Comparison of Magnetic Resonance Imaging-Based Risk Calculators to Predict Prostate Cancer Risk.

Importance: Magnetic resonance imaging (MRI)-based risk calculators can replace or augment traditional prostate cancer (PCa) risk prediction tools. However, few data are available comparing performance of different MRI-based risk calculators in external cohorts across different countries or screening paradigms. Objective: To externally validate and compare MRI-based PCa risk calculators (Prospective Loyola University Multiparametric MRI [PLUM], UCLA [University of California, Los Angeles]-Cornell, Van Leeuwen, and Rotterdam Prostate Cancer Risk Calculator-MRI [RPCRC-MRI]) in cohorts from Europe and North America. Design, Setting, and Participants: This multi-institutional, external validation diagnostic study of 3 unique cohorts was performed from January 1, 2015, to December 31, 2022. Two cohorts from Europe and North America used MRI before biopsy, while a third cohort used an advanced serum biomarker, the Prostate Health Index (PHI), before MRI or biopsy. Participants included adult men without a PCa diagnosis receiving MRI before prostate biopsy. Interventions: Prostate MRI followed by prostate biopsy. Main Outcomes and Measures: The primary outcome was diagnosis of clinically significant PCa (grade group ≥2). Receiver operating characteristics for area under the curve (AUC) estimates, calibration plots, and decision curve analysis were evaluated. Results: A total of 2181 patients across the 3 cohorts were included, with a median age of 65 (IQR, 58-70) years and a median prostate-specific antigen level of 5.92 (IQR, 4.32-8.94) ng/mL. All models had good diagnostic discrimination in the European cohort, with AUCs of 0.90 for the PLUM (95% CI, 0.86-0.93), UCLA-Cornell (95% CI, 0.86-0.93), Van Leeuwen (95% CI, 0.87-0.93), and RPCRC-MRI (95% CI, 0.86-0.93) models. All models had good discrimination in the North American cohort, with an AUC of 0.85 (95% CI, 0.80-0.89) for PLUM and AUCs of 0.83 for the UCLA-Cornell (95% CI, 0.80-0.88), Van Leeuwen (95% CI, 0.79-0.88), and RPCRC-MRI (95% CI, 0.78-0.87) models, with somewhat better calibration for the RPCRC-MRI and PLUM models. In the PHI cohort, all models were prone to underestimate clinically significant PCa risk, with best calibration and discrimination for the UCLA-Cornell (AUC, 0.83 [95% CI, 0.81-0.85]) model, followed by the PLUM model (AUC, 0.82 [95% CI, 0.80-0.84]). The Van Leeuwen model was poorly calibrated in all 3 cohorts. On decision curve analysis, all models provided similar net benefit in the European cohort, with higher benefit for the PLUM and RPCRC-MRI models at a threshold greater than 22% in the North American cohort. The UCLA-Cornell model demonstrated highest net benefit in the PHI cohort. Conclusions and Relevance: In this external validation study of patients receiving MRI and prostate biopsy, the results support the use of the PLUM or RPCRC-MRI models in MRI-based screening pathways regardless of European or North American setting. However, tools specific to screening pathways incorporating advanced biomarkers as reflex tests are needed due to underprediction.

Robotic transperitoneal versus retroperitoneal approach for anterior renal mass nephron-sparing surgery.

