Significant Prostate Cancer Research Articles

Incidence and mortality of prostate cancer in France from 2010 to 2021, using a real-life database (National Health Data System - SNDS) - the CaPCo Study.

Prostate cancer (PCa) was the leading incident cancer and 3rd leading cause of cancer death in men in France in 2015 with inter-regional disparities. The objectives were to describe PCa incidence and mortality in France and by region, using real life data from the National Health Data System and to identify the factors associated with all-cause or PCa-specific mortality. Men aged ≥ 18years hospitalized and/or on long-term care for PCa (ICD-10 code C61) in France between 2010 and 2021 were included. An incident case was defined by the absence of any cancer in the five years preceding the first coding. Incidence and mortality estimates were age-standardized: France 2018f standardized rates (FSR), all-cause mortality (SMR) and PCa-specific mortality (SMRspe). Factors associated with death were identified using cause-specific Cox models. The mean annual incidence was 47,081cases/year (FSR:179.6/100,000men), increasing over the period except 2020. All-cause mortality was 20,259 deaths/year (77.3/100,000men), and PCa-specific mortality was 7,265 deaths/year (27.7/100,000men). A PCa-specific mortality excess was found in Centre-Val-de-Loire (SMRspe = 1.21), Bretagne (1.18), Hauts-de-France (1.17) Normandie (1.15). After adjustment, significant PCa mortality excess was observed in Bretagne (HR = 1,29;95%IC[1.09-1.46]) and Hauts-de-France (HR = 1.19[1.03-1.34]). The other factors associated with death were an age ≥ 60years, an increasing comorbidity index, metastatic disease at onset (major weight in specific mortality with hazard ratio HR = 16.1[15.2-17.0]), precariousness, affiliation to the agricultural scheme, and the COVID period in all-cause mortality. This study updated incidence and mortality data in France. It showed differences in mortality between regions in France. The adjustment moderates regional findings based on raw mortality data.

The Role of Digital Rectal Examination for Early Detection of Significant Prostate Cancer in the Era of Magnetic Resonance Imaging

The role of digital rectal examination (DRE) in the early detection of significant prostate cancer (PCa) is being questioned in the era of magnetic resonance imaging (MRI). However, some men with suspected PCa may still be identified solely through DRE, even with low serum prostate-specific antigen (PSA) levels. Additionally, most predictive models designed to improve significant PCa diagnostic pathways incorporate DRE findings. We assessed the role of DRE among 5005 men with serum PSA levels > 3.0 ng/mL and/or suspicious DRE findings, who underwent pre-biopsy MRI and targeted and/or systematic biopsies, as part of the significant PCa opportunistic screening program in Catalonia (Spain) between 2016 and 2023. Significant PCa, defined as grade group > 2, was detected in 2097 men (41.9%). Suspicion of PCa was based solely on DRE in 206 cases (4.1%) with significant PCa detected in 50 of them (2.4%). Two pathways using the Barcelona predictive models, before and after MRI, with and without DRE findings showed specificities of 52.8 and 38.7%, respectively (p < 0.001), after fixing sensitivity at 90%. Prostate biopsy was avoided in 35.1 and 26.7%, respectively (p < 0.001), while its efficacy increased from 52.8 to 58%. We conclude that DRE improved the effectiveness of an opportunistic significant PCa-screening program.

A sustainable and expedited ‘One‐Stop’ prostate cancer diagnostic pathway to reduce environmental impact and enhance accessibility

AbstractObjectiveTo assess the carbon footprint, accessibility, and diagnostic performance of an expedited ‘One‐Stop’ prostate cancer (PCa) diagnostic pathway.Materials and methodsA total of 1083 consecutive patients undergoing magnetic resonance imaging (MRI) followed by transrectal ultrasound fusion‐guided prostate biopsy (PBx) were identified from a prospective database. The patients were divided according to the diagnostic pathway: One‐Stop, with MRI and same‐day PBx (3 hours apart), or Standard, with MRI followed by a second visit for PBx. Socioeconomic status was evaluated by the Distressed Communities Index (DCI) and the carbon footprint by the United States (U.S.) Environmental Protection Agency Greenhouse Gases Equivalencies Calculator.ResultsOverall, 260 patients underwent the One‐Stop and 823 the Standard pathway. The One‐Stop patients lived farther from the hospital (163 vs. 23 km; p < 0.001), had lower socioeconomic status with DCI scores of 49 versus 30 (p < 0.001), and were more likely to be Latinos (21% vs. 13%, p < 0.001) compared to the Standard patients, respectively. The One‐Stop saved 69 575 km in round trips, over 16 tons of travel‐related CO2 emissions, and $8214 U.S. dollars. For patients with Prostate Imaging Reporting & Data System (PIRADS) 3–5, the clinically significant PCa detection (53% vs. 50%, p = 0.55) was similar for the One‐Stop and Standard pathways, respectively.ConclusionsThe One‐Stop PCa diagnostic pathway reduces carbon footprint, distance travelled, and patient‐level cost while maintaining clinical outcomes comparable to the Standard pathway. It facilitates access to tertiary‐level care for minorities and underserved populations.

