Tumor Gleason Score Research Articles

The effect of surgical margin features on oncologic outcomes after radical prostatectomy

BackgroundEvaluation of the effect of additional surgical margin parameters on biochemical recurrence (BCR) in patients with positive surgical margins (PSM) after radical prostatectomy (RP).MethodsClinicopathological and outcome data from 91 patients with PSM who underwent RP were retrospectively analyzed. Additional surgical margin parameters (PSM length, highest Gleason grade (GG), localization of PSM (apex, bladder neck, or posterolateral), and unifocality or multifocality) were examined and their effects on BCR were investigated.ResultsFifty patients with PSM were included in the study. The mean age of the patients was 63.6 ± 6.9 years. The laparoscopic approach was undertaken more frequently, used for 36 (72%) patients compared to open RP performed in 14 cases (28%). The median follow-up time was 57.0 months (24.0–125.0 months). BCR developed in 14 (28%) patients during the follow-up period. Although mean BCR-free survival was shorter in cases with PSM length ≥ 3 mm compared to those with PSM length < 3 mm (90.4 vs. 108.2 months), multifocality compared to those with unifocality (62 vs. 97.4 months) and surgical margin GG ≥ 4 compared to those with GG 3 (87.4 vs. 97.5 months), the differences were not statistically significant (p = 0.251, p = 0.509 and p = 0.317, respectively). In addition, none of the PSM localizations affected BCR-free survival (p = 0.619). In univariate Cox regression analysis, PSM length affected BCR at a level close to statistical significance (HR = 1.16; p = 0.052). In multiple Cox regression analysis, main tumor Gleason score was determined to be a risk factor associated with BCR (HR = 4.75; p = 0.041).ConclusionsAlthough BCR-free survival was shortened in the presence of poor prognostic features (multifocal PSM, PSM length ≥ 3 mm, surgical margin GG ≥ 4) at the surgical margin, none of these parameters affected BCR at a statistically significant level. Gleason score of the main tumor was found to be a better prognostic factor for BCR.

Abstract 2745: Sequential tracking of PD-L1 expression on circulating epithelial tumor cells (CETCs) in men with primary non-metastatic prostate cancer

Abstract Background: Radiotherapy (RT) is an essential component of multimodality therapy in the primary or postoperative treatment of prostate cancer with curative intent by preventing local recurrence and distant metastases, indicating its impact on residual occult tumor, such as circulating tumor cells. Immunogenic changes in cancer cells induced by RT can lead to adaptive up-regulation of PD-L1 expression. As immune checkpoint inhibition plays an increasingly important role in prostate cancer, radiogenic PD-L1 upregulation may be of therapeutic importance. The aim of this study was to determine PD-L1 status on CETCs before and during RT. Methods: Peripheral blood samples were collected from 52 primary non-metastatic prostate cancer patients. CETCs were enumerated and analyzed for PDL-L1 expression prior to (baseline), 3 and 6 weeks after the start of RT using fluorescence scanning microscopy. Results: PD-L1 expression was detectable in CETCs and localized in the membrane and/or cytoplasm. We found a correlation between PD-L1 status in CETCs and aggressiveness of cancer disease prior to RT. The frequency of PD-L1 positive CETCs depended on the grading and Gleason score of the primary tumor. Patients with a high Gleason score and G3 tumors had significantly more PD-L1 positive CETCs compared to patients with a low Gleason Score and G1 tumors. Moreover, patients in stage I/II had significantly less PD-L1 positive CETCs compared to patients in stage III/IV (mean 54.25 vs. mean 69.65; p&amp;lt;0.05). A higher number of PD-L1 positive CETCs were detected in patients who had radical prostatectomy before start of RT than in those who had no surgical intervention (mean 66.24 vs. mean 47.46; p&amp;lt;0.01). Interestingly, the fraction of PD-L1 positive CETCs decreased significantly during RT only in patients with G3 tumors and a high Gleason Score. Conclusion: Our results indicated that PD-L1 in CETCs is closely related to the aggressiveness of the primary tumor and may be a co-factor associated with the progression of prostate cancer. PD-1/PD-L1 blockade combined with RT represents a novel and promising treatment strategy that could contribute to improve the treatment efficacy of prostate cancer. Citation Format: Dorothea Schott, Monika Pizon, Ulrich Pachmann, Katharina Pachmann, Matthias Mäurer. Sequential tracking of PD-L1 expression on circulating epithelial tumor cells (CETCs) in men with primary non-metastatic 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 2745.

