Suspicion Of Prostate Cancer Research Articles

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.

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.

Development of prediction models based on risk scores for clinically significant prostate cancer on MRI/TRUS fusion biopsy

BackgroundThe implementation of population screening for prostate cancer has increased the number of patients with biochemical suspicion. Prediction models may reduce the number of unnecessary biopsies by identifying patients who benefit the most from them. Our aim is to develop a prediction model that is easily applicable in patients with suspicion of prostate cancer in the urology clinic setting to avoid unnecessary biopsies. MethodsWe developed prediction models based on risk scores for the detection of prostate cancer and clinically significant prostate cancer using the TRIPOD guidelines. For this, we conducted an observational and retrospective review of computerised medical records of 204 patients undergoing prostate fusion biopsy between 2018 and 2021. We also reviewed other prediction models for prostate cancer including radiological parameters and targeted sampling of suspicious lesions. ResultsA total of 204 patients underwent a biopsy, 138 were diagnosed of prostate cancer, and from them, 60 of clinically significant prostate cancer. Multivariate regression and random forest analysis were performed. Age, PSA density, diameter of the index lesions and PIRADS score on MRI were identified as predictors with an Area Under the Curve ranging between 0.71 and 0.80 and acceptable calibration results. Risk scores may avoid between 21.7% and 48.1% of biopsies. ConclusionOur prediction models are characterised by ease of use and may reduce unnecessary biopsies with satisfactory discrimination and calibration results while bringing benefits to the healthcare system and patients.

Incorporation of mpMRI before prostate biopsy shall be universal or selective: A prospective observational study

Purpose: The aim of this study is to evaluate the role of multiparametric magnetic resonance imaging (mpMRI) as a triage workup in the diagnostic pathway of suspected prostate cancer (PCa) in our population. Material and methods: This prospective observational study was conducted at lesser than details of site are removed for blinded peer review &gt; on biopsy-naive patients from May 2021 to December 2022. We included patients aged 40 to 80 years with clinical suspicion of PCa, prostate-specific antigen (PSA) level &gt;4 ng/mL, abnormal digital rectal examination (DRE), or all the above. All patients first underwent 1.5-T mpMRI and transrectal ultrasound-guided biopsy using the cognitive biopsy technique. Results: A total of 95 patients were included, with the majority of them (64.21%) being ≥66 years old. Of these, 69 patients had abnormal DRE findings, 89 had PSA ≥4 ng/mL, and 64 had both elevated PSA and abnormal DRE findings. PCa was detected in 6.25%, 54.84%, 71.43%, and 96.43% of patients with lesions of Prostate Image Reporting and Data System scores of 2, 3, 4, and 5, respectively. Using Prostate Image Reporting and Data System score of 3 as a biopsy threshold resulted in high sensitivity (98.31%) and low specificity (41.67%) for PCa detection. The proportion of Gleason score of ≥7 cancer-detected cores in the magnetic resonance imaging-guided cognitive biopsy was significantly higher than that in the standard 12-core biopsy (86.54% versus 61.45%; P &lt; 0.001). Conclusion: The incorporation of prebiopsy mpMRI could be used as a diagnostic pathway for suspected PCa before transrectal ultrasound-guided biopsy.

Methylated DNA Markers in Voided Urine for the Identification of Clinically Significant Prostate Cancer.

Non-invasive assays are needed to better discriminate patients with prostate cancer (PCa) to avoid over-treatment of indolent disease. We analyzed 14 methylated DNA markers (MDMs) from urine samples of patients with biopsy-proven PCa relative to healthy controls and further studied discrimination of clinically significant PCa (csPCa) from healthy controls and Gleason 6 cancers. To evaluate the panel, urine from 24 healthy male volunteers with no clinical suspicion for PCa and 24 men with biopsy-confirmed disease across all Gleason scores was collected. Blinded to clinical status, DNA from the supernatant was analyzed for methylation signal within specific DNA sequences across 14 genes (HES5, ZNF655, ITPRIPL1, MAX.chr3.6187, SLCO3A1, CHST11, SERPINB9, WNT3A, KCNB2, GAS6, AKR1B1, MAX.chr3.8028, GRASP, ST6GALNAC2) by target enrichment long-probe quantitative-amplified signal assays. Utilizing an overall specificity cut-off of 100% for discriminating normal controls from PCa cases across the MDM panel resulted in 71% sensitivity (95% CI: 49-87%) for PCa detection (4/7 Gleason 6, 8/12 Gleason 7, 5/5 Gleason 8+) and 76% (50-92%) for csPCa (Gleason ≥ 7). At 100% specificity for controls and Gleason 6 patients combined, MDM panel sensitivity was 59% (33-81%) for csPCa (5/12 Gleason 7, 5/5 Gleason 8+). MDMs assayed in urine offer high sensitivity and specificity for detection of clinically significant prostate cancer. Prospective evaluation is necessary to estimate discrimination of patients as first-line screening and as an adjunct to prostate-specific antigen (PSA) testing.