Prospective evaluation of PI-RADSv2.1 using multiparametric and biparametric MRI for detecting clinically significant prostate cancer based on MRI/US fusion-guided biopsy.

To evaluate the cancer detection rates for each category of Prostate Imaging-Reporting and Data System version 2.1 (PI-RADSv2.1) using multiparametric magnetic resonance imaging (mpMRI) and biparametric MRI (bpMRI) based on MRI/ultrasound (US)-fusion biopsy. This prospective study included participants who underwent mpMRI or bpMRI with a PI-RADSv2.1 interpretation and subsequently received MRI/US-fusion biopsy between August 2022 and December 2023. The lesion-based detection rates of clinically significant prostate cancer (csPCa) in each PI-RADSv2.1 category and the correlation between PI-RADSv2.1 categories and International Society of Urological Pathology (ISUP) grade groups were analyzed. The diagnostic performance of PI-RADSv2.1 in predicting csPCa was evaluated, and diagnostic performance of mpMRI and bpMRI was compared using cut-offs, with PI-RADSv2.1 categories ≥ 3 or ≥ 4 defined as positive. A total of 247 lesions from 216 participants were included in this study. A total of 157 patients underwent mpMRI and the remaining 59 underwent bpMRI. The csPCa detection rates for each PI-RADSv2.1 category of mpMRI and bpMRI were as follows: category 1, 0% (0/11); 2, 13% (3/23); 3, 16% (5/31); 4, 60% (43/72); 5, 65% (26/40), in mpMRI; category 1, 0% (0/4); 2, 33% (1/3); 3, 25% (3/12); 4, 61% (19/31); 5, 75% (15/20) in bpMRI. PI-RADSv2.1 categories were significantly positively associated with csPCa detection rates in both mpMRI and bpMRI (p < 0.0001 and p = 0.00048, respectively). PI-RADSv2.1 categories correlated with ISUP grade groups for mpMRI and bpMRI (p < 0.0001 for both). There were no significant differences in the detection rates between mpMRI and bpMRI for PI-RADS v2.1 positive and negative lesions. PI-RADSv2.1 using mpMRI and bpMRI could stratify the risk of csPCa, and the csPCa detection rate of bpMRI was compatible with that of mpMRI using cut-offs of PI-RADSv2.1 categories ≥ 3 or ≥ 4.

Investigation of association between clinically significant prostate cancer, obesity and platelet to-lymphocyte ratio and neutrophil -to-lymphocyte ratio

IntroductionSeveral blood markers of inflammation are elevated in prostate cancer (PCa) and have prognostic value. Little is known about the relationship between these markers, PCa, and other factors associated with chronic inflammation, such as smoking and obesity. We analyzed the interaction between neutrophil and platelet counts indexed to lymphocyte count (NLR and PLR, resp.) and clinically significant PCa (csPCa), accounting for the potential confounding factors of systemic inflammation.MethodsNLR and PLR were evaluated in a multicenter prospective study in 443 patients. CsPCa was defined as a Gleason ≥ 4 + 3. Differences between patients with csPCa and non-csPCA were evaluated using the chi-square test, analysis of variance or the Kruskal-Wallis test. Multivariable logistic regression analysis adjusted for smoking, hypertension, diabetes, and cardiovascular disease, and in separate models, either body mass index or waist-to-hip ratio was used to characterize the relationship between inflammation and csPCa.ResultsNone of the factors such as plateletcrit, NLR, and PLR were significantly different between patients with csPCa or non-significant PCa. After adjustment, there was no association between PLR, NLR, plateletcrit or platelet count and csPCa. In an exploratory analysis, there was no association between markers of inflammation and PSA levels > 10 ng/mL. When testing different NLR cutoffs to predict csPCa in ROC analysis, none reached a clinically meaningful value.ConclusionIn contrast to previous studies, we found no significant association between easily available blood markers of inflammation and indices of PCa aggressiveness. Further research is required to determine whether inflammation promotes PCa. (ClinicalTrials.gov: NCT03127631. Date of registration: April 25, 2017.

Prostate cancer screening: Is it time for a new approach? A review article.

