CRISPR-Cas genome editing in ex-vivo human lungs to rewire the translational path of genome-targeting therapeutics.

The ongoing advancements in CRISPR-Cas technologies can significantly accelerate the preclinical development of both in vivo and ex-vivo organ genome-editing therapeutics. One of the promising applications is to genetically modify donor organs prior to implantation. The implantation of optimized donor organs with long-lasting immunomodulatory capacity holds promise for reducing the need for lifelong potent whole-body immunosuppression in recipients However, assessing genome-targeting interventions in a clinically-relevant manner prior to clinical trials remains a major challenge due to the limited modalities available. This study introduces a novel platform for testing genome editing in human lungs ex vivo, effectively simulating pre-implantation genetic engineering of donor organs. We identified gene regulatory elements whose disruption via Cas nucleases led to the upregulation of the immunomodulatory gene IL-10. We combined this approach with adenoviral vector (AdV)-mediated IL-10 delivery to create favorable kinetics for early (immediate post-implantation) graft immunomodulation. Using ex-vivo organ machine perfusion and precision-cut tissue slice technology, we demonstrated the feasibility of evaluating CRISPR genome editing in human lungs. To overcome the assessment limitations in ex-vivo perfused human organs, we conducted an in vivo rodent study and demonstrated both early gene induction and sustained editing of the lung. Collectively, our findings lay the groundwork for a first-in-human-organ study to overcome the current translational barriers of genome-targeting therapeutics.

Racial and Ethnic Variation in Receipt and Intensity of Active Surveillance for Older Patients With Localized Prostate Cancer.

INTRODUCTION: The use of active surveillance (AS) for prostate cancer is increasing, and racial disparities have been identified in its implementation. We investigated differences by race and ethnicity in the utilization and intensity of AS by race and ethnicity among older men with low- and favorable intermediate-risk prostate cancer, with particular focus on the integration of multiparametric MRI (mpMRI) into AS protocols. METHODS: Using the Surveillance, Epidemiology, and End Results and Medicare fee-for-service linked database, we identified a cohort of men diagnosed between 2010 and 2017 with low- or favorable intermediate-risk prostate cancer. The odds of receiving AS were compared by patient race and ethnicity using multivariable logistic regression models, while the rates of usage of PSA tests, biopsy, and mpMRI within 2 years of diagnosis among men on AS were assessed using multivariable Poisson regression models. RESULTS: Our cohort included 33,542 men. The proportion of men with low-risk disease who underwent AS increased from 29.5% in 2010 to 51.7% in 2017, while the proportion among men with favorable intermediate disease grew from 11.4% to 17.2%. Hispanic (odds ratio [OR] = 0.68, 95% CI 0.58-0.79) and non-Hispanic Black men (OR = 0.78, 95% CI 0.68-0.89) were less likely to receive AS than non-Hispanic White men for low-risk disease, while non-Hispanic Black men were more likely to receive AS for favorable intermediate disease (OR = 1.21, 95% CI 1.04-1.39). Non-Hispanic Black men receiving AS underwent prostate MRI at a lower rate compared to non-Hispanic White men, regardless of whether they had low-risk (incidence rate ratio = 0.77, 95% CI 0.61-0.97) or favorable intermediate-risk (incidence rate ratio = 0.61, 95% CI 0.44-0.83) disease, respectively. CONCLUSIONS: The overall adoption of AS for low-risk prostate cancer increased among Medicare fee-for-service beneficiaries. However, a significant disparity exists for non-Hispanic Black men, as they exhibit lower rates of AS utilization. Moreover, non-Hispanic Black men are less likely to have access to novel technologies, such as mpMRI, as part of their AS protocols.

Comparative Effectiveness of Partial Gland Cryoablation Versus Robotic Radical Prostatectomy for Cancer Control.