Robotic nephron-sparing surgery is traditionally performed via a transperitoneal (TP) approach. However, the retroperitoneal (RP) approach has gained popularity, particularly for posterolateral renal masses. The RP approach is associated with shorter operative time, less blood loss, and shorter length of stay, while preserving oncologic outcomes in selected masses. Here, we aim to assess the feasibility of the RP approach in excising anterior renal masses. Patients ≥ 18 years of age who underwent robotic nephron-sparing surgery for anterior renal masses were retrospectively identified (2008-2022). Baseline demographics, tumor characteristics, and perioperative data were collected and characterized based on TP vs RP approaches. Wilcoxon rank sum test and Pearson's Chi-squared test were used to compare continuous and categorical variables, respectively. Two hundred and sixteen patients were included-178 (82.4%) underwent TP approach and 38 (17.6%) underwent RP approach. Baseline demographics, preoperative tumor size, and renal nephrometry scores were similar. The RP approach was associated with shorter operative (150 vs 203 min, p < 0.001) and warm ischemia time (12 vs 21 min, p < 0.001), and less blood loss (20 vs 100 cc, p = 0.002) (Table 1). The RP approach was associated with shorter length of stay (1 vs 2 days, p < 0.001) and less total complications (5.3% vs 19.1%, p = 0.038). Major complication (Clavien-Dindo Grade > 3) rates were similar. There was no difference in positive surgical margin rates or pathologic characteristics. Robotic RP approach for nephron-sparing surgery is feasible for eligible anterior tumors and is associated with favorable perioperative outcomes with preserved negative surgical margin rates. Table 1 Patient baseline demographics Overall Transperitoneal Retroperitoneal p value Median/N IQR/% Median/N IQR/% Median/N IQR/% N 216 178 82.4% 38 17.6% Age (years) 60.5 (52.1-67.7) 60.4 (52.8-67.7) 61.6 (49.1-69.2) 0.393 Sex Male 126 58.3% 100 56.2% 26 68.4% Female 90 41.7% 78 43.8% 12 31.6% 0.165 Race White 162 75.0% 137 77.0% 25 65.8% Asian 4 1.9% 2 1.1% 2 5.3% Black 21 9.7% 18 10.1% 3 7.9% Hispanic 26 12.0% 18 10.1% 8 21.1% Other 2 0.9% 2 1.1% 0 0.0% 0.197 Body mass index (kg/m2) < 25 32 14.8% 25 14.0% 7 18.4% 25-30 68 31.5% 55 30.9% 13 34.2% 30-35 60 27.8% 50 28.1% 10 26.3% 35 + 56 25.9% 48 27.0% 8 21.1% 0.808 Prior abdominal surgery Yes 118 54.6% 104 58.4% 14 36.8% No 98 45.4% 74 41.6% 24 63.2% 0.015 Prior kidney surgery Yes 10 4.6% 9 5.1% 1 2.6% No 206 95.4% 169 94.9% 37 97.4% 0.518 Chronic kidney disease stage ≥ 3 Yes 45 20.8% 38 21.3% 7 18.4% No 171 79.2% 140 78.7% 31 81.6% 0.687 Charlson comorbidity index 0 138 63.9% 116 65.2% 22 57.9% 1 46 21.3% 38 21.4% 8 21.1% 2 19 8.8% 13 7.3% 6 15.8% ≥ 3 13 6.0% 11 6.2% 2 5.3% 0.412 Tumor size (cm) 2.7 (2-3.6) 2.8 (2-3.5) 2.55 (2-3.7) 0.796 Tumor laterality Left 100 46.3% 78 43.8% 22 57.9% Right 116 53.7% 100 56.2% 16 42.1% 0.114 Clinical T stage cT1a 186 86.1% 152 85.4% 34 89.5% cT1b 30 13.9% 26 14.6% 4 10.5% 0.509 RENAL Nephrometry score Low (4 to 6) 94 43.5% 76 42.7% 18 47.4% Intermediate (7 to 9) 112 51.9% 94 52.8% 18 47.4% High (≥ 10) 19 4.6% 8 4.5% 2 5.3% 0.829 TE tumor enucleation, SPN standard margin partial nephrectomy, IQR interquartile range.

Variability in prostate cancer detection among radiologists and urologists using MRI fusion biopsy.

Objectives: The aim of this study is to evaluate the impact of radiologist and urologist variability on detection of prostate cancer (PCa) and clinically significant prostate cancer (csPCa) with magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) fusion prostate biopsies. Patients and methods: The Prospective Loyola University MRI (PLUM) Prostate Biopsy Cohort (January 2015 to December 2020) was used to identify men receiving their first MRI and MRI/TRUS fusion biopsy for suspected PCa. Clinical, MRI and biopsy data were stratified by radiologist and urologist to evaluate variation in Prostate Imaging-Reporting and Data System (PI-RADS) grading, lesion number and cancer detection. Multivariable logistic regression (MVR) models and area under the curve (AUC) comparisons assessed the relative impact of individual radiologists and urologists. Results: A total of 865 patients (469 biopsy-naïve) were included across 5 urologists and 10 radiologists. Radiologists varied with grading 15.4% to 44.8% of patients with MRI lesions as PI-RADS 3. PCa detection varied significantly by radiologist, from 34.5% to 66.7% (p = 0.003) for PCa and 17.2% to 50% (p = 0.001) for csPCa. Urologists' PCa diagnosis rates varied between 29.2% and 55.8% (p = 0.013) and between 24.6% and 39.8% (p = 0.36) for csPCa. After adjustment for case-mix on MVR, a fourfold to fivefold difference in PCa detection was observed between the highest-performing and lowest-performing radiologist (OR 0.22, 95%CI 0.10-0.47, p < 0.001). MVR demonstrated improved AUC for any PCa and csPCa detection when controlling for radiologist variation (p = 0.017 and p = 0.038), but controlling for urologist was not significant (p = 0.22 and p = 0.086). Any PCa detection (OR 1.64, 95%CI 1.06-2.55, p = 0.03) and csPCa detection (OR 1.57, 95%CI 1.00-2.48, p = 0.05) improved over time (2018-2020 vs. 2015-2017). Conclusions: Variability among radiologists in PI-RADS grading is a key area for quality improvement significantly impacting the detection of PCa and csPCa. Variability for performance of MRI-TRUS fusion prostate biopsies exists by urologist but with less impact on overall detection of csPCa.

Risk of pseudoaneurysm and bleeding complications after partial nephrectomy: comparison of tumor enucleation to standard margin technique.