Prostate cancer screening has presented a challenge to clinicians. Although the implementation of screening tests such as prostate-specific antigen (PSA) and digital rectal exam (DRE) has had a significant impact on prostate-cancer-specific mortality, these traditional screening tests have a relatively poor positive predictive value of clinically significant prostate cancer (CSPC), leading to unnecessary biopsies and treatment with a host of potential complications. Fortunately, much research has been done to optimize prostate cancer screening. This includes the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which underwent a secondary analysis to identify an association between PSA level and CSPC, and the IP1-PROSTAGRAM Tri.

Advanced Imaging for Localized Prostate Cancer

Background/Objectives: Prostate cancer is a prevalent malignancy often presenting without early symptoms. Advanced imaging technologies have revolutionized its diagnosis and management. This review discusses the principles, benefits, and clinical applications of multiparametric magnetic resonance imaging (mpMRI), micro-ultrasound (microUS), and prostate-specific membrane antigen positron emission tomography–computed tomography (PSMA PET/CT) in localized prostate cancer. Methods: We conducted a comprehensive literature review of recent studies and guidelines on mpMRI, microUS, and PSMA PET/CT in prostate cancer diagnosis, focusing on their applications in biopsy-naïve patients, those with previous negative biopsies, and patients under active surveillance. Results: MpMRI has demonstrated high sensitivity and negative predictive value in detecting clinically significant prostate cancer (csPCa). MicroUS, a newer technology, has shown promising results in early studies, with sensitivity and specificity comparable to mpMRI. PSMA PET/CT has emerged as a highly sensitive and specific imaging modality, particularly valuable for staging and detecting metastatic disease. All three technologies have been incorporated into urologic practice for prostate cancer diagnosis and management, with each offering unique advantages in different clinical scenarios. Conclusions: Advanced imaging techniques, including mpMRI, microUS, and PSMA PET/CT, have significantly improved the accuracy of prostate cancer diagnosis, staging, and management. These technologies enable more precise targeting of suspicious lesions during biopsy and therapy planning. However, further research, especially randomized controlled trials, is needed to fully establish the optimal use and inclusion of these imaging modalities in various stages of prostate cancer care.

Using a novel PSMA-PET and PSA-based model to enhance the diagnostic accuracy for clinically significant prostate cancer and avoid unnecessary biopsy in men with PI-RADS ≤ 3 MRI.

The diagnostic evaluation of men with suspected prostate cancer (PCa) yet inconclusive MRI (PI-RADS ≤ 3) presents a common clinical challenge. [68Ga]Ga-labelled prostate-specific membrane antigen ([68Ga]Ga-PSMA) positron emission tomography/computed tomography (PET/CT) has shown promise in identifying clinically significant PCa (csPCa). We aim to establish a diagnostic model incorporating PSMA-PET to enhance the diagnostic process of csPCa in PI-RADS ≤ 3 men. This study retrospective included 151 men with clinical suspicion of PCa and PI-RADS ≤ 3 MRI. All men underwent [68Ga]Ga-PSMA PET/CT scans and ultrasound/MRI/PET fusion-guided biopsies. csPCa was defined as Grade Group ≥ 2. PRIMARY-scores from PSMA-PET scans were evaluated. A diagnostic model incorporating PSMA-PET and prostate-specific antigen (PSA)-derived parameters was developed. The discriminative performance and clinical utility were compared with conventional methods. Internal validation was conducted using a fivefold cross-validation with 1000 iterations. In this PI-RADS ≤ 3 cohort, areas-under-the-curve (AUCs) for detecting csPCa were 0.796 (95%CI, 0.738-0.853), 0.851 (95%CI, 0.783-0.918) and 0.806 (95%CI, 0.742-0.870) for PRIMARY-score, SUVmax and routine clinical PSMA-PET assessment, respectively. The diagnostic model comprising PRIMARY-score, SUVmax and serum free PSA/total PSA (fPSA/tPSA) achieved a significantly higher AUC of 0.906 (95%CI, 0.851-0.961) compared to strategies based on PRIMARY-score or SUVmax (P < 0.05) and markedly superior to conventional strategies typically based on PSA density (P < 0.001). The average fivefold cross-validated AUC with 1000 iterations was 0.878 (95%CI, 0.820-0.954). Theoretically, using a threshold of 21.6%, the model could have prevented 78% of unnecessary biopsies while missing only 7.8% of csPCa cases in this cohort. A novel diagnostic model incorporating PSMA-PET derived metrics-PRIMARY-score and SUVmax-along with serum fPSA/tPSA, has been developed and validated. The integrated model may assist clinical decision-making with enhanced diagnostic accuracy over the individual conventional metrics. It has great potential to reduce unnecessary biopsies for men with PI-RADS ≤ 3 MRI results and warrants further prospective and external evaluations.

