Grade Prostate Research Articles

Patient and tumour characteristics in older patients (70 years or older) undergoing transperineal prostate biopsy: a retrospective cohort study.

PSA screening is advocated in men with a life expectancy of >10 years. With a rising mean life expectancy of 81 years in Australia, many men in their 70s have life expectancies of >10 years. Additionally, advanced age is an independent risk factor for high grade prostate cancer. Hence, we aimed to identify patient and disease characteristics and outcomes of men >70 years undergoing transperineal prostate biopsies (TPB) for suspected prostate cancer. All patients aged 70 years old and above who underwent TPB for suspected prostate cancer between 1st January 2019 and 1st July 2022 at a large tertiary centre were identified. Data including patient Charlson Comorbidity Indices (CCI), pre-operative PSA, Multiparametric prostate MRI (mpMRI), histopathological results, subsequent intervention, and treatment intent (curative vs palliative) were obtained via scanned and electronic medical records. Of 229 patients, median age was 74 years and 72.5% patients had a CCI of ≤4 (>53% estimated 10-year survival). 80.8% were diagnosed with prostate cancer and 65.9% had ISUP ≥ 2 disease. 86.4% of patients with PIRADS 4 or 5 lesions resulted in clinically significant prostate cancer. 3.9% had mild biopsy complications. 76.8% of those with prostate cancer underwent treatment with curative intent. Men >70 years of age have a higher risk of clinically significant prostate cancer and low biopsy risk. Hence, many may benefit from early diagnosis and treatment. Decision on screening and further investigation should be based on assessment of individual risks, benefits and life expectancy.

Physical Color Calibration of Digital Pathology Scanners for Robust Artificial Intelligence Assisted Cancer Diagnosis.

The potential of artificial intelligence (AI) in digital pathology is limited by technical inconsistencies in the production of whole slide images (WSIs). This causes degraded AI performance and poses a challenge for widespread clinical application, as fine-tuning algorithms for each site is impractical. Changes in the imaging workflow can also compromise diagnostic accuracy and patient safety. Physical color calibration of scanners, relying on a biomaterial-based calibrant slide and a spectrophotometric reference measurement, has been proposed for standardizing WSI appearance, but its impact on AI performance has not been investigated. We evaluated whether physical color calibration can enable robust AI performance. We trained fully supervised and foundation model based AI systems for detecting and Gleason grading prostate cancer using WSIs of prostate biopsies from the STHLM3 clinical trial (n=3,651) and evaluated their performance in three external cohorts (n=1,161) with and without calibration. With physical color calibration, the fully supervised system's concordance with pathologists' grading (Cohen's linearly weighted kappa) improved from 0.439 to 0.619 in the Stavanger University Hospital cohort (n=860), from 0.354 to 0.738 in the Karolinska University Hospital cohort (n=229), and from 0.423 to 0.452 in the Aarhus University Hospital cohort (n=72). The foundation model's concordance improved from 0.739 to 0.760 (Karolinska), from 0.424 to 0.459 (Aarhus) and from 0.547 to 0.670 (Stavanger). The study demonstrates that physical color calibration provides a potential solution to the variation introduced by different scanners, making AI-based cancer diagnostics more reliable and applicable in diverse clinical settings.

ANALYSIS OF CD10 EXPRESSION IN PROSTATE ADENOCARCINOMA AND ITS CORRELATION WITH DIFFERENT CLINICOPATHOLOGICAL PARAMETERS AT RNTMC, UDAIPUR

Objective: The study aimed to analyze the expression of CD10 in prostate adenocarcinoma to aid in early diagnosis and anti-CD10 targeted therapy. Methods: This was a cross-sectional study conducted in the Histopathology section of the Department of Pathologyat RNTMC, Udaipur, after approval from the ethical committee and institutional review board. This study was conducted on 92 patients suspected to have prostate cancer. The cases were assessed for Gleason score, Gleason Grade, and Serum Prostate Specific Antigen (PSA) levels. We performed IHC detection of CD10 in prostatic specimens and correlated the various patterns of CD10 expression concerning histopathological diagnosis. Results: In our study, we found membranous expression in low-grade carcinomas with low Gleason score and grade. The high-grade carcinomas with high Gleason score and Grade predominantly showed cytoplasmic expression. The increased CD10 cytoplasmic expression was correlated with serum PSA level. Conclusion: In our study, CD10 was found to be relevant. The low-grade carcinomas showed membranous positivity and high-grade carcinomas showed cytoplasmic expression. One hypothesis states that cytoplasmic expression is due to the localization of CD10 in the cytoplasm. Our study favors this hypothesis as there is cytoplasmic expression in high-grade tumors. In the future, this could be used as a diagnostic marker.