Stockholm3 in a Multiethnic Cohort for Prostate Cancer Detection (SEPTA): A Prospective Multicentered Trial.

Asian, Black, and Hispanic men are underrepresented in prostate cancer (PCa) clinical trials. Few novel prostate cancer biomarkers have been validated in diverse cohorts. We aimed to determine if Stockholm3 can improve prostate cancer detection in a diverse cohort. An observational prospective multicentered (17 sites) clinical trial (2019-2023), supplemented by prospectively recruited participants (2008-2020) in a urology clinic setting included men with suspicion of PCa and underwent prostate biopsy. Before biopsy, sample was collected for measurement of the Stockholm3 risk score. Parameters include prostate-specific antigen (PSA), free PSA, KLK2, GDF15, PSP94, germline risk (single-nucleotide polymorphisms), age, family history, and previous negative biopsy. The primary endpoint was detection of International Society of Urological Pathology (ISUP) Grade ≥2 cancer (clinically significant PCa, csPC). The two primary aims were to (1) demonstrate noninferior sensitivity (0.8 lower bound 95% CI noninferiority margin) in detecting csPC using Stockholm3 compared with PSA (relative sensitivity) and (2) demonstrate superior specificity by reducing biopsies with benign results or low-grade cancers (relative specificity). A total of 2,129 biopsied participants were included: Asian (16%, 350), Black or African American (Black; 24%, 505), Hispanic or Latino and White (Hispanic; 14%, 305), and non-Hispanic or non-Latino and White (White; 46%, 969). Overall, Stockholm3 showed noninferior sensitivity compared with PSA ≥4 ng/mL (relative sensitivity: 0.95 [95% CI, 0.92 to 0.99]) and nearly three times higher specificity (relative specificity: 2.91 [95% CI, 2.63 to 3.22]). Results were consistent across racial and ethnic subgroups: noninferior sensitivity (0.91-0.98) and superior specificity (2.51-4.70). Compared with PSA, Stockholm3 could reduce benign and ISUP 1 biopsies by 45% overall and between 42% and 52% across racial and ethnic subgroups. In a substantially diverse population, Stockholm3 significantly reduces unnecessary prostate biopsies while maintaining a similar sensitivity to PSA in detecting csPC.

Does the type of the previous biopsy affect the fusion prostate biopsy results?

BackgroundIt has been more than a decade since fusion prostate biopsy (FPB) has been used in the diagnosis of prostate cancer (PCa). Therefore, patients with a previous history of negative FPB and ongoing suspicion of PCa are beginning to emerge. This study investigated whether the first biopsy type (standard or fusion) should be effective in deciding on a second biopsy. MethodsMale patients aged 40–75, with a serum prostate-specific antigen (PSA) value of less than 10 ng/mL and a negative biopsy history within the last 24 months, who underwent FPB in our clinic due to persistent PSA elevation and/or suspicious multiparametric prostate magnetic resonance imaging (MpMRI) findings were included to the study. Patients were divided into groups according to the type of first biopsy (Group 1; those whose first biopsy was FPB, Group 2; those whose first biopsy was standard prostate biopsy). Some demographic and clinical data of the groups, as well as PCa detection rates, were compared. A p value of less than 0.05 was considered statistically significant. ResultsA total of 275 patients (Group 1: 84, Group 2: 191) were included in this study. The groups were similar in terms of age, PSA values before the first biopsy, PSA values before the second biopsy, family history of PCa, and prostate volume. PCa was detected at a higher rate in Group 2 than Group 1 (23% vs 15.5%, p = 0.044). ConcluisonThe data obtained from this study indicate that the type of initial biopsy should be taken into account when deciding on FPB in secondary patients with a previous negative biopsy history.