Partial nephrectomy (PN) is the gold standard for the resection of amenable small renal masses. Some surgeons have adopted tumor enucleation (TE) over the standard margin PN (SPN) technique based on preservation of healthy renal parenchyma by following the tumor pseudocapsule. However, TE may also confer additional advantages due to avoidance of sharp incision including reduction in perioperative and bleeding complications. Therefore, we evaluated the rate of pseudoaneurysms and other complications following TE vs. SPN. A retrospective cohort study of patients undergoing PN (TE and SPN) between 2008 and 2020 was conducted. Baseline characteristics were compared between the TE and SPN cohorts with univariable and multivariable logistic regression models. A total of 534 patients were included, 195 (36.5%) receiving TE and 339 (63.5%) SPN. There were no differences in baseline patient demographics. There was no difference in RENAL nephrometry scores between the two groups (p = 0.47). TE had lower rates of postoperative complications (11.3 vs. 21.5%, p = 0.002). TE had less bleeding complications (2.1 vs. 8.0%, p = 0.002) with no pseudoaneurysm events following TE compared to 12 following SPN (0.0 vs. 3.5%, p = 0.008). Need for interventional radiology largely reflected pseudoaneurysm differences (0 (0.0%) TE vs. 13 (3.8%) SPN, p = 0.006. Readmission occurred less often after TE vs. SPN (4.1 vs. 8.3%, p = 0.07). Patients receiving TE experienced no clinically significant pseudoaneurysm formation and were less likely to have any bleeding complication or major complication postoperatively. TE may be preferred when minimizing morbidity aligns with patient selection and preferences.

Robotic versus open radical cystectomy for bladder cancer: evaluation of complications, survival, and opioid prescribing patterns.

We aim to compare complications, readmission, survival, and prescribing patterns of opioids for post-operative pain management for Robotic-assisted laparoscopic radical cystectomy (RARC) as compared to open radical cystectomy (ORC). Patients that underwent RARC or ORC for bladder cancer at a tertiary care center from 2005 to 2021 were included. Recurrence-free survival (RFS) and overall survival (OS) were evaluated with Kaplan-Meier curves and multivariable Cox proportional hazards regression models. Comparisons of narcotic usage were completed with oral morphine equivalents (OMEQ). Multivariable linear regression was used to assess predictors of OMEQ utilization. A total of 128 RARC and 461 ORC patients were included. There was no difference in rates of Clavien-Dindo grade ≥ 3 complications between RARC and ORC (36.7 vs 30.1%, p = 0.16). After a mean follow up of 3.4 years, RFS (HR 0.96, 95%CI 0.58-1.56) and OS (HR 0.69, 95%CI 0.46-1.05) were comparable between RARC and ORC. There was no difference in the narcotic usage between patients in the RARC and ORC groups during the last 24 h of hospitalization (median OMEQ: 0 vs 0, p = 0.33) and upon discharge (median OMEQ: 178 vs 210, p = 0.36). Predictors of higher OMEQ discharge prescriptions included younger age [(- )3.46, 95%CI (-)5.5-(-)0.34], no epidural during hospitalization [- 95.85, 95%CI (- )144.95-(- )107.36], and early time-period of surgery [(- )151.04, 95%CI (- )194.72-(- )107.36]. RARC has comparable 90-day complication rates and early survival outcomes to ORC and remains a viable option for bladder cancer. RARC results in comparable levels of opioid utilization for pain management as ORC.

Urinary comprehensive genomic profiling predicts urothelial carcinoma recurrence and identifies responders to intravesical therapy.

Intravesical therapy (IVT) is the standard of care to decrease risk of recurrence and progression for high-grade nonmuscle-invasive bladder cancer. However, post-IVT recurrence remains common and the ability to risk-stratify patients before or after IVT is limited. In this prospectively designed and accrued cohort study, we examine the utility of urinary comprehensive genomic profiling (uCGP) for predicting recurrence risk following transurethral resection of bladder tumor (TURBT) and evaluating longitudinal IVT response. Urine was collected before and after IVT instillation and uCGP testing was done using the UroAmp™ platform. Baseline uCGP following TURBT identified patients with high (61%) and low (39%) recurrence risk. At 24 months, recurrence-free survival (RFS) was 100% for low-risk and 45% for high-risk patients with a hazard ratio (HR) of 9.3. Longitudinal uCGP classified patients as minimal residual disease (MRD) Negative, IVT Responder, or IVT Refractory with 24-month RFS of 100%, 50%, and 32%, respectively. Compared with MRD Negative patients, IVT Refractory patients had a HR of 10.5. Collectively, uCGP enables noninvasive risk assessment of patients following TURBT and induction IVT. uCGP could inform surveillance cystoscopy schedules and identify high-risk patients in need of additional therapy.

F-SHARP: a Phase I/II trial of focal salvage high-dose-rate brachytherapy for Radiorecurrent prostate cancer.

