Vesical Invasion Research Articles

Pathological Assessment of Men with Grade Group 2 Prostate Cancer.

A variety of treatment options are now available for men with localized prostate cancer (PC); however, there is still debate in determining how and when to intervene for Grade Group (GG) 2 disease. Our study aims to formulate strategies to identify men at risk of upgrading and having adverse pathological outcomes. This retrospective study includes 243 patients with GG2 PC that were treated with radical prostatectomy between 2015 and 2021. Patients on active surveillance, previous history of prostate biopsy, hormonal and/or radiation therapy prior to surgery were excluded from this study. A retrospective analysis was conducted using clinicopathological data obtained from medical records. Prostate-specific antigen (PSA) and Prostate Imaging Reporting and Data System (PI-RADS) score were statistically significant variables for risk of upgrading. In men who had presence of composite poor outcomes, PSA, PI-RADS score, presence of extraprostatic extension and seminal vesical invasion on MRI, number of positive cores, percentage of high grade (pattern 4/5) on prostate biopsy and Gleason pattern 4 volume on biopsy were all statistically significant variables. Strategy 8 (PI-RADS 5 lesion or percentage high grade [Gleason pattern 4] on prostate biopsy grade >10% or >3 cores positive on prostate biopsy) had significant association to identifying the highest number of men with upgrading and composite poor outcomes. Our study supports the use of strategy 8 in treatment decision making of men with GG2 PC. Further validation of the use of this strategy is warranted.

Fluorine-18 Prostate-Specific Membrane Antigen–1007 PET/CT vs Multiparametric MRI for Locoregional Staging of Prostate Cancer

Prostate-specific membrane antigen (PSMA) demonstrates overexpression in prostate cancer and correlates with tumor aggressiveness. PSMA positron emission tomography (PET) is superior to conventional imaging for the metastatic staging of prostate cancer per current research but studies of second-generation PSMA PET radioligands for locoregional staging are limited. To determine the accuracy of fluorine-18 PSMA-1007 PET/computed tomography (18F-PSMA-1007 PET/CT) compared to multiparametric magnetic resonance imaging (MRI) in the primary locoregional staging of intermediate-risk and high-risk prostate cancers. The Next Generation Trial was a phase 2 prospective validating paired cohort study assessing the accuracy of 18F-PSMA-1007 PET/CT and MRI for locoregional staging of prostate cancer, with results of histopathologic examination as the reference standard comparator. Radiologists, nuclear medicine physicians, and pathologists were blinded to preoperative clinical, pathology, and imaging data. Patients underwent all imaging studies and radical prostatectomies at 2 tertiary care hospitals in Alberta, Canada. Eligible participants included men with intermediate-risk or high-risk prostate cancer who consented to radical prostatectomy. Participants who underwent radical prostatectomy were included in the final analysis. Patients were recruited between March 2022 and June 2023, and data analysis occurred between July 2023 and December 2023. All participants underwent both 18F-PSMA-1007 PET/CT and MRI within 2 weeks of one another and before radical prostatectomy. The primary outcome was the correct identification of the prostate cancer tumor stage by each imaging test. The secondary outcomes were correct identification of the dominant nodule, laterality, extracapsular extension, and seminal vesical invasion. Of 150 eligible men with prostate cancer, 134 patients ultimately underwent radical prostatectomy (mean [SD] age at prostatectomy, 62.0 [5.7] years). PSMA PET was superior to MRI for the accurate identification of the final pathological tumor stage (61 [45%] vs 38 [28%]; P = .003). PSMA PET was also superior to MRI for the correct identification of the dominant nodule (126 [94%] vs 112 [83%]; P = .01), laterality (86 [64%] vs 60 [44%]; P = .001), and extracapsular extension (100 [75%] vs 84 [63%]; P = .01), but not for seminal vesicle invasion (122 [91%] vs 115 [85%]; P = .07). In this phase 2 prospective validating paired cohort study, 18F-PSMA-1007 PET/CT was superior to MRI for the locoregional staging of prostate cancer. These findings support PSMA PET in the preoperative workflow of intermediate-risk and high-risk tumors.

Biochemical Relapse-Free Survival in Post-Prostatectomy Patients Receiving 18F-Fluciclovine-Guided Prostate Bed Only Radiation: Post-Hoc Analysis of a Prospective Randomized Trial

