From Diabetes to Oncology: Glucagon-like Peptide-1 (GLP-1) Receptor Agonist's Dual Role in Prostate Cancer.

Glucagon-like peptide-1 (GLP-1), an incretin hormone renowned for its role in post-meal blood sugar regulation and glucose-dependent insulin secretion, has gained attention as a novel treatment for diabetes through GLP-1 receptor agonists (GLP-1-RA). Despite their efficacy, concerns have been raised regarding the potential associations between GLP-1-RA and certain malignancies, including medullary thyroid cancer. However, evidence of its association with prostate cancer (PCa) remains inconclusive. This review delves into the intricate relationship between GLP-1-RA and PCa, exploring the mechanisms through which GLP-1-Rs may impact PCa cells. We discuss the potential pathways involving cAMP, ERK, AMPK, mTOR, and P27. Furthermore, we underscore the imperative for additional research to elucidate the impact of GLP-1-RA treatment on PCa progression, patient outcomes, and potential interactions with existing therapies. Translational studies and clinical trials are crucial for a comprehensive understanding of the role of GLP-1-RA in PCa management.

Quantification and molecular correlates of tertiary lymphoid structures in primary prostate cancer.

OBJECTIVE: To morphologically describe tertiary lymphoid structures (TLS) in prostatectomy specimens and correlate them with clinical and transcriptomic features. METHODOLOGY: A total of 72 consecutive cases of entirely submitted radical prostatectomy (RP) patients tested with the Decipher Genomic Classifier were included in the study. Images were manually annotated using QuPath tools to denote tumor regions and each cluster of TLS. Clusters of lymphocytes that were surrounded on all four sides by tumor were defined as intra-tumor TLS (IT-TLS). Clusters of lymphocytes at the leading edge of carcinoma with either the prostatic pseudocapsule or benign parenchyma at one end were defined as peri-tumor TLS (PT-TLS). A classification algorithm to distinguish lymphocytes from non-lymphocytic cells using a supervised machine learning model was used. The associations between TLS formation and 265 gene expression-based signatures were examined. RESULTS: The magnitude of total TLS correlations with primary tumor gene expression signatures was moderate (~0.35-0.5) with several HLA, T-cell and B-cell Cluster signatures, showing positive correlation with various metrics for quantification of TLS. On the other hand, immune suppressive signatures (Treg, MDSC) were negatively correlated. While signatures for macrophages, NK cells and other immune cell types were uncorrelated for the most part. PT-TLS was associated with MHC signatures while IT TLS correlated with MHC and T-cell signatures. CONCLUSIONS: Clusters of inflammatory cells in the RP specimen can be divided spatially into PT TLS and IT-TLS, each with its unique molecular correlates of tumor immune microenvironment. The presence of TLS is positively correlated with MHC signatures, T- cell and B-cell cluster signatures but, negatively correlated with immune suppressive signatures. A subset of prostate cancer demonstrate a robust inflammatory response, and warrant further characterization in larger cohorts.

Single-Port vs Multiport Robot-Assisted Partial Nephrectomy: A Meta-Analysis.

