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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.
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Background and objective: Micro-ultrasound (MUS) uses a high-frequency transducer with superior resolution to conventional ultrasound, which may differentiate prostate cancer from normal tissue and thereby allow targeted biopsy. Preliminary evidence has shown comparable sensitivity to magnetic resonance imaging (MRI), but consistency between users has yet to be described. Our objective was to assess agreement of MUS interpretation across multiple readers. Methods: After institutional review board approval, we prospectively collected MUS images for 57 patients referred for prostate biopsy after multiparametric MRI from 2022 to 2023. MUS images were interpreted by six urologists at four institutions with varying experience (range 2-6 yr). Readers were blinded to MRI results and clinical data. The primary outcome was reader agreement on the locations of suspicious lesions, measured in terms of Light's κ and positive percent agreement (PPA). Reader sensitivity for identification of grade group (GG) ≥2 prostate cancer was a secondary outcome. Key findings and limitations: Analysis revealed a κ value of 0.30 (95% confidence interval [CI] 0.21-0.39). PPA was 33% (95% CI 25-42%). The mean patient-level sensitivity for GG ≥2 cancer was 0.66 ± 0.05 overall and 0.87 ± 0.09 when cases with anterior lesions were excluded. Readers were 12 times more likely to detect higher-grade cancers (GG ≥3), with higher levels of agreement for this subgroup (κ 0.41, PPA 45%). Key limitations include the inability to prospectively biopsy reader-delineated targets and the inability of readers to perform live transducer maneuvers. Conclusions and clinical implications: Inter-reader agreement on the location of suspicious lesions on MUS is lower than rates previously reported for MRI. MUS sensitivity for cancer in the anterior gland is lacking. Patient summary: The ability to find cancer on imaging scans can vary between doctors. We found that there was frequent disagreement on the location of prostate cancer when doctors were using a new high-resolution scan method called micro-ultrasound. This suggests that the performance of micro-ultrasound is not yet consistent enough to replace MRI (magnetic resonance imaging) for diagnosis of prostate cancer.
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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.
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Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Alberta/epidemiologia , Canadá/epidemiologia , Negro ou Afro-Americano/estatística & dados numéricos , Gradação de Tumores , População Negra/estatística & dados numéricos , Estadiamento de Neoplasias , Antígeno Prostático Específico/sangueRESUMO
The current prostate cancer (PCa) screen test, prostate-specific antigen (PSA), has a high sensitivity for PCa but low specificity for high-risk, clinically significant PCa (csPCa), resulting in overdiagnosis and overtreatment of non-csPCa. Early identification of csPCa while avoiding unnecessary biopsies in men with non-csPCa is challenging. We built an optimized machine learning platform (ClarityDX) and showed its utility in generating models predicting csPCa. Integrating the ClarityDX platform with blood-based biomarkers for clinically significant PCa and clinical biomarker data from a 3448-patient cohort, we developed a test to stratify patients' risk of csPCa; called ClarityDX Prostate. When predicting high risk cancer in the validation cohort, ClarityDX Prostate showed 95% sensitivity, 35% specificity, 54% positive predictive value, and 91% negative predictive value, at a ≥ 25% threshold. Using ClarityDX Prostate at this threshold could avoid up to 35% of unnecessary prostate biopsies. ClarityDX Prostate showed higher accuracy for predicting the risk of csPCa than PSA alone and the tested model-based risk calculators. Using this test as a reflex test in men with elevated PSA levels may help patients and their healthcare providers decide if a prostate biopsy is necessary.