Reinterpretation of prostate cancer pathology by Appl1, Sortilin and Syndecan-1 biomarkers

The diagnosis of prostate cancer using histopathology is reliant on the accurate interpretation of prostate tissue sections. Current standards rely on the assessment of Haematoxylin and Eosin (H&E) staining, which can be difficult to interpret and introduce inter-observer variability. Here, we present a digital pathology atlas and online resource of prostate cancer tissue micrographs for both H&E and the reinterpretation of samples using a novel set of three biomarkers as an interactive tool, where clinicians and scientists can explore high resolution histopathology from various case studies. The digital pathology prostate cancer atlas when used in conjunction with the biomarkers, will assist pathologists to accurately grade prostate cancer tissue samples.

A selective CutMix approach improves generalizability of deep learning-based grading and risk assessment of prostate cancer

The Gleason score is an important predictor of prognosis in prostate cancer. However, its subjective nature can result in over- or under-grading. Our objective was to train an artificial intelligence (AI)-based algorithm to grade prostate cancer in specimens from patients who underwent radical prostatectomy (RP) and to assess the correlation of AI-estimated proportions of different Gleason patterns with biochemical recurrence-free survival (RFS), metastasis-free survival (MFS), and overall survival (OS). Training and validation of algorithms for cancer detection and grading were completed with three large datasets containing a total of 580 whole-mount prostate slides from 191 RP patients at two centers and 6218 annotated needle biopsy slides from the publicly available Prostate Cancer Grading Assessment dataset. A cancer detection model was trained using MobileNetV3 on 0.5 mm × 0.5 mm cancer areas (tiles) captured at 10× magnification. For cancer grading, a Gleason pattern detector was trained on tiles using a ResNet50 convolutional neural network and a selective CutMix training strategy involving a mixture of real and artificial examples. This strategy resulted in improved model generalizability in the test set compared with three different control experiments when evaluated on both needle biopsy slides and whole-mount prostate slides from different centers. In an additional test cohort of RP patients who were clinically followed over 30 years, quantitative Gleason pattern AI estimates achieved concordance indexes of 0.69, 0.72, and 0.64 for predicting RFS, MFS, and OS times, outperforming the control experiments and International Society of Urological Pathology system (ISUP) grading by pathologists. Finally, unsupervised clustering of test RP patient specimens into low-, medium-, and high-risk groups based on AI-estimated proportions of each Gleason pattern resulted in significantly improved RFS and MFS stratification compared with ISUP grading. In summary, deep learning-based quantitative Gleason scoring using a selective CutMix training strategy may improve prognostication after prostate cancer surgery.

MicroRNA (miRNA) PROFILING IN PROSTATE CANCER CARCINOGENESIS: EXPLORATORY RESEARCH

Future research will continue to be carried out in terms of looking for molecular markers involved in the early processes of carcinogenesis, metastasis and therapeutic targets in prostate cancer patients. MicroRNAs (miRNAs) are small noncoding RNAs that contribute to prostate cancer progression by controlling genes involved in the androgen receptor (AR) signaling pathway, ectopic expression of proteins involved in the cell cycle and apoptosis, epithelial-mesenchymal transition (EMT) and metastasis of cancer stem cells (CSCs). This study was an exploratory study, the aim was to assess miRNA expression in low histopathological grade prostate cancer compared with high histopathological grade prostate cancer. The novelty of this research is to assess the 25 most increased (up-regulated) and 25 lowest (down-regulated) miRNAs from 800 types of miRNA. Next, we will analyze the mechanisms and confirm the carcinogenesis of prostate cancer. The research results can be used for further research data, especially for targeted therapy in prostate cancer patients.

