Disparities in prostate cancer screening, diagnoses, management, and outcomes between Indigenous and non-Indigenous men in a universal health care system.

BACKGROUND: Indigenous Peoples have higher morbidity rates and lower life expectancies than non-Indigenous Canadians. Identification of disparities between Indigenous and non-Indigenous men regarding prostate cancer (PCa) screening, diagnoses, management, and outcomes was sought. METHODS: An observational cohort of men diagnosed with PCa between June 2014 and October 2022 was studied. Men were prospectively enrolled in the province-wide Alberta Prostate Cancer Research Initiative. The primary outcomes were tumor characteristics (stage, grade, and prostate-specific antigen [PSA]) at diagnosis. Secondary outcomes were PSA testing rates, time from diagnosis to treatment, treatment modality, and metastasis-free, cancer-specific, and overall survivals. RESULTS: Examination of 1,444,974 men for whom aggregate PSA testing data were available was performed. Men in Indigenous communities were less likely to have PSA testing performed than men outside of Indigenous communities (32 vs. 46 PSA tests per 100 men [aged 50-70 years] within 1 year; p < .001). Among 6049 men diagnosed with PCa, Indigenous men had higher risk disease characteristics: a higher proportion of Indigenous men had PSA ≥ 10 ng/mL (48% vs. 30%; p < .01), TNM stage ≥ T2 (65% vs. 47%; p < .01), and Gleason grade group ≥ 2 (79% vs. 64%; p < .01) compared to non-Indigenous men. With a median follow-up of 40 months (interquartile range, 25-65 months), Indigenous men were at higher risk of developing PCa metastases (hazard ratio, 2.3; 95% CI, 1.2-4.2; p < .01) than non-Indigenous men. CONCLUSIONS: Despite receiving care in a universal health care system, Indigenous men were less likely to receive PSA testing and more likely to be diagnosed with aggressive tumors and develop PCa metastases than non-Indigenous men.

Prostate Cancer Among Black Men in Canada.

Importance: Prostate cancer is a prevalent disease among men worldwide, exhibiting substantial heterogeneity in presentation and outcomes influenced by various factors, including race and ethnicity. Disparities in incidence, stage at diagnosis, and survival rates have been observed between Black men and those of other races and ethnicities. Objective: To compare prostate cancer outcomes between Black men and men with other race (Asian, Hispanic, Indigenous, Middle Eastern, White, Multiracial, and Other) in a universal health care system, with race and ethnicity self-reported. Design, Setting, and Participants: This was a prospective, observational cohort study of men diagnosed with prostate cancer between June 1, 2014, and August 28, 2023, who self-identified race and ethnicity. Participants included men who had been prospectively enrolled in the Alberta Prostate Cancer Research Initiative from the 2 major urology referral centers in Alberta (University of Alberta and University of Calgary). All men with prostate cancer enrolled in the initiative were included. Exposure: Race and ethnicity. Main Outcomes and Measures: The primary outcome was the stage and grade of prostate cancer at diagnosis. Further outcomes included age and prostate-specific antigen level at diagnosis, initial treatment modality, time from diagnosis to initial treatment, and prostate cancer-specific, metastasis-free, and overall survivals. Results: A total of 6534 men were included; 177 (2.7%) were Black, and 6357 (97.3%) had another race or ethnicity. Men who identified as Black were diagnosed with prostate cancer at an earlier age (mean [SD], 62.0 [8.2] compared with 64.6 [7.7] years; P < .001) and had a lower Charlson Comorbidity Index rating (14% compared with 7% ≤ 1; P < .001) compared with men of other races. Men who identified as Black had similar prostate-specific antigen levels at diagnosis, TNM category (74% vs 74% with T1-T2; P = .83) and Gleason Grade Group (34% compared with 35% Gleason Grade Group 1; P = .63). Black men had similar rates of prostate cancer-specific (hazard ratio [HR], 1.10; 95% CI, 0.41-2.97; P = .85), metastasis-free (HR, 0.88; 95% CI, 0.42-1.46; P = .44), and overall (HR, 0.55; 95% CI, 0.25-1.24; P = .15) survival. Conclusions and Relevance: The findings of this cohort study suggest that Black men, despite being diagnosed at a younger age, experience comparable prostate cancer outcomes compared with men of other races.

Complication rates of ciprofloxacin alone vs. ciprofloxacin plus fosfomycin for transrectal prostate biopsy.