An NMR-based metabolic signature to identify clinically significant prostate cancer in patients undergoing biopsy.

Despite clinical suspicion of prostate cancer (PCa), 20-25% of patients exhibit a tumor-negative biopsy result. To assess the serum metabolic profile of clinically significant (cs) compared to clinically insignificant (ci) PCa or benign (Be) patients. 1078 serum samples were analyzed. Nuclear magnetic resonance (NMR) spectroscopy was used to quantify 73 metabolites, Random Forest for model algorithm. We identified a 22-metabolite panel, which discriminated csPCa (ISUP 2-5, n=328) from ciPCa (ISUP 1, n=101) and benign patients (negative biopsy, n=649) with a higher performance when combined with the standard clinical parameters age, prostate specific antigen (PSA), and percentage free PSA (%fPSA) (AUC 0.84) than the clinical parameters alone (AUC 0.73). Our study further revealed significant dysregulations of the urea cycle and the choline pathway along with changes in tricarboxylic acid (TCA) cycle, cholesterol metabolism, and a significant increase of the inflammation marker GlycB in csPCa patients. In particular, ornithine and dimethylglycine were the 2 most important features to discriminate csPCa from Be+ciPCa with significantly higher ornithine and lower dimethylglycine levels in patients with csPCa (ornithine: 63.7 ± 26.5 µmol/l, dimethylglycine: 12.6 ± 6.3 µmol/l, p<0.001) compared to Be+ciPCa patients (ornithine: 50.3 ± 31.6 µmol/l, dimethylglycine: 14.9 ± 7.7 µmol/l). This study discovered a 22-metabolite panel to discriminate patients with csPCa from Be+ciPCa patients when combined with age, PSA, and %fPSA. It may therefore be used as supportive biomarker to reduce the number of unnecessary biopsies and also to identify novel therapeutic targets in the future.

Quantitative MRI biomarker for classification of clinically significant prostate cancer: Calibration for reproducibility across echo times.

The purpose of the present study is to develop a calibration method to account for differences in echo times (TE) and facilitate the use of restriction spectrum imaging restriction score (RSIrs) as a quantitative biomarker for the detection of clinically significant prostate cancer (csPCa). This study included 197 consecutive patients who underwent MRI and biopsy examination; 97 were diagnosed with csPCa (grade group ≥ 2). RSI data were acquired three times during the same session: twice at minimum TE ~75ms and once at TE=90ms (TEmin1, TEmin2, and TE90, respectively). A linear regression model was determined to match the C-maps of TE90 to the reference C-maps of TEmin1 within the interval ranging from 95th to 99th percentile of signal intensity within the prostate. RSIrs comparisons were made at the 98th percentile within each patient's prostate. We compared RSIrs from calibrated TE90 (RSIrsTE90corr) and uncorrected TE90 (RSIrsTE90) to RSIrs from reference TEmin1 (RSIrsTEmin1) and repeated TEmin2 (RSIrsTEmin2). Calibration performance was evaluated with sensitivity, specificity and area under the ROC curve (AUC). Scaling factors for C1, C2, C3, and C4 were estimated as 1.68, 1.33, 1.02, and 1.13, respectively. In non-csPCa cases, the 98th percentile of RSIrsTEmin2 and RSIrsTEmin1 differed by 0.27±0.86SI (mean±standard deviation), whereas RSIrsTE90 differed from RSIrsTEmin1 by 1.82±1.20SI. After calibration, this bias was reduced to -0.51±1.21SI, representing a 72% reduction in absolute error. For patients with csPCa, the difference was 0.54±1.98SI between RSIrsTEmin2 and RSIrsTEmin1 and 2.28±2.06SI between RSIrsTE90 and RSIrsTEmin1. After calibration, the mean difference decreased to -1.03SI, a 55% reduction in absolute error. At the Youden index for patient-level classification of csPCa (8.94SI), RSIrsTEmin1 has a sensitivity of 66% and a specificity of 72%. The proposed linear calibration method produces similar quantitative biomarker values for acquisitions with different TE, reducing TE-induced error by 72% and 55% for non-csPCa and csPCa, respectively.