Whole pelvis (WP) radiation therapy (XRT) significantly improved biochemical relapse free survival (bRFS) compared to prostate-bed (PB)-only XRT in RTOG 0534, yet increased toxicity and was performed in an era prior to PET staging (Pollack et al, Lancet, 2022). Separately, 18F-fluciclovine PET/CT (PET)-guided post-prostatectomy XRT demonstrated improved bRFS compared to XRT guided by conventional imaging alone. We hypothesized that patients whose decisions were changed from whole pelvic XRT to PB-only XRT after PET imaging would have bRFS that was (a) not significantly different than patients initially planned for PB-only XRT, and (b) significantly improved over patients planned for WP XRT without PET guidance. We conducted a post-hoc analysis of a prospective, randomized, single-institution trial comparing conventional (Arm A) v. PET-guided (Arm B) post-prostatectomy XRT. For patients randomized to Arm B, pre-PET treatment field decisions were recorded, and post-fluciclovine fields were rigidly defined per protocol: pN0 patients with no pelvic or extrapelvic PET uptake received PB-only XRT. Three- and four-year bRFS were compared in patients initially planned for WP with change to PB-only XRT [Arm B (WP→PB)] v Arm B patients initially planned for PB-only with final XRT to PB-only [Arm B(PB→PB)] & Arm A patients treated with whole pelvic XRT [Arm A(WP)] using Z test and log-rank test. Demographics were compared using Chi-square test, Fisher's exact test, or ANOVA as appropriate. We identified 10 Arm B (WP→PB), 31 Arm B (PB→PB), and 25 Arm A (WP) patients. Androgen deprivation was used in 50.0% of Arm B (WP→PB) and 3.2% of Arm B (PB→PB) patients, p<0.01. Mean pre-XRT PSA was significantly higher (1.56 v 0.32 ng/mL, respectively, p<0.01) in Arm B (WP→PB) v Arm B (PB→PB) patients, however, there was no significant difference in extracapsular extension (p = 1.00), seminal vesical invasion (p = 1.00), Gleason score ≥8 (p = 0.58) or margin positivity (p = 0.73) between cohorts. Three- and four-year bRFS was 80% in Arm B (WP→PB) & 87.4% in Arm B (PB→PB), p = 0.47, respectively. Arm A (WP) patients had significantly worse three- (35.2%) and four-year (13.2%) bRFS compared to Arm B (WP→PB), p<0.01. Patients initially planned for WP XRT whose treatment field decisions were changed to PB-only XRT after PET guidance had, in this post-hoc analysis, (a) relapse rates not significantly different than patients initially planned for PB-only XRT and (b) improved relapse rates over patients treated with WP XRT without PET guidance. PET-guided volume de-escalation in selected patients may be one approach to mitigating excess toxicity seen with WP XRT without compromising outcomes and warrants further exploration.

Relative impact of lymph-node metastasis and seminal vesical invasion on oncologic outcomes following radical prostatectomy.

While both seminal vesicle (SVI) and lymph-node invasion (LNI) have been identified as adverse prognostic variables among men undergoing radical prostatectomy (RP), the relative impact of each of these features on subsequent oncologic outcomes has not been well defined. We assessed the impact of LNI on long-term oncologic outcomes among patients with SVI at RP. We reviewed 19,519 patients who underwent RP and identified 2043 with SVI. Metastasis-free (MFS), cancer-specific (CSS), and overall survival (OS) were estimated for patients with SVI, stratified by the presence and number of pelvic lymph node metastases. Cox proportional hazards models were used to evaluate the independent association of the number of metastatic nodes and lymph node density with oncologic outcomes among patients with SVI, controlling for age, year of surgery, margin status, preoperative PSA, pathologic Gleason score, extraprostatic extension, and use of adjuvant therapies. At a median follow up of 12.1 years (IQR 7.0,18.6), 548 patients developed metastatic disease and 1331 died, including 406 who died from prostate cancer (PCa). We found that, among patients with SVI, the presence of a single positive lymph node was not associated with incrementally adverse oncologic outcomes compared to no nodal metastasis at RP, with 10-year MFS, CSS, and OS rates of 81.3% versus 78.3%(p = 0.18), 86.5% versus 89.8%(p = 0.32), and 72.8% versus 76.7%(p = 0.53), respectively. In contrast, on multivariable analyses, the presence of ≥2 metastatic nodes and a 20% lymph-node density cut off remained independently associated with worse survival. SVI represents an adverse pathologic feature such that the presence of a single positive pelvic lymph node did not further adversely impact prognosis. Meanwhile, a significant number of involved nodes was associated with decreased survival. These findings may aid in risk-stratification as well as clinical trial design for such high-risk patients following surgery.

Gut microbiota-derived short-chain fatty acids promote prostate cancer progression via inducing cancer cell autophagy and M2 macrophage polarization

We have previously demonstrated abnormal gut microbial composition in castration-resistant prostate cancer (CRPC) patients, here we revealed the mechanism of gut microbiota-derived short-chain fatty acids (SCFAs) as a mediator linking CRPC microbiota dysbiosis and prostate cancer (PCa) progression. By using transgenic TRAMP mouse model, PCa patient samples, in vitro PCa cell transwell and macrophage recruitment assays, we examined the effects of CRPC fecal microbiota transplantation (FMT) and SCFAs on PCa progression. Our results showed that FMT with CRPC patients’ fecal suspension increased SCFAs-producing gut microbiotas such as Ruminococcus, Alistipes, Phascolarctobaterium in TRAMP mice, and correspondingly raised their gut SCFAs (acetate and butyrate) levels. CRPC FMT or SCFAs supplementation significantly accelerated mice's PCa progression. In vitro, SCFAs enhanced PCa cells migration and invasion by inducing TLR3-triggered autophagy that further activated NF-κB and MAPK signalings. Meanwhile, autophagy of PCa cells released higher level of chemokine CCL20 that could reprogramme the tumor microenvironment by recruiting more macrophage infiltration and simultaneously polarizing them into M2 type, which in turn further strengthened PCa cells invasiveness. Finally in a cohort of 362 PCa patients, we demonstrated that CCL20 expression in prostate tissue was positively correlated with Gleason grade, pre-operative PSA, neural/seminal vesical invasion, and was negatively correlated with post-operative biochemical recurrence-free survival. Collectively, CRPC gut microbiota-derived SCFAs promoted PCa progression via inducing cancer cell autophagy and M2 macrophage polarization. CCL20 could become a biomarker for prediction of prognosis in PCa patients. Intervention of SCFAs-producing microbiotas may be a useful strategy in manipulation of CRPC.

