scholarly journals Integrative molecular tumor and immunological profiling of high-grade primary prostate cancer identifies patients with a biomarker profile that favors the combination of standard of care (SOC) therapy with immunotherapy

2020 ◽  
Author(s):  
Evisa Gjini
Keyword(s):  
Prostate Cancer ◽  
Standard Of Care ◽  
High Grade ◽  
Primary Prostate Cancer

scholarly journals Isotropic Expansion of the Intraprostatic Gross Tumor Volume of Primary Prostate Cancer Patients Defined in MRI—A Correlation Study With Whole Mount Histopathological Information as Reference

2020 ◽  
Vol 10 ◽  
Author(s):  
Maria Kramer ◽  
Simon K. B. Spohn ◽  
Selina Kiefer ◽  
Lara Ceci ◽  
August Sigle ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gross Tumor Volume ◽  
Tumor Volume ◽  
Ex Vivo ◽  
Standard Of Care ◽  
Volumetric Analysis ◽  
Correlation Study ◽  
Lesion Detection ◽  
Coverage Ratio ◽  
Primary Prostate Cancer

IntroductionAn accurate delineation of the intraprostatic gross tumor volume (GTV) is of importance for focal treatment in patients with primary prostate cancer (PCa). Multiparametric MRI (mpMRI) is the standard of care for lesion detection but has been shown to underestimate GTV. This study investigated how far the GTV has to be expanded in MRI in order to reach concordance with the histopathological reference and whether this strategy is practicable in clinical routine.Patients and MethodsTwenty-two patients with planned prostatectomy and preceded 3 Tesla mpMRI were prospectively examined. After surgery, PCa contours delineated on histopathological slides (GTV-Histo) were superimposed on MRI using ex-vivo imaging as support for co-registration. According to the PI-RADSv2 classification, GTV was manually delineated in MRI (GTV-MRI) by two experts in consensus. For volumetric analysis, we compared GTV-MRI and GTV-Histo. Subsequently, we isotropically enlarged GTV-MRI in 1 mm increments within the prostate and also compared those with GTV-Histo regarding the absolute volumes. For evaluating the spatial accuracy, we considered the coverage ratio of GTV-Histo, the Sørensen–Dice coefficient (DSC), as well as the contact with the urethra.ResultsIn 19 of 22 patients MRI underestimated the intraprostatic tumor volume compared to histopathological reference: median GTV-Histo (4.7 cm3, IQR: 2.5–18.8) was significantly (p<0.001) lager than median GTV-MRI (2.6 cm3, IQR: 1.2–6.9). A median expansion of 1 mm (range: 0–4 mm) adjusted the initial GTV-MRI to at least the volume of GTV-Histo (GTVexp-MRI). Original GTV-MRI and expansion with 1, 2, 3, and 4 mm covered in median 39% (IQR: 2%–78%), 62% (10%–91%), 70% (15%–95%), 80% (21–100), 87% (25%–100%) of GTV-Histo, respectively. Best DSC (median: 0.54) between GTV-Histo and GTV-MRI was achieved by median expansion of 2 mm. The urethra was covered by initial GTVs-MRI in eight patients (36%). After applying an expansion with 2 mm the urethra was covered in one more patient by GTV-MRI. ConclusionUsing histopathology as reference, we demonstrated that MRI underestimates intraprostatic tumor volume. A 2 mm–expansion may improve accurate GTV-delineation while respecting the balance between histological tumor coverage and overtreatment.