Comparison of Multiparametric MRI-targeted and Systematic Biopsies for Detection of Cribriform and Intraductal Carcinoma Prostate Cancer.

Background Intraductal carcinoma (IDC) and invasive cribriform (Cr) subtypes of prostate cancer (PCa) are an indication of aggressiveness, but the evidence regarding whether MRI can be used to detect Cr/IDC-pattern PCa is contradictory. Purpose To compare the detection of Cr/IDC-pattern PCa at multiparametric MRI (mpMRI)-targeted biopsy versus systematic biopsy in biopsy-naive men at risk for PCa. Materials and Methods This study was a secondary analysis of a prospective randomized controlled trial that recruited participants with a clinical suspicion of PCa between April 2017 and November 2019 at five centers. Participants were randomized 1:1 to either the MRI arm or the systematic biopsy arm. Targeted biopsy was performed in participants with a Prostate Imaging Reporting and Data System score of at least 3. MRI features were recorded, and biopsy slides and prostatectomy specimens were reviewed for the presence or absence of Cr/IDC histologic patterns. Comparison of Cr/IDC patterns was performed using generalized linear mixed modeling. Results A total of 453 participants were enrolled, with 226 in the systematic biopsy arm (median age, 65 years [IQR, 59-70 years]; 196 biopsies available for assessment) and 227 in the mpMRI-targeted biopsy arm (median age, 67 years [IQR, 60-72 years]; 132 biopsies available for assessment). Identification of Cr/IDC PCa was lower in the systematic biopsy arm compared with the mpMRI arm (31 of 196 biopsies [16%] vs 33 of 132 biopsies [25%]; P = .01). No evidence of a difference in mean cancer core length (CCL) (11.3 mm ± 4.4 vs 9.7 mm ± 4.5; P = .09), apparent diffusion coefficient (685 µm2/sec ± 178 vs 746 µm2/sec ± 245; P = .52), or dynamic contrast-enhanced positivity (27 [82%] vs 37 [90%]; P = .33) for clinically significant PCa (csPCa) was observed between participants with or without Cr/IDC disease in the MRI arm. Cr/IDC-positive histologic patterns overall had a higher mean CCL compared with Cr/IDC-negative csPCa (11.1 mm ± 4.4 vs 9.2 mm ± 4.1; P = .009). Conclusion MRI-targeted biopsy showed increased detection of Cr/IDC histologic patterns compared with systematic biopsy. Clinical trial registration no. NCT02936258 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Scialpi and Martorana in this issue.

A prospective evaluation of the prostate microbiome in malignant and benign tissue using transperineal biopsy.

The link between the prostate microbiome and prostate cancer remains unclear. Few studies have analyzed the microbiota of prostate tissue, and these have been limited by potential contamination by transrectal biopsy. Transperineal prostate biopsy offers an alternative and avoids fecal cross-contamination. We aim to characterize the prostate microbiome using transperineal biopsy. Patients with clinical suspicion for prostate cancer who were to undergo transperineal prostate biopsy with magnetic resonance imaging(MRI) fusion guidance were prospectively enrolled from 2022 to 2023. Patients were excluded if they had Prostate Imaging Reporting and Data System lesions with scores ≤ 3, a history of prostate biopsy within 1 year, a history of prostate cancer, or antibiotic use within 30 days of biopsy. Tissue was collected from the MRI target lesions and nonneoplastic transitional zone. Bacteria were identified using 16S ribosomal RNA gene sequencing. Across the 42 patients, 76% were found to have prostate cancer. Beta diversity indices differed significantly between the perineum, voided urine, and prostate tissue. There were no beta diversity differences between cancerous or benign tissue, or between pre- and postbiopsy urines. There appear to be unique genera more abundant in cancerous versus benign tissue. There were no differences in alpha diversity indices relative to clinical findings including cancer status, grade, and risk group. We demonstrate a rigorous method to better characterize the prostate microbiome using transperineal biopsy and to limit contamination. These findings provide a framework for future large-scale studies of the microbiome of prostate cancer.

LGALS3 cfDNA methylation in seminal fluid as a novel prostate cancer biomarker outperforming PSA.