Short term pathologic outcomes and biochemical recurrence rates of single port transvesical retzius-sparing radical prostatectomy as compared to multiport radical prostatectomy.

369 Background: Single port radical prostatectomy with a transvesical Retzius-sparing approach (SPRP) has shown technical feasibility and early evidence of improved time to urinary continence. How this novel approach leads to differences in pathologic outcomes and biochemical recurrence rates (BCR) as compared to multiport radical prostatectomy (MPRP) has yet to be investigated. Our goal was thus to study the pathologic and short term survival outcomes of patients undergoing SPRP as compared to those undergoing MPRP. Methods: Single center, single surgeon retrospective review of prospectively collected data on 169 patients with low and intermediate risk prostate cancer, whom either underwent SPRP or MRPR (2017-2022). Preoperative clinicopathologic and radiographic characteristics were compared. Following RP, pathologic outcomes, including T stage, grade group (GG), margin status, extraprostatic extension (EPE), seminal vesical invasion (SVI), node retrieval rates, lymph node invasion (LNI) and other adverse histopathologic features were compared between both groups. Cox proportional hazards univariate analysis was used to evaluate the impact of SPRP on biochemical recurrence free survival as compared to MPRP with a three year follow up. Results: A total of 84 patients underwent MPRP and 85 patients underwent SPRP. The SPRP cohort had a higher proportion of clinical T stage one as compared to the MPRP cohort (99% vs 85%, p=0.04), however both groups did not differ preoperatively in terms of median total PSA (6.9 MPRP vs 6.2 SPRP, p=0.24), PI-RADS score (p=0.60) or biopsy GG (p=0.52). Following RP, both groups had similar pathologic outcomes including final grade group, T stage, EPE rates, SVI and Cribriform/intraductal rates (p&gt;0.05). SPRP did yield a lower median number of nodes as compared to MPRP (2 (0-5) vs 6(4-9), p&lt;0.001), but this did not translate to differences in LNI (p=0.08). At a median of approximately 12 months of follow up, there were no differences in the biochemical recurrence-free survival rates among both groups (p=0.38). Cox proportional hazards univariate analysis did not consider SPRP to be an independent predictor of biochemical recurrence (HR 0.53, 95% CI 0.13-2.23, p=0.39). Conclusions: In well selected men, SPRP yields similar short term oncologic control as MPRP with equal rates of margin status, EPE/SVI invasion rates and rates of biochemical recurrence at 1 year. In this small, early, single surgeon experience, SPRP appears to be oncologically safe for low and intermediate risk prostate cancer patients, however longer follow up is necessary, larger numbers and multi- institutional comparisons are needed.

The Clinical Significance of Maximum Tumor Diameter on MRI in Men Undergoing Radical Prostatectomy or Definitive Radiotherapy for Locoregional Prostate Cancer.

Maximum tumor diameter (MTD) on pretreatment magnetic resonance imaging (MRI) has the potential to further risk stratify for men with prostate cancer (PCa) prior to definitive local therapy. We aim to evaluate the prognostic impact of radiographic maximum tumor diameter (MTD) in men with localized prostate cancer. From a single-center retrospective cohort of men receiving definitive treatment for PCa (radical prostatectomy [RP] or radiotherapy [RT]) with available pretreatment MRI, we conducted univariable and multivariable Cox proportional-hazards models for progression using clinical variables including age, NCCN risk group, radiographic extracapsular extension (ECE), radiographic seminal vesical invasion (SVI), and MTD. RP and RT cohorts were analyzed separately. Covariates were used in a classification and regression tree (CART) analysis and progression-free survival was estimated with the Kaplan-Meier method and groups were compared using log-rank tests. The cohort included 631 patients (n=428 RP, n=203 RT). CART analysis identified 4 prognostic groups for patients treated with RP and 2 prognostic groups in those treated with RT. In the RP cohort, NCCN low/intermediate risk group patients with MTD>=15 mm had significantly worse PFS than those with MTD <= 14 mm, and NCCN high-risk patients with radiographic ECE had significantly worse PFS than those without ECE. In the RT cohort, PFS was significantly worse in the cohort with MTD >= 23 mm than those <= 22 mm. Radiographic MTD may be a useful prognostic factor for patients with locoregional prostate cancer. This is the first study to illustrate that the importance of pretreatment tumor size may vary based on treatment modality.