Surveillance after Focal Therapy - a Comprehensive Review.

to date, no standardized, evidence-based follow-up schemes exist for the monitoring of patients who underwent focal therapy (FT) and expert centers rely mainly on their own experience and/or institutional protocols. We aimed to perform a comprehensive review of the most advantageous follow-up strategies and their rationale after FT for prostate cancer (PCa). a narrative review of the literature was conducted to investigate different follow-up protocols of FT for PCa. Outcomes of interest were post-ablation oncological and functional outcomes and complications. Oncological success after FT was generally defined as the biopsy-confirmed absence of clinically significant PCa in the treated zone. De novo PCa in the untreated area usually reflects an inaccurate patient selection and should be treated as primary PCa. During follow-up, oncological outcomes should be evaluated with periodic PSA, multiparametric MRI and prostate biopsy. The use of PSA derivatives and new biomarkers is still controversial and therefore not recommended. The first MRI after FT should be performed between 6-12 months to avoid ablation-related artifacts and diagnostic delay in case of FT failure. Other imaging modalities, such as PSMA PET/CT scan, are promising but still need to be validated in the post-FT setting. A 12-month "for-protocol" prostate biopsy, including targeted and systematic biopsy, was generally considered the preferred biopsy method to rule out tumor persistence/recurrence. Subsequent mpMRIs and biopsies should follow a risk-adapted approach depending on the clinical scenario. Functional outcomes should be periodically assessed using validated questionnaires within the first year, when typically recover to a new baseline. Complications, despite uncommon, should be strictly monitored mainly in the first month. FT follow-up is a multifaceted process involving clinical, radiological, and histological assessment. Studies evaluating the impact of different follow-up strategies and ideal timings are needed to produce standardized protocols following FT.

Quantitative Prostate MRI, From the AJR Special Series on Quantitative Imaging.

Prostate MRI has traditionally relied on qualitative interpretation. However, quantitative components hold the potential to markedly improve performance. The ADC from DWI is probably the most widely recognized quantitative MRI biomarker and has shown strong discriminatory value for clinically significant prostate cancer (csPCa) as well as for recurrent cancer after treatment. Advanced diffusion techniques, including intravoxel incoherent motion, diffusion kurtosis, diffusion tensor imaging, and specific implementations such as restriction spectrum imaging, purport even better discrimination, but are more technically challenging. The inherent T1 and T2 of tissue also provide diagnostic value, with more advanced techniques deriving luminal water imaging and hybrid-multidimensional MRI. Dynamic contrast-enhanced imaging, primarily using a modified Tofts model, also shows independent discriminatory value. Finally, quantitative size and shape features can be combined with the aforementioned techniques and be further refined using radiomics, texture analysis, and artificial intelligence. Which technique will ultimately find widespread clinical use will depend on validation across a myriad of platforms use-cases.

Predictive ability of MRI for detecting prostate cancer and its clinical significance in MRI-targeted biopsy for PI-RADS ≥3 lesions

BackgroundIdentifying the index lesion in prostate cancer (PCa) is vital for its treatment. Therefore, various coefficients and parameters are employed to improve the diagnostic accuracy of magnetic resonance imaging (MRI). PurposeThis study aimed to analyze MRI data, utilized as a triage test before prostate biopsy, to identify independent risk factors affecting negative biopsy results in PCa and investigate the ability of these factors to predict clinically significant and insignificant PCa (csPCa and ciPCa, respectively). MethodsA retrospective analysis was conducted on data from 364 patients with a prostate imaging reporting and data system (PI-RADS) v2.1 score of 3 or higher, who underwent cognitive MRI-targeted biopsy (MRI-TB). Of the patients, 226 (62.1%) had benign lesions, 75 (20.6%) were diagnosed with ciPCa, and 63 (17.3%) with csPCa. The study assessed patients’ demographic, biochemical, and radiologic characteristics, including apparent diffusion coefficient (ADC) and ADC coefficient of variation (ADCCoV) values. ResultsThe multivariate analysis performed to differentiate PCa from benign pathologies revealed that only MRI parameters, specifically the presence of PI-RADS 4 and 5 lesions (odds ratio [OR]: 12, p<0.001 and OR: 73, p=0.008, respectively), a lower ADC value (OR: 0.996, p=0.041) and a higher ADCCoV value (OR: 1.07, p=0.003), were independent risk factors. No MRI findings had significant predictive power for csPCa, with total PSA (OR: 1.17, p=0.019) found to be the only independent risk factor. ConclusionThe results of this study suggest that data obtained from MRI can predict PCa but not csPCa.