BACKGROUND AND OBJECTIVE: There is an absence of high-level evidence comparing oncologic endpoints for partial gland ablation, and most series use prostate-specific antigen (PSA) rather than biopsy endpoints. Our aim was to compare oncologic outcomes between partial gland cryoablation (PGC) and radical prostatectomy (RP) for prostate cancer. METHODS: This was a retrospective, single-center analysis of subjects treated with PGC (n = 98) or RP (n = 536) between January 2017 and December 2022 as primary treatment for intermediate-risk (Gleason grade group [GG] 2-3) prostate cancer. Oncologic endpoints included surveillance biopsies per protocol after PGC in comparison to serial PSA testing after RP. The primary outcome was treatment failure, defined as a need for any salvage treatment or development of metastatic disease. Treatment failure and survival analyses were conducted using Cox proportional-hazard regression and Kaplan Meier survival curves. KEY FINDINGS AND LIMITATIONS: After applying the inclusion/exclusion criteria, the PGC (n = 75) and RP (n = 298) groups were compared. PGC patients were significantly older (71 vs 64 yr; p < 0.001), but there were no differences in PSA, biopsy GG, or treatment year between the groups. The PGC group had higher rates of treatment failures at 24 mo (33% vs 11%; p < 0.001) and 48 mo (43% vs 14%; p < 0.001). One PGC patient (2.1%) and one RP patient (0.7%) developed metastases by 48-mo follow-up (p = 0.4). On adjusted analysis, PGC was associated with a higher risk of treatment failure (hazard ratio 4.6, 95% confidence interval 2.7-7.9; p < 0.001). Limitations include observational biases associated with the retrospective study design. CONCLUSIONS: This is the first comparative effectiveness study of cancer control outcomes for PGC versus RP. The results demonstrate an almost fivefold higher risk of treatment failure with PGC during short-term follow-up. PATIENT SUMMARY: We compared cancer control outcomes for patients with intermediate-risk prostate cancer treated with partial gland cryoablation versus radical prostatectomy. We found that partial gland cryoablation had an almost fivefold higher risk of treatment failure. Men with prostate cancer should be counseled regarding this difference in treatment failure.

Prostate Cancer Detection Rate of Transperineal Prostate Biopsy: Cognitive vs Software Fusion, A Multicenter Analysis.

OBJECTIVE: To compare clinically significant prostate cancer detection with TP-TBx utilizing software vs cognitive fusion. It is established that MRI prior to prostate biopsy improves detection of clinically significant cancer (csPCa, Grade Group ≥2). MRI/US fusion targeted biopsy via a transperineal approach (TP-TBx) is increasing in utilization due to the clean percutaneous approach that greatly reduces postbiopsy infection. However, the comparative effectiveness of formal software fusion over cognitive fusion remains under studied. MATERIALS AND METHODS: We performed a retrospective multicenter study from June 2020 to July 2022 including age, race, prostate-specific antigen (PSA), prostate volume, PI-RADS, lesion size(s), number of cores sampled, indication (elevated PSA, prior negative, active surveillance) and anesthesia type. Surgeon preference determined use of cognitive (PrecisionPoint) vs software fusion techniques. Multivariable logistic regression determined factors associated with TP-TBx detection of csPCa. RESULTS: We identified 490 patients (201 cognitive, 289 software fusion) who underwent TP-TBx. Patient age, PSA, number of targets, and PI-RADS were similar (all P > .05). Software fusion TP-TBx had 4 [95% confidence interval (CI) 3-5] more (estimated median difference) systematic cores sampled. csPCa was detected in 44% of all patients. In adjusted analysis, cognitive vs software fusion was similar in detection of csPCa (odds ratio 1.46, 95% CI 0.82-2.58). CONCLUSION: Cognitive vs software fusion TP-TBx has similar csPCa detection, despite fewer systematic cores taken with cognitive fusion. The expense, additional time requirement, and similar outcomes of software fusion platforms confers higher value to cognitive TP-Bx.

Oncologic Outcomes of Testosterone Therapy for Men on Active Surveillance for Prostate Cancer: A Population-based Analysis.