Neoadjuvant Systemic Therapy Prior to Radical Prostatectomy for Clinically Localized High-Risk Prostate Cancer

Radical prostatectomy (RP) remains a standard treatment option for clinically localized high-risk prostate cancer. While RP provides excellent local control, patients with high-risk disease remain at considerable risk for recurrence after surgery. Disease relapse may be the result of occult distant metastases or regional micrometastatic disease at the time of surgery. Accordingly, the role of systemic (neoadjuvant) therapy prior to RP has been investigated. Proposed neoadjuvant regimens: include monotherapy or combinations of chemotherapy, hormonal deprivation, and immunologic agents. Randomized trials using androgen deprivation have demonstrated improved pathologic outcomes, including pathologic downstaging and decreased risk of positive surgical margins, extracapsular extension, and seminal vesical invasion. However, these, albeit early, trials did not reliably demonstrate improved post-prostatectomy oncologic outcomes. More recent trials have evaluated novel combinations of chemo-hormonal therapy and immunologic based therapies. These studies are currently maturing and offer the promise, pending findings, of potentially informing future practice. In this review, we highlight the pathophysiologic basis and contemporary evidence for neoadjuvant therapy prior to RP for clinically localized high-risk prostate cancer.

MP11-03 PERFORMANCE OF 3T MULTIPARAMETRIC MRI FOR THE DETECTION OF SEMINAL VESICAL INVASION IN PATIENTS WITH PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Staging (MP11)1 Sep 2021MP11-03 PERFORMANCE OF 3T MULTIPARAMETRIC MRI FOR THE DETECTION OF SEMINAL VESICAL INVASION IN PATIENTS WITH PROSTATE CANCER Sohrab Afshari Mirak, Anthony Sisk, Ely Felker, David Lu, Robert Reiter, and Steven Raman Sohrab Afshari MirakSohrab Afshari Mirak More articles by this author , Anthony SiskAnthony Sisk More articles by this author , Ely FelkerEly Felker More articles by this author , David LuDavid Lu More articles by this author , Robert ReiterRobert Reiter More articles by this author , and Steven RamanSteven Raman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001984.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Accurate Prostate Cancer (PCa) staging is critical in guiding a patient’s treatment decision and it could prevent both under treatment and over treatment. The emergence of focal therapy options has further increased the importance of accurate staging. Patients with pT3b disease (seminal vesical invasion (SVI)) exhibit a poorer prognosis due to increased treatment failure and tumor recurrence. In this study, we investigated the performance of 3T multiparametric Magnetic Resonance Imaging (3TmpMRI) for per-patient detection of SVI in patients with prostate cancer (PCa) with wholemount histopathology (WMHP) reference. METHODS: This IRB approved, HIPAA compliant observational study comprised of 647 consecutive men, who underwent 3TmpMRI prior to robotic radical prostatectomy. 3TmpMRI studies were performed with and without an endorectal coil (ERC) in 46.1% (270/586) and 53.9% (316/584) of cases, respectively. 3TmpMRI assessment for probability of SVI was evaluated on a Likert scale (1-5) and cases with score > 2 were considered suspicious for SVI. Per-patient performance of 3TmpMRI for the detection of SVI including sensitivity, specificity, PPV and NPV were evaluated in patients with at least one Region of Interest for PCa on MRI and the clinical (Age and PSA density (PSAD)), imaging (MRI assessment of SVI, ERC, index lesion's PIRADSv2 category, size, level, zone and average ADC) and biopsy (ratio of positive to total cores in systematic biopsy, maximum percentage of the core and highest Gleason Score (low=6 vs high >6)) parameters were compared between patients with and without SVI using bivariate analysis followed by multivariate analysis. RESULTS: SVI was present on WMHP in 8.9% (52/586) of the patients. Sensitivity, specificity, PPV and NPV were; 30.8% (16/52), 99.3% (530/534), 80% (16/20) and 93.6% (530/566), respectively. On multivariate regression analysis, older age (OR=1.11, p=0.001), PSAD (OR=26.3, p <0.001), 3TmpMRI SVI suspicion (OR=26, p<0.001) and lesion in the peripheral zone (PZ) (OR=16.6, p=0.008) and base (OR=2.4, p=0.023) were significantly associated with presence of SVI. The AUC for the ROC analysis of the final regression model was 0.84. CONCLUSIONS: 3TmpMRI has a high specificity, PPV and NPV and fair sensitivity for the detection of SVI. Patients with SVI tend to have older age, higher PSAD and higher likelihood of the index lesion in PZ and base of the prostate. Source of Funding: This work was supported by funds from the Integrated Diagnostics Program, Department of Radiological Sciences and Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e178-e178 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sohrab Afshari Mirak More articles by this author Anthony Sisk More articles by this author Ely Felker More articles by this author David Lu More articles by this author Robert Reiter More articles by this author Steven Raman More articles by this author Expand All Advertisement Loading ...