BACKGROUND: Intraprostatic local radiorecurrence (LRR) after definitive radiation is being increasingly identified due to the implementation of molecular positron emission tomography (PET)/computed tomography (CT) imaging for the evaluation of biochemical recurrence. Salvage high-dose rate (HDR) brachytherapy offers a promising local therapy option, with encouraging toxicity and efficacy based on early series. Furthermore, the incorporation of advanced imaging allows for focal HDR to further reduce toxicity to maximise the therapeutic ratio. The objectives of the 'focal salvage HDR brachytherapy for locally recurrent prostate cancer in patients treated with prior radiotherapy' (F-SHARP) trial are to determine the acute and late toxicity and efficacy outcomes of focal salvage HDR brachytherapy for LRR prostate cancer. STUDY DESIGN: The F-SHARP is a multi-institutional two-stage Phase I/II clinical trial of salvage focal HDR brachytherapy for LRR prostate cancer enrolling patients at three centres. ENDPOINTS: The primary endpoint is the acute radiation-related Grade ≥3 Common Terminology Criteria for Adverse Events (CTCAE, version 4.03) genitourinary (GU) and gastrointestinal (GI) toxicity rate, defined as within 3 months of brachytherapy. Secondary endpoints include acute and late CTCAE toxicity, biochemical failure, patterns of clinical progression, disease-specific and overall survival, and health-related quality of life, as measured by the International Prostate Symptom Score and 26-item Expanded Prostate Cancer Index Composite instruments. PATIENTS AND METHODS: Key eligibility criteria include: biopsy confirmed LRR prostate adenocarcinoma after prior definitive radiation therapy using any radiotherapeutic modality, no evidence of regional or distant metastasis, and cT1-3a Nx or N0 prostate cancer at initial treatment. All patients will have multiparametric magnetic resonance imaging and molecular PET/CT imaging if possible. In Stage 1, seven patients will be accrued. If there are two or more GI or GU Grade ≥3 toxicities, the study will be stopped. Otherwise, 17 additional patients will be accrued (total of 24 patients). For Stage 2, the cohort will expand to 62 subjects to study the efficacy outcomes, long-term toxicity profile, quality of life, and compare single- vs multi-fraction HDR. Transcriptomic analysis of recurrence biopsies will be performed to identify potential prognostic and predictive biomarkers.

Neoadjuvant Chemotherapy Before Radical Cystectomy for Muscle-Invasive Bladder Cancer: Elective and Eligibility Factors Impacting Utilization.

INTRODUCTION: We aimed to assess utilization of neoadjuvant chemotherapy (NAC) and etiologies for lack of NAC receipt among patients with muscle-invasive bladder cancer (MIBC). METHODS: Patients diagnosed with MIBC undergoing radical cystectomy at a single institution (2005-2021) were included. Patients were categorized by receipt of NAC, and reasons for no NAC were categorized into eligibility and elective factors. Overall survival was analyzed using univariable and multivariable Cox proportional hazards regression models and modeled with Kaplan-Meier curves. RESULTS: Three hundred eighty patients with MIBC were included; 154 (40.5%) received NAC. Patients were not candidates for NAC due to renal dysfunction (16.6%), clinical contraindications (4.7%), salvage setting (2.1%), and histology (5.3%; total N = 109). Among 271 (71.3%) who were eligible, utilization increased from early (2005-2016) to recent (2016-2021) time periods (34.2% to 85.7% among NAC-eligible, P < .001; 22.8% vs 67.1% among all MIBC, P < .001). Elective factors for not receiving NAC included patient symptoms (7.8%), disease progression concern (7.0%), patient preference/refusal (20.3%) and provider discretion (8.1%) among 271 NAC-eligible patients. Notably, patient preference/refusal decreased from 33.6% to 3.4% in recent years (P < .001). On multivariable analysis, lack of NAC utilization due to renal dysfunction (HR 2.18, P = .002), clinical contraindications (HR 2.62, P = .01), and elective factors (HR 1.88, P = .01) were associated with worse overall survival. CONCLUSIONS: NAC utilization increased over time with 85.7% of eligible patients with MIBC receiving NAC in recent years. Renal dysfunction, patient preference, and clinical contraindications were primary etiologies for lack of NAC. Fewer patients refused NAC in recent years leading to a potential ceiling for NAC utilization.

Multi-institutional feasibility and safety outcomes of retroperitoneal robot-assisted partial nephrectomy in morbidly obese patients.

Background: Robotic-assisted partial nephrectomy (RAPN) is an established treatment modality for small renal masses. While retroperitoneal RAPN (rRAPN) has the benefit of avoiding the peritoneal cavity and provides more direct access to the renal hilum and posterior kidney, there is concern about the feasibility of rRAPN particularly in morbidly obese [body mass index (BMI) ≥40 kg/m2] patients. We present a large scale multi-institutional study on the outcomes of rRAPN in morbidly obese patients. Methods: A retrospective review of a cohort of morbidly obese patients who underwent rRAPN at two academic institutions was performed. Patient characteristics, operative data, and postoperative complication rates were assessed. Results: A total of 22 morbidly obese patients were included for analysis, with a median follow-up duration of 52 months. Median patient age was 61 years and median BMI was 44.9 kg/m2. Based on nephrometry score, 55% of the masses had low complexity and 32% had intermediate complexity. Median operative time was 186.0 minutes and median warm ischemia time was 23.5 minutes. Median postoperative length of stay was 2 days, and only one patient experienced a high-grade complication within 30 days of surgery. Conclusions: rRAPN in select morbidly obese patients appears to have acceptable operative and postoperative outcomes. Further studies and follow-up are needed to better generalization and understand long-term impacts.

Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancer.

Introduction: Intravesical therapy (IVT), including Bacillus Calmette-Guérin (BCG), is the standard of care for high grade (HG) non-muscle invasive bladder cancer (NMIBC). Despite the use of IVT, many patients recur after treatment. The bladder microbiome and its role in disease processes has recently risen to prominence. We aim to characterize changes that occur in the bladder microbiome over the course of intravesical therapy and assess whether these changes correlate with outcomes in patients with NMIBC. Methods: Patients with NMIBC undergoing induction BCG or intravesical therapy were prospectively enrolled from January 2019 to March 2020. Patients with clinical T2 or greater pathology or active urinary tract infection at enrollment were excluded. Twenty-nine patients had catheterized (bladder) urine samples collected prior to induction intravesical therapy and prior to each IVT instillation. Twenty-seven received BCG while 2 received intravesical gemcitabine. Bacteria were identified using 16S ribosomal RNA gene sequencing. Bladder microbiome changes were evaluated and differences between patients who recurred and patients who did not recur after IVT were investigated. Results: Across the 29 patients analyzed, bacterial richness decreased significantly following intravesical therapy (Richness, P=0.01). Evenness and overall diversity did not change significantly (Pielou, P=0.62; Shannon, P=0.13). Patients who experienced recurrence had a higher relative abundance of Aerococcus in their urine (P<0.01), while those who did not recur had significantly more Ureaplasma (P=0.01) and Escherichia/Shigella species (P=0.05). Patients with decreased levels of alpha diversity were more likely to fall within the non-recurrence cohort. Conclusion: IVT for NMIBC appears to change the urinary microbiome by decreasing richness while not altering evenness or overall diversity. The presence of Aerococcus species may be predictive of a poor cancer response to IVT, while the presence of Ureaplasma and Escherichia/Shigella may predict a favorable response to IVT. Further studies are warranted to elucidate and confirm the significance of changes in the bladder microbiome.

The rising incidence of ductal adenocarcinoma and intraductal carcinoma of the prostate: Diagnostic accuracy of biopsy, MRI-visibility, and outcomes.

INTRODUCTION: Ductal adenocarcinoma (DA) and intraductal carcinoma (IDC) of the prostate are associated with higher stage disease at radical prostatectomy (RP). We evaluated diagnostic accuracy of biopsy, MRI-visibility, and outcomes for patients undergoing RP with DA/IDC histology compared to pure acinar adenocarcinoma (AA) of the prostate. MATERIALS AND METHODS: A retrospective cohort study of men receiving RP between 2014 and 2021 revealing AA, DA, or IDC on final pathology was conducted. Multivariable logistic regression and Cox proportional hazards regression models were employed. RESULTS: A total of 609 patients were included with 103 found to have DA/IDC. Patients with DA/IDC were older and had higher PSA, biopsy grade group (GG), RP GG, and other pathologic findings (extraprostatic extension, lymphovascular invasion, perineural invasion, pN stage) compared to AA patients (all P < 0.05). On multivariable analysis, higher age, RP GG, and pT3a were associated with DA/IDC on RP (all P < 0.05). Sensitivity and specificity of biopsy compared to RP for diagnosis of DA/IDC was 29.1% (16.7% DA, 27.8% IDC) and 96.6% (99.3% DA, 96.6% IDC), respectively. In a subset of 281 men receiving MRI, PI-RADS distribution was similar for patients with DA/IDC vs. AA (90.7% vs. 80.7% with PI-RADS 4-5 lesions, P = 0.23) with slightly higher biopsy sensitivity (41.9%). DA/IDC was associated with worse BCR (HR = 1.77, P = 0.02) but not biopsy DA/IDC (P = 0.90). CONCLUSIONS: Sensitivity of prostate biopsy was low for detection of DA/IDC histology at RP. Patients with DA/IDC histology had unfavorable pathologic features at RP and worse BCR. Of patients with DA/IDC at RP, 90.7% were categorized as PI-RADS 4 to 5 on preoperative MRI.

MRI versus non-MRI diagnostic pathways before radical prostatectomy: Impact on nerve-sparing, positive surgical margins, and biochemical recurrence.