INTRODUCTION: Infectious complications after transrectal prostate biopsy have been increasing, driven in large part, by rates of antibiotic resistance to conventional prophylaxis, such as ciprofloxacin. This study was designed to compare conventional antibiotic prophylaxis (oral ciprofloxacin) with ciprofloxacin and fosfomycin combination therapy prior to biopsy. METHODS: This was a retrospective study looking at men between September 2021 and April 2023, who underwent transrectal prostate biopsy at several institutions in Alberta. The primary outcome was infectious complications within 30 days of prostate biopsy. Secondary outcomes included Clostridium difficile infections, urinary retention, gross hematuria, diarrhea, emergency room (ER ) visits, hospital admissions, and intensive care unit (ICU) admissions. Data was collected on resistance patterns and pathogens isolated in culture. RESULTS: During the study period, 2168 men underwent transrectal prostate biopsy. A total of 1216 men received ciprofloxacin alone and 877 received fosfomycin and ciprofloxacin. Infectious complications were significantly higher in the ciprofloxacin alone group (5.8% vs. 0.5%, p<0.0001). Thirty-day complications (7.2% vs. 2.1%, p<0.0001), 30-day ER visits (7.1% vs. 1.8%, p<0.0001), and 30-day hospitalizations (2.7% vs. 0.7%, p<0.001) were all higher in the ciprofloxacin alone group. The most isolated pathogen was E. coli in 54/60 (90%). Ciprofloxacin resistance in the isolated pathogens was high, with 52/60 (87%) showing resistance to ciprofloxacin and 51/54 (94%) E. coli strains resistant. No difference was seen in retention, C. difficile infections, bleeding, or diarrhea. CONCLUSIONS: The addition of fosfomycin for antibiotic prophylaxis prior to transrectal prostate biopsy was associated with significant improvement in infectious complications and healthcare utilization.

Value of Incremental Biopsy Cores for Microultrasound Targeted Prostate Biopsies.

OBJECTIVE: To determine the optimal number of cores needed during microultrasound-informed prostate biopsy for the detection of clinically significant prostate cancer (csPCa, defined as Gleason Grade Group ≥2). METHODS: A retrospective review of 1011 consecutive patients between September 2021 and July 2023 at our institution were identified; 536 underwent microultrasound biopsy and 475 underwent magnetic resonance imaging (MRI)/ultrasound (US) targeted biopsy. Lesions were given a Prostate Risk Identification using Microultrasound (PRI-MUS) score, with lesions PRI-MUS ≥3 targeted. MRI lesions were scored with Prostate Imaging-Reporting and Data System (PI-RADS) and lesions PI-RADS ≥3 were targeted. The primary outcome is the detection of csPCa stratified by number of cores. RESULTS: One hundred thirty-eight patients underwent targeted biopsies for microultrasound only lesions, 182 for microultrasound and MRI lesions and 426 underwent MRI/US for MRI lesions. The first targeted core detected 78.0% (46/59), 77.8% (63/81), and 78.8% (216/274) of csPCa for microultrasound, microultrasound+MRI, and MRI/US, respectively. Comparing first to third core, there was not a significant difference in overall detection of csPCa by microultrasound, though MRI/US was significantly different (28.4% vs 36.4% P = .12, 32.5% vs 41.8% P = .06, 42.5% vs 53.9% P < .001 for microultrasound, microultrasound+MRI, and MRI/US, respectively). PI-RADS 3 and PRI-MUS 3 lesions had lower first core detection rates compared to PI-RADS 5 and PRI-MUS 5 lesions (44.4% vs 85.4% P = .01, 65.2% vs 81.4% P = .14, 60% vs 83.1% P = .07 for microultrasound, microultrasound+MRI, and MRI/US, respectively). CONCLUSION: A three-core targeted biopsy per microultrasound lesion improves detection rate of csPCa and should be considered to improve diagnostic accuracy.

Micro-ultrasound for the detection of clinically significant prostate cancer in biopsy-naive men with negative MRI.

