Prostate cancer grade migration and facility-level treatment trends for grade group 1 disease.

Overdiagnosis and overtreatment of low-grade prostate cancer (PCa) reflect poor quality of care and prompted changes to guidelines over the past decade. We used the National Cancer Database to characterize Gleason Grade Group (GG)1 PCa diagnosis trends and assess facility-level treatment variability. Between 2010 and 2019, GG1 PCa incidence had a clinically and statistically significant decline, from 45% to 25% at biopsy and from 33% to 9.8% at radical prostatectomy (RP) pathology. Similarly, active surveillance (AS) uptake significantly increased to 49% and 62% among nonacademic and academic sites, respectively. Decreasing rates of definitive therapies were identified: among academic sites, RP decreased from 61.1% to 25.3% and radiation therapy (RT) from 25.2% to 12%, whereas among nonacademic sites, RP decreased from 53.6% to 28% and RT from 37.8% to 21.9% (Ptrend < .001). Declines in the diagnosis and treatment of low-grade disease demonstrate an encouraging shift in PCa epidemiology. However, heterogeneity in AS utilization remains and reflects opportunities for improvement.

Technical surgical skill assessment of neurovascular bundle dissection and urinary continence recovery after robotic-assisted radical prostatectomy.

Purpose: To examine the association between the quality of neurovascular bundle dissection and urinary continence recovery after robotic-assisted radical prostatectomy. Materials and Methods: Patients who underwent RARPs from 2016 to 2018 in two institutions with ≥1-year postoperative follow-up were included. The primary outcomes were time to urinary continence recovery. Surgical videos were independently assessed by 3 blinded raters using the validated Dissection Assessment for Robotic Technique (DART) tool after standardized training. Cox regression was used to test the association between DART scores and urinary continence recovery while adjusting for relevant patient features. Results: 121 RARP performed by 23 surgeons with various experience levels were included. The median follow-up was 24 months (95% CI 20 - 28 months). The median time to continence recovery was 7.3 months (95% CI 4.7 - 9.8 months). After adjusting for patient age, higher scores of certain DART domains, specifically tissue retraction and efficiency, were significantly associated with increased odds of continence recovery (p<0.05). Conclusions: Technical skill scores of neurovascular bundle dissection vary among surgeons and correlate with urinary continence recovery. Unveiling the specific robotic dissection skillsets which impact patient outcomes has the potential to focus surgical training.

Pooled outcomes of performing freehand transperineal prostate biopsy with the PrecisionPoint Transperineal Access System.

Objectives: To report the results of a pooled analysis evaluating the cancer detection rates, complications, and tolerability of prostate biopsies performed using the PrecisionPoint Transperineal Access System. Patients and Methods: The medical literature was reviewed to identify studies published prior to 1 October 2021 evaluating the PrecisionPoint device for performance of transperineal prostate biopsy. Pooled analyses were performed to assess overall and clinically significant cancer detection rates. Additionally, data on complications as well as patient tolerability of the procedure when performed under local anaesthesia were extracted. Results: Transperineal biopsy with the PrecisionPoint Transperineal Access System achieved overall and clinically significant cancer detection rates of 67.9% and 42.6%, respectively. Among patients with Prostate Imaging Reporting and Data System 3, 4, and 5 lesions on prostate magnetic resonance imaging, clinically significant disease was found in 31.7%, 55.7%, and 71.8% of patients, respectively. Complications were rare, with sepsis reported in 4 (0.1%) of 3411 procedures despite frequent omission of antibiotic prophylaxis. Patients reported acceptable tolerability of the procedure when performed under local anaesthesia. Conclusions: Within the available medical literature, there is uniform evidence supporting the use of the PrecisionPoint Transperineal Access System for performing prostate biopsy procedures. The reported cancer detection and infectious complication rates with this device are in line with other methods for performing transperineal prostate biopsy. A unique aspect of the PrecisionPoint device is its ability to facilitate performing transperineal prostate biopsy under local anaesthesia. This factor will likely lead to increased adoption of the beneficial transperineal approach to prostate biopsy.