Efficacy of Magnetic Resonance Imaging/ Ultrasound-Guided Target Biopsy in Detecting Clinically Significant Prostate Cancer

Introduction: Prostate cancer remains a formidable health challenge, demanding diagnostic strategies that balance accuracy and invasiveness. To enhance early detection and accurate risk stratification, various diagnostic methods have been developed. Magnetic Resonance Imaging (MRI) is considered the standard imaging modality for the detection and localization of prostate cancer. Prostate Imaging Reporting and Data System (PI-RADS) is a standardized system that assigns scores to suspicious lesions based on MRI findings. This system helps distinguish the likelihood of clinically significant prostate cancer (CsPCa), guiding clinicians in decision-making. Magnetic Resonance Imaging/Ultrasound-Guided fusion target biopsy (MRI/US) has emerged as a promising technique in diagnosis of prostate cancer, fusing advanced imaging modalities with real-time ultrasound guidance. Material and methods: A retrospective study was carried out from January 2019 to June 2023. Patients included in the study had elevated tPSA levels and underwent MRI of the prostate. MRI findings were characterized on the basis of PIRADS grading. All patients with a score equal or higher than PI-RADS 3 underwent MRI/US-guided fusion target biopsy. The histopathological results were retrospectively analyzed. Results: 375 patients were included in the study. The mean age of the patients in our study was 67.8 ± 8.2 years. tPSA levels ranged 17.21 ± 31.36 ng/ml and mean prostate volume was 52.67 ± 19.6 cc. 87.5 % of the patients had a negative rectal digital exam and 12.5 % had a positive one. 29.4 % of the MRI exams had lesions scored as PI-RADS 3, 47.1 % – as PI-RADS 4 and 22.5 % as PI-RADS 5. 67.1 % of detected lesions were located in the peripheral zone, 26.5 % – in the transitional zone, 4.5 % in the anterior zone and 1.6% of the lesions were apical. 35.7 % patients had a negative for carcinoma histopathological result and were diagnosed with benign prostatic hyperplasia; 39.2 % of the histopathological results were classified as low grade prostate carcinoma and 29.5 % as high grade prostate carcinoma. All results were classified according to the Gleason score. 30.1 % were Gleason score 3+3=6, 25.1 % were Gleason 7 (13.1 % as Gleason 3+4 and 12 % as 4+3), 5.1 % were Gleason 8 and 5.6 % were Gleason 4+5 or 5+4. Conclusion: The integration of MRI/US fusion biopsy into the diagnostic pathway has significantly improved the detection and characterization of clinically significant prostate cancer. This approach enables more personalized and precise management strategies for patients with prostate cancer.

Combination of prostate volume and apparent diffusion coefficient can stratify patients with a PI-RADS score of 3 to reduce unnecessary prostate biopsies.

Nowadays, there are many patients who undergo unnecessary prostate biopsies after receiving a prostate imaging reporting and data system (PI-RADS) score of 3. Our purpose is to identify cutoff values of the prostate volume (PV) and minimum apparent diffusion coefficient (ADCmin) to stratify those patients to reduce unnecessary prostate biopsies. Data from 224 qualified patients who received prostate biopsies from January 2019 to June 2023 were collected. The Mann-Whitney U test was used to compare non-normal distributed continuous variables, which were recorded as median (interquartile ranges). The correlation coefficients were calculated using Spearman's rank correlation analysis. Categorical variables are recorded by numbers (percentages) and compared by χ2 test. Both univariate and multivariate logistic regression analysis were used to determine the independent predictors. The receiver-operating characteristic curve and the area under the curve (AUC) were used to evaluate the diagnostic performance of clinical variables. Out of a total of 224 patients, 36 patients (16.07%) were diagnosed with clinically significant prostate cancer (csPCa), whereas 72 patients (32.14%) were diagnosed with any grade prostate cancer. The result of multivariate analysis demonstrated that the PV (p < 0.001, odds ratio [OR]: 0.952, 95% confidence interval [95% CI]: 0.927-0.978) and ADCmin (p < 0.01, OR: 0.993, 95% CI: 0.989-0.998) were the independent factors for predicting csPCa. The AUC values of the PV and ADCmin were 0.779 (95% CI: 0.718-0.831) and 0.799 (95% CI: 0.740-0.849), respectively, for diagnosing csPCa. After stratifying patients by PV and ADCmin, 24 patients (47.06%) with "PV < 55 mL and ADCmin < 685 μm2/s" were diagnosed with csPCa. However, only one patient (1.25%) with PV ≥ 55 mL and ADCmin ≥ 685 μm2/s were diagnosed with csPCa. In this study, we found the combination of PV and ADCmin can stratify patients with a PI-RADS score of 3 to reduce unnecessary prostate biopsies. These patients with "PV ≥ 55 mL and ADCmin ≥ 685 μm2/s" may safely avoid prostate biopsies.