Osteonectin (SPARC) prognostic value in prostate cancer

BackgroundProstate cancer (PCa) is common malignancy among men worldwide. To date only few molecular markers are available to predict its course and outcome. SPARC is considered to be promising prognostic marker of PCa due to its involvement in various cancer processes. Materials and methodsstudy was conducted on PCa surgical primary tumor samples, obtained from 84 patients. Level of SPARC mRNA expression was estimated using RT-qPCR. To identify SPARC protein (osteonectin) in prostate tissue, immunohistochemical analysis was conducted. Bioinformatical analysis was performed on UALCAN and TNMplot resources. Resultsbioinformatical analysis demonstrated that SPARC mRNA levels are decreased in PCa samples, in comparison to normal tissue. In patients with lymph node metastases its levels are 1.26 times higher; p = 4.66E-02, than in N0 category. Ex vivo study demonstrated that SPARC expression was elevated on both mRNA and protein levels in PCa patients with lymph node metastases (by 2.34 and 1.91, respectively, p < 0.05). We established higher levels of SPARC mRNA and protein in PCa patients with T3 tumors, as well as high Gleason score. Estimation of survival rates demonstrated that PCa patients with a high level of SPARC mRNA and protein have decreased overall 2-year survival. ConclusionsSPARC protein was overexpressed on mRNA and protein levels in patients with presence of lymph node metastases and higher Gleason score of tumors. Also, both mRNA and protein upregulation were associated with worse survival rates. The current study has therefore provided further evidence that SPARC is indeed linked to the prognosis and aggressiveness of human PCa.

Robotik retropubik prostatektomiye aşina cerrahlar için robot yardımlı perineal prostatektomi için öğrenme eğrisi

Objective: To investigate the learning curve for robot assisted laparoscopic radical perineal prostatectomy (robotic RPP) for surgeons who already perform transperitoneal robot assisted laparoscopic radical prostatectomy. Material and Methods: A total of initial 120 robotic RPP cases were analyzed for perioperative data from single surgeon performing to determine the learning curve. Perioperative all data are collected including operation time, estimated blood loss, postoperative length of stay, complications and positive surgical margin results. The consecutive patients were classified into four groups: cases 1–30 (Group 1), cases 31–60 (Group 2), cases 61–90 (Group 3) and cases 91-120 (Group 4). Results: Median age of 61.4 (46-73) years and PSA level was 8.4 (2-32). Mean operative time was 143.2 minutes, and the length of surgery progressively decreased over time (from group 1 to group 4; P&lt;001). Mean console time was 90.6 minutes and significant differences was found group 3 vs. 4 (p=0.047). The mean length of stay was 1.6 days, and significantly decrease after 60 cases over time (P&lt;0.001). Mean removal of the urethral catheter significantly earlier in group 4 (P1vs4=0.012). There was no statistically significant difference between the groups with respect to pathologic tumor Gleason score, positive surgical margine of the specimen and complications. Conclusions: This study suggests that surgical qualification for robotic RPP can be obtained at least after 90 cases for an experienced robotic surgeon. Keywords: prostatectomy, robot-assisted, perineal, learning curve, prostate cancer

Study of Immunohistochemical Marker Psma and Ki 67 Expression and Its Relation with Grading in Prostate Carcinoma

Background Prostate cancer (PCa) is the second most frequent malignancy (after lung cancer) in men worldwide .In prostate cancer, immunohistochemistry (IHC) has an important role in the diagnostic confirmation. Gleason score, tumour volume, surgical margins and Ki-67 index are the most significant prognostic factors. The value of different biomarkers like p53, Ki-67, PSMA, androgen receptor mutations, IGF, E-cadherin remains to be applied in clinical practice. In the present study we studied the expression of PSMA and Ki 67 IHC marker in prostatic carcinoma cases and its relation with Gleason score and Gleason grade group of tumour. Method A total of 52 cases of prostate carcinoma diagnosed on histopathology as adenocarcinoma in the Department of surgical pathology within 2.5 years duration were further studied immunohistochemically by PSMA and Ki 67 antibodies. Results At the time of presentation most of the cases have serum PSA level 11-50 ng/ml and with increasing Gleason score it can be ≥100ng/ml. Majority of cases have Gleason score 7 and the most common Gleason grade group is 2. PSMA and Ki 67 IHC marker is significantly correlated with Gleason score and Gleason grade group. PSMA expression is significantly correlated with perineural invasion and Ki 67 with bone metastasis. Conclusion PSMA and Ki 67 IHC marker can be used in conjunction with or as a substitute to Gleason scoring system for proper risk.