Evolving Trends in the Management of Low-Risk Prostate Cancer.

INTRODUCTION: Deferred treatment is a growing management strategy for low-risk prostate cancer. However, it is unknown whether this growth is mediated by patient factors. In this study, we sought to evaluate factors associated with deferred treatment in patients with low-risk prostate cancer and shifts in these factors after recent incorporation of active surveillance into national guidelines. MATERIALS AND METHODS: We identified 137,915 men diagnosed with low-risk prostate cancer (prostate-specific antigen <10 ng/mL, Gleason score ≤6, stage cT1-cT2a) in the National Cancer Database from 2010 to 2017. Multivariate logistic regression models were used to determine factors associated with deferred treatment. Interaction variables were added to determine whether trends in use of deferred treatment over time depend on race, income, education, and insurance status. RESULTS: The use of deferred treatment among men with low-risk prostate cancer increased from 14.7% in 2010-2011 to 46.3% in 2016-2017 (P < .001). On multivariate analysis, deferred treatment was associated with older age, more contemporary year of diagnosis, black race, lower income, higher educational attainment, government insurance, being uninsured, treatment at an academic/research facility, and treatment at a facility in New England (each P < .05). Incorporation of interaction variables showed that black race, belonging to the two lowest income quartiles, government insurance, and being uninsured became less associated with deferred treatment in recent years. CONCLUSIONS: The use of deferred treatment among men with low-risk prostate cancer increased significantly from 2010 to 2017. However, patients who were black, low-income, and not privately insured experienced smaller increases in deferred treatment. Interventions to increase uptake in these groups present opportunities to improve quality of care.

Role of Prophylactic Antibiotics in Transperineal Prostate Biopsy: A Systematic Review and Meta-analysis.

CONTEXT: Transperineal prostate biopsy is associated with a significantly lower risk of infectious complications than the transrectal approach. In fact, the risk of infectious complications with transperineal prostate biopsy is so low that the utility of administering periprocedural antibiotics with this procedure has come under question. OBJECTIVE: To perform a systematic review and meta-analysis to assess for differences in the rates of infectious complications (septic, nonseptic, and overall) after performing transperineal prostate biopsy with and without the administration of periprocedural antibiotic prophylaxis. EVIDENCE ACQUISITION: Three electronic databases (PubMed, Embase, and MEDLINE) were searched, and studies were included if they included patients who underwent transperineal prostate biopsy, were published after January 2000, included information on periprocedural antibiotic administration, and reported postbiopsy complications. Preferred Reporting Items for Systematic Reviews and Meta-analyses and Agency for Healthcare Research and Quality guidelines were utilized. EVIDENCE SYNTHESIS: A total of 106 unique studies describing 112 cohorts of patients were identified, of which 98 (37 805 men) received antibiotic prophylaxis and 14 (4772 men) did not receive it. All patients were included in the analysis of septic complications. In total, there were 19/37 805 (0.05%) episodes of sepsis in the group of men who received antibiotics, which was similar to the no antibiotic group with 4/4772 (0.08%) episodes (p = 0.2). For overall infections (septic plus nonseptic), there were 403/29 880 (1.35%) versus 58/4772 (1.22%) events among men with evaluable data who received and did not receive antibiotic prophylaxis, respectively (p = 0.8). Restricting our analysis to studies with a comparable low number of biopsy cores (<25 cores), there remained no difference in the rates of sepsis between groups, but there was a small, statistically significant lower risk of infectious complications with antibiotic administration-67/12 140 (0.55%) versus 58/4772 (1.22%; p < 0.01). CONCLUSIONS: The likelihood of septic infections after transperineal prostate biopsy is low with and without antibiotic prophylaxis. The omission of periprocedural antibiotics with this procedure stands to benefit patients by avoiding potential drug reactions. Furthermore, this practice is in line with calls throughout the medical community for improved antibiotic stewardship. PATIENT SUMMARY: In a large systematic review and meta-analysis, we evaluated infectious complications after transperineal prostate biopsy with or without the administration of prophylactic antibiotics. We conclude that prophylactic antibiotics do not decrease the rate of postbiopsy sepsis but may have a small benefit in terms of preventing less serious infections.