Background and objective: There is insufficient evidence on the oncologic risks of testosterone therapy for men with prostate cancer managed with active surveillance. We carried out a retrospective study to assess the effect of testosterone therapy on oncologic outcomes for men on active surveillance for prostate cancer. Methods: Surveillance, Epidemiology and End Results (SEER)-Medicare linked data were used to identify men diagnosed with prostate cancer from 2008 to 2017 who were managed with active surveillance and received testosterone (n = 167) or no testosterone (n = 6658) therapy. Outcomes included conversion from active surveillance to active treatment (radical prostatectomy, cryotherapy, radiation, or androgen deprivation therapy), prostate cancer-specific mortality, and overall mortality. Statistically significant factors on univariable analysis were included in a Cox proportional-hazards regression model for multivariable analysis. Key findings and limitations: The median age was 71 yr (interquartile range [IQR] 68-74) in the testosterone group and 72 yr (IQR 69-75) in the no-testosterone group, with corresponding median follow-up after prostate cancer diagnosis of 5.2 yr (IQR 3.4-7.8) and 4.7 yr (IQR 3.2-6.9). There were no prostate cancer-specific deaths in the testosterone group and 39 (0.6%) in the no-testosterone group. Testosterone therapy was not associated with conversion to active treatment (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.46-0.97; p = 0.033) or overall mortality (HR 1.02, 95% CI 0.68-1.53; p > 0.9). Conclusions and clinical implications: In the first population-based, nationally representative study of testosterone therapy for men on active surveillance for prostate cancer, testosterone therapy did not increase the risk of conversion to active therapy or worsen mortality. Prospective studies are needed to confirm these findings. Patient summary: For men on active surveillance for prostate cancer, we assessed the effect of testosterone therapy. We found that testosterone therapy did not increase the risk of proceeding to active therapy or of death from prostate cancer.

Long-term outcomes of pelvic-fascia sparing robotic-assisted radical prostatectomy versus standard technique: Superior urinary function and quality of life without compromising oncologic efficacy in a single-surgeon series.

BACKGROUND: Prostatic fascia-sparing robotic-assisted radical prostatectomy (PFS-RARP) has improved short-term postoperative continence compared to standard prostatectomy (S-RARP) but long-term differences remain unclear. MATERIALS AND METHODS: One hundred two S-RARP followed by 239 PFS-RARPs were performed by a single surgeon. Univariate analyses were performed with t-test, χ2, Wilcoxon rank sum, Fisher exact, and analysis of variance (ANOVA). Regression models analyzed associates of EPIC-CP scores and oncologic outcomes. Cox proportional hazards modeling assessed postoperative continence. Primary outcomes included patient-reported urinary incontinence (UI) via EPIC-CP and continence rates. Secondary outcomes included EPIC-CP scores, positive surgical margins (PSM), and biochemical recurrence (BCR). Perioperative outcomes and time to continence were measured. RESULTS: Median follow-up for PFS-RARP vs. S-RARP was 26 vs. 65 months. PFS-RARP demonstrated improved EPIC-CP UI and total scores at 24 months. On multivariate analysis, PFS-RARP was associated with improved EPIC-CP UI and total scores through 18 months, but not with PSM or BCR. PFS-RARP had a 39% and 66% reduced risk of incontinence using 0 and 0 to 1 pad-use definitions (HR 0.61, 95% CI 0.39 - 0.95; HR:0.34, 95% CI 0.16 - 0.76). Continence returned faster with PFS-RARP (0 PPD: 91.0 days vs. 261 days, P < 0.001; 0-1 PPD: 32.7 days vs. 171 days, P < 0.001). There were no differences in PSM (35% vs. 25%, P = 0.064). There were more anterior PSM in PFS-RARP vs. S-RARP (47% vs. 26% P = 0.035), but no differences in BCR (16% vs. 22% P = 0.241). CONCLUSIONS: PFS-RARP improves continence and patient-reported QOL up to 24 months postoperatively without compromising oncologic outcomes.