Abstract 1853: Prostate specific membrane antigen (PSMA) glycoforms and prostate cancer progression

Abstract Introduction: Prostate cancer (PCa) is the most common non-skin malignancy and the second leading cause of cancer related death in men. Prostate cancer is a heterogeneous disease with diverse clinical outcomes ranging from indolent asymptomatic cases to very aggressive and potentially lethal metastatic forms of the disease. Early detection of PCa is predominantly through determination of serum PSA levels and digital rectal examinations (DRE). Subsequently, biopsy based Gleason Grade Scores and TNM staging, tumor size or mpMRI are used to assess disease severity and progression. However, due to the low specificity of PSA concentration in diagnosis and prognosis, biopsy complications, and high mpMRI costs, there is still a critical need to identify and develop novel noninvasive biomarkers that discriminate indolent from aggressive PCa upon diagnosis. Our long-term objective is to discover biomarkers for aggressive PCa, develop and to implement them into robust clinical testing minimally invasive assays for PCa risk stratification at diagnosis. The current focus is on Prostate-Specific Membrane Antigen (PSMA), a membrane bound glycoprotein, that is significantly over-expressed in aggressive and metastatic prostate carcinomas and with poor patient prognosis. The role of its glycosylation status and composition in disease progression and its glycoforms on biomarker development and therapeutics is unknown. Aberrant glycosylation of glycoproteins occurs in many cancers, and it influences disease progression. We rationalize that differential glycosylation of PSMA correlate with progression to aggressive PCa and that PSMA glycopeptides and glycoforms can be used as diagnostics and prognosticators for aggressive disease. Methods/Results: PSMA was isolated from risk Grade Group stratified post-DRE urines, seminal plasma and prostate cancer cell lines with different metastatic phenotypes cell line lysates. Intact glycopeptides were isolated, purified and analyzed by qualitative and quantitative mass spectrometry to identify site specific glycoforms. Our data demonstrate differential expression of unique PSMA glycoforms that correlate with disease risk and severity. Conclusions: Differential glycosylation of PSMA correlates with PCa disease progression to aggressive phenotypes and may have utility in disease stratification. Ongoing studies focus on determining if these qualitative and quantitative changes have diagnostic/prognostic value and if these be integrated with other PCa biomarkers to improve their prognostic power in discriminating aggressive PCa. Acknowledgements: This work was supported by the DOD, USAMRAA, through the Prostate Cancer Research Program under Award No. W81XWH18-1-0228. Opinions, interpretations, and conclusions are those of the author and are not necessarily endorsed by the USAMRAA. Citation Format: Stephen Mackay, Ian O. Oduor, Tanya Burch, Dean A. Troyer, Oliver J. Semmes, Julius O. Nyalwidhe. Prostate specific membrane antigen (PSMA) glycoforms and prostate cancer progression [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 1853.

Abstract 2149: West African genetic ancestry and origin of the BRCA1 locus in Jamaican men with high grade prostate cancer

Abstract Introduction: Men of West African (WA) ancestry are at higher risk for prostate cancer than men of European (EU) or Asian descent. Caribbean populations provide an opportunity to identify potential founder mutations that contribute to cancer risk. Jamaica has among the highest rates of prostate cancer incidence and mortality in the world and the majority of the population are of WA ancestry. However, there is a significant amount of genetic admixture of EU and Asian ancestry from historic migration patterns. Thus, the population provides a unique cohort for studying the complex interplay between genetic ancestry and prostate cancer. In this pilot study, we characterized the overall and gene locus-specific ancestry of Jamaican prostate cancer patients to explore potential associations with clinicopathologic disease features. We specifically focused this analysis on the BRCA1 locus based on its known association with inherited prostate cancer risk and also with breast cancer risk in patients from the Caribbean. Methods: A retrospective cohort of 31 Jamaican men (non-US citizens/residents) who travelled to the University of Miami (2015-2020) specifically for robotic prostatectomy were included in the analysis. DNA was prepared from normal prostate tissue and analyzed using the Illumina Global Screening Array version 3 with Multi-Disease Drop-In that includes more than 650,000 genetic markers. Both overall genetic ancestry and allele specific ancestries were determined for each study subject. Clinical and pathological features (age, PSA, stage, grade group (GG)) were also recorded and analyzed using descriptive statistics. Results: Median age was 67 years, median pre-op PSA was 6.7. The majority of patients were cT1c (91%) and GG 2 (29%) on biopsy. On final pathology most men were ≥pT3 (51%) and the proportion of GG 1, 2 and ≥ 3 was 3%, 52% and 45% respectively. The mean overall West African genetic ancestry was 51.2% (SD 28.4%). Overall % West African ancestry was not associated with pathological GG. In contrast, 50% of the men who were homozygous for African ancestry alleles at the BRCA1 locus had high-grade prostate cancer (GG 3, 4, 5) versus 37% of the men with non-African or heterozygous BRCA1 genotypes. Conclusions: In a select cohort of Jamaican men, we found that half of patients with BRCA1 alleles derived from West African ancestry also have high grade prostate cancer. BRCA1 of African ancestral origin may contribute to the relatively high prevalence of aggressive prostate cancer in men from Jamaica. Work in progress focuses on an expanded study of associations between allele-specific genetic ancestry and prostate cancer in high-risk populations. Citation Format: Sandra M. Gaston, Anthony J. Griswold, Oleksandr N. Kryvenko, Tianjie Gu, Guan-Nan Zhang, Nachiketh S. Prakash, Yuval Avda, Tarek Ajami, Chad R. Ritch. West African genetic ancestry and origin of the BRCA1 locus in Jamaican men with high grade prostate cancer [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 2149.