The unmet challenge in prostate cancer (PCa) management is to discriminate it from benign prostate hyperplasia (BPH) due to the lack of specific diagnostic biomarkers. Contemporary research on potential PCa biomarkers is directed towardmethylated cell-free DNA (cfDNA) from liquid biopsies since epigenetic mechanisms are strongly involved in PCa development. In the present research, cfDNA methylation of the LGALS3 gene in blood and seminal plasma of PCa and BPH patients was assessed using pyrosequencing, as well as LGALS3 DNA methylation in tissue biopsies. Liquid biopsy samples were taken from patients with clinical suspicion of PCa, who were subsequently divided into two groups, that is, 42 with PCa and 55 with BPH, according to the histopathological analysis. Statistically significant higher cfDNA methylation of LGALS3 in seminal plasma of BPH than in PCa patients was detected by pyrosequencing. ROC curve analysis showed that it could distinguish PCa and BPH patients with 56.4% sensitivity and 70.4% specificity, while PSA did not differ between the two patient groups. In contrast, there was no statistically significant difference in LGALS3 cfDNA methylation in blood plasma between the two patient groups. In prostate tumor tissue, there was a statistically significant DNA hypermethylation of LGALS3 compared to surrounding nontumor tissue and BPH tissue. The DNA hypermethylation of the LGALS3 gene represents an event specific to PCa development. In conclusion, LGALS3 cfDNA methylation in seminal fluid discriminates early PCa and BPH presenting itself as a powerful novel PCa biomarker highly outperforming PSA.

Long-term follow-up results of multiparametric prostate MRI and the prognostic value of PI-RADS: a single-center retrospective cohort study

We aim to examine the long-term outcomes of patients who underwent multiparametric prostate magnetic resonance imaging (mp-MRI) for suspected prostate cancer (PCa), specifically based on their initial Prostate Imaging Reporting and Data System (PI-RADS) categories and various clinical factors. Our secondary aim is to evaluate the prognostic value of the PI-RADS through the National Comprehensive Cancer Network (NCCN) risk group distribution. This research was conducted as a single-center retrospective cohort study in a tertiary care hospital. A total of 1,359 cases having at least one histopathological examination after the initial mp-MRI and/or adequate clinical/radiological follow-up data were included in the clinically significant PCa (cs-PCa) diagnosis-free survival analysis. Initial mp-MRI dates were accepted as the start of follow-up for the time-to-event analysis. The event was defined as cs-PCa diagnosis (International Society of Urological Pathology ≥2). Patients who were not diagnosed with cs-PCa during follow-up were censored according to predefined literature-based criteria at the end of the maximum follow-up duration with no reasonable suspicion of PCa and no biopsy indication. The impact of various factors on survival was assessed using a log-rank test and multivariable Cox regression. Subsequently, 394 cases diagnosed with PCa during follow-up were evaluated, based on initial PI-RADS categories and NCCN risk groups. Three main risk factors for cs-PCa diagnosis during follow-up were an initial PI-RADS 5 category, initial PI-RADS 4 category, and high MRI-defined PSA density (mPSAD), with average hazard ratios of 29.52, 14.46, and 3.12, respectively. The PI-RADS 3 category, advanced age group, and biopsy-naïve status were identified as additional risk factors (hazard ratios: 2.03, 1.54-1.98, and 1.79, respectively). In the PI-RADS 1-2 cohort, 1, 3, and 5-year cs-PCa diagnosis-free survival rates were 99.1%, 96.5%, and 93.8%, respectively. For the PI-RADS 3 cohort, 1, 3, and 5-year cs-PCa diagnosis-free survival rates were 94.9%, 90.9%, and 89.1%, respectively. For the PI-RADS 4 cohort, 1, 3, and 5-year cs-PCa diagnosis-free survival rates were 56.6%, 55.1%, and 55.1%, respectively. These rates were found to all be 24.2% in the PI-RADS 5 cohort. Considering the 394 cases diagnosed with PCa during follow-up, PI-RADS ≥4 cases were more likely to harbor unfavorable PCa compared to PI-RADS ≤3 cases (P < 0.001). In the PI-RADS 3 subgroup analysis, a low mPSAD (<0.15 ng/mL2) was found to be a protective prognostic factor against unfavorable PCa (P = 0.005). The PI-RADS category has a significant impact on patient management and provides important diagnostic and prognostic information. Higher initial PI-RADS categories are associated with decreased follow-up losses, a shorter time to PCa diagnosis, increased biopsy rates, a higher likelihood of developing cs-PCa during follow-up, and a worse PCa prognosis. Combining mPSAD with PI-RADS categories could enhance diagnostic stratification in the identification of cs-PCa.