Comparison between 18F-DCFPyL PET/MRI-guided ultrasound fusion targeted biopsy and systematic biopsy for tumor detection and grading in selected patients: A prospective randomized controlled trial

ObjectiveTo compare the upgrade rate and cancer detection rate between 18F-DCFPyL PET/MRI-guided ultrasound fusion targeted biopsy and systematic biopsy in selected patients with suspected prostate cancer (the multiparametric MRI prostate imaging reporting and data system score ≥4 and molecular imaging prostate-specific membrane antigen score of prostate-specific membrane antigen PET image ≥2). MethodsEighty-seven selected biopsy-naive patients were randomized into two groups: targeted biopsy (n=41) and systematic biopsy (control; n=46). Those with negative initial results underwent a repeat biopsy using the alternative method. Patients diagnosed with clinically significant prostate cancer proceed to radical prostatectomy. The primary outcome was the upgrade rate. Additional outcomes, including the cancer detection rate, incidence of repeat biopsy, positive surgical margin, complications, and prostate-specific antigen level at 6 weeks postoperatively, were compared between the groups using Pearson or Fisher's exact tests, as appropriate. ResultsIn the study, prostate cancer was ultimately detected in all patients. The targeted biopsy group successfully identified all tumors, whereas five patients in the control group initially missed their tumors. The pathological upgrade rates for the targeted biopsy and control groups were 31.7 % and 56.5 %, respectively. Overall, the detection rate for clinically significant prostate cancer (the International Society of Urological Pathology grade ≥2) was significantly higher in the targeted biopsy group (92.7 %) compared with the control group (76.1 %, p=0.035). However, no significant difference was found in the detection rate of all prostate cancer. Complications (Clavien–Dindo grade ≤2) occurred in both the targeted biopsy group (n=11) and the control group (n=13). No statistically significant difference was observed between the groups in terms of positive surgical margin, complications, and 6-week postoperative prostate-specific antigen level. The main limitation is the small population. Conclusion18F-DCFPyL PET/MRI-guided ultrasound fusion targeted biopsy alone was an efficient modality in diagnosing selected patients with prostate cancer.

Evaluating Biparametric Versus Multiparametric Magnetic Resonance Imaging for Diagnosing Clinically Significant Prostate Cancer: An International, Paired, Noninferiority, Confirmatory Observer Study

Background and objectiveBiparametric magnetic resonance imaging (bpMRI), excluding dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), is a potential replacement for multiparametric MRI (mpMRI) in diagnosing clinically significant prostate cancer (csPCa). An extensive international multireader multicase observer study was conducted to assess the noninferiority of bpMRI to mpMRI in csPCa diagnosis. MethodsAn observer study was conducted with 400 mpMRI examinations from four European centers, excluding examinations with prior prostate treatment or csPCa (Gleason grade [GG] ≥2) findings. Readers assessed bpMRI and mpMRI sequentially, assigning lesion-specific Prostate Imaging Reporting and Data System (PI-RADS) scores (3–5) and a patient-level suspicion score (0–100). The noninferiority of patient-level bpMRI versus mpMRI csPCa diagnosis was evaluated using the area under the receiver operating curve (AUROC) alongside the sensitivity and specificity at PI-RADS ≥3 with a 5% margin. The secondary outcomes included insignificant prostate cancer (GG1) diagnosis, diagnostic evaluations at alternative risk thresholds, decision curve analyses (DCAs), and subgroup analyses considering reader expertise. Histopathology and ≥3 yr of follow-up were used for the reference standard. Key findings and limitationsSixty-two readers (45 centers and 20 countries) participated. The prevalence of csPCa was 33% (133/400); bpMRI and mpMRI showed similar AUROC values of 0.853 (95% confidence interval [CI], 0.819–0.887) and 0.859 (95% CI, 0.826–0.893), respectively, with a noninferior difference of –0.6% (95% CI, –1.2% to 0.1%, p < 0.001). At PI-RADS ≥3, bpMRI and mpMRI had sensitivities of 88.6% (95% CI, 84.8–92.3%) and 89.4% (95% CI, 85.8–93.1%), respectively, with a noninferior difference of –0.9% (95% CI, –1.7% to 0.0%, p < 0.001), and specificities of 58.6% (95% CI, 52.3–63.1%) and 57.7% (95% CI, 52.3–63.1%), respectively, with a noninferior difference of 0.9% (95% CI, 0.0–1.8%, p < 0.001). At alternative risk thresholds, mpMRI increased sensitivity at the expense of reduced specificity. DCA demonstrated the highest net benefit for an mpMRI pathway in cancer-averse scenarios, whereas a bpMRI pathway showed greater benefit for biopsy-averse scenarios. A subgroup analysis indicated limited additional benefit of DCE MRI for nonexperts. Limitations included that biopsies were conducted based on mpMRI imaging, and reading was performed in a sequential order. Conclusions and clinical implicationsIt has been found that bpMRI is noninferior to mpMRI in csPCa diagnosis at AUROC, along with the sensitivity and specificity at PI-RADS ≥3, showing its value in individuals without prior csPCa findings and prostate treatment. Additional randomized prospective studies are required to investigate the generalizability of outcomes.

Clinical value of a radiomics model based on machine learning for the prediction of prostate cancer.