PD61-04 PRELIMINARY PHASE 1 SAFETY AND EFFICACY RESULTS OF A PROSTATE SPECIFIC MEMBRANE ANTIGEN (PSMA) TARGETING FLUOROPHORE IN PATIENTS UNDERGOING ROBOTIC PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy V (PD61)1 Sep 2021PD61-04 PRELIMINARY PHASE 1 SAFETY AND EFFICACY RESULTS OF A PROSTATE SPECIFIC MEMBRANE ANTIGEN (PSMA) TARGETING FLUOROPHORE IN PATIENTS UNDERGOING ROBOTIC PROSTATECTOMY Hao Nguyen, Alexander Antaris, Nynke Van den Berg, Lingru Xue, Scott Greenberg, Anna Muchnik, Alwin Klaassen, Jeff Simko, Sanjeev Dutta, Jonathan Sorger, and Peter Carroll Hao NguyenHao Nguyen More articles by this author , Alexander AntarisAlexander Antaris More articles by this author , Nynke Van den BergNynke Van den Berg More articles by this author , Lingru XueLingru Xue More articles by this author , Scott GreenbergScott Greenberg More articles by this author , Anna MuchnikAnna Muchnik More articles by this author , Alwin KlaassenAlwin Klaassen More articles by this author , Jeff SimkoJeff Simko More articles by this author , Sanjeev DuttaSanjeev Dutta More articles by this author , Jonathan SorgerJonathan Sorger More articles by this author , and Peter CarrollPeter Carroll More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002098.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recurrence rates following surgery for high–risk prostate cancer remain unchanged due, in large part, to the failure to completely excise locally extensive and/or regional disease. This stems from a fundamental inability to differentiate cancer from healthy tissue. IS-002 is a novel near-infrared PSMA targeted fluorophore that is designed to enhance intraoperative cancer visualization during robotic prostatectomy for compete tumor removal. We hypothesize that IS-002 fluorescence-guided surgery (FGS) may improve oncological outcomes by assisting in cancer detection and thus enabling complete cancer excision. Objective: Evaluation of IS-002 safety, pharmacokinetics, and efficacy in a Phase I dose-escalation study (n=24) in patients undergoing robotic prostatectomy using the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA) equipped with Sensitive FireflyTM 800 nm near-infrared imaging capability (SF). METHODS: Patients with high-risk prostate cancer (CAPRA 6-10) received IS-002 intravenously 24 hr. prior to surgery. Six subjects per cohort were dosed at 50, 100, 150 or 200 µg/kg. Safety (adverse events, labs, UA, and ECG) was assessed during a 14-day period. Intraoperative and ex-vivo imaging results were confirmed using histopathology for ground truth cancer determination. RESULTS: IS-002 was studied in 9 subjects (24 planned) with adverse events limited to expected green urine and feces and no major adverse events. Among the 7 patients with complete histopathology data, IS-002 successfully achieved pathologically confirmed tumor fluorescence in 7/7 (100%). Ex vivo tumor-to-background ratio quantification spanned 38.8 – 220.6 in the 50 µg/kg dose cohort. Surgeons using SF + IS-002 reported excellent tumor discrimination over background (Figure 1), and fluorescence outperformed standard imaging (MRI,CT,TRUS, white light endoscopy) at revealing bladder neck invasion (2/2), seminal vesical invasion (2/2), neurovascular bundle involvement (2/2), and lymph node involvement (3/3). CONCLUSIONS: IS-002 is safe and well tolerated for FGS at evaluated doses for intraoperative tumor detection beyond the prostate and margin assessment during robotic prostatectomy. Source of Funding: Intuitive Surgical Inc. and Goldberg-Benioff Program in Translational Cancer Biology © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1067-e1068 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hao Nguyen More articles by this author Alexander Antaris More articles by this author Nynke Van den Berg More articles by this author Lingru Xue More articles by this author Scott Greenberg More articles by this author Anna Muchnik More articles by this author Alwin Klaassen More articles by this author Jeff Simko More articles by this author Sanjeev Dutta More articles by this author Jonathan Sorger More articles by this author Peter Carroll More articles by this author Expand All Advertisement Loading ...

Prostat Karsinomunda Enerji Metabolizmasının Yeniden Programlanması: İn Siliko Analiz

Prostate carcinoma is known to be a hypoxic and lipogenic solid tumor, exhibiting a remarkable oncogenic modulated metabolic programming. Increasing intake of glucose and aerobic glycolysis, called the Warburg effect, are main metabolic changes in hypoxic tumors. Protein,nucleid acid , and lipid biosynthesis are the other metabolic processes associated with cancer metabolic rewiring. In addition to “Warburg effect” in prostate carcinoma, fatty acids, glutamine, and mitochondrial oxidative phosphorylation in alternative metabolic pathways are considered main contributors to tumorigenesis. The aim of this study is to investigate reprogramming of energy metabolism in well and poorly differentiated prostate carcinomas with seminal vesical invasion. The GSE32448 gene’s microarray data were downloaded from the "Gene Expression OmniBus". Differences in gene expression levels were generated by re-analyzing the mRNA transcripts of tissues obtained from 40 patients specimens. "Biobase", "Limma" and "Geoquery" libraries were obtained with bioinformatics analysis using R program. Statistically significant differences were found in genes related to fatty acid metabolism. Increased awareness of the role of lipid metabolism in prostate cancer can lead to developing better treatment strategies against this malignancy.