INTRODUCTION: Despite a negative magnetic resonance imaging (MRI), some patients may still harbor clinically significant prostate cancer (csPCa, Gleason grade group ≥2). High-resolution micro-ultrasound (microUS) is a novel imaging technology that could visualize csPCa that is missed by MRI. METHODS: This retrospective review included 1011 consecutive patients biopsied between September 2021 and July 2023 in Alberta, Canada. Among them were 103 biopsy-naive patients with negative MRI (Prostate Imaging Reporting & Data System [PI-RADS] ≤2) undergoing microUS-informed prostate biopsy (n=56) scored using Prostate Risk Identification Using Micro-ultrasound (PRI-MUS) or standard transrectal ultrasound prostate biopsy (n=47). The primary outcome was detection rate of csPCa stratified by biopsy technique and PRI-MUS score. RESULTS: MicroUS biopsy identified csPCa in 14/56 (25%) compared to standard biopsy in 8/47 (17%) (p=0.33). Patients with lesions PRI-MUS ≥3 had csPCa detected at a higher rate compared to patients with PRI-MUS ≤2 (42% vs. 16%, p=0.03). The csPCa detection rate was significantly different comparing patients with prostate-specific antigen (PSA) density <0.15 and PRI-MUS ≤2 compared to patients with PSA density ≥0.15 and PRI-MUS ≥3 (14% vs. 60%, p=0.02). CONCLUSIONS: MicroUS may aid in the detection of csPCa for patients with negative MRI.

Fluorine-18 Prostate-Specific Membrane Antigen-1007 PET/CT vs Multiparametric MRI for Locoregional Staging of Prostate Cancer.

Importance: Prostate-specific membrane antigen (PSMA) demonstrates overexpression in prostate cancer and correlates with tumor aggressiveness. PSMA positron emission tomography (PET) is superior to conventional imaging for the metastatic staging of prostate cancer per current research but studies of second-generation PSMA PET radioligands for locoregional staging are limited. Objective: To determine the accuracy of fluorine-18 PSMA-1007 PET/computed tomography (18F-PSMA-1007 PET/CT) compared to multiparametric magnetic resonance imaging (MRI) in the primary locoregional staging of intermediate-risk and high-risk prostate cancers. Design, Setting, and Participants: The Next Generation Trial was a phase 2 prospective validating paired cohort study assessing the accuracy of 18F-PSMA-1007 PET/CT and MRI for locoregional staging of prostate cancer, with results of histopathologic examination as the reference standard comparator. Radiologists, nuclear medicine physicians, and pathologists were blinded to preoperative clinical, pathology, and imaging data. Patients underwent all imaging studies and radical prostatectomies at 2 tertiary care hospitals in Alberta, Canada. Eligible participants included men with intermediate-risk or high-risk prostate cancer who consented to radical prostatectomy. Participants who underwent radical prostatectomy were included in the final analysis. Patients were recruited between March 2022 and June 2023, and data analysis occurred between July 2023 and December 2023. Exposures: All participants underwent both 18F-PSMA-1007 PET/CT and MRI within 2 weeks of one another and before radical prostatectomy. Main Outcomes and Measures: The primary outcome was the correct identification of the prostate cancer tumor stage by each imaging test. The secondary outcomes were correct identification of the dominant nodule, laterality, extracapsular extension, and seminal vesical invasion. Results: Of 150 eligible men with prostate cancer, 134 patients ultimately underwent radical prostatectomy (mean [SD] age at prostatectomy, 62.0 [5.7] years). PSMA PET was superior to MRI for the accurate identification of the final pathological tumor stage (61 [45%] vs 38 [28%]; P = .003). PSMA PET was also superior to MRI for the correct identification of the dominant nodule (126 [94%] vs 112 [83%]; P = .01), laterality (86 [64%] vs 60 [44%]; P = .001), and extracapsular extension (100 [75%] vs 84 [63%]; P = .01), but not for seminal vesicle invasion (122 [91%] vs 115 [85%]; P = .07). Conclusions and Relevance: In this phase 2 prospective validating paired cohort study, 18F-PSMA-1007 PET/CT was superior to MRI for the locoregional staging of prostate cancer. These findings support PSMA PET in the preoperative workflow of intermediate-risk and high-risk tumors.

Detection of clinically significant prostate cancer by micro-ultrasound-informed systematic biopsy during MRI/micro-ultrasound fusion biopsy.