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BACKGROUND: The tumor suppressor and proapoptotic transcription factor P53 is induced (and activated) in several forms of heart failure, including cardiotoxicity and dilated cardiomyopathy; however, the precise mechanism that coordinates its induction with accessibility to its transcriptional promoter sites remains unresolved, especially in the setting of mature terminally differentiated (nonreplicative) cardiomyocytes. METHODS: Male and female control or TRIM35 (tripartite motif containing 35) overexpression adolescent (aged 1-3 months) and adult (aged 4-6 months) transgenic mice were used for all in vivo experiments. Primary adolescent or adult mouse cardiomyocytes were isolated from control or TRIM35 overexpression transgenic mice for all in vitro experiments. Adenovirus or small-interfering RNA was used for all molecular experiments to overexpress or knockdown, respectively, target genes in primary mouse cardiomyocytes. Patient dilated cardiomyopathy or nonfailing left ventricle samples were used for translational and mechanistic insight. Chromatin immunoprecipitation and DNA sequencing or quantitative real-time polymerase chain reaction (qPCR) was used to assess P53 binding to its transcriptional promoter targets, and RNA sequencing was used to identify disease-specific signaling pathways. RESULTS: Here, we show that E3-ubiquitin ligase TRIM35 can directly monoubiquitinate lysine-120 (K120) on histone 2B in postnatal mature cardiomyocytes. This epigenetic modification was sufficient to promote chromatin remodeling, accessibility of P53 to its transcriptional promoter targets, and elongation of its transcribed mRNA. We found that increased P53 transcriptional activity (in cardiomyocyte-specific Trim35 overexpression transgenic mice) was sufficient to initiate heart failure and these molecular findings were recapitulated in nonischemic human LV dilated cardiomyopathy samples. CONCLUSIONS: These findings suggest that TRIM35 and the K120Ub-histone 2B epigenetic modification are molecular features of cardiomyocytes that can collectively predict dilated cardiomyopathy pathogenesis.
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Insuficiência Cardíaca , Histonas , Camundongos Transgênicos , Miócitos Cardíacos , Proteína Supressora de Tumor p53 , Ubiquitinação , Animais , Feminino , Humanos , Masculino , Camundongos , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/patologia , Células Cultivadas , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/patologia , Histonas/metabolismo , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Regiões Promotoras Genéticas , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genéticaRESUMO
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.
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BACKGROUND: Urinary incontinence (UI), erectile dysfunction and cardiometabolic conditions are common after prostatectomy for prostate cancer (PCa). Although physical activity could improve overall survival and quality of survivorship, fear of UI can restrict participation in exercise. Individuals with PCa could benefit from therapeutic exercise programming to support continence recovery and cardiometabolic health. AIM: The main objective of this study is to determine the feasibility and the effects of a combined pelvic health rehabilitation and exercise fitness program on UI after prostatectomy. The combined exercise program will be delivered both in-person and virtually. METHODS: This study follows a modified Zelen, two-arm parallel randomized controlled trial design. A total of 106 individuals with PCa will be recruited before prostatectomy surgery. Participants will be randomized between two groups: one receiving usual care and one receiving a combined exercise fitness and intensive pelvic floor muscle training program. Exercise programming will begin 6-8 weeks after prostatectomy and will last 12 weeks. Outcomes include: the 24-h pad test (primary outcome for UI); physical fitness, metabolic indicators, and patient-reported outcomes on erectile function, self-efficacy, severity of cancer symptoms and quality of life. Important timepoints for assessments include before surgery (T0), after surgery (T1), after intervention (T3) and at one-year after surgery (T4). CONCLUSION: This study will inform the feasibility of offering comprehensive exercise programming that has the potential to positively impact urinary continence, erectile function and cardiometabolic health of individuals undergoing prostatectomy for prostate cancer. CLINICALTRIALS REGISTRATION NUMBER: NCT06072911.
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Doenças Cardiovasculares , Disfunção Erétil , Neoplasias da Próstata , Incontinência Urinária , Masculino , Humanos , Disfunção Erétil/etiologia , Disfunção Erétil/reabilitação , Qualidade de Vida , Estudos de Viabilidade , Diafragma da Pelve , Terapia por Exercício/métodos , Incontinência Urinária/etiologia , Incontinência Urinária/cirurgia , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Exercício Físico , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
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.
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Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Imageamento por Ressonância Magnética , Biópsia , Instalações de SaúdeRESUMO
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.