Abstract 6001: Phosphorylation of the retinoblastoma protein at Serine 249 and the cadherin switch as clinically informative biomarkers for the discrimination between indolent and aggressive forms of prostate cancer

Abstract Prostate cancer (PCa) is the second most frequent malignancy in men worldwide. This disease is the cause of most cancer death among Puerto Rican men, representing 18.9% of overall cancer deaths. However, a patient outcome depends on the type of tumor, which can be indolent or aggressive. The indolent PCa is of slow tumor growth and favorable prognosis, whereas the aggressive form is of rapid tumor spread and high mortality. The discrimination between the indolent and aggressive forms of PCa has resulted in a significant problem of overtreating those patients with the indolent form of the disease. Thus, biomarkers that aid in the decision-making process regarding active surveillance in very low-, low-, and favorable intermediate-risk PCa face a large unmet need. For this purpose, we evaluate the expression of phospho-Rb S249 and epithelial to mesenchymal transition markers (E-cadherin, N-cadherin, B-catenin) to create a combination that can help distinguish between the indolent and aggressive forms of PCa. We hypothesize that the biomarkers E-cadherin, and B-catenin could be useful to identify indolence among PCa patients, whereas phospho-Rb S249 and N-cadherin could identify the aggressive form of the disease. As part of our methodology, we have conducted immunohistochemistry (N=182) against the expression of these biomarkers on PCa tumor microarrays (TMA’s). Correlation coefficient analyses were conducted to assess if the expression of these biomarkers could correlate with any of the patient’s clinical parameters (stage, grade, tumor size, lymph nodes metastasis, metastasis to distant sites, Gleason score, and Gleason grade). In addition, we created a linear regression analysis to determine if the combined proteins could precisely predict the staging, grade, or Gleason score of the patients. Results have shown that the combination of phospho-Rb S249, N-cadherin, E-cadherin, and B-catenin had a precision of 68% correctly predicting the staging of the patients, and adding the tumor size, lymph nodes metastasis, and metastasis to distant sites to the equation increased the prediction to a 96%. Additionally, we identified that E-cadherin and B-catenin negatively correlated with the tumor size, grade, stage, Gleason grade, and Gleason score of the patients. Whereas N-cadherin and phospho-Rb S249 positively correlate with the tumor size, stage, and Gleason grade. These results suggest that the expression of phospho-Rb S249, N-cadherin, E-cadherin, and B-catenin could be used as a potential tool to discriminate between the indolent and aggressive forms of PCa. This will contribute to enhancing the clinical decision of which patients should be treated or undergo active surveillance. Citation Format: Sheila M. Valle Cortes, Pedro Santiago Cardona, Carlos Diaz Osterman, Harold Saavedra, Shannalee R. Martinez, Gilberto Ruiz Deya, Jaileene Perez Morales, Adam B. Murphy. Phosphorylation of the retinoblastoma protein at Serine 249 and the cadherin switch as clinically informative biomarkers for the discrimination between indolent and aggressive forms of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6001.

RASAL2 regulates the cell cycle and cyclin D1 expression through PI3K/AKT signalling in prostate tumorigenesis

Prostate cancer (PCa) growth and progression are uniquely dependent on androgens, making the androgen receptor pathway a prime target for therapy; however, cancer progression to androgen independence leads to treatment failure and poor prognosis. In recent years, alternative therapeutic pathways for PCa have been extensively explored, such as the PTEN/PI3K/AKT pathway, cell cycle, and DNA repair. In the present study, we discovered that RASAL2, a RAS-GTPase-activating protein, acted as an oncogene to regulate cancer cell proliferation and the cell cycle and contributed to tumorigenesis via the PI3K/AKT/cyclin D1 pathway. First, RASAL2 expression was higher in PCa tumour and metastatic lymph node tissues than in matched adjacent nontumor tissues and was associated with higher PCa tumour stage, Gleason score and poorer prognosis. Mechanistically, we found that RASAL2 promoted tumour cell proliferation, the transition from G1 to S phase in vitro and tumour growth in vivo. Furthermore, we demonstrated that RASAL2 facilitated phosphorylation of AKT, which in turn increased the expression of cyclin D1 encoded by the CCND1 gene. In addition, there was a positive correlation between the expression of RASAL2 and cyclin D1 in subcutaneous xenografts and clinical specimens. Taken together, these findings indicate that RASAL2 plays an oncogenic role in prostate cancer and may promote PCa tumorigenesis through PI3K/AKT signalling and cyclin D1 expression.

PACE4-altCT isoform of proprotein convertase PACE4 as tissue and plasmatic biomarker for prostate cancer

The proprotein convertase PACE4 has demonstrated value as a viable therapeutic target in prostate cancer (PCa). A novel isoform named PACE4-altCT, which arises in neoplastic lesions, plays an important role in tumor progression and has been validated as a pharmacological target. With the discovery of its overexpression in PCa and the alternative splicing of its pre-RNA to generate an oncogenic C-terminally modified isoform named PACE4-altCT, understanding and validating its value as a potential biomarker is of great interest either from prognostic or targeted therapy intervention. Expression of ERG in LNCaP cells was used to investigate the relationship between ERG expression occurring in PCa cells and PACE4-altCT expression by Western blot and qPCR. Using immunohistochemistry, the expression levels of PACE4 isoforms in patient tissues were investigated and correlated with ERG tumor status and Gleason score. An ELISA method was developed using affinity purified recombinant protein and used for quantitative analysis of plasma concentrations of PACE4-altCT and used for correlation. In contrast with the consensual isoform, PACE4-altCT was only strongly overexpressed in prostate cancer patients, correlated with ERG expression levels. Despite its intracellular retention PACE4-altCT could be detected in the plasma of most patients with prostate cancer, whereas it was only found at low levels in normal patients whereas total plasmatic PACE4 levels did not vary significantly between groups. Our study demonstrates that PACE4-altCT is strongly overexpressed in prostate cancer using both immunohistochemical and ELISA techniques and may have some interesting potential as a biomarker.