Skewing Towards Neuroendocrine Phenotype in High Grade or High Stage Androgen-Responsive Primary Prostate Cancer

2005 ◽  
Vol 48 (2) ◽  
pp. 215-223 ◽  
Author(s):  
Luca Puccetti ◽  
Claudiu T. Supuran ◽  
Pier P. Fasolo ◽  
Enrico Conti ◽  
Giancarlo Sebastiani ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Grade ◽  
High Stage ◽  
Primary Prostate Cancer

scholarly journals A urine extracellular vesicle circRNA classifier for detection of high-grade prostate cancer in patients with prostate-specific antigen 2–10 ng/mL at initial biopsy

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ya-Di He ◽  
Wen Tao ◽  
Tao He ◽  
Bang-Yu Wang ◽  
Xiu-Mei Tang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Standard Of Care ◽  
Circular Rna ◽  
Extracellular Vesicle ◽  
High Grade ◽  
Clinical Workflow ◽  
Grade Group ◽  
Training Cohort

AbstractThe aim of this study was to identify a urine extracellular vesicle circular RNA (circRNA) classifier that could detect high-grade prostate cancer (PCa) of Grade Group (GG) 2 or greater. For this purpose, we used RNA sequencing to identify candidate circRNAs from urinary extracellular vesicles from 11 patients with high-grade PCa and 11 case-matched patients with benign prostatic hyperplasia. Using ddPCR in a training cohort (n = 263), we built a urine extracellular vesicle circRNA classifier (Ccirc, containing circPDLIM5, circSCAF8, circPLXDC2, circSCAMP1, and circCCNT2), which was evaluated in two independent cohorts (n = 497, n = 505). Ccirc showed higher accuracy than two standard of care risk calculators (RCs) (PCPT-RC 2.0 and ERSPC-RC) in both the training cohort and the validation cohorts. In all three cohorts, this novel urine extracellular vesicle circRNA classifier plus RCs was statistically more predictive than RCs alone for predicting ≥ GG2 PCa. This assay, which does not require precollection digital rectal examination nor special handling, is repeatable, noninvasive, and can be easily implemented as part of the basic clinical workflow.

ATM loss in primary prostate cancer: Analysis of >1000 cases using a validated clinical-grade immunohistochemistry (IHC) assay.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5069-5069 ◽  
Author(s):  
Emmanuel S. Antonarakis ◽  
Harsimar B Kaur ◽  
Jessica Hicks ◽  
Colin C. Pritchard ◽  
Angelo M De Marzo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tissue Microarrays ◽  
Early Event ◽  
High Grade ◽  
Clinical Grade ◽  
Protein Loss ◽  
Gleason Pattern ◽  
Primary Prostate Cancer ◽  
Atm Protein ◽  
Prostate Cancers

5069 Background: ATM is a protein kinase acting as the main signal transducer of double-strand DNA break repair, in addition to mediating other cellular functions. Germline and somatic pathogenic mutations in ATM occur in a significant fraction of prostate cancers, and targeted therapies for ATM-deficient tumors ( e.g. ATR inhibitors) appear promising. Because DNA sequencing assays frequently cannot distinguish mono-allelic from bi-allelic ATM alterations, a clinical-grade protein IHC assay for ATM loss is needed to select men for these trials and better characterize ATM-deficient tumors. Methods: We validated an automated dichotomously-scored IHC assay to detect ATM protein loss in primary prostate cancer using prostate cancer cell lines with and without bi-allelic ATM inactivation and 49 high-grade (primary Gleason pattern 5) prostate tumors with known ATM genomic status. We then examined the frequency of ATM loss among 23 tumors with pathogenic germline ATM mutations, as well as > 1000 additional primary prostate carcinomas using tissue microarrays (TMA). Results: ATM loss by IHC was found in 14% (7/49) of primary Gleason pattern 5 (5+4 = 9 and 5+5 = 10) tumors. Of these, all cases with adequate tumor content and DNA yield had underlying pathogenic ATM mutations. Of the remaining 42 cases without ATM protein loss, none had ATM alterations. Among men with pathogenic germline ATM mutations, 74% (17/23) had ATM loss by IHC. Of these, 76% (13/17) had homogeneous loss of ATM protein in all tumor cells within a dominant tumor nodule, suggesting that ATM loss was an early clonal event. On TMA analysis, 90% (944/1044) of tumors were evaluable for ATM status by IHC. Among these, ATM loss was seen in 3.3% (31/944), and was significantly more common in tumors with Gleason scores 9-10 (20/198; 10.1%) than in those of all other Gleason grades (11/746; 1.5%) ( P< 0.0001). Conclusions: Validated ATM IHC is a sensitive assay for detecting underlying genomic ATM alterations. ATM protein loss appears to be an early event occurring in the majority of tumors with underlying germline pathogenic ATM mutations, and is significantly enriched in high-grade prostate cancers (especially Gleason grades 9-10).