Transperineal Versus Transrectal Magnetic Resonance Imaging-targeted and Systematic Prostate Biopsy to Prevent Infectious Complications: The PREVENT Randomized Trial.

BACKGROUND AND OBJECTIVE: The transrectal biopsy approach is traditionally used to detect prostate cancer. An alternative transperineal approach is historically performed under general anesthesia, but recent advances enable transperineal biopsy to be performed under local anesthesia. We sought to compare infectious complications of transperineal biopsy without antibiotic prophylaxis versus transrectal biopsy with targeted prophylaxis. METHODS: We assigned biopsy-naïve participants to undergo transperineal biopsy without antibiotic prophylaxis versus transrectal biopsy with targeted prophylaxis (rectal culture screening for fluoroquinolone-resistant bacteria and antibiotic targeting to culture and sensitivity results) through a multicenter, randomized trial. The primary outcome was post-biopsy infection captured by a prospective medical review and patient report on a 7-d survey. The secondary outcomes included cancer detection, noninfectious complications, and a numerical rating scale (0-10) for biopsy-related pain and discomfort during and 7-d after biopsy. KEY FINDINGS AND LIMITATIONS: A total of 658 participants were randomized, with zero transperineal versus four (1.4%) transrectal biopsy infections (difference -1.4%; 95% confidence interval [CI] -3.2%, 0.3%; p = 0.059). The rates of other complications were very low and similar. Importantly, detection of clinically significant cancer was similar (53% transperineal vs 50% transrectal, adjusted difference 2.0%; 95% CI -6.0, 10). Participants in the transperineal arm experienced worse periprocedural pain (0.6 adjusted difference [0-10 scale], 95% CI 0.2, 0.9), but the effect was small and resolved by 7-d. CONCLUSIONS AND CLINICAL IMPLICATIONS: Office-based transperineal biopsy is tolerable, does not compromise cancer detection, and did not result in infectious complications. Transrectal biopsy with targeted prophylaxis achieved similar infection rates, but requires rectal cultures and careful attention to antibiotic selection and administration. Consideration of these factors and antibiotic stewardship should guide clinical decision-making. PATIENT SUMMARY: In this multicenter randomized trial, we compare prostate biopsy infectious complications for the transperineal versus transrectal approach. The absence of infectious complications with transperineal biopsy without the use of preventative antibiotics is noteworthy, but not significantly different from transrectal biopsy with targeted antibiotic prophylaxis.

Robot-Assisted Surgery and Racial and Ethnic Disparities in Post-Prostatectomy Outcomes Among Prostate Cancer Patients.

BACKGROUND: We sought to determine whether the differences in short-term outcomes between patients undergoing robot-assisted radical prostatectomy (RARP) and those treated with open radical prostatectomy (ORP) differ by race and ethnicity. METHODS: This observational study used New York State Cancer Registry data linked to discharge records and included patients undergoing radical prostatectomy for localized prostate cancer during 2008-2018. We used logistic regression to examine the association between race and ethnicity (non-Hispanic White [NHW], non-Hispanic Black [NHB], Hispanic), surgical approach (RARP, ORP), and postoperative outcomes (major events, prolonged length of stay [pLOS], 30-day re-admission). We tested interaction between race and ethnicity and surgical approach on multiplicative and additive scales. RESULTS: The analytical cohort included 18,926 patients (NHW 14,215 [75.1%], NHB 3195 [16.9%], Hispanic 1516 [8.0%]). The average age was 60.4 years (standard deviation 7.1). NHB and Hispanic patients had lower utilization of RARP and higher risks of postoperative adverse events than NHW patients. NHW, NHB, and Hispanic patients all had reduced risks of adverse events when undergoing RARP versus ORP. The absolute reductions in the risks of major events and pLOS following RARP versus ORP were larger among NHB {relative excess risk due to interaction (RERI): major events -0.32 [95% confidence interval (CI) -0.71 to -0.03]; pLOS -0.63 [95% CI -0.98 to -0.35]) and Hispanic (RERI major events -0.27 [95% CI -0.77 to 0.09]; pLOS -0.93 [95% CI -1.46 to -0.51]) patients than among NHW patients. The interaction was absent on the multiplicative scale. CONCLUSIONS: RARP use has not penetrated and benefited all racial and ethnic groups equally. Increasing utilization of RARP among NHB and Hispanic patients may help reduce disparities in patient outcomes after radical prostatectomy.