Impact of Gleason score of the tumor at the positive surgical margin as a prognostic factor

Although numerous studies have reported that a positive surgical margin (PSM) is the most important predictive factor for biochemical recurrence (BCR) of prostate cancer (PCa), only a small number of studies have evaluated the predictive value of the Gleason score (GS) of the tumor at the margin in radical prostatectomy (RP). The present study aimed to investigate the preoperative factors that predict PSM and the significant predictive factors for BCR in cases with PSM. In addition, it was examined whether documenting the GS of the tumor at the margin in pathological reports is useful as a predictive factor for BCR. Data of 241 patients with PCa who underwent RP at Kurume University Hospital (Kurume, Japan) between January 2007 and December 2011 were retrospectively reviewed. The median follow-up period was 72 months and 122 patients had at least one PSM. The time to BCR was significantly shorter in patients with PSM than in those with a negative surgical margin. Multivariate analysis demonstrated that >10 ng/ml prostate-specific antigen at diagnosis (P=0.024) and >25% positive core at biopsy (P=0.041) were independent prognostic preoperative factors for PSM. The GS of the tumor at the margin was equal, lower and higher than those of the main tumor in 74 (60.7%), 16 (13.1%) and 32 (26.2%) RPs, respectively. The BCR rates were 35.7, 55.1 and 82.1% in patients whose GS of the tumor at the margin was 6, 7 and 8-10, respectively (P=0.0017). The GS of the tumor at the PSM (P=0.038) and anatomic location of the PSM (P=0.04) were identified as independent prognostic preoperative factors for BCR, whereas the GS of the main tumor and margin length were not. These results suggest that documenting the GS at the margin in pathological reports is useful as a predictive factor for BCR.

Bioinformatics analysis of the clinical relevance of CDCA gene family in prostate cancer.

Background:Prostate cancer (PCa) is the second most frequent cancer in men worldwide, and its mortality rate is increasing every year. The cell division cycle-associated (CDCA) gene family plays vital roles in the cell cycle process, but an analysis of these proteins in PCa is still lacking.Methods:UALCAN and GEPIA were used to examine the transcriptional data and survival of the CDCA gene family in PCa patients. CDCA genetic alterations, prognostic value of genetic alterations, and correlations of CDCAs with each other in PCa were downloaded from cBioPortal. The functional enrichment data of CDCA-related genes were analyzed using DAVID.Results:Six CDCA genes were upregulated in PCa tissues relative to those in normal tissues (P < .001), including NUF2, CDCA2, CDCA3, CDCA5, CBX2, and CDCA8. The expression levels of the 6 CDCAs were related to the tumor Gleason score (P < .05). In addition, survival analysis using GEPIA suggested that PCa patients with increased NUF2, CBX2, and CDCA2/3/5/8 expression levels had poor relapse-free survival (P < .05). Distinct patterns of genetic alterations of the 6 CDCAs were observed in PCa, and pairwise comparison of the mRNA expression of the 6 CDCAs displayed a close relationship. The biological functions of CDCA-related genes are principally associated with the activation of the following pathways: cell cycle, Fanconi anemia pathway, microRNAs in cancer, oocyte meiosis, and homologous recombination.Conclusions:Upregulated CDCA (NUF2, CBX2, and CDCA2/3/5/8) expression in PCa tissues may play a crucial role in the occurrence of PCa. These CDCAs can predict relapse-free survival prognosis and the Gleason score of patients with PCa. Moreover, CDCAs probably exert their functions in tumorigenesis through the cell cycle and miRNAs in the cancer pathway.

Detection efficacy of PET/CT with 18F-FSU-880 in patients with suspected recurrent prostate cancer: a prospective single-center study.

