng/mL. Pre-operative PGG1 was identified in 12 (71%) men and PGG2 in 5 (29%) men. Median (IQR) lesion volume was 2 mL(0.86, 3.1). Preoperative median IIEF-5 and IPSS scores were 19.5 and 5, and decreased to 19 and 4, post-operatively. All patients remained continent with no change in sexual function. All post-procedure targeted biopsies of the treated cancers were negative. CONCLUSION: Our pilot study demonstrates the feasibility of treating APCs with image-guided targeted focal cryoablation as a good balance between short-term oncologic control and near complete preservation of genitourinary function. Further follow-up is necessary to examine the potential benefits long-term.

Considerations of germline testing in prostate cancer screening.

Prostate cancer screening remains controversial in the medical field. While screening men above 50 years can impose overdiagnosis and overtreatment, targeted screening of males with pathologic variants of genetic mutations is evolving and viewed as sensible. Identifying such patients requires genetic testing in males having family history of prostate cancer or certain ethnicity. Such strategies will likely occur as routine practice once favorable results of ongoing studies assessing genetic predisposition are released.