Lectin-nanoparticle concept for free PSA glycovariant providing superior cancer specificity

BackgroundUsing lectins to target cancer-associated modifications of PSA glycostructure for identification of clinically significant prostate cancers, e.g., Gleason score (GS) ≥ 7, from benign and indolent cancers (GS 6), is highly promising yet technically challenging. From previous findings to quantify increased PSA fucosylation in urine, we set out to construct a robust, specific test concept suitable for plasma samples. MethodsMacrophage galactose‐binding lectin (MGL) coupled to 100 nm Eu3 + -nanoparticles was used to probe PSA captured from cancer cell lines, seminal plasma, and plasma samples from 249 patients with a clinical suspicion of prostate cancer onto 3 mm dense spots of free PSA antibody fab fragments. Results were compared to four kallikrein tests: tPSA, fPSA, iPSA and hK2. ResultsThe fPSAMGLglycovariant provided superior discrimination of the GS ≥ 7 and benign + GS 6 groups (p 0.0003) compared to fPSA (NS). The corresponding AUC in ROC analysis was 0.70 compared to 0.66 for tPSA. In contrast to all four kallikrein tests, the fPSAMGLGV was independent of prostate gland volume. Using a logistic regression analysis the fPSAMGLGV significantly improved on the four-kallikrein model. ConclusionsDue to Eu-nanoparticles and a dense fPSA capture spot, the fPSAMGL glycovariant identifies an fPSA subform with the highest cancer specificity compared to the four conventional kallikreins.

Are systematic prostate biopsy still necessary in biopsy naive men?

Multiparametric MRI and the transperineal approach have become standard in the diagnostic pathway for suspected prostate cancer. Targeting of MRI lesions is performed at most centers, but the routine use of systematic cores is controversial. We aim to assess the value of obtaining systematic cores in patients undergoing cognitive fusion targeted double-freehand transperineal prostate biopsy. Patients who underwent a cognitive fusion, freehand TPB at a single tertiary urology service (Perth, Australia) between November 2020 and November 2021 were retrospectively reviewed. Patients were included if they were biopsy naive and had a clinical suspicion of prostate cancer, based on their mpMRI results. Both targeted and systematic cores were taken at the time of their biopsy. One hundred forty patients suited the selection criteria. Clinically significant cancer was identified in 63% of patients. Of those that had clinically significant cancer, the target lesion identified 91% of the disease, missing 9% of patients whom the target biopsy detected non-clinically significant cancer but was identified in the systematic cores. Higher PI-RADS category patients were also found to be associated with an increasing likelihood of identifying clinically significant cancer within the target. In patients with PI-RADS 3 and higher, the target biopsy can miss up to 9% of clinically significant cancer. Systematic cores can add value as they can also change management by identifying a high-risk disease where only intermediate cancer was identified in the target. A combination of targeted and systematic cores is still required to detect cancer.

Abstract 3751: Diagnostic assessment of Filamin A (FLNA) as a serum biomarker for identification of benign prostatic hyperplasia vs aggressive prostate cancer in a prospective Mexican cohort