Our objective was to investigate the efficacy of PET/CT with a novel prostate-specific membrane antigen (PSMA)-targeted PET probe, 18F-FSU-880, for detection and localization of recurrent disease in prostate cancer patients in whom recurrence was suspected based on an increase in plasma prostate-specific antigen (PSA) levels after initial treatment. This study was a prospective institutional review board-approved study of 72 patients (age 56-84years, PSA level 0.22-40.00ng/ml) with suspected relapse of prostate cancer after primary therapy, including radical prostatectomy (RP) (n = 35) or radiation therapy (RT) (n = 37). Patients underwent PET/CT approximately 1h and 3h after injection of 18F-FSU-880 (101.8-380MBq). The correlation between patient-based detection rate and Gleason score (GS) of the primary tumor and plasma PSA levels at the time of PET/CT was evaluated. Maximum standardized uptake values (SUVmax) of the positive uptakes at 1h post-injection were compared with those at 3h post-injection. In total, 51 patients (71%) showed at least one positive PSMA PET result. The PSA-stratified detection rates were 22% (2/9), 36% (4/11), 89% (16/18) and 85% (29/34) for PSA levels of 0.2 to < 0.5, 0.5 to < 1.0, 1.0 to < 2.0 and ≥ 2.0ng/ml, respectively. The GS-stratified detection rates were 33% (2/6), 67% (16/24), 70% (16/23) and 89% (17/19) for GS 6, 7, 8 and 9, respectively. In lesion-based analysis, 157 positive lesions were detected at 3h post-injection, 18 in the prostate or prostate bed, 65 in lymph nodes, 71 in the bone and 3 in the lung. Two local recurrences, eight pelvic lymph nodes and one distant lymph node were depicted only at 3h post-injection. SUV max at 3h post-injection was significantly higher than SUVmax at 1h post-injection (p < 0.001). Our preliminary data suggest that 18F-FSU-880 might be a promising new PSMA-targeting tracer for detecting recurrence after initial treatment in patients with prostate cancer.

Evaluation of ERG Expression in Prostate Adenocarcinoma and Its Prognostic Impact in Patients Survival Rate

Background & Objective: Some certain markers, including prostatic specific antigen (PSA), are being used to screen prostate cancer (PC), but none of them have sufficient sensitivity and specificity for evaluation of prognosis. Currently, genetic variants have found their place in the prognosis of PC. ETS-related gene (ERG) expression and its intensity have contradictory evidence regarding ERG expression with PC incidence or associating outcome. Our purpose was to survey the relationship of ERG expression and its intensity with PC and relative clinical outcome.Methods: We studied the immunohistochemichal (IHC) expression of ERG in 101 radical prostatectomy specimens with PC of different histologic grades. All samples were chosen from pathology department of Sina hospital in Tehran-Iran from 2011 to 2018. Positive ERG expression and its association with Gleason score, preoperative PSA, metastasis status, stage and grade of tumors was evaluated.Results: In total, ERG expression was observed in 42 cases (41.58%) and of these, 7 (16.66%) were categorized as weak, 13 (30.95%) moderate and 22(52.38%) as strong. There was no significant correlation between ERG expression and age, preoperative PSA, Gleason score, lymph node involvement, metastatic pattern, stage, and grade of the tumor (P>0.05). ERG expression frequency in the two groups of survived and expired patients was 42.85% and 0%, respectively; despite the noticeable difference, it was not statistically significance (P=0.264).Conclusion: Evaluation of ERG expression and its intensity may have no essential role as an acceptable prognostic factor in Iranian’s population for anticipating whether PC itself or the outcomes accompanied. This relation is vigorously under the influence of geographical/ethnical features.

Evaluation of circulating β2-microglobulin as a prognostic factor for biochemical recurrence after radical prostatectomy

Objectives: One of the most challenging issues after radical prostatectomy (RP) is biochemical recurrence (BCR). The prediction of BCR can determine the selection of modality and its continuation. Currently, preoperative PSA level, Gleason score, and stage of tumor are used for prediction of BCR. The association of β2-microglobulin (B2MG) with hematologic and solid tumors, such as prostate cancer, was suggested in previous studies. The circulating B2MG, as a risk factor for BCR, has been applied for the first time in the current study. Circulating B2MG likely provides a good environment for the growth of cancer cells due to its angiogenesis and tumorigenesis properties. Methods and materials: A cohort study of 59 patients who underwent RP from 2012 to 2013 was carried out. B2MG was measured in the stored serum samples taken from the patients who underwent biopsy. Patients were monitored for BCR and metastasis caused by prostate cancer over a five-year period. The association of B2MG level with the PSA rising were investigated using multivariate models by adjustment for age, PSA, and Gleason's score effects. Results: Mean concentration of B2MG varied significantly according to patient age, PSA, and Gleason's score. One unit increase in the B2MG may significantly increase the hazard of PSA rising (HR=2.528; 95% CI 1.101–5.319; p-value=0.015). Hazard of PSA rising in high-risk groups was a 2.543-fold increase with a unit increase in B2MG. Conclusion: B2MG could help identify those who would derive the greatest benefit from additional systemic or local treatment. Level of evidence: Not applicable for this multicentre audit.