Abstract 6835: Profiling of new prostate cancer vulnerabilities through single-nucleus RNAseq implicates the CAF-specific TGF-β pathway in tumor progression

Abstract Background: Transcriptomic profiles of primary high grade prostate cancer (hgPCa) have been extensively studied and prognostic gene expression signatures to classify patients for risk have been identified. However, such studies have employed bulk genomic techniques that blur the contributions of the different cell types. Indeed, tumor microenvironment (TME) cells can significantly contribute to these transcriptomic signatures thereby confounding the lineage of potential therapeutic targets. These challenges underscore the potential of single-nucleus (sn)RNAseq to elucidate new PCa vulnerabilities. We set out to assess whether the TME, particularly cancer-associated fibroblasts (CAFs) drive poor outcome in PCa. Methods: We obtained 15 treatment-naïve frozen primary high risk PCa tissue samples, mostly Gleason &amp;gt;=8. A PCa nuclei dissociation protocol was adapted for single nucleus snRNAseq (10X Genomics). Sample profiling included all cell populations in the tissue including tumor and TME. Output was analyzed using Seurat (v.4.1.1), corrected for ambient RNA expression with CellBender (v.0.3.1) and detected and removed doublets with Scds (v.3.9). Tumor cells were distinguished from normal epithelium cells by a combination of inferCNV (v.1.12.0) and supervised learning with random forests classification. Results: Through snRNAseq, we show that CAFs, and not tumor cells, entirely drive the expression of previously validated poor prognostic signatures (Mortensen, 2015). Our analysis revealed that the TGFβ pathway expression, TGF-β1 in particular, is upregulated in CAFs rather than PCa cells. This pathway, along with poor prognosis signatures are selectively elevated in CAFs from patients with Gleason high compared to low, implicating the TGFb axis as a PCa vulnerability. We also derived a snRNAseq CAF signature that differentiates non-responders to immune checkpoint therapy in mCRPC (Nivolumab+Ipilimumab). Furthermore, cluster profiling of tumor nuclei revealed that hgPCa harbors high heterogeneity with distinct niches of hgPC, mCRPC or neuroendocrine phenotypes for each patient. Conclusions: Through snRNAseq we show that CAFs are the main contributors to prior bulk RNAseq classifiers of poor response, resulting in a refined CAF signature that allows for direct investigation of the contribution of CAFs in other patient segments (mCRPC). Our findings point to a hgPCa patient segment with high CAF representation that may benefit from the addition of a CAF targeting agent (ie.TGFbi) to androgen deprivation therapy. This data has the potential to help refine our prognostic classifiers for patient selection and clinical applicability. Further study of the reported tumor heterogeneity will inform rational combination therapies to tackle resistance mechanisms. Citation Format: Alexandre P. Alloy, Sharmila Chamling Rai, Brendan O'Brien, Anna Lyubetskaya, Arnaud Amzallag, Benjamin Chen, Ana Lako. Profiling of new prostate cancer vulnerabilities through single-nucleus RNAseq implicates the CAF-specific TGF-β pathway in tumor progression [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 6835.