Abstract Prostate cancer (PCa) exhibits a significant health risk to aging men, in which effective diagnosis of high gleason (Gleason &amp;gt;7) cancers is of critical need. Currently, the main screening tool utilized for detection of prostate cancer is prostate specific antigen (PSA), however, PSA exhibits limited utility in men with benign prostatic hyperplasia (BPH) due to inherent elevated PSA as the result of an enlarged prostate, resulting in increasing unnecessary biopsies. In Mexico, there is currently a higher incidence of aggressive PCa due to the risk within the overall population as well as the need for increased screening tools. Since, there is a critical unmet need to evaluate novel PCa diagnostic test that could serve as a reflex test within the screening paradigm, we evaluated the recently developed test, pSTATEdx, which measures the cleaved portion of Filamin A (FLNA) via IP-MRM mass spectrometry in conjunction with the patients age, to determine the overall risk of aggressive prostate cancer. In the current study, we analyzed a prospective cohort from Mexico City and Guadalajara evaluating 34 BPH and 44 PCa in men exhibiting symptoms with PSA levels between 4-10 ng/mL, who were all referred for 12 core prostate biopsies due to suspicion of prostate cancer. Additionally, we assessed 41 non-diseased men as controls who had PSA below 1.5 ng/mL, who were not assessed further. Comparison of non-diseased controls with BPH/PCa men exhibited an AUC of 0.99, PPV 0.96, NPV 0.89, OR 118, and P value 2 e-20, thus demonstrating that pSTATEdx had significant utility in assessing prostate health independent of PSA. In comparison with previously published data, FLNA mean levels were 24 ng/mL in previously published American study cohort and 55 ng/mL in the Mexican BPH/PCa cohort with a P value of &amp;lt;0.001. Assessment of patient populations revealed that there was superior diagnostic performance of FLNA for patients between PSA 4-7, which represents an increased unmet need for biopsy decision support. Analysis of BPH compared to all PCa exhibited a sensitivity of 0.94 and specificity of 0.53, PPV 0.64, NPV of 0.91, and OR of 16.4. Diagnostic analysis of BPH compared to high gleason PCa exhibited a sensitivity of 1, specificity of 0.21, PPV 0.38, NPV of 1, and OR of inf in this pilot study. This assessment revealed promising insight that aggressive PCa was not missed using pSTATEdx. pSTATEdx demonstrated diagnostic utility in prevention of unnecessary biopsies in the Mexican population as a reflex test to those patients with PSA levels between 4-7 as well as demonstrated that aggressive prostate cancers were not missed with the risk score. Additional studies are planned in the future to expand the utility of pSTATEdx in Latin America. Citation Format: Arturo Rodriguez, Arturo Mendoza, Matthew Rosenburg, José de J. Castaneda, Alejandro A. Melgar, Bernardo Ciseros, Adrian G. Gangemi, Nischal M. Chand, Poornima Tekumalla, Greg Miller, Anjan Thakurta, Diego Banuelos, Juan J. Real, Diego A. Joya, Alejandro Romero, Juan D. Farias, Eduardo Cabeza, Hector H. Remess, Julio J. Delgado, Hector M. Sanchez, Ignacio Barragan, Mabel Rodriguez, Barbara Garcia, David A. Sanchez, Juan Izquierdo, Elizabeth M. Lopez, Juan Hanao, Jeronimo G. Frusch, Niven R. Narain, Michael A. Kiebish. Diagnostic assessment of Filamin A (FLNA) as a serum biomarker for identification of benign prostatic hyperplasia vs aggressive prostate cancer in a prospective Mexican cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3751.

Key learnings from concordant systematic biopsies in prostate-specific membrane antigen positron emission tomography/computed tomography-guided prostate biopsies: Enhancing targeting accuracy.

Prostate cancer (PCa) diagnosis and staging have evolved with the advent of 68Ga-Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT). This study investigates the role of complementary systematic biopsies (SB) during PSMA-PET/CT-guided targeted prostate biopsies (PET-TB) for PCa detection, grading, and distribution. We address the uncertainty surrounding the necessity of SB in conjunction with PET-TB. We analyzed PCa grading and distribution in 30 men who underwent PET-TB and SB because of contraindication to magnetic resonance imaging or high clinical suspicion of PCa. Tumor distribution was assessed in relation to the PET-highlighted lesions. Standardized reporting schemes, encompassing SUVmax, PRIMARY score, and miTNM classification, were evaluated. 80% of patients were diagnosed with PCa, with 70% classified as clinically significant (csPCa). SB detected more csPCa cases than PET-TB, but the differences were not statistically significant. Discordant results were observed in 25% of cases, where SB outperformed PET-TB. Spatial analysis revealed that tumor-bearing cores from SB were often located in close proximity to the PET-highlighted region. Reporting schemes showed potential for csPCa detection with significantly increased SUVmax in csPCA patients. Subsequent follow-up data underscored the importance of SB in precise PCa grading and staging. While PET-TB can simplify prostate biopsy and reduce invasiveness by core number, SB cannot be omitted yet due to potential PET-TB targeting errors. Factors such as limited spatial resolution and fusion inaccuracies contribute to the need for SB. Standardization in reporting schemes currently cannot compensate for targeting errors highlighting the need for refinement.