INTRODUCTION: High-resolution micro-ultrasound (microUS) is a novel imaging technique that may visualize clinically significant prostate cancer (csPCa), including those missed by magnetic resonance imaging (MRI ), in real time during prostate biopsy. METHODS: From September 2021 to January 2022, 75 consecutive biopsy-naive men were entered into an observational cohort. All men underwent an MRI /microUS fusion prostate biopsy, completed by a single surgeon using the ExactVU device. At time of biopsy, each biopsy core was given a Prostate Risk Identification using MicroUS (PRI-MUS) score. Anonymized data were entered into a RED Cap database. Cancer detection stratified by Prostate Imaging-Reporting & Data System (PI-RADS ) and PRI-MUS score, and imaging modality was captured. Our primary outcome was the detection rate of csPCa in microUS-informed systematic biopsy cores, taken outside MRI-visible lesions, during MRI /microUS fusion prostate biopsy. RESULTS: A median of three MRI-targeted and 12 microUS-informed systematic cores were taken per patient. MRI /microUS biopsy detected PCa in 84%, with csPCa detected in 52%. Of the 900 microUS-informed systematic cores, 105 cores were PRI-MUS ≥3 and 795 cores were PRI-MUS ≤2. csPCa was detected in 35% of the PRI-MUS ≥3 cores compared to 10% of the PRI-MUS ≤2 cores (p<0.0001). Detection of csPCa varied by core type: 8% of patients were diagnosed by MRI-targeted cores only, 38% were diagnosed by microUS-informed systematic cores only, and 54% were diagnosed by both. CONCLUSIONS: MicroUS-informed systematic biopsy may be a useful adjunct to MRI, with PRI-MUS ≥3 systematic cores having a 3.5-fold increased risk of csPCa compared to PRI-MUS ≤2 cores.

Gleason Grade Group 4 prostate biopsy with no cancer seen on final pathology in the magnetic resonance imaging and Prostate Specific Membrane Antigen-Positron Emission Tomography era.

Introduction: The absence of prostate cancer on final surgical pathology after biopsy-proven prostate cancer is a rare finding. Case presentation: Case of pT0 prostate cancer following Gleason Grade Group 4 in 1 out of 12 cores from a transrectal ultrasound-guided biopsy in a man who underwent both magnetic resonance imaging and 18F-PSMA-1007 Positron Emission Tomography prior to radical prostatectomy. Conclusion: pT0 prostate cancer is rare. The use of novel imaging modalities may help in the workup of prostate cancer.

Micro-ultrasound Versus Magnetic Resonance Imaging in Prostate Cancer Active Surveillance.

Accurate assessment of tumor grade is critical for active surveillance (AS) in prostate cancer. We compared magnetic resonance imaging (MRI) and micro-ultrasound scoring (Prostate Imaging-Reporting and Data System [PI-RADS] v2.1 vs Prostate Risk Identification using Micro-ultrasound [PRI-MUS]) in 128 men on AS. The primary outcome was upgrading to Gleason grade group (GG) ≥2. There was no difference in GG ≥2 detection between the imaging techniques (PRI-MUS score ≥3: 33/34, 98%; PI-RADS score ≥3: 29/34, 85%; p = 0.22). The sensitivity, specificity, and positive and negative predictive values for GG ≥2 detection were 97%, 32%, 34%, and 97% with PRI-MUS ≥3, and 85%, 53%, 40%, and 91% with PI-RADS ≥3, respectively. Upgrading to GG ≥2 was more likely for PRI-MUS ≥3 than for PRI-MUS ≤2 scores (odds ratio 15.5, 95% confidence interval 2.0-118.5). A limitation is the lack of blinding to the MRI results. In conclusion, detection of upgrading to GG ≥2 during AS appears similar when using micro-ultrasound or MRI to inform prostate biopsy. Patient summary: We looked at a novel imaging technology, micro-ultrasound, in patients undergoing biopsy during active surveillance for prostate cancer. We found that micro-ultrasound can detect prostate cancer that may require treatment at a similar rate to that with magnetic resonance imaging (MRI) scans.

Suppression of genetic defects within the RAD6 pathway by srs2 is specific for error-free post-replication repair but not for damage-induced mutagenesis.

srs2 was isolated during a screen for mutants that could suppress the UV-sensitive phenotype of rad6 and rad18 cells. Genetic analyses led to a proposal that Srs2 acts to prevent the channeling of DNA replication-blocking lesions into homologous recombination. The phenotypes associated with srs2 indicate that the Srs2 protein acts to process lesions through RAD6-mediated post-replication repair (PRR) rather than recombination repair. The RAD6 pathway has been divided into three rather independent subpathways: two error-free (represented by RAD5 and POL30) and one error-prone (represented by REV3). In order to determine on which subpathways Srs2 acts, we performed comprehensive epistasis analyses; the experimental results indicate that the srs2 mutation completely suppresses both error-free PRR branches. Combined with UV-induced mutagenesis assays, we conclude that the Polzeta-mediated error-prone pathway is functional in the absence of Srs2; hence, Srs2 is not required for mutagenesis. Furthermore, we demonstrate that the helicase activity of Srs2 is probably required for the phenotypic suppression of error-free PRR defects. Taken together, our observations link error-free PRR to homologous recombination through the helicase activity of Srs2.