A multi-center international study to evaluate the safety, functional and oncological outcomes of irreversible electroporation for the ablation of prostate cancer

BackgroundIrreversible electroporation (IRE) is a novel technique to treat localized prostate cancer with the aim of achieving oncological control while reducing related side effects. We present the outcomes of localized prostate cancer treated with IRE from a multi-center prospective registry.MethodsMen with histologically confirmed prostate cancer were recruited to receive IRE. All the patients were proposed for prostate biopsy at 1-year post-IRE ablation. The functional outcomes were measured by the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5) questionnaires. The safety of IRE was graded by the treatment-related adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE).Results411 patients were recruited in this study from July 2015 to April 2020. The median follow-up time was 24 months (IQR 15–36). 116 patients underwent repeat prostate biopsy during 12–18 months after IRE. Clinically significant prostate cancer (Gleason ≥ 3 + 4) was detected in 24.1% (28/116) of the patients; any grade prostate cancers were found in 59.5% (69/116) of the patients. The IPSS score increased significantly from 7.1 to 8.2 (p = 0.015) at 3 months but decreased to 6.1 at 6 months (p = 0.017). Afterwards, the IPSS level remained stable during follow-up. The IIEF-5 score decreased at 3 months from 16.0 to 12.1 (p < 0.001) and then maintained equable afterwards. The rate of AEs was 1.8% at 3 months and then dropped to less than 1% at 6 months and remained stable until 48 months after IRE. Major AEs (Grade 3 or above) were rare.ConclusionFor men with localized prostate cancer, IRE could achieve good urinary and sexual function outcomes and a reasonable oncological result. The real-world data are consistent with earlier studies, including recently published randomized controlled studies. The long-term oncological results need further investigation and follow-up.

High-grade prostate cancer demonstrates preferential growth in the cranio-caudal axis and provides discrimination of disease grade in an MRI parametric model.

To determine if multiparametric MRI prostate cancer (PC) lesion dimensions in different axes could distinguish between PC, grade group (GG) >2, and GG >3 on targeted transperineal biopsy and create and validate a predictive model on a separate cohort. The maximum transverse, anterio-posterior, and cranio-caudal lesion dimensions were assessed against the presence of any cancer, GG >2, and GG >3 on biopsy by binary logistic regression. The optimum multivariate models were evaluated on a separate cohort. One hundred and ninety-three lesions from 148 patients were evaluated. Increased lesion volume, Prostate Specific Antigen (PSA), Prostate Imaging Reporting and Data System score, and decreased Apparent Diffusion Coefficient (ADC) were associated with increased GG (P < .001). The ratio of cranio-caudal to anterior-posterior lesion dimension increased from 1.20 (95% CI, 1.14-1.25) for GG ≤ 3 to 1.43 (95% CI, 1.28-1.57) for GG > 3 (P = .0022). The cranio-caudal dimension of the lesion was the strongest predictor of GG >3 (P = .000, area under the receiver operator characteristic curve [AUC] = 0.81). The best multivariate models had an AUC of 0.84 for cancer, 0.88 for GG > 2, and 0.89 for GG > 3. These models were evaluated on a separate cohort of 40 patients with 61 lesions. They demonstrated an AUC, sensitivity, and specificity of 0.82, 82.3%, and 55.5%, respectively, for the detection of cancer. For GG > 2, the models achieved an AUC of 0.84, sensitivity of 91.7%, and specificity of 69.4%. Additionally, for GG > 3, the models showed an AUC of 0.92, sensitivity of 88.9%, and specificity of 98.1%. Cranio-caudal lesion dimension when used in conjunction with other parameters can create a model superior to the Prostate Imaging Reporting and Data Systems score in predicting cancer. Higher-grade PC has a propensity to grow in the cranio-caudal direction, and this could be factored into MRI-based predictive models of prostate biopsy grade.

Brachytherapy for high grade prostate cancer induces distinct changes in circulating CD4 and CD8 T cells – Implications for systemic control

This exploratory study is a follow up to our previous investigation of immune response in the circulation of high-grade Gleason 9 prostate cancer patients treated with EBRT + BT compared to EBRT alone. Notably, EBRT + BT demonstrates the potential to elicit an effect on CD4/CD8 ratio which may have attributed to improved clinical response to therapy. Our findings show promise for leveraging circulating immune cells as predictive biomarkers for radiotherapy response.