PURPOSE: Magnetic resonance imaging (MRI) prior to biopsy has improved detection of clinically significant prostate cancer (CaP), but its impact on surgical outcomes is less well established. We compared MRI vs. non-MRI diagnostic pathways among patients receiving radical prostatectomy (RP) for impact on surgical outcomes. MATERIALS AND METHODS: Men diagnosed with CaP and receiving RP at Loyola University Medical Center (2014-2021) were categorized into MRI or non-MRI diagnostic pathways based on receipt of MRI before prostate biopsy. Primary outcomes of interest included positive surgical margin (PSM) rates, the performance of bilateral nerve-sparing, and biochemical recurrence (BCR). Multivariable logistic regression models, Kaplan-Meier curves, and Cox proportional hazards regression were employed. RESULTS: Of 609 patients, 281 (46.1%) were in the MRI and 328 (53.9%) in the non-MRI groups. MRI patients had similar PSA, biopsy grade group (GG) distribution, RP GG, pT stage, and RP CaP volume compared to non-MRI patients. PSM rates were not statistically different for the MRI vs. non-MRI groups (22.8% vs. 26.8%, P = 0.25). Bilateral nerve-sparing rates were higher for the MRI vs. non-MRI groups (OR 1.95 (95%CI 1.32-2.88), P = 0.001). The MRI group demonstrated improved BCR (HR 0.64 (95%CI 0.41-0.99), P = 0.04) after adjustment for age, PSA, RP GG, pT, pN, and PSM status. On meta-analysis, a 5.2% PSM reduction was observed but high heterogeneity for use of nerve-sparing. CONCLUSIONS: An MRI-based diagnostic approach selected patients for RP with a small reduction in PSM rates, greater utilization of bilateral nerve-sparing, and improved cancer control by BCR compared to a non-MRI approach even after adjustment for known prognostic factors.

A prostate biopsy risk calculator based on MRI: development and comparison of the Prospective Loyola University multiparametric MRI (PLUM) and Prostate Biopsy Collaborative Group (PBCG) risk calculators.

OBJECTIVES: To develop and validate a prostate cancer (PCa) risk calculator (RC) incorporating multiparametric magnetic resonance imaging (mpMRI) and to compare its performance with that of the Prostate Biopsy Collaborative Group (PBCG) RC. PATIENTS AND METHODS: Men without a PCa diagnosis receiving mpMRI before biopsy in the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (2015-2020) were included. Data from a separate institution were used for external validation. The primary outcome was diagnosis of no cancer, grade group (GG)1 PCa, and clinically significant (cs)PCa (≥GG2). Binary logistic regression was used to explore standard clinical and mpMRI variables (prostate volume, Prostate Imaging-Reporting Data System [PI-RADS] version 2.0 lesions) with the final PLUM RC, based on a multinomial logistic regression model. Receiver-operating characteristic curve, calibration curves, and decision-curve analysis were evaluated in the training and validation cohorts. RESULTS: A total of 1010 patients were included for development (N = 674 training [47.8% PCa, 30.9% csPCa], N = 336 internal validation) and 371 for external validation. The PLUM RC outperformed the PBCG RC in the training (area under the curve [AUC] 85.9% vs 66.0%; P < 0.001), internal validation (AUC 88.2% vs 67.8%; P < 0.001) and external validation (AUC 83.9% vs 69.4%; P < 0.001) cohorts for csPCa detection. The PBCG RC was prone to overprediction while the PLUM RC was well calibrated. At a threshold probability of 15%, the PLUM RC vs the PBCG RC could avoid 13.8 vs 2.7 biopsies per 100 patients without missing any csPCa. At a cost level of missing 7.5% of csPCa, the PLUM RC could have avoided 41.0% (566/1381) of biopsies compared to 19.1% (264/1381) for the PBCG RC. The PLUM RC compared favourably with the Stanford Prostate Cancer Calculator (SPCC; AUC 84.1% vs 81.1%; P = 0.002) and the MRI-European Randomized Study of Screening for Prostate Cancer (ERSPC) RC (AUC 84.5% vs 82.6%; P = 0.05). CONCLUSIONS: The mpMRI-based PLUM RC significantly outperformed the PBCG RC and compared favourably with other mpMRI-based RCs. A large proportion of biopsies could be avoided using the PLUM RC in shared decision making while maintaining optimal detection of csPCa.

MRI vs Transrectal Ultrasound to Estimate Prostate Volume and PSAD: Impact on Prostate Cancer Detection.

OBJECTIVES: To compare multiparametric magnetic resonance imaging (mpMRI) and transrectal ultrasound (TRUS) to estimate prostate volume and prostate specific antigen density (PSAD) as well as subsequent impact on prostate cancer (PCa) detection. METHODS: Patients referred for mpMRI prior to mpMRI-TRUS fusion-guided prostate biopsy between 2015 and 2020 were identified. Volume and calculated PSAD by mpMRI and TRUS were compared. Associations with presence of any PCa and clinically significant PCa (csPCa; Gleason ≥3 + 4) were evaluated using linear regression (interaction by volume quartile), logistic regression, and receiver operating characteristics. RESULTS: Among 640 men, TRUS underestimated prostate volume relative to mpMRI (median 49.2cc vs. 54.1cc) with 8% lower volume per cc up to 77.5cc (First-third quartile) and 39% lower volume per additional cc above 77.5cc (fourth quartile). For men undergoing radical prostatectomy, mpMRI had a higher correlation coefficient relative to TRUS (0.913 vs 0.878) when compared to surgical pathology. mpMRI PSAD had slightly higher odds vs TRUS PSAD for detecting any PCa (OR 2.94 and OR 2.78, both P <.001) or csPCa (OR 4.20 and OR 4.02, both P <.001). AUC improvements were of borderline significance for mpMRI vs. TRUS PSAD for any PCa (0.689 vs 0.675, P = .05) and not significant for csPCa (0.732 vs 0.722, P = .20). PSAD was not associated with PCa detection for prostates ≥77.5cc. CONCLUSION: TRUS underestimates prostate volume relative to mpMRI. PSAD based on mpMRI may be better associated with detection of PCa compared to TRUS, but utility of PSAD may be limited for larger prostates.