Low serum testosterone and prostate cancer behaviour - any correlation

Background and Objective: Prostate cancer is one amongst the most common medical diseases affecting elderly men. Carcinoma of the prostate is being the most common non-cutaneous cancer diagnosed. The lifetime risk of prostatic carcinoma is 16.7 % and the risk of death during the entire lifetime is around 2.6% for men but the overall lifetime risk of death due to prostate malignancy is low in comparison to lifetime risk of diagnosis. Prostate cancer is a hormone dependant cancer and the clinical course of prostate cancer varies with individual and again it varies within the individual in relationship to serum testosterone levels. The present study is to find out the role of low serum testosterone level in predicting prostate cancer behaviour in comparison with normal serum testosterone level patients and to find out the relationship between low serum testosterone level and serum PSA levels in TRUS biopsy proven cancer prostate patients. The primary aim and objective of our study is to determine the association of low serum testosterone and prostate cancer behaviour and with a Secondary objective to determine the relationship of serum PSA level in cancer prostate patients with low serum testosterone. Methodology: Informed consent was obtained from all patients. All TRUS biopsy proven caner prostate patients were enrolled to a maximum number of 100. All details were recorded. Blood investigations like serum PSA, serum testosterone and other baseline investigations were obtained. The serum determinations of Testosterone obtained between 7 – 9.30 am. The serum Testosterone levels measured by appropriate standard protocols. Patients were divided into two groups based on the serum testosterone levels. Patients with low serum testosterone levels ( 250 ng/dl) were categorized as Group B and the findings between two groups will be compared. Results: Total of 106 patients with cancer prostate were taken into our study of which 5 patients on 5 alpha reductase inhibitors and 1 patient on testosterone replacement therapy were excluded from our study and finally 100 patients were enrolled in our study of which patients with low testosterone level ( 250 ng/dl) were categorized as group B. The majority (74%) of patients in low testosterone group has got a serum PSA of more than 20 values compared with only 34% of patients in the corresponding group. P value is found to be statistically significant. Most of the patients (82.6%) in low testosterone group had a higher Gleason grade (8-10) compared to the normal testosterone group. P value is found statistically significant. Conclusion: Low total serum testosterone is associated with higher proportion of predominant Gleason pattern 4, an indicator of aggressive prostate cancer. Patients with low serum testosterone levels were associated with an increased serum PSA levels compared with patients in normal serum testosterone levels. Patients with low testosterone who were managed by radical prostatectomy had a higher proportion of positive surgical margin, extra capsular extension and seminal Vesical invasion suggesting an aggressive prostate cancer behaviour. Preoperative total testosterone should be routinely added to serum prostate specific antigen estimation to improve prostate cancer management.

Open Radical Retropubic Prostatectomy as a Saviour in the Era of Robotics- A Single Surgeon Experience

Background Outcome of its safety, perioperative outcomes, functional outcomes, oncologic outcomes in open radical retropubic prostatectomy for organ confined prostate cancers in the era of robotic surgery. Methods A prospective study of radical retropubic prostatectomy performed at SKIMS between 2013 and 2020 was conducted. Work up of the patients in the study (n=42) included age, comorbidities, serum prostate-specific antigen levels, digital rectal examination, MPMRI prostate, prostatic biopsy (Gleasons score), bone scan and optional PSMA PET scan. Intraoperative findings and pathological variables -T stage, nodal status, any extraprostatic extension, apical margin, bladder neck, seminal vesical invasion, lymph nodal status, post operative BCR need for any hormonal and salvage radiotherapy were recorded. On follow up particular emphasis was given on trifecta as cancer control, urinary continence, erectile function and overall satisfaction. Results Out of 42 patients 7 patients were continent at 1 month follow up, 27 at 3 months, 39 at 6 months and 41 at 12 months. One patient continued to be incontinent at 1 year. Out of 16 patients with nerve sparing RPP 10 patients were potent with PD 5 inhibitor assistance at 6 months and all at 1 year ( Potency was defined as the ability to have erections adequate enough for penetration more than 50% of the times). Three patients had Biochemical recurrence on follow up and both were subjected to hormonal and salvage radiotherapy. Thirty nine patients were disease free at last follow up. Conclusions Radical prostatectomy is the standard of care for organ confined prostatic carcinoma. Aim of the procedure is trifecta as cancer control, urinary continence, and erectile function. Minimally invasive techniques as Robotics should not be a limiting factor especially when affordablity and non availability is concern.

Oncological safety and functional outcomes of testosterone replacement therapy in symptomatic adult-onset hypogonadal prostate cancer patients following robot-assisted radical prostatectomy.