Role of psa levels and pathological stadiation before radiation therapy in predicting mp-MRI results in patients with prostate cancer recurrence after radical prostatectomy

ObjectiveTo evaluate PSA value in mp-MRI results prediction, analyzing patients with high (GS≥8, pT≥3, pN1) and low grade (GS<8, pT<3, pN0) Prostate Cancer (PCa). Materials and methodsOne hundred eighty-eight patients underwent 1.5-Tmp-MRI after Radical Prostatectomy (RP) and before Radiotherapy (RT). They were divided into 2 groups: A and B, for patients with biochemical recurrence (BCR) and without BCR but with high local recurrence risk. Considering Gleason Score (GS), pT and pN as independent grouping variables, ROC analyses of PSA levels at primary PCa diagnosis and PSA before RT were performed in order to identify the optimal cut-off to predict mp-MRI result. ResultsGroup A and B showed higher AUC for PSA before RT than PSA at PCa diagnosis, in low and high grade tumors. For low grade tumors the best AUC was 0.646 and 0.685 in group A and B; for high grade the best AUC was 0.705 and 1 in group A and B, respectively. For low grade tumors the best PSA cut-off was 0.565−0.58ng/mL in group A (sensitivity, specificity: 70.5%, 66%), and 0.11−0.13ng/mL in B (sensitivity, specificity: 62.5%, 84.6%). For high grade tumors, the best PSA cut-off obtained was 0.265−0.305ng/mL in group A (sensitivity, specificity: 95%, 42.1%), and 0.13−0.15ng/mL in B (sensitivity, specificity: 100%). ConclusionMp-MRI should be performed as added diagnostic tool always when a BCR is detected, especially in high grade PCa. In patients without BCR, mp-MRI results, although poorly related to pathological stadiation, still have a good diagnostic performance, mostly when PSA>0.1−0.15ng/mL.

El papel del antígeno prostático específico (PSA) y el estadio patológico antes de la radioterapia en la predicción de los resultados de la resonancia magnética multiparamétrica (RMmp) en pacientes con recidiva del cancer de próstata tras prostatectomía radical

ObjectiveTo evaluate prostate-specific antigen (PSA) value in multiparametric magnetic resonance imagin (mp-MRI) results prediction, analyzing patients with high (Gleason Score ≥8, pT≥3, pN1) and low grade (Gleason Score <8, pT<3, pN0) prostate cancer (PCa). Materials and methodsOne hundred eighty-eight patients underwent 1.5-T mp-MRI after radical prostatectomy and before radiotherapy. They were divided into 2 groups: A and B, for patients with biochemical recurrence (BCR) and without BCR but with high local recurrence risk. Considering Gleason Score, pT and pN as independent grouping variables, ROC analyses of PSA levels at primary PCa diagnosis and PSA before radiotherapy were performed in order to identify the optimal cut-off to predict mp-MRI result. ResultsGroup A and B showed higher area under the curve for PSA before radiotherapy than PSA at PCa diagnosis, in low and high grade tumors. For low grade tumors the best area under the curve was 0.646 and 0.685 in group A and B; for high grade the best area under the curve was 0.705 and 1 in group A and B, respectively. For low grade tumors the best PSA cut-off was 0.565-0.58ng/ml in group A (sensitivity, specificity: 70.5%, 66%), and 0.11-0.13ng/ml in B (sensitivity, specificity: 62.5%, 84.6%). For high grade tumors, the best PSA cut-off obtained was 0.265-0.305ng/ml in group A (sensitivity, specificity: 95%, 42.1%), and 0.13-0.15ng/ml in B (sensitivity, specificity: 100%). ConclusionMp-MRI should be performed as added diagnostic tool always when a BCR is detected, especially in high grade PCa. In patients without BCR, mp-MRI results, although poorly related to pathological stadiation, still have a good diagnostic performance, mostly when PSA>0.1-0.15ng/ml.