New Endoscopic In-office Surgical Therapies for Benign Prostatic Hyperplasia: A Systematic Review.

CONTEXT: In recent years, new technologies have been developed to treat benign prostatic enlargement (BPE). Three of these devices may be utilized in office and are promising additions. OBJECTIVE: To systematically review all clinical trials investigating prostatic urethral lift (PUL), water vapor thermal therapy (WVTT), and temporary implantable nitinol device (TIND), with emphasis on clinical efficacy and complications. EVIDENCE ACQUISITION: We performed a systematic review of PubMed/Medline database in November 2020 according to Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. EVIDENCE SYNTHESIS: Of 168 articles identified, 18 met the inclusion criteria. Evidence consisted of few randomized controlled trials, and multiple single-arm prospective and retrospective studies. Among the three modalities, PUL demonstrates rare occurrence of serious complications but higher retreatment rates at short- and long-term follow-up. WVTT offers lower retreatment rates with a similar safety profile. TIND studies report varying rates of retreatment and complications. All technologies offer low rates of erectile and ejaculatory dysfunction, although the risk appears to be highest for WVTT (<10.8%). CONCLUSIONS: Among the emerging technologies introduced to treat BPE, the in-office PUL, WVTT, and TIND systems are valuable additions to the current surgical options. These systems offer unique advantages that should be considered in the shared decision-making process. PATIENT SUMMARY: In this report, we identified all clinical trials reporting on the efficacy and safety of the in-office prostatic urethral lift (PUL), water vapor thermal therapy (WVTT), and temporary implantable nitinol device (TIND) systems for the treatment of benign prostatic enlargement. We found that PUL and WVTT demonstrate acceptable outcomes in terms of functional improvement, retreatment, and complications. More data with longer follow-up are required to further evaluate TIND, but early results are promising.

Perceptions of partial gland ablation for prostate cancer among men on active surveillance: A qualitative study.

OBJECTIVES ­: Partial gland ablation (PGA) therapy is an emerging treatment modality that targets specific areas of biopsy proven prostate cancer (PCa) to minimize treatment-related morbidity by sparing benign prostate. This qualitative study aims to explore and characterize perceptions and attitudes toward PGA in men with very-low-risk, low-risk, and favorable intermediate-risk PCa on active surveillance (AS). DESIGN ­: 92 men diagnosed with very-low-risk, low-risk, and favorable intermediate-risk PCa on AS were invited to participate in semi-structured telephone interviews on PGA. SETTING ­: Single tertiary care center located in New York City. PARTICIPANTS ­: 20 men with very-low-risk, low-risk, and favorable intermediate-risk PCa on AS participated in the interviews. MAIN OUTCOME MEASURES ­: Emerging themes on perceptions and attitudes toward PGA were developed from transcripts inductively coded and analyzed under standardized methodology. RESULTS ­: Four themes were derived from twenty interviews that represent the primary considerations in treatment decision-making: (1) the feeling of psychological safety associated with low-risk disease; (2) preference for minimally invasive treatments; (3) the central role of the physician; (4) and the pursuit of treatment options that align with disease severity. Eleven men (55%) expressed interest in pursuing PGA only if their cancer were to progress, while 9 men (45%) expressed interest at the current moment. CONCLUSIONS ­: Though an emerging treatment modality, patients were broadly accepting of PGA for PCa with men primarily debating the risks versus benefits of proactively treating low-risk disease. Additional research on men's preferences and attitudes toward PGA will further guide counseling and shared decision-making for PGA.