Cost-Effectiveness of Annual Prostate MRI and Potential MRI-Guided Biopsy After Prostate-Specific Antigen Test Results.

Importance: Magnetic resonance imaging (MRI) and potential MRI-guided biopsy enable enhanced identification of clinically significant prostate cancer. Despite proven efficacy, MRI and potential MRI-guided biopsy remain costly, and there is limited evidence regarding the cost-effectiveness of this approach in general and for different prostate-specific antigen (PSA) strata. Objective: To examine the cost-effectiveness of integrating annual MRI and potential MRI-guided biopsy as part of clinical decision-making for men after being screened for prostate cancer compared with standard biopsy. Design, Setting, and Participants: Using a decision analytic Markov cohort model, an economic evaluation was conducted projecting outcomes over 10 years for a hypothetical cohort of 65-year-old men in the US with 4 different PSA strata (<2.5 ng/mL, 2.5-4.0 ng/mL, 4.1-10.0 ng/mL, >10 ng/mL) identified by screening through Monte Carlo microsimulation with 10 000 trials. Model inputs for probabilities, costs in 2020 US dollars, and quality-adjusted life-years (QALYs) were from the literature and expert consultation. The model was specifically designed to reflect the US health care system, adopting a federal payer perspective (ie, Medicare). Exposures: Magnetic resonance imaging with potential MRI-guided biopsy and standard biopsy. Main Outcomes and Measures: Incremental cost-effectiveness ratios (ICERs) using a willingness-to-pay threshold of $100 000 per QALY was estimated. One-way and probabilistic sensitivity analyses were performed. Results: For the 3 PSA strata of 2.5 ng/mL or greater, the MRI and potential MRI-guided biopsy strategy was cost-effective compared with standard biopsy (PSA 2.5-4.0 ng/mL: base-case ICER, $21 131/QALY; PSA 4.1-10.0 ng/mL: base-case ICER, $12 336/QALY; PSA >10.0 ng/mL: base-case ICER, $6000/QALY). Results varied depending on the diagnostic accuracy of MRI and potential MRI-guided biopsy. Results of probabilistic sensitivity analyses showed that the MRI and potential MRI-guided biopsy strategy was cost-effective at the willingness-to-pay threshold of $100 000 per QALY in a range between 76% and 81% of simulations for each of the 3 PSA strata of 2.5 ng/mL or more. Conclusions and Relevance: This economic evaluation of a hypothetical cohort suggests that an annual MRI and potential MRI-guided biopsy was a cost-effective option from a US federal payer perspective compared with standard biopsy for newly eligible male Medicare beneficiaries with a serum PSA level of 2.5 ng/mL or more.

Differential Use of Radiotherapy Fractionation Regimens in Prostate Cancer.