Safety, efficacy and cost of intra-operative cell salvage during open radical prostatectomy.

BackgroundWe aim to examine the safety and efficacy of intra-operative cell salvage (ICS) in radical prostatectomy.MethodsA retrospective cohort study was performed, enrolling consecutive patients undergoing open radical prostatectomy at two institutions during 01/01/18–31/12/19. Patients were grouped by ICS use. Primary outcomes were allogeneic transfusion rates, and biochemical recurrence (prostate specific antigen >0.2 mg/mL). Secondary outcomes were use of adjuvant therapies, Clavien-Dindo complications and transfusion-related cost (allogeneic transfusion + ICS setup + ICS reinfusion).ResultsIn total, 168 men were enrolled. Patients were grouped based on whether they received no blood conservation technique (126 men) or ICS (42 men). Groups were similar in median age, pre- and post-operative haemoglobin and length of stay. They also had similar post-operative tumour Gleason score, TNM-stage and positive surgical margin rates. Compared with controls, the ICS group had shorter follow up (336 vs. 225 days; P=0.003). The groups had similar rates of biochemical recurrence (17% vs. 14%; P=0.90), adjuvant therapy use (30% vs. 29%; P=0.85) and complications (14% vs. 19% patients; P=0.46). There was no metastatic progression or cancer-specific mortality in either group. Although a similar proportion of patients received allogenic transfusion (2.4% vs. 4.8%; P=0.33) and units of packed red blood cells (PRBC) (9 vs. 5 units), transfusion-related costs were higher amongst the ICS group (AUD $11,422 vs. $43,227).ConclusionsICS use in radical prostatectomy was not associated with altered rates of allogeneic transfusion, complications, biochemical recurrence or adjuvant or salvage therapies. Transfusion related costs were higher in the ICS group.

Evaluation of ERG Expression in Prostate Adenocarcinoma and Its Prognostic Impact in Patients Survival Rate.

Background & Objective:Some certain markers, including prostatic specific antigen (PSA), are being used to screen prostate cancer (PC), but none of them have sufficient sensitivity and specificity for evaluation of prognosis. Currently, genetic variants have found their place in the prognosis of PC. ETS-related gene (ERG) expression and its intensity have contradictory evidence regarding ERG expression with PC incidence or associating outcome. Our purpose was to survey the relationship of ERG expression and its intensity with PC and relative clinical outcome.Methods:We studied the immunohistochemichal (IHC) expression of ERG in 101 radical prostatectomy specimens with PC of different histologic grades. All samples were chosen from pathology department of Sina hospital in Tehran-Iran from 2011 to 2018. Positive ERG expression and its association with Gleason score, preoperative PSA, metastasis status, stage and grade of tumors was evaluated.Results:In total, ERG expression was observed in 42 cases (41.58%) and of these, 7 (16.66%) were categorized as weak, 13 (30.95%) moderate and 22(52.38%) as strong. There was no significant correlation between ERG expression and age, preoperative PSA, Gleason score, lymph node involvement, metastatic pattern, stage, and grade of the tumor (P>0.05). ERG expression frequency in the two groups of survived and expired patients was 42.85% and 0%, respectively; despite the noticeable difference, it was not statistically significance (P=0.264). Conclusion:Evaluation of ERG expression and its intensity may have no essential role as an acceptable prognostic factor in Iranian’s population for anticipating whether PC itself or the outcomes accompanied. This relation is vigorously under the influence of geographical/ethnical features.

Can mean ADC value and ADC ratio of benign prostate tissue to prostate cancer assist in the prediction of clinically significant prostate cancer within the PI-RADSv2 scoring system?

BackgroundThe aim of this study is to investigate whether quantitative DW metrics can provide additive value to the reliable categorization of lesions within existing PI-RADSv2 guidelines. Fifty-eight patients with clinically suspicious prostate cancer who underwent PR examination, PSA serum levels, sextant TRUS-guided biopsies, and bi-parametric MR imaging were included in the study.ResultsSixty-six lesions were detected by histopathological analysis of surgical specimens. The mean ADC values were significantly lower in tumor than non-tumor tissue. The mean ADC value inversely correlated with Gleason score of tumors with a significant p value < 0.001.Conversely, a positive relationship was found between the ADC ratio (ADC of benign prostatic tissue to prostate cancer) and the pathologic Gleason score with a significant elevation of the ADC ratio along with an increase of the pathologic Gleason score (p < 0.001). ROC curves constructed for the tumor ADC and ADC ratio helped to distinguish pathologically aggressive (Gleason score ≥ 7) from non-aggressive (Gleason score ≤ 6) tumors and to correlate it with PIRADSv2 scoring to predict the presence of clinically significant PCA (PIRADSv2 DW ≥ 4). The ability of the tumor ADC and ADC ratio to predict highly aggressive tumors (GS> 7) was high (AUC for ADC and ADC ratio, 0.946 and 0.897; p = 0.014 and 0.039, respectively). The ADC cut-off value for GS ≥ 7 was < 0.7725 and for GS ≤ 6 was > 0.8620 with sensitivity and specificity 97 and 94%. The cutoff ADC ratio for predicting (GS > 7) was 1.42 and for GS ≤ 6 was > 1.320 with sensitivity and specificity 97 and 92%. By applying this ADC ratio cut-off value the sensitivity and specificity of reader 1 for correct categorization of PIRADSv2 DW > 4 increased from 90 and 68% to 95 and 90% and that of reader 2 increased from 94 and 88% to 97 and 92%, respectively.ConclusionEstimation of DW metrics (ADC and ADC ratio between benign prostatic tissue and prostate cancer) allow the non-invasive assessment of biological aggressiveness of prostate cancer and allow reliable application of the PIRADSv2 scoring to determine clinically significant cancer (DW score > 4) which may contribute in planning initial treatment strategies.