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BACKGROUND: Conservative management is an option for prostate cancer (PCa) patients either with the objective of delaying or even avoiding curative therapy, or to wait until palliative treatment is needed. PIONEER, funded by the European Commission Innovative Medicines Initiative, aims at improving PCa care across Europe through the application of big data analytics. OBJECTIVE: To describe the clinical characteristics and long-term outcomes of PCa patients on conservative management by using an international large network of real-world data. DESIGN, SETTING, AND PARTICIPANTS: From an initial cohort of >100 000 000 adult individuals included in eight databases evaluated during a virtual study-a-thon hosted by PIONEER, we identified newly diagnosed PCa cases (n = 527 311). Among those, we selected patients who did not receive curative or palliative treatment within 6 mo from diagnosis (n = 123 146). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patient and disease characteristics were reported. The number of patients who experienced the main study outcomes was quantified for each stratum and the overall cohort. Kaplan-Meier analyses were used to estimate the distribution of time to event data. RESULTS AND LIMITATIONS: The most common comorbidities were hypertension (35-73%), obesity (9.2-54%), and type 2 diabetes (11-28%). The rate of PCa-related symptomatic progression ranged between 2.6% and 6.2%. Hospitalization (12-25%) and emergency department visits (10-14%) were common events during the 1st year of follow-up. The probability of being free from both palliative and curative treatments decreased during follow-up. Limitations include a lack of information on patients and disease characteristics and on treatment intent. CONCLUSIONS: Our results allow us to better understand the current landscape of patients with PCa managed with conservative treatment. PIONEER offers a unique opportunity to characterize the baseline features and outcomes of PCa patients managed conservatively using real-world data. PATIENT SUMMARY: Up to 25% of men with prostate cancer (PCa) managed conservatively experienced hospitalization and emergency department visits within the 1st year after diagnosis; 6% experienced PCa-related symptoms. The probability of receiving therapies for PCa decreased according to time elapsed after the diagnosis.
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Diabetes Mellitus Tipo 2 , Neoplasias da Próstata , Masculino , Adulto , Humanos , Big Data , Neoplasias da Próstata/terapia , Neoplasias da Próstata/diagnóstico , Intervalo Livre de Doença , Europa (Continente)RESUMO
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.
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PURPOSE: To develop and validate a micro-ultrasound risk score that predicts the likelihood of significant prostate cancer in the anterior zone. METHODS: Patients were enrolled from three expert institutions familiar with micro-ultrasound. The study was conducted in two phases. First, the PRI-MUS anterior score was developed by assessing selected prostate videos from patients who subsequently underwent radical prostatectomy. Second, seven urology readers with varying levels of experience in micro-ultrasound examination evaluated prostate loops according to the PRI-MUS anterior score. Each reader watched the videos and recorded the likelihood of the presence of significant cancer in the anterior part of the prostate in a three-point scale. The coherence among the readers was calculated using the Fleiss kappa and the Cronbach alpha. RESULTS: A total of 102 selected prostate scans were used to develop the risk assessment for anterior zone cancer in the prostate. The score comprised three categories: likely, equivocal, and unlikely. The median (IQR) sensitivity, specificity, positive predictive value, and negative predictive value for the seven readers were 72% (68-84), 68% (64-84), 75% (72-81), and 73% (71-80), respectively. The mean SD ROC AUC was 0.75 ± 2%, while the Fleiss kappa and the Cronbach alpha were 0.179 and 0.56, respectively. CONCLUSION: Micro-ultrasound can detect cancerous lesions in the anterior part of the prostate. When combined with the PRI-MUS protocol to assess the peripheral part, it enables an assessment of the entire prostate gland. Pending external validation, the PRI-MUS anterior score developed in this study might be implemented in clinical practice.
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Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/patologia , Ultrassonografia/métodos , Pelve , Medição de Risco , Imageamento por Ressonância MagnéticaRESUMO
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.