Addition of Prostate Volume and Prostate-specific Antigen Density to Memorial Sloan Kettering Cancer Center Prostate Cancer Nomograms.

Prostate-specific antigen (PSA) density is an established prognostic marker for prostate cancer. We investigated whether the inclusion of PSA density or prostate volume in the Memorial Sloan Kettering Cancer Center nomograms improves the prediction of biochemical recurrence (BCR) after radical prostatectomy (RP). Among the 11 725 men included, 2140 developed BCR. Neither PSA density nor prostate volume was associated with BCR when added to either the pre-RP or post-RP model (all p values ≥0.10) and changes in the C index were very small (largest change, 0.002). The results were robust to exclusion of outlying prostate volumes and restriction to patients treated after 2005. There is no justification for adding prostate volume or PSA density to BCR nomograms. PATIENT SUMMARY: Addition of prostate volume or prostate-specific antigen density to Memorial Sloan Kettering Cancer Center prediction schemes did not improve the prediction of recurrence of prostate cancer after removal of the prostate.

Tissue-Based Biomarkers for the Risk Stratification of Men With Clinically Localized Prostate Cancer.

Risk stratification of men with clinically localized prostate cancer has historically relied on basic clinicopathologic parameters such as prostate specific antigen level, grade group, and clinical stage. However, prostate cancer often behaves in ways that cannot be accurately predicted by these parameters. Thus, recent efforts have focused on developing tissue-based genomic tests that provide greater insights into the risk of a given patient's disease. Multiple tests are now commercially available and provide additional prognostic information at various stages of the care pathway for prostate cancer. Indeed, early evidence suggests that these assays may have a significant impact on patient and physician decision-making. However, the impact of these tests on oncologic outcomes remains less clear. In this review, we highlight recent advances in the use of tissue-based biomarkers in the treatment of prostate cancer and identify the existing evidence supporting their clinical use.

IDEAL Stage 2a experience with in-office, transperineal MRI/ultrasound software fusion targeted prostate biopsy.

OBJECTIVE: Although the feasibility of transperineal biopsy under local anesthesia has been demonstrated, little is known regarding the application of MRI/ultrasound software fusion targeted biopsy for transperineal biopsy under local anesthesia. The objective of our study is to describe our initial experience with in-office transperineal MRI/ultrasound software fusion targeted biopsy (Idea, Development, Exploration, Assessment, Long-term Follow-up [IDEAL] Stage 2a). METHODS: Between October 2017 and July 2019, 33 men underwent in-office transperineal MRI-targeted biopsy using the Artemis (Eigen, Grass Valley, CA, USA) fixed-robotic arm system. The indication for biopsy was elevated prostate specific antigen (PSA) (n=14), prior negative biopsy (n=10), active surveillance (n=6), and surveillance after partial gland cryoablation (n=3). We prospectively captured patient demographic and clinical characteristics, biopsy outcomes, and complications. Complications were classified according to Common Terminology Criteria for Adverse Events (CTCAE) V.5.0. RESULTS: The median patient age was 67 years (IQR 61-71) and the median serum PSA level was 7.0 ng/mL (IQR 5.1-11.4). The median duration of in-office MRI-targeted transperineal biopsy was 26 min (IQR 23-28). Overall, transperineal MRI-targeted biopsy detected prostate cancer in 18 (54.6%) men, with 8 (24.2%) being clinically significant (Gleason Score ≥3+4, Grade Group ≥2). Clinically significant prostate cancer was detected in four (28.6%) biopsy naïve men, two (20.0%) men with a prior negative, one (16.7%) man on active surveillance and one (33.3%) man following partial gland ablation. Three (9.1%) men experienced complications: two hematuria and one urinary retention. CONCLUSION: Our findings demonstrate the feasibility of the fixed-robotic arm fusion platform for in-office transperineal MRI-targeted biopsy and a low rate of adverse events. However, larger prostate size precludes MRI/ultrasound software fusion and pubic arch interference hindered the transperineal MRI-targeted approach in 9.1% of men. Pubic arch interference was overcome by a free-hand approach with software fusion guidance.