Abstract 3536: Genetic validation of an ATM immunohistochemistry assay for genomic and clinical-pathologic characterization of primary prostate cancers with ATM loss

Abstract Background: ATM, a protein kinase involved in double-strand DNA break repair, is mutated in a significant fraction of prostate cancers, and targeted therapies such as ATR inhibitors appear promising for ATM-deficient tumors. However, few ATM-deficient primary prostate cancers have been clinically and genomically characterized. Design: We validated an automated and dichotomously-scored clinical-grade immunohistochemistry (IHC) assay to detect ATM protein loss using prostate cancer cell lines and 52 very high-grade prostate tumors (Gleason score 5+4=9 or 5+5=10) with known ATM genomic status. We examined the frequency of ATM protein loss among 29 tumors with known pathogenic germline ATM mutations or variants of unknown significance (VUS). Finally, we screened more than 800 additional primary prostate carcinomas using tissue microarrays (TMA) for ATM protein loss. Targeted somatic genomic sequencing using HRD Plus (Myriad Genetics) or UW-OncoPlex was conducted in a subset of immunostained tumors in each cohort. Results: ATM protein loss by IHC was found in 13% (7/52) of very high-grade (primary Gleason pattern 5) tumors with somatic genomic sequencing data. Of 7 cases with ATM protein loss, 4 had a deleterious ATM mutation and 3 had apparent single copy ATM genomic loss. Of the remaining 45 cases without ATM protein loss, none had ATM genomic alterations. In the cohort of tumors with pathogenic germline ATM mutations, 74% (17/23) had ATM protein loss, but only 45% (9/20) with evaluable sequencing had a second pathogenic alteration in ATM detected (all of these had protein loss). Of those with germline mutations and ATM protein loss, the majority (76% or 13/17) had an apparent clonal alteration with homogeneous protein loss in all tumor cells sampled. In contrast, among 6 cases with germline ATM VUS, only one had protein loss. On TMA analysis, ATM loss was present in 3% (25/824) of evaluable tumors overall, and was significantly more common in tumors from Grade Group 5 (12/130; 9.2%) compared to all other Grade Groups (13/694; 1.9%) (P&amp;lt;0.0001). Of tumors found by TMA screening with available sequencing, 80% (4/5) with homogeneous ATM protein loss and 58% (7/12) with heterogeneous ATM protein loss had detectable pathogenic alterations in ATM. Of these, 82% (9/11) were inferred to have somatic ATM variants. Conclusions: Validated ATM IHC is a sensitive assay for detecting underlying ATM alterations and may be useful to evaluate VUS in ATM. However, not all tumors with ATM protein loss have detectable genomic alterations. ATM protein loss is likely an early clonal event in tumors with germline mutations and is significantly enriched in high-grade prostate cancers. Citation Format: Harsimar Kaur, Jessica Hicks, Colin Pritchard, Angelo De Marzo, William Isaacs, Jerry Lanchbury, Kirsten Timms, Emmanuel Antonarakis, Tamara L. Lotan. Genetic validation of an ATM immunohistochemistry assay for genomic and clinical-pathologic characterization of primary prostate cancers with ATM loss [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3536.