Background: Several centers have reported their experience with single-port robot-assisted partial nephrectomy (SP-RAPN); however, it is uncertain if utilization of this platform represents an improvement in outcomes compared to multiport robot-assisted partial nephrectomy (MP-RAPN). To evaluate this, we performed a meta-analysis to compare the perioperative, oncological, and functional outcomes between SP-RAPN and MP-RAPN. Methods: For relevant articles, three electronic databases, including PubMed, Scopus, and Web of Science, were searched from their inception until January 1, 2023. A meta-analysis has been reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and assessing the methodological quality of systematic reviews (AMSTAR) guidelines. The odds ratio (OR) and weighted mean difference (MD) were applied for the comparison of dichotomous and continuous variables with 95% confidence intervals (CI). Results: Of the 374 retrieved abstracts, 29 underwent full-text review, and 8 studies were included in the final analysis, comprising a total cohort of 1007 cases of RAPN (453 SP-RAPN cases and 554 MP-RAPN cases). Compared to MP-RAPN, the SP-RAPN group had a significantly longer ischemia time (MD = 4.6 minutes, 95% CI 2.8 to 6.3, p < 0.001), less estimated blood loss (MD = -12.4 mL, 95% CI -24.6 to -0.3, p = 0.045), higher blood transfusion rate (OR = 2.97, 95% CI 1.33 to 6.65, p = 0.008), and higher postoperative estimated glomerular filtration rate (eGFR) at 6 months (MD = 4.9 mL/min, 95% CI 0.2 to 9.7, p = 0.04). There was no significant difference in other outcomes between the two approaches, including the intraoperative complication, overall postoperative complication, minor postoperative complication (Clavien-Dindo I - II), major postoperative complication (Clavien-Dindo III-V), conversion to radical nephrectomy, pain score on day #1, pain score on discharge, morphine milligram equivalent usage, hospital stay, positive surgical margins, and postoperative eGFR. Conclusions: SP-RAPN represents an emerging technique using a novel platform. Initial studies have demonstrated that SP-RAPN is a safe and feasible approach to performing partial nephrectomy, although with inferior outcomes for ischemia time and blood transfusion rates. Further studies will be necessary to define the best usage of SP-RAPN within the surgeon's armamentarium.

Understanding the Termination of Urologic Cancer Clinical Trials: Insights and Challenges.

PURPOSE: Clinical trials are valuable evidence for managing urologic malignancies. Early termination of clinical trials is associated with a waste of resources and may substantially affect patient care. We sought to study the termination rate of urologic cancer clinical trials and identify factors associated with trial termination. METHODS: A cross-sectional search of ClinicalTrials.gov identified completed and terminated kidney, prostate, and bladder cancer clinical trials started. Trials were assessed for reasons for termination. Multivariable analyses were conducted to determine the significant factors associated with the termination. RESULTS: Between 2000 and 2020, 9,145 oncology clinical trials were conducted, of which 11.30% (n = 1,033) were urologic cancer clinical trials. Of the urologic cancer clinical trials, 25.38% (n = 265) were terminated, with low patient accrual being the most common reason for termination, 52.9% (n = 127). Multivariable analysis showed that only the university funding source odds ratio (OR) of 2.20 (95% CI, 1.45 to 3.32), single-center studies OR of 2.11 (95% CI, 1.59 to 2.81), and sample size of <50 were significant predictors of clinical trial termination OR of 5.26 (95% CI, 3.85 to 7.69); all P values are <.001. CONCLUSION: The termination rate of urologic cancer clinical trials was 25%, with low accrual being the most frequently reported reason. Trials funded by a university, single-center trials, and small trials (sample size <50) were associated with early termination. A better understanding of these factors might help researchers, funding agencies, and other stakeholders prioritize resource allocations for multicenter trials that aim to recruit a sufficient number of patients.

Utility of noninvasive biomarker testing and MRI to predict a prostate cancer diagnosis.

PURPOSE: To assess the diagnostic performance and utility of the ExoDx IntelliScore and an OPKO4K score to predict prostate cancer in men presenting with elevated PSA-both as independent predictors and in combination with clinical/MRI characteristics. METHODS: Patients with elevated PSA were retrospectively reviewed. Abnormal tests were defined as an OPKO4K score ≥ 7.5% and an ExoDx IntelliScore ≥ 15.6. Four regression models and ROC curves were generated based on: (1) age, PSA, and DRE, (2) model 1 + OPKO4K 4Kscore ≥ 7.5%, (3) model 2 + ExoDx IntelliScore ≥ 15.6, and (4) model 3 + MRI PIRADS 4-5. RESULTS: 359 men received an OPKO4K test, 307 had MRI and 113 had ExoDx tests. 163 men proceeded to prostate biopsy and 196 (55%) were saved from biopsy. Mean age was 65.0