The association between pre‐diagnostic levels of psychological distress and adverse effects after radical prostatectomy

AbstractObjectivesTo prospectively analyse the associations between pre‐diagnostic levels of anxiety and depression and patient‐reported urinary and sexual adverse effects after radical prostatectomy in a population‐based setting.Patients and MethodsIn three Norwegian county hospitals, men referred with a suspicion of prostate cancer were asked to fill out a patient‐reported outcome measurement (PROM) questionnaire prior to prostate biopsy. Those who later underwent radical prostatectomy were stratified into three distress groups according to their Hopkins Symptom Checklist 5‐score. Additional PROM questionnaires, including the EPIC‐26 to measure adverse effects, were collected at 6 and 12 months postoperatively. Multivariable mixed models were estimated and post hoc pairwise comparisons performed to explore differences in adverse effects between distress groups.ResultsA total of 416 men were included at baseline and of those, 365 (88%) returned questionnaires at 6 months and 360 (87%) at 12 months. After adjusting for confounders, men with high distress at baseline had worse urinary incontinence domain score (58.9 vs. 66.8, p = 0.028), more urinary bother (64.7 vs. 73.6, p = 0.04) and a higher risk of using incontinence pads (70.6% vs. 54.2%, p = 0.034) at 6 months than those with low distress. There was no difference in the sexual domain scores between distress groups postoperatively, but the high‐distress group expressed more sexual bother (24.9 vs. 37.5, p = 0.015) and the intermediate‐distress group had a greater probability of using sexual medications or devices (63.8% vs. 50.0%, p = 0.015) than the low‐distress group at 6 months. At 12 months scores generally improved slightly and differences between distress groups were less evident.ConclusionMen with higher levels of anxiety and depression before prostate biopsy report more urinary and sexual adverse effects after radical prostatectomy. This should be considered both in treatment decision‐making and during follow‐up after radical prostatectomy.

PI-RADS upgrading as the strongest predictor for the presence of clinically significant prostate cancer in patients with initial PI-RADS-3 lesions

PurposeUnclear lesions on multiparametric magnetic resonance tomography (mpMRI) are challenging for the indication of biopsy in patients with clinical suspicion of prostate cancer (PCa). The aim of this study is the validation of the detection rate of clinically significant PCa (csPCa) in patients with PI-RADS 3 findings and to determine the appropriate follow-up strategy.MethodsIn this retrospective single-center study, patients with maximum PI-RADS 3 lesions underwent targeted MRI/ultrasound-fusion biopsy (tPbx) combined with systematic 12-core biopsy (sPbx) and follow-up mpMRI with further control biopsy. We assessed the evolution of MRI findings (PI-RADS, volume of the lesion), clinical parameters and histopathology in follow-up MRI and biopsies. The primary objective is the detection rate of csPCa, defined as ISUP ≥ 2 findings.ResultsA total of 126 patients (median PSA 6.65 ng/ml; median PSA-density (PSAD) 0.13 ng/ml2) were included. The initial biopsy identified low-risk PCa in 24 cases (19%). During follow-up biopsy, 22.2% of patients showed PI-RADS upgrading (PI-RADS > 3), and 29 patients (23%) exhibited a tumor upgrading. Patients with PI-RADS upgrading had a higher risk of csPCa compared to those without PI-RADS upgrading (42.9% vs. 9.18%, p < 0.05). PI-RADS upgrading was identified as an independent predictor for csPCa in follow-up biopsy (OR 16.20; 95% CI 1.17–224.60; p = 0.038).ConclusionPatients with stable PI-RADS 3 findings may not require a follow-up biopsy. Instead, it is advisable to schedule an MRI, considering that PI-RADS upgrading serves as an independent predictor for csPCa.

High-resolution prostate diffusion MRI using eddy current-nulled convex optimized diffusion encoding and random matrix theory-based denoising.