scholarly journals Immune molecular profiling of a multiresistant primary prostate cancer with a neuroendocrine-like phenotype

2020 ◽  
Author(s):  
Scott G Williams ◽  
Franco Caramia ◽  
Han Xian Aw Yeang ◽  
Catherine Mitchell ◽  
David J Byrne ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hormone Therapy ◽  
Molecular Profiling ◽  
Therapeutic Interventions ◽  
High Grade ◽  
Genomic Features ◽  
Molecular Features ◽  
Primary Prostate Cancer ◽  
Prostate Cancers

Understanding the drivers of recurrence in aggressive prostate cancers requires detailed molecu-lar and genomic understanding in order to aid therapeutic interventions. Here we present a case study of a 70 year old male with high-grade clinically-localised acinar adenocarcinoma treated with definitive hormone therapy and radiotherapy. The patient progressed rapidly with rising PSA and succumbed without metastasis 52 months after diagnosis. We provide here a descrip-tion of histological, transcriptional, proteomic, immunological, and genomic features associated with this disease - identifying hallmarks of canonical neuroendocrine PC disease and other nov-el molecular features.

PET/CT WITH 68GA-PSMA-11 IN DETECTION OF PRIMARY TUMOR AND RECURRENCE OF PROSTATE CANCER

2018 ◽  
Vol 64 (6) ◽  
pp. 799-804
Author(s):  
Darya Ryzhkova ◽  
M. Poyda
Keyword(s):  
Prostate Cancer ◽  
Primary Tumor ◽  
Biochemical Recurrence ◽  
Whole Body ◽  
Negative Results ◽  
Primary Prostate Cancer ◽  
Pet Ct ◽  
The Relationship ◽  
Positive Results ◽  
T Category

Purpose: To study the diagnostic value of PET-CT with 68Ga-PSMA-11 in the diagnosis of a primary prostate cancer, preoperative staging, and the detection of recurrence of prostate cancer (PCa). Methods: 28 patients aged 64.7 ± 8.74 years were included. 10 patients primary prostate cancer, and 18 patients with biochemical recurrence of the disease after radical treatment were examined. All patients underwent PET-CT with 68Ga-PSMA-11 according the whole body protocol. Interpretation of images was performed visually and quantitatively by calculation of SUL max. Results: High focal or diffuse 68Ga-PSMA-11 uptake was found in prostate parenchyma in patients with primary prostate cancer. Additionally metastases in regional lymph nodes were diagnosed in 4 patients and bone metastases were found in one patient. The correlation between 68Ga-PSMA-11 uptake level and Gleason index in the primary tumor (R Spearmen = 0.25, p = 0.57) was not observed. PET-positive results were obtained in 14 patients and PET-negative results in 4 patients with biochemical recurrence of PCa. The relationship between the frequency of PET-positive results and Gleason index was not revealed (R Spearmen = 0.2, p = 0.39). We found a weak but significant correlation between the frequency of PET-positive results and the prostate tumor stage according to the T category (R Spearmen = 0.49, p = 0.049). In patients with low values of PSA (less than 1.0 ng/ml) in 4 out of 9 cases, PET-negative results were obtained. In patients with PSA level more than 1.0 ng/ml PET-positive results were obtained in all cases. Conclusions: PET/CT with 68Ga-PSMA-11 allows to diagnose the primary prostate cancer, to establish the stage of the disease in categories N and M, and also to determine the localization and dissemination of the tumor in patients with biochemical recurrence of prostate cancer. The relationship between 68Ga-PSMA-11 uptake in primary tumor and Gleason index was not found. The probability of obtaining PET-positive results in cases of biochemical recurrence is affected by a PSA level above 1 ng/ml and a high stage of the disease according to the T category (T3-T4).

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