Prostate Cancer in New York City: Impact of Neighborhood Level Social Determinants of Care

Social determinants of health may impact stage and aggressiveness of cancer presentation. As neighborhoods may influence adjacent neighborhoods across often porous and arbitrary borders, an analysis that measures the spatial impact of these social determinants provides a more holistic evaluation than an analysis that treats each neighborhood as independent and unrelated units. In this paper, we study the impact of sociodemographic and environmental characteristics of neighborhoods on cancer presentation in New York City, using both patient-level analysis and spatial autoregression on the New York State Public Access Cancer Epidemiology Data (NYSPACED) and the NYC Open neighborhood-level dataset. Two outcomes of interest were chosen: Presentation with high grade prostate cancer and presentation with distant disease. We performed logistic regression on individual patient level analysis. We created generalized cross sectional autoregressive spatial regression models to assess direct and indirect (via adjacent neighborhoods) impact of neighborhood level independent variables. We analyzed the following neighborhood level variables: 1) Percent population that was Black, 2) Percent population living in poverty, 3) Percent population obese based on self-reported height and weight, 4) Percent who report being current smokers, 5) Percent who report eating one or more servings of fruits and/or vegetables in the last day, and 6) annual average micrograms of fine particulate matter per cubic meter of air. We identified 95,749 patients diagnosed with prostate adenocarcinoma in New York City from 2001-2018. With reported Black race as the referent value, White patients were less likely to present with high grade disease (OR 0.92 [95% CI 0.89-0.95]). Similarly, self-identified White patients were also less likely to present with distant disease (vs. Black, OR 0.76 [95% CI 0.72-0.81]). Spatial autoregression models revealed no neighborhood level variables associated with direct or indirect impacts on presentation with high grade disease. However, there were several variables initially associated with distant disease presentation, including race, poverty, obesity, fruit and vegetable consumption, and air pollution. However, only neighborhood poverty and obesity levels continued to have significant direct impact on presentation with distant disease when included in the regression model with percent Black residents. In conclusion, we discovered a strong association between Race and poverty with the likelihood of presenting with advanced prostate cancer, at both the individual and neighborhood levels. Geographically targeted outreach to improve prostate cancer screening and access to care should be focused on Black men and neighborhoods with high levels of poverty.

Prostate Cancer Severity in Relation to Level of Food Processing.

The level of food processing has gained interest as a potential determinant of human health. The aim of this study was to assess the relationship between the level of food processing and prostate cancer severity. A sample of 120 consecutive patients were examined for the following: their dietary habits, assessed through validated food frequency questionnaires; their dietary intake of food groups, categorized according to the NOVA classification; and their severity of prostate cancer, categorized into risk groups according to European Association of Urology (EAU) guidelines. Uni- and multivariate logistic regression analyses were performed to test the association between the variables of interest. Individuals reporting a higher consumption of unprocessed/minimally processed foods were less likely to have greater prostate cancer severity than those who consumed less of them in the energy-adjusted model (odds ratio (OR) = 0.38, 95% confidence interval (CI): 1.17-0.84, p = 0.017 and OR = 0.33, 95% CI: 0.12-0.91, p = 0.032 for medium/high vs. low grade and high vs. medium/low grade prostate cancers, respectively); however, after adjusting for potential confounding factors, the association was not significant anymore. A borderline association was also found between a higher consumption of ultra-processed foods and greater prostate cancer severity in the energy-adjusted model (OR = 2.11, 95% CI: 0.998-4.44; p = 0.051), but again the association was not significant anymore after adjusting for the other covariates. The level of food processing seems not to be independently associated with prostate cancer severity, while potentially related to other factors that need further investigation.

The post-finasteride syndrome: possible etiological mechanisms and symptoms.

Finasteride and dutasteride, synthetic 5α-reductase inhibitors (5ARIs) are recommended in many guidelines for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms and alopecia despite a variety of side effects like sexual, neurological, psychiatric, endocrinological, metabolic and ophthalmological dysfunctions and the increased incidence of high grade prostate cancer. The sexual side effects are common during the use of the drug but in a small subgroup of patients, they can persist after stopping the drug. This so-called post-finasteride syndrome has serious implications for the quality of life without a clear etiology or therapy. Three types of 5α-reductases are present in many organs in- and outside the brain where they can be blocked by the two 5ARIs. There is increasing evidence that 5ARIs not only inhibit the conversion of testosterone to 5α-dihydrotestosterone (DHT) in the prostate and the scalp but also in many other tissues. The lipophilic 5ARIs can pass the blood-brain barrier and might block many other neurosteroids in the brain with changes in the neurochemistry and impaired neurogenesis. Further research and therapeutic innovations are urgently needed that might cure or relieve these side effects. More awareness is needed for physicians to outweigh these health risks against the benefits of 5ARIs.

Oral 36 - Variations in the Reporting of Low Grade Prostate Cancer in Irish hospitals

Oral 36 - Variations in the Reporting of Low Grade Prostate Cancer in Irish hospitals