Radiomics models have demonstrated good performance for the diagnosis and evaluation of prostate cancer (PCa). However, there are currently no validated imaging models that can predict PCa or clinically significant prostate cancer (csPCa). Therefore, we aimed to identify the best such models for the prediction of PCa and csPCa. We performed a retrospective study of 942 patients with suspected PCa before they underwent prostate biopsy. MRI data were collected to manually segment suspicious regions of the tumor layer-by-layer. We then constructed models using the extracted imaging features. Finally, the clinical value of the models was evaluated. A diffusion-weighted imaging (DWI) plus apparent diffusion coefficient (ADC) random-forest model and a T2-weighted imaging plus ADC and DWI multilayer perceptron model were the best models for the prediction of PCa and csPCa, respectively. Areas under the curve (AUCs) of 0.942 and 0.999, respectively, were obtained for a training set. Internal validation yielded AUCs of 0.894 and 0.605, and external validation yielded AUCs of 0.732 and 0.623. Models based on machine learning comprising radiomic features and clinical indicators showed good predictive efficiency for PCa and csPCa. These findings demonstrate the utility of radiomic models for clinical decision-making.

Unlocking Precision Enhancing Prostate Cancer Detection and Reducing Unnecessary Biopsies with Combined Prostate-Specific Antigen Density and PI-RADS Score.

To determine clinically significant prostate cancer (csPCa) detection rate by combining the prostate-specific antigen density (PSAD) and prostate imaging-reporting and data system (PI-RADS) scores. Descriptive study. Place and Duration of the Study: Department of Urology, University of Health Sciences, Ankara Oncology Training and Research Hospital, from January 2018 to April 2023. Patients who underwent prostate biopsies after multiparametric magnetic resonance imaging (mpMRI) were included in the study. PI-RADS 4 and 5 lesions were considered as MR positive. The cut-off values for PSAD were also determined to evaluate csPCa. csPCa detection rates were evaluated by grouping the patients based on the PSAD and mpMRI findings. PSAD cut-off value of 0.165 ng/mL/mL (sensitivity 80%, specificity 72%) was detected to predict csPCa (AUC = 0.81, 95% CI:0.756-0.866, p<0.001). csPCa detection rate was low (3%) in patients who have low PI-RADS scores (1-3) and a PSAD <0.165 ng/mL/mL. On the other hand, csPCa detection rate was high (50.5%) in patients who have a high PI-RADS score (4-5 lesions) and with a PSAD ≥0.165 ng/mL/mL. csPCa detection rates are low in patients with PI-RADS 1-3 lesions and low PSAD values. Unnecessary biopsy may be avoided in these patients. Gleason score, PI-RADS, Prostate cancer, Prostate-specific antigen, Prostate-specific antigen density.

Concordance Between the Expert Reading of Biparametric-MRI and the Nonexpert Multiparametric-MRI for the Detection of Clinically Significant Prostate Cancer: Clinical Implications

PurposeProstate-magnetic resonance imaging (MRI) interpretation is challenging, with expertise playing a crucial role. Biparametric MRI (bpMRI) is gaining popularity in experienced centers due to its time and cost advantages over multiparametric MRI (mpMRI). We aim to analyze concordance between nonexpert radiologist PI-RADS from mpMRI and expert radiologist PI-RADS from bpMRI, and its clinical implications. Material and Methods222 men suspected of having prostate cancer (PCa) and mpMRI reported by nonexpert radiologists were referred to a reference center for transperineal MRI-TRUS fusion biopsy where an expert radiologist reported bpMRI PI-RADS 2.1 and segmentation, blinded to external mpMRI. Mapping targeted suspected lesions and 12-core systematic biopsies were performed. Clinically significant PCa (csPCa) was diagnosed when ISUP-grade group was ≥2. ResultsConcordance between both PI-RADS existed in 49.1% of cases (Kappa index 0.288). In 102 cases (45.9%), expert reclassification to lower PI-RADS existed, while an increase existed in 11 cases (5.0%), P < .001. Agreement existed in 30.8% of nonexpert PI-RADS 3, 43.6% of PI-RADS 4, and 83.7% of PI-RADS 5, P < .001. Potential clinical implications included 27% reduction in prostate biopsies when using expert bpMRI readings compared to nonexpert mpMRI readings (P < 0.001), while undetected csPCa were 4.2% and 3.4%, respectively, P = .669. Over-detection reduction of insignificant PCa was 29.4% and 0%, respectively, P = .034. ConclusionsConcordance between nonexpert PI-RADS mpMRI and expert PI-RADS bpMRI was low, increasing with nonexpert PI-RADS. Expert reclassification would reduce prostate biopsies by more than one quarter and over-detection of iPCa, while csPCa detection remained similar.