Pharmacologic modeling of primary mitochondrial respiratory chain dysfunction in zebrafish.

Mitochondrial respiratory chain (RC) disease is a heterogeneous and highly morbid group of energy deficiency disorders for which no proven effective therapies exist. Robust vertebrate animal models of primary RC dysfunction are needed to explore the effects of variation in RC disease subtypes, tissue-specific manifestations, and major pathogenic factors contributing to each disorder, as well as their pre-clinical response to therapeutic candidates. We have developed a series of zebrafish (Danio rerio) models that inhibit, to variable degrees, distinct aspects of RC function, and enable quantification of animal development, survival, behaviors, and organ-level treatment effects as well as effects on mitochondrial biochemistry and physiology. Here, we characterize four pharmacologic inhibitor models of mitochondrial RC dysfunction in early larval zebrafish, including rotenone (complex I inhibitor), azide (complex IV inhibitor), oligomycin (complex V inhibitor), and chloramphenicol (mitochondrial translation inhibitor that leads to multiple RC complex dysfunction). A range of concentrations and exposure times of each RC inhibitor were systematically evaluated on early larval development, animal survival, integrated behaviors (touch and startle responses), organ physiology (brain death, neurologic tone, heart rate), and fluorescence-based analyses of mitochondrial physiology in zebrafish skeletal muscle. Pharmacologic RC inhibitor effects were validated by spectrophotometric analysis of Complex I, II and IV enzyme activities, or relative quantitation of ATP levels in larvae. Outcomes were prioritized that utilize in vivo animal imaging and quantitative behavioral assessments, as may optimally inform the translational potential of pre-clinical drug screens for future clinical study in human mitochondrial disease subjects. The RC complex inhibitors each delayed early embryo development, with short-term exposures of these three agents or chloramphenicol from 5 to 7 days post fertilization also causing reduced larval survival and organ-specific defects ranging from brain death, behavioral and neurologic alterations, reduced mitochondrial membrane potential in skeletal muscle (rotenone), and/or cardiac edema with visible blood pooling (oligomycin). Remarkably, we demonstrate that treating animals with probucol, a nutrient-sensing signaling network modulating drug that has been shown to yield therapeutic effects in a range of other RC disease cellular and animal models, both prevented acute rotenone-induced brain death in zebrafish larvae, and significantly rescued early embryo developmental delay from either rotenone or oligomycin exposure. Overall, these zebrafish pharmacologic RC function inhibition models offer a unique opportunity to gain novel insights into diverse developmental, survival, organ-level, and behavioral defects of varying severity, as well as their individual response to candidate therapies, in a highly tractable and cost-effective vertebrate animal model system.

Coffin-Siris syndrome: phenotypic evolution of a novel SMARCA4 mutation.

Coffin-Siris Syndrome (CSS) is an intellectual disability disorder caused by mutation of components of the SWI/SNF chromatin-remodeling complex. We describe the evolution of the phenotypic features for a male patient with CSS from birth to age 7 years and 9 months and by review of reported CSS patients, we expand the phenotype to include neonatal and infantile hypertonia and upper airway obstruction. The propositus had a novel de novo heterozygous missense mutation in exon 17 of SMARCA4 (NM_001128849.1:c.2434C>T (NP_001122321.1:p.Leu812Phe)). This is the first reported mutation within motif Ia of the SMARCA4 SNF2 domain. In summary, SMARCA4-associated CSS is a pleiotropic disorder in which the pathognomic clinical features evolve and for which the few reported individuals do not demonstrate a clear genotype-phenotype correlation.