Testosterone replacement therapy (TRT) remains controversial in men with treated prostate cancer. We assessed its safety and functional impacts in patients after definitive surgical treatment with robotic-assisted radical prostatectomy (RARP). We performed a retrospective analysis of 1303 patients who underwent RARP during the years 2006-2019. We identified men with symptoms of andropause and low serum testosterone who received TRT post-RARP; then we divided the cohort into two groups accordingly for comparison. Biochemical recurrence (BCR) was the primary endpoint. Secondary endpoints included functional outcomes. Predictors of BCR, including the effect of TRT on BCR, were evaluated using univariable and multivariable logistic regression. Among the forty-seven men who received TRT, the mean age was 60.83years with a median follow-up of 48months. Three (6.4%) and 157 (12.56%) patients experienced BCR in TRT and non-TRT groups, respectively. Baseline characteristics were similar between both groups except for higher mean BMI in the TRT group (p = 0.03). In the multivariate analysis (MVA), higher pre-RARP prostate-specific antigen (PSA) (p = 0.043), higher International Society of Urological Pathology score (p < 0.001), seminal vesical invasion (p = 0.018) and positive surgical margin (p < 0.001) were predictors of BCR. However, TRT was not (p = 0.389). In addition, there was a significant change in the Sexual Health Inventory for Men (p = 0.022), and serum testosterone level (p < 0.001) before and 6months after initiation of TRT. Our findings suggest that TRT, in well-selected, closely followed, symptomatic men post-RARP is an oncologically safe and functionally effective treatment in prostate cancer patients post-RARP.

Prostate-specific membrane antigen positron emission tomography (PSMA-PET) for local staging of prostate cancer: a systematic review and meta-analysis

PurposeProstate-specific membrane antigen positron emission tomography (PSMA-PET) has shown promise for detecting nodal and distant prostate cancer (PCa) metastases. However, its performance for local tumor staging is not as well established. The purpose of this study was to review the diagnostic performance of PSMA-PET for determining seminal vesical invasion (SVI) and extraprostatic extension (EPE).MethodsPubmed and Embase databases were searched until January 12, 2020. Studies assessing accuracy of PSMA-PET in determining SVI and EPE were included. Study quality was evaluated with the revised Quality Assessment of Diagnostic Accuracy Studies-2 tool. Pooled sensitivity and specificity were calculated using hierarchical summary receiver operating characteristics modeling. Heterogeneity was explored using meta-regression analyses for anatomical imaging component (MRI vs CT) and by testing for a threshold effect.ResultsTwelve studies (615 patients) were included. Pooled sensitivity and specificity were 0.68 (95% CI 0.53-0.81) and 0.94 (95% CI 0.90-0.96) for SVI and 0.72 (95% CI 0.56-0.84) and 0.87 (95% CI 0.72-0.94) for EPE. Meta-regression analyses showed that for SVI, PET/MRI demonstrated greater sensitivity than PET/CT (0.87 [95% CI 0.75-0.98] vs 0.60 [95% CI 0.47-0.74]; p = 0.02 for joint model) while specificity was comparable (0.91 [95% CI 0.84-0.97] vs. 0.96 [95% CI 0.93-0.99]) but not for EPE (p = 0.08). A threshold effect was present for studies assessing EPE (correlation coefficient = 0.563 [95% CI, −0.234-0.908] between sensitivity and false-positive rate).ConclusionPSMA-PET has moderate sensitivity and excellent specificity for assessing local tumor extent in patients with PCa. PET/MRI showed potential for greater sensitivity than PET/CT in assessing SVI.

Preoperative %p2PSA and Prostate Health Index Predict Pathological Outcomes in Patients with Prostate Cancer Undergoing Radical Prostatectomy

To evaluate the predictive accuracy of the %p2PSA and prostate health index (PHI) in predicting aggressive pathological outcomes in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP), we enrolled 91 patients with organ-confined PCa who were treated with robot-assisted RP. p2PSA levels and the PHI were investigated for their ability to predict pathological results. The %p2PSA and PHI were both significantly higher in patients with ≥pT3 disease, high-risk disease, positive surgical margin, or seminal vesical invasion (SVI). In univariable analysis, p2PSA derivatives were significant predictors of the presence of ≥pT3 disease, high-risk disease, positive surgical margin, and SVI. To predict adverse pathological outcomes at a sensitivity of 90%, p2PSA derivatives had higher specificity than standard PSA derivatives. In multivariable analysis, additional increases in the area under the receiver operating characteristic curve (AUC) were observed with the %p2PSA and PHI for ≥pT3 disease, high-risk disease, and positive surgical margin (8.2% and 2.7%, 6.2% and 4.1%, and 8.6% and 5.4%, respectively). A PHI ≥61.26 enhanced the predictive accuracy of the model for SVI by increasing the AUC from 0.624 to 0.819 (p = 0.009). The preoperative %p2PSA and PHI accurately predict adverse pathological results and are useful for decision-making.