Prostat kanseri tanısında kan nötrofil / lenfosit dağılımının yeri

Objective: Neutrophil to lymphocyte ratio (NLR) is a recently popular diagnostic marker. We sought answers to questions such as whether this marker has a role in the diagnosis of prostate cancer, any cut off value can be calculated, compared to platelet lymphocyte ratio (PLR) and it has a relationship with Gleason score and percentage of tumors detected in biopsy cores. In addition, we aimed to share the findings of patients undergoing transrectal ultrasound (TRUS) guided biopsy. Materials and Methods : The results of 679 patients who underwent TRUS-guided prostate biopsy with prostate specific antigen (PSA) values above 2.5 ng / ml in our clinic between August 2014 and February 2017 were retrospectively analyzed. Patients were between 2.5-3.9 ng / ml (Group 1), 4-9.9 ng / ml (Group 2), 10-19.9 ng / ml (Group 3), 20 ng / ml and above (Group 4) according to PSA values, divided into four groups. The diagnostic value of NLR was evaluated in these groups. Results: NLR was found as a diagnostic marker in groups 2,3 and 4. The cut off value was calculated as 2.5. It had similar diagnostic power as PLR. There was a poor correlation with Gleason score and percentage of tumor in cores. It was not important in predicting bone metastasis. The difference between PSA density and DRE was statistically significant in groups with pathologic prostate cancer (PCa) or benign prostatic hyperplasia (BPH). Conclusion: Although NLR is not very strong in the diagnosis of PCa, it has a diagnostic value. It can be used as a marker to support PSA.

Social connectedness and mortality after prostate cancer diagnosis: A prospective cohort study.

Men with prostate cancer experience side effects for which a supportive social environment may be beneficial. We examined the association between four measures of social connectedness and mortality after a prostate cancer diagnosis. Male participants in the Melbourne Collaborative Cohort Study in 1990-1994, who developed incident prostate cancer and attended follow-up in 2003-2007, were eligible for the study. Information on social connectedness, collected at follow-up, included (i) living arrangement; (ii) frequency of visits to friends/relatives and (iii) from friends/relatives; (iv) weekly hours of social activities. A total of 1,421 prostate cancer cases was observed (338 all-cause deaths, 113 from prostate cancer), including 867 after follow-up (150 all-cause deaths, 55 from prostate cancer) and 554 before follow-up (188 all-cause deaths, 58 from prostate cancer). Cox models stratified by tumour Gleason score and stage, and sequentially adjusted for socioeconomic, health- and lifestyle-related confounders, were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between social connectedness and all-cause mortality after prostate cancer. Men who reported living alone before diagnosis had higher overall mortality (HR = 1.6, 95% CI: 1.0-2.5), after adjustment for socioeconomic, health and lifestyle confounders. Lower mortality was observed for men with more social activities (p-trend = 0.07), but not in comprehensively adjusted models. Consistent with these findings, men living alone after prostate cancer diagnosis had higher mortality (HR = 1.3, 95% CI: 0.9-1.9). Lower mortality was observed with increasing socializing hours in the age-adjusted model (p-trend = 0.06) but not after more comprehensive adjustment. Our findings suggest that living with someone, but not other aspects of social connectedness, may be associated with decreased mortality for men with prostate cancer.

Radiological semantics discriminate clinically significant grade prostate cancer

BackgroundIdentification of imaging traits to discriminate clinically significant prostate cancer is challenging due to the multi focal nature of the disease. The difficulty in obtaining a consensus by the Prostate Imaging and Data Systems (PI-RADS) scores coupled with disagreements in interpreting multi-parametric Magnetic Resonance Imaging (mpMRI) has resulted in increased variability in reporting findings and evaluating the utility of this imaging modality in detecting clinically significant prostate cancer. This study assess the ability of radiological traits (semantics) observed on multi-parametric Magnetic Resonance images (mpMRI) to discriminate clinically significant prostate cancer.MethodsWe obtained multi-parametric MRI studies from 103 prostate cancer patients with 167 targeted biopsies from a single institution. The study was approved by our Institutional Review Board (IRB) for retrospective analysis. The biopsy location had been identified and marked by a clinical radiologist for targeted biopsy based on initial study interpretation. Using the target locations, two study radiologists independently re-evaluated the scans and scored 16 semantic traits on a point scale (up to 5 levels) based on mpMRI images. The semantic traits describe size, shape, and border characteristics of the prostate lesion, as well as presence of disease around lymph nodes (lymphadenopathy). We built a linear classifier model on these semantic traits and related to pathological outcome to identify clinically significant tumors (Gleason Score ≥ 7). The discriminatory ability of the predictors was tested using cross validation method randomly repeated and ensemble values were reported. We then compared the performance of semantic predictors with the PI-RADS predictors.ResultsWe found several semantic features individually discriminated high grade Gleason score (ADC-intensity, Homogeneity, early-enhancement, T2-intensity and extraprostatic extention), these univariate predictors had an average area under the receiver operator characteristics (AUROC) ranging from 0.54 to 0.68. Multivariable semantic predictors with three features (ADC-intensity; T2-intensity, enhancement homogenicity) had an average AUROC of 0.7 [0.43, 0.94]. The PI-RADS based predictor had average AUROC of 0.6 [0.47, 0.75].ConclusionWe find semantics traits are related to pathological findings with relatively higher reproducibility between radiologists. Multivariable predictors formed on these traits shows higher discriminatory ability compared to PI-RADS scores.