Inter-reader reliability and diagnostic accuracy of PI-RADS scoring between academic and community care networks: How wide is the gap?

ImportanceThe Prostate Imaging Reporting & Data System (PI-RADS) scoring guidelines were developed to address the substantial variation in interpretation and reporting of prostate cancer (PCa) multiparametric MRI (mpMRI) results, and subsequent updates have sought to further improve inter-reader reliability. Nonetheless, the variability of PI-RADS scoring in real-world settings may represent a continuing challenge to the widespread standardization of prostate mpMRI and limit its overall clinical benefit. ObjectiveTo assess variability in mpMRI interpretation and reporting of PCa, we evaluated the discrepancies in PI-RADS scoring between community practices and a tertiary academic care center. Design, setting, and participantsWe identified 262 mpMRI studies from nonacademic facilities, reinterpreted by radiologists at our institution between January 2016 and July 2022. Results of targeted MRI fusion biopsy were identified for 193 of these patients, totaling 302 lesions. PI-RADS scoring from both community and academic interpreters were recorded in addition to presence of clinically significant PCa (csPCa) on pathological analysis of targeted cores. Main Outcome and measuresThe primary outcome was inter-reader reliability via intraclass correlation (ICC) and the kappa statistic. We also assessed the diagnostic accuracy of PI-RADS scoring for detecting csPCa for both cohorts via receiver operator characteristics (ROC) analysis and compared these findings using paired-sample area difference under curve analysis. ResultsInter-reader agreement and reliability of PI-RADS scoring per lesion was generally poor (absolute agreement ICC = 0.393, 95% CI: 0.288–0.488; consistency ICC = 0.407, 95% CI: 0.308–0.497; kappa = 0.336, 95% CI: 0.267–0.406). Reliability results from studies obtained after the publication of PI-RADSv2.1 were similar to those of the overall analysis. No agreement was observed in the subgroup of lesions scored as PIRADS 3 by community interpreters. No statistically significant difference in diagnostic accuracy was observed between cohorts (ROC area under curve [AUC]: 0.759 vs. 0.785, respectively; P = 0.337). PI-RADS 3 was determined to be the optimal cutoff for detecting clinically significant disease in both cohorts. Conclusions and relevanceOur results suggest that mpMRI diagnostic accuracy for detecting csPCa is not significantly different between academic and community practices. However, significantly poor reliability of mpMRI was observed between cohorts, suggesting the risk of introducing practice variation for community prostate cancer management. Variability, particularly for PI-RADS 3 lesions, can lead to inconsistent biopsy recommendations, which may result in missed csPCa or unnecessary biopsies.

A Targeted Methylation-Based Multicancer Early Detection Blood Test Preferentially Detects High-Grade Prostate Cancer While Minimizing Overdiagnosis of Indolent Disease.

Indolent prostate cancer (PCa) is prevalent in the intended use population (adults age 50-79 years) for blood-based multicancer early detection (MCED) tests. We examined the detectability of PCa by a clinically validated, targeted methylation-based MCED test. Detectability by Gleason grade group (GG), clinical stage, association of detection status with tumor methylated fraction (TMeF), and overall survival (OS) were assessed in substudy 3 of Circulating Cell-Free Genome Atlas (CCGA; ClinicalTrials.gov identifier: NCT02889978) and PATHFINDER (ClinicalTrials.gov identifier: NCT04241796) studies. Test sensitivity for PCa in substudy 3 of CCGA was 11.2% (47/420). The test detected 0 (0%) of 58 low-grade (GG1), 3 (1.9%) of 157 favorable intermediate-grade (GG2), 4 (5.1%) of 78 unfavorable intermediate-grade (GG3), and 36 (31.9%) of 113 high-grade (GG4 and 5) cancers and 3 (3.2%) of 95 stage I, 11 (4.7%) of 235 stage II, 7 (14.9%) of 47 stage III, and 22 (81.5%) of 27 stage IV cases. The median TMeF was higher for detected than nondetected cases (2,106.0 parts per million [PPM]; IQR, 349.8-24,376.3 v 24.4 PPM; IQR, 17.8-38.5; P < .05). Nondetected cases had better OS (P < .05; hazard ratio [HR], 0.263 [95% CI, 0.104 to 0.533]) and detected cases had similar survival (P = .2; HR, 0.672 [95% CI, 0.323 to 1.21]) compared with SEER adjusted for age, GG, and stage. Performance was similar in PATHFINDER, with no detected GG1/2 (0/13) or stage I/II (0/16) cases. This MCED test preferentially detects high-grade, clinically significant PCa. Use in population-based screening programs in addition to standard-of-care screening is unlikely to exacerbate overdiagnosis of indolent PCa.