To develop and evaluate a technique combining eddy current-nulled convex optimized diffusion encoding (ENCODE) with random matrix theory (RMT)-based denoising to accelerate and improve the apparent signal-to-noise ratio (aSNR) and apparent diffusion coefficient (ADC) mapping in high-resolution prostate diffusion-weighted MRI (DWI). MATERIALS ANDMETHODS: Eleven subjects with clinical suspicion of prostate cancer were scanned at 3T with high-resolution (HR) (in-plane: 1.0 × 1.0 mm2) ENCODE and standard-resolution (1.6 × 2.2 mm2) bipolar DWI sequences (both had 7 repetitions for averaging, acquisition time [TA] of 5 min 50 s). HR-ENCODE was retrospectively analyzed using three repetitions (accelerated effective TA of 2 min 30 s). The RMT-based denoising pipeline utilized complex DWI signals and Marchenko-Pastur distribution-based principal component analysis to remove additive Gaussian noise in images from multiple coils, b-values, diffusion encoding directions, and repetitions. HR-ENCODE with RMT-based denoising (HR-ENCODE-RMT) was compared with HR-ENCODE in terms of aSNR in prostate peripheral zone (PZ) and transition zone (TZ). Precision and accuracy of ADC were evaluated by the coefficient of variation (CoV) between repeated measurements and mean difference (MD) compared to the bipolar ADC reference, respectively. Differences were compared using two-sided Wilcoxon signed-rank tests (P < 0.05 considered significant). HR-ENCODE-RMT yielded 62% and 56% higher median aSNR than HR-ENCODE (b = 800 s/mm2) in PZ and TZ, respectively (P < 0.001). HR-ENCODE-RMT achieved 63% and 70% lower ADC-CoV than HR-ENCODE in PZ and TZ, respectively (P < 0.001). HR-ENCODE-RMT ADC and bipolar ADC had low MD of 22.7 × 10-6 mm2/s in PZ and low MD of 90.5 × 10-6 mm2/s in TZ. HR-ENCODE-RMT can shorten the acquisition time and improve the aSNR of high-resolution prostate DWI and achieve accurate and precise ADC measurements in the prostate.

Interim analyses from the PROSPET-BX trial: [G8Ga]PSMA PET/CT vs. mpMRI in patients with suspicion of prostate cancer and previous negative biopsy.

282 Background: Herein we present the results of the interim analyses of our prospective trial (Identifier: NCT05297162), designed to compare [68Ga]PSMA PET/CT with mpMRI in men with a high suspicion of prostate cancer (PCa) after at least one previous negative biopsy. Methods: From April 2022 until September 2023, overall, 94 patients were screened, 78 were enrolled and 64 completed all study investigations. Inclusion criteria: PSA&gt;4.0ng/ml; free-to-total PSA ratio &lt;20%; progressive rise of PSA levels in two consecutive samples; at least one previous negative biopsy; negative digital rectal examination. [68Ga]PSMA PET/CT and 3T mpMRI were performed within one month, followed by TRUS-fusion prostate biopsy. Target lesions were defined based on PI-RADS v2.1 for mpMRI and Primary Score, SUVmax and SUVratio for [68Ga]PSMA PET/CT, then correlated to pathology findings. Results: Median age was 64 years (range 51-83) and median PSA 10.4 ng/ml (range 4.3-25,9). Most patients (76.6%) had one previous negative biopsy. According to re-biopsy results, 10 patients presented with clinically significant PCa (csPCa), 4 with GS 6, while the majority had a negative biopsy (78%). mpMRI results were: 40 patients with PI-RADS 2 (62.5%), 3 with PI-RADS 3 (4.7%), 15 with PI-RADS 4 (23.4%), and 6 with PI-RADS 5 (9.4%). Primary scores were: 45 score 1-2 (70%), and 19 score 3-5. PI-RADS and Primary scores were significantly correlated (P=0.0006). Median SUVmax and SUVratio were 3.7 and 1.35 for benign versus 8.9 and 3 for malignancy, respectively (P&lt;0.001). ROC analyses identified optimal cut-off points for csPCA, with SUVmax&gt;7.48 (AUC 0.756; 95%CI 0.633-0.855) and SUVratio&gt;2.79 (AUC 0.748; 95%CI 0.624-0.848). PI-RADS, Primary score, SUVmax and SUVratio proved significantly associated to biopsy results. When combining [68Ga]PSMA PET/CT with mpMRI data, the detection rate was 90% for csPCa, and the combination of both modalities could spare 87.5% of unnecessary re-biopsies. Conclusions: In these interim results, [68Ga]PSMA PET/CT parameters predict biopsy results as mpMRI in patients who are candidates to re-biopsy; the combination of both modalities can spare most unnecessary re-biopsies, by granting a 90% detection rate for csPCa. Clinical trial information: NCT05297162 .