Prostatic ductal adenocarcinoma with cribriform architecture has worse prognostic features than non-cribriform-type

Prostatic ductal adenocarcinoma (PDA) is a rare histologic subtype of prostate cancer characterized by large glands lined with tall columnar pseudostratified epithelium. PDA has several architectural patterns, with papillary and cribriform being the most common. The cribriform pattern of acinar carcinoma has shown to be associated with a worse prognosis in terms of disease progression and disease-specific mortality. However, the significance of cribriform pattern in PDA is unknown. In this study, we sought to compare the adverse pathologic features between cribriform-type and non-cribriform-type PDA, and between PDA and acinar carcinoma with Gleason scores 8–10. We identified PDA cases diagnosed between 2008 and 2018 and 428 radical prostatectomy (RP) specimens containing Gleason 8–10 acinar carcinoma. The slides of all PDA cases were reviewed, and pathologic features were recorded. We found that the vast majority of PDA contained admixed acinar carcinoma, with a median percentage of the ductal component of 50% (range 5–100). 29% of PDA was graded as Grade Group 4 and 35.5% as Grade Group 5. At the time of RP, 45.2% of cases presented as pathologic stage T3a and 29% as T3b. Cribriform-type PDA demonstrated a significantly higher likelihood of extraprostatic extension (84% vs 33.3%, p = 0.01), seminal vesical invasion (36% vs 0%, p = 0.04), lymphovascular invasion (40% vs 0%, p = 0.03) and advanced pathologic stage (84% vs 33.3%, p = 0.01) compared to PDA without cribriform architecture. The proportion of stage ≥pT3 tumors in PDA was similar compared to that in Gleason 8–10 acinar carcinoma (74.2% vs 70.8%, p = 0.68).

Grade Groups Provides Improved Predictions of Pathologic and Early Oncologic Outcomes Compared with Gleason Score Risk Groups

PurposeThe grade grouping (GG) system was introduced in 2013. Data from academic centers suggests GG better distinguishes between prostate cancer risk groups than the Gleason score (GS) risk groups. We compared the performance of both for predicting pathological/recurrence outcomes using data from Michigan Urological Surgery Improvement Collaborative (MUSIC). Materials and MethodsPatients undergoing biopsy and radical prostatectomy (RP) within MUSIC (3/2012-6/2017) were classified according to GG and GS. Outcomes included presence/absence of extraprostatic extension (EPE), seminal vesical invasion (SVI), positive lymph nodes (N1), positive surgical margins (PSM), and time to cancer recurrence (defined by having post-operative PSA≥0.2). Logistic and cox regression models were used to compare the difference in outcomes. Results8052 patients were identified. Controlling for patient characteristics, significantly higher risks of EPE, SVI, and N1 were observed for biopsy GG3 vs. GG2, and for GG5 vs. GG4 (p<0.001). Biopsy GG3, GG4, and GG5 also had shorter time to biochemical recurrence (BCR) when compared to GG2, GG3, and GG4, respectively (p<0.001). GG3, GG4, and GG5 at RP were each associated with greater probability of recurrence compared to the next lower GG (p<0.001). GG (vs. GS) had better predictive power for EPE, SVI , N1, and BCR. ConclusionsGG at biopsy and RP allows for better discrimination of recurrence-free survival between individual risk groups than GS risk groups with GG2, GG3, GG4, and GG5 each incrementally associated with increased risk.

Prognostic utility of neutrophil-to-lymphocyte and platelets-to-lymphocyte ratio in predicting biochemical recurrence post robotic prostatectomy.

Utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting biochemical recurrence (BCR) in patients with localized prostate cancer. Retrospective analysis of patients operated by robot-assisted radical prostatectomy. Variables included were: NLR, PLR pre-operative prostate specific antigen, pathological Gleason score, surgical margins status, extracapsular extension, seminal vesical invasion, and lymph node status. Out of 321 patients, no association between NLR or PLR and BCR was detected. Predictors of BCR were pathological Gleason score, extracapsular extension and positive surgical margins. On multivariate analysis, the Gleason Score, extracapsular extension and positive surgical margins remained the only predictors of BCR. Neither elevated NLR nor PLR predicted an increased risk of BCR.

The Impact of Pathologic Upgrading of Gleason Score 7 Prostate Cancer on the Risk of the Biochemical Recurrence after Radical Prostatectomy.

Objective To investigate the impact of pathologic upgrading of Gleason score (GS) 7 prostate cancer on the risk of the biochemical recurrence. Materials and Methods A total of 1678 patients with postoperative GS 7 prostate cancer without lymph node metastasis were reviewed retrospectively. The patients were categorized into four groups depending on pathologic upgrading: upgraded GS 3+4, nonupgraded GS 3+4, upgraded GS 4+3, and nonupgraded GS 4+3. Kaplan-Meier multivariate model was created. Results The mean age was significantly higher in the nonupgraded GS 4+3 group than in other groups, whereas the mean prostate-specific antigen (PSA) level was lower in the upgraded GS 3+4 group. Pathologic findings, such as extracapsular extension, seminal vesical invasion, and the surgical margin rate, were different from each other. Five-year biochemical recurrence-free survival rate was 85%, 73%, 69%, and 60% in upgraded GS 3+4, nonupgraded GS 3+4, upgraded GS 4+3, and nonupgraded GS 4+3 group, respectively. There was significant difference between the nonupgraded 4+3 and upgraded 4+3 group, as well as between upgraded 3+4 and nonupgraded 3+4 group. However, the two middle patient groups, that is, the nonupgraded GS 3+4 group and the upgraded GS 4+3 group, did not show the statistical difference (Log-rank test, p value = 0.259). Conclusion The information on pathologic upgrading in the biopsy reports of patients could help to provide more detailed analysis for the biochemical recurrence of GS 7 prostate cancer.