Differentiating Oncocytic Renal Tumors from Chromophobe Renal Cell Carcinoma: Comparison of Peak Early-phase Enhancement Ratio to Clinical Risk Factors and Rater Predictions.

Background: Most surgically resected benign renal tumors are found to be oncocytomas or indolent hybrid oncocytic tumors, which are difficult to differentiate from chromophobe renal cell carcinoma (chRCC) on renal mass biopsy. Both often exhibit CD117+ staining. Objective: To evaluate the ability of the peak early-phase enhancement ratio (PEER) to distinguish oncocytomas from chRCC and compare its discrimination to traditional clinical risk factors and blinded clinical raters. Design setting and participants: This was a diagnostic case-control study of patients (2006-2020) with oncocytoma or chRCC according to surgical pathology. Intervention: Partial or radical nephrectomy. Outcome measurements and statistical analysis: Three clinical raters blinded to histology measured the PEER and the presence of stellate scar and predicted the final histology for each tumor. Averaged and individual PEER values were compared to surgical pathology and assessed for interobserver variability. Subanalyses were conducted for patients with confirmed CD117+ status. Results and limitations: For the 76 patients identified, PEER was higher among the 32 (42.1%) oncocytomas than among the 44 (57.9%) chRCCs (median 0.81 vs 0.43; p < 0.001), with high correlation across raters (correlation coefficients ≥0.85). A PEER cutoff of <0.60 was strongly associated with identification of chRCC (OR 95.7 (95% CI 19.9-460.8), p < 0.001). In the overall and CD117+ cohorts, sensitivity was 93.2% and 97.0%, the negative predictive value was 90.3% and 95.5%, and the area under the receiver operating characteristic curve (AUC) on multivariable modeling was 95.0% and 98.1%, respectively. PEER outperformed models with clinical risk factors alone (AUC 70.4%) and histology predictions by three raters (AUC 51.6%, 62.5%, and 63.1%). Limitations include reliance on surgical pathology and inclusion of a mix of early contrast-enhanced phases. Conclusions: PEER reliably differentiated benign renal oncocytomas and indolent hybrid tumors from malignant chRCC with excellent diagnostic performance. A diagnostic pathway with biopsy, CD117 staining, and PEER deserves further study to potentially avoid unnecessary surgery for oncocytic renal tumors. Patient summary: We assessed a measurement called PEER on computed tomography (CT) scans and found higher values for benign and lower values for malignant kidney masses, so we were able to tell these apart. PEER was reliable for identifying tumors with positive staining for the CD117 protein biomarker as well as in the overall patient group. Our results show that PEER could be considered for use with biopsy and CD117 staining to potentially avoid unnecessary surgery for benign kidney masses.

Imaging Features of Renal Masses to Select Optimal Candidates for Tumor Enucleation Partial Nephrectomy.

PURPOSE OF REVIEW: The goal of this paper was to critically evaluate preoperative findings that optimally select candidates for renal tumor enucleation partial nephrectomy. RECENT FINDINGS: Tumor enucleation has been widely accepted as a management option for patients with chronic kidney disease, hereditary renal cell carcinoma, or multifocal disease. Recent evidence suggests safety and efficacy in the management of routine small renal masses. With recent advances in imaging, the literature for ruling out aggressive renal cell carcinoma and selection for tumor enucleation is robust. As the incidence of renal cell carcinoma rises, partial nephrectomy continues to be the mainstay of treatment for localized renal cell carcinoma. Tumor enucleation maximizes preservation of renal parenchyma without hindering oncologic outcomes. It is important to recognize key tumor radiologic findings which urologists may use to optimize patient selection for tumor enucleation.

SPATA16 promoter hypermethylation and downregulation in male infertility.

Spermatogenesis associated 16 (SPATA16) gene plays an important role in acrosome formation. In this study, we analysed SPATA16 promoter methylation in 29 oligozoospermic infertile and 16 normozoospermic fertile sperm samples and in testicular biopsy from 16 non-obstructive azoospermic and 2 obstructive azoospermic individuals. Next, we analysed SPATA16 level in sperm from 8 oligozoospermic infertile, 6 normozoospermic fertile, 9 IVF failed normozoospermic and 10 IVF successful normozoospermic samples by immunoblotting. This was followed by the analysis of SPATA16 expression in testicular biopsy from azoospermic individuals (n = 8) in comparison to normozoospermic individuals (n = 2). Oligozoospermic infertile sperm samples showed significantly higher methylation in the SPATA16 promoter region. Similarly, testicular biopsy from azoospermic men also showed significantly higher level of DNA methylation. Sub-group analysis of infertile sperm and testicular biopsy samples showed a direct correlation between DNA methylation and the degree of spermatogenic impairment. Oligozoospermic infertile samples and IVF failed samples showed reduced SPATA16 expression in comparison to normozoospermic fertile and IVF successful samples, respectively. Human biopsy analysis showed a significant decrease in SPATA16 expression in hypospermatogenesis, maturation arrest and Sertoli cell only syndrome. In conclusion, hypermethylation in SPATA16 promoter shows a highly significant correlation with infertility, which is consistent with its down-regulation in infertility.