Importance: Technical advances in treatment of prostate cancer and a better understanding of prostate cancer biology have allowed for hypofractionated treatment courses using a higher dose per fraction. Use of ultrahypofractionated stereotactic body radiotherapy (SBRT) has also been characterized. Objective: To characterize US national trends of different RT fractionation schemes across risk groups of prostate cancer. Design, Setting, and Participants: This retrospective cohort study used data collected by the National Cancer Database (NCDB) to characterize the fractionation regimens used for 302 035 patients diagnosed as having prostate cancer from January 1, 2004, to December 31, 2020, who underwent definitive RT. The analysis was performed between February 1 and April 30, 2023. Exposure: Stereotactic body RT or ultrahypofractionation, defined as 5 or fewer fractions of external beam RT (EBRT), moderate hypofractionation, defined as 20 to 28 fractions of EBRT, or conventional fractionation, defined as all remaining EBRT fractionation schemes. Main Outcomes and Measures: Temporal trends and clinical and sociodemographic factors associated with SBRT, moderate hypofractionation, and conventional fractionation use. Results: A total of 302 035 men receiving EBRT for localized prostate cancer between 2004 and 2020 were identified (40.1% aged 60-69 years). Black patients comprised 17.6% of this cohort; White patients, 77.9%; and other races and ethnicities, 4.5%. Patients with low-risk disease comprised 17.5% of the cohort; favorable intermediate-risk disease, 23.5%; unfavorable intermediate-risk disease, 23.9%; and high-risk disease, 35.1%. Treatment consisted of conventional fractionation for 81.2%, moderate hypofractionation for 12.9%, and SBRT for 6.0%. The rate of increase over time in patients receiving SBRT compared with conventional fractionation was higher (adjusted odds ratio [AOR] for 2005 vs 2004, 3.18 [95% CI, 2.04-4.94; P < .001]; AOR for 2020 vs 2004, 264.69 [95% CI, 179.33-390.68; P < .001]) than the rate of increase in patients receiving moderate hypofractionation compared with conventional fractionation (AOR for 2005 vs 2004, 1.05 [95% CI, 0.98-1.12; P = .19]; AOR for 2020 vs 2004, 4.41 [95% CI, 4.15-4.69; P < .001]). Compared with White patients, Black patients were less likely to receive SBRT compared with conventional fractionation or moderate hypofractionation (AOR for conventional fractionation, 0.84 [95% CI, 0.80-0.89; P < .001]; AOR for moderate hypofractionation, 0.77 [95% CI, 0.72-0.81; P < .001]). Compared with 2019, patients treated with all fractionation regimens declined in 2020 by 24.4%. Conclusions and Relevance: In this hospital-based cohort study of patients with prostate cancer treated with definitive EBRT, use of moderate hypofractionation and SBRT regimens for definitive prostate cancer treatment has increased from 2004 to 2020. Despite this increasing trend, findings suggest potential health care disparities for Black patients receiving EBRT for localized prostate cancer. The number of patients treated with EBRT in the year 2020 decreased, coinciding with official onset of the COVID-19 pandemic in March 2020.

Guiding Clinical Decision Making for Surgical Incontinence Treatment After Prostatectomy: A Review of the Literature.

PURPOSE OF REVIEW: Stress urinary incontinence after prostatectomy is a common and debilitating side effect. Immediate post-prostatectomy management emphasizes pelvic floor muscle exercises. Per American Urologic Association guidelines, if incontinence persists for more than 12 months postoperatively, surgical interventions are the mainstay of treatment. Treatment decisions depend on a multitude of factors. The goal of this paper is to review recent literature updates regarding the diagnosis of male SUI to better guide surgical treatment decision-making. RECENT FINDINGS: Patient history is a critical component in guiding surgical decision making with severity and bother being primary factors driving treatment decisions. Recent studies indicate that a history of pelvic radiation continues to impact the overall duration and complication rate associated with artificial urinary sphincters (AUS). Cystoscopy should be done on every patient preparing to undergo surgical SUI treatment. Urodynamics and standing cough stress tests are additional diagnostic testing options; these tests may augment the diagnosis of SUI and better delineate which patients may benefit from a male sling versus AUS. Treatment of SUI after prostatectomy can improve health-related quality of life. A patient history focused on severity and degree of bother in addition to the use of ancillary office testing can help guide surgical treatment decisions to optimize patient continence goals.

Use of the Decipher genomic classifier among men with prostate cancer in the United States.