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Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Antígeno Prostático Específico , Detecção Precoce de Câncer , Assistência de Saúde Universal , Canadá/epidemiologiaRESUMO
BACKGROUND: There is an unmet clinical need for minimally invasive diagnostic tests to improve the detection of grade group (GG) ≥3 prostate cancer relative to prostate antigen-specific risk calculators. We determined the accuracy of the blood-based extracellular vesicle (EV) biomarker assay (EV Fingerprint test) at the point of a prostate biopsy decision to predict GG ≥3 from GG ≤2 and avoid unnecessary biopsies. METHODS: This study analyzed 415 men referred to urology clinics and scheduled for a prostate biopsy, were recruited to the APCaRI 01 prospective cohort study. The EV machine learning analysis platform was used to generate predictive EV models from microflow data. Logistic regression was then used to analyze the combined EV models and patient clinical data and generate the patients' risk score for GG ≥3 prostate cancer. RESULTS: The EV-Fingerprint test was evaluated using the area under the curve (AUC) in discrimination of GG ≥3 from GG ≤2 and benign disease on initial biopsy. EV-Fingerprint identified GG ≥3 cancer patients with high accuracy (0.81 AUC) at 95% sensitivity and 97% negative predictive value. Using a 7.85% probability cutoff, 95% of men with GG ≥3 would have been recommended a biopsy while avoiding 144 unnecessary biopsies (35%) and missing four GG ≥3 cancers (5%). Conversely, a 5% cutoff would have avoided 31 unnecessary biopsies (7%), missing no GG ≥3 cancers (0%). CONCLUSIONS: EV-Fingerprint accurately predicted GG ≥3 prostate cancer and would have significantly reduced unnecessary prostate biopsies.
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Vesículas Extracelulares , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Antígeno Prostático Específico , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Biópsia , Vesículas Extracelulares/patologiaRESUMO
BACKGROUND: Partial gland ablation (PGA) is a new option for treatment of prostate cancer (PCa). Cryotherapy, an early method of PGA, has had favorable evaluations, but few studies have employed a strict protocol using biopsy endpoints in men with clinically significant prostate cancer (csPCa). METHODS: 143 men with unilateral csPCa were enrolled in a prospective, observational trial of outpatient PGA-cryotherapy. Treatment was a 2-cycle freeze of the affected prostate part. Participants were evaluated with MRI-guided biopsy (MRGB) at baseline and at 6 months and 18 months after treatment. Absence of csPCa upon MRGB was the primary endpoint; quality-of-life at baseline and at 6 months after treatment was assessed by EPIC-CP questionnaires in the domains of urinary and sexual function. RESULTS: Of the 143 participants, 136 (95%) completed MRGB at 6 months after treatment. In 103/136 (76%), the biopsy revealed no csPCa. Of the 103, 71 subsequently had an 18-month comprehensive biopsy; of the 71 with 18-month biopsies, 46 (65%) were found to have no csPCa. MRI lesions became undetectable in 96/130 (74%); declines in median serum PSA levels (6.9 to 2.5 ng/mL), PSA density (0.15 to 0.07), and prostate volume (42 to 34cc) were observed (all p < 0.01). Neither lesion disappearance on MRI nor PSA decline correlated with biopsy outcome. Urinary function was affected only slightly and sexual function moderately. CONCLUSION: In the near to intermediate term, partial gland ablation with cryotherapy was found to be a safe and moderately effective treatment of intermediate-risk prostate cancer. Eradication of cancer was better determined by MRI-guided biopsy than by MRI or PSA.
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Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Estudos Prospectivos , Neoplasias da Próstata/cirurgia , Crioterapia/efeitos adversos , Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética/métodosRESUMO
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.
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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.
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An epithelial-to-mesenchymal transition (EMT) phenotype with cancer stem cell-like properties is a critical feature of aggressive/metastatic tumors, but the mechanism(s) that promote it and its relation to metabolic stress remain unknown. Here we show that Collapsin Response Mediator Protein 2A (CRMP2A) is unexpectedly and reversibly induced in cancer cells in response to multiple metabolic stresses, including low glucose and hypoxia, and inhibits EMT/stemness. Loss of CRMP2A, when metabolic stress decreases (e.g., around blood vessels in vivo) or by gene deletion, induces extensive microtubule remodeling, increased glutamine utilization toward pyrimidine synthesis, and an EMT/stemness phenotype with increased migration, chemoresistance, tumor initiation capacity/growth, and metastatic potential. In a cohort of 27 prostate cancer patients with biopsies from primary tumors and distant metastases, CRMP2A expression decreases in the metastatic versus primary tumors. CRMP2A is an endogenous molecular brake on cancer EMT/stemness and its loss increases the aggressiveness and metastatic potential of tumors.