Qualitative and quantitative assessment of sperm miRNAs identifies hsa-miR-9-3p, hsa-miR-30b-5p and hsa-miR-122-5p as potential biomarkers of male infertility and sperm quality.

BACKGROUND: In contrast with the preceding stages of the germ cells, spermatozoa are unusually rich in small non-coding RNAs in comparison to the coding RNAs. These small RNAs may have had an essential role in the process of spermatogenesis or may have critical roles in the post-fertilization development. Sporadic efforts have identified a few differentially expressed miRNAs in infertile individuals, which do not replicate in other studies. METHODS: In order to identify miRNAs signatures of infertility or poor sperm quality, we compared miRNA differential expression data across nine datasets, followed by their analysis by real-time PCR in a case-control study. This was followed by the validation of potential biomarkers in yet another set of cases and controls. For this, total RNA was isolated from 161 sperm samples. miRNA expression levels in infertile cases and fertile controls were measured using TaqMan real-time PCR. Meta-analyses of two miRNAs (hsa-miR-9-3p and hsa-miR-122-5p) were performed using Comprehensive Meta-Analysis Software (version 2). All statistical analyses were performed with the help of GraphPad Prism Software (version 8). RESULTS: Literature search identified seven miRNAs (hsa-let-7a-5p, hsa-miR-9-3p, hsa-miR-22-5p, has-miR-30b-5p, hsa-miR-103-3p, hsa-miR-122-5p and hsa-miR-335-5p) showing consistent dysregulation in infertility across a minimum of four studies. In the discovery phase, six miRNAs showed strong association with infertility with four (hsa-miR-9-3p, hsa-miR-30b-5p, hsa-miR-103-3p and hsa-miR-122-5p) showing consistent differential regulation across all sub-groups. Receiver operating characteristic (ROC) curve analysis showed that the area under curve of > 0.75 was achieved by three (hsa-mir-9-3p, hsa-miR-30b-5p and hsa-miR-122-5p) miRNAs. In the validation phase, these three miRNAs showed consistent association with infertility (hsa-mir-9-3p, hsa-miR-30b-5p, and hsa-miR-122-5p). Meta-analysis on hsa-miR-122-5p showed its significant quantitative association with infertility [Hedge's g = -2.428, p = 0.001 (Random effects)]. CONCLUSIONS: Three miRNAs (hsa-miR-9-3p, hsa-miR-30b-5p and hsa-miR-122-5p) have strong linkage with infertility and a high potential as sperm quality biomarkers.

Multifocality of Prostate Cancer and Candidacy for Focal Therapy Based on Magnetic Resonance Imaging.

OBJECTIVES: To determine the prevalence of multiparametric magnetic resonance imaging (mpMRI)-detected and targeted biopsy-confirmed multifocal and unifocal prostate cancer (PCa) among patients with Prostate Imaging Reporting and Data System (PI-RADS) ≥3 lesions. Focal therapy (FT) options for PCa are tied to accurate spatial identification on mpMRI. METHODS: Men without prior diagnosis of PCa receiving mpMRI, targeted and systematic prostate biopsy in the Prospective Loyola Urology mpMRI (PLUM) Prostate Biopsy Cohort from 2015-2021 were included. Patients with PI-RADS ≥3 lesions were classified by mpMRI lesion location, targeted biopsy, and systematic biopsy. Patients with single biopsy-confirmed grade group (GG) 2 lesions and concordant systematic biopsy were defined as FT candidates. Multivariable logistic regression evaluated predictors of mpMRI-undetected contralateral PCa. RESULTS: Of 897 patients, 450 (50.2%) had a single, 141 (15.7%) had multiple unilateral, and 306 (34.1%) had bilateral mpMRI lesions. 28.7% had a single targeted biopsy-confirmed lesion while 10.4% were multifocal. Among single targeted biopsy-confirmed patients, 92/257 (35.8%) had contralateral PCa missed by mpMRI with DRE, PSA, and biopsy history identified as independent predictors. Systematic biopsy findings dropped the rate of single confirmed lesions from 28.7% to 18.4% and multifocal PCa increased from 10.4% to 20.6%. After GG restrictions, 61/897 (6.8%) remained potential FT candidates. CONCLUSIONS: Among men with clinical suspicion of prostate cancer receiving mpMRI, 28.7% had a single targeted biopsy-confirmed lesion and 10.4% had multifocality on mpMRI, but many mpMRI-undetected contralateral PCa were identified. Only 6.0% of biopsy-naïve men remained with a single GG2 mpMRI lesion potentially amenable to FT.