BACKGROUND: Management of localized or recurrent prostate cancer since the 1990s has been based on risk stratification using clinicopathological variables, including Gleason score, T stage (based on digital rectal exam), and prostate-specific antigen (PSA). In this study a novel prognostic test, the Decipher Prostate Genomic Classifier (GC), was used to stratify risk of prostate cancer progression in a US national database of men with prostate cancer. METHODS: Records of prostate cancer cases from participating SEER (Surveillance, Epidemiology, and End Results) program registries, diagnosed during the period from 2010 through 2018, were linked to records of testing with the GC prognostic test. Multivariable analysis was used to quantify the association between GC scores or risk groups and use of definitive local therapy after diagnosis in the GC biopsy-tested cohort and postoperative radiotherapy in the GC-tested cohort as well as adverse pathological findings after prostatectomy. RESULTS: A total of 572 545 patients were included in the analysis, of whom 8927 patients underwent GC testing. GC biopsy-tested patients were more likely to undergo active active surveillance or watchful waiting than untested patients (odds ratio [OR] =2.21, 95% confidence interval [CI] = 2.04 to 2.38, P < .001). The highest use of active surveillance or watchful waiting was for patients with a low-risk GC classification (41%) compared with those with an intermediate- (27%) or high-risk (11%) GC classification (P < .001). Among National Comprehensive Cancer Network patients with low and favorable-intermediate risk, higher GC risk class was associated with greater use of local therapy (OR = 4.79, 95% CI = 3.51 to 6.55, P < .001). Within this subset of patients who were subsequently treated with prostatectomy, high GC risk was associated with harboring adverse pathological findings (OR = 2.94, 95% CI = 1.38 to 6.27, P = .005). Use of radiation after prostatectomy was statistically significantly associated with higher GC risk groups (OR = 2.69, 95% CI = 1.89 to 3.84). CONCLUSIONS: There is a strong association between use of the biopsy GC test and likelihood of conservative management. Higher genomic classifier scores are associated with higher rates of adverse pathology at time of surgery and greater use of postoperative radiotherapy.In this study the Decipher Prostate Genomic Classifier (GC) was used to analyze a US national database of men with prostate cancer. Use of the GC was associated with conservative management (ie, active surveillance). Among men who had high-risk GC scores and then had surgery, there was a 3-fold higher chance of having worrisome findings in surgical specimens.

Evaluating the Learning Curve for In-office Freehand Cognitive Fusion Transperineal Prostate Biopsy.

OBJECTIVE: To define the learning curve of the in-office, freehand MRI-ultrasound cognitive fusion transperineal prostate biopsy (CTPB) by assessing cancer detection, biopsy core quantity and quality, procedure times, and complications over the initial experience. METHODS: We reviewed 110 consecutive CTPB performed March 2021-September 2022 by a urologist inexperienced with the PrecisionPoint platform. The study period was divided into quarters to assess for temporal variation in outcomes. Univariable and multivariable analysis modeled the learning curve. RESULTS: Across quarters, there were no differences in the detection of clinically significant prostate cancer (Q1:50%, Q2:52%, Q3:50%, Q4:48%, P > .9) or Gleason grade group upgrading by targeted vs systematic biopsy (P = .6). Median procedure times improved with experience (Q1:17 minutes, Q2:14 minutes, Q3:12 minutes, Q4:13 minutes, P = .018). On multivariable analysis, procedure times decreased by 1minute per 20 cases (P < .001). On linear regression, CTPB procedure times approximated transrectal biopsy times after 90 cases (P < .001). The histopathologic core quality did not differ, as evidenced by consistent core length (P = .13) and presence of minimal fibromuscular tissue (P > .9). The most common complications, hematuria and hematospermia, were similar across quarters (P = .7, P = .3, respectively). There was a single episode of urinary retention and no reported infections. CONCLUSION: There is no evidence of a learning curve for CTPB as shown by consistent clinically significant prostate cancer detection, high-quality biopsy cores, and low complications. However, CTPB procedural times begin to approximate cognitive targeted transrectal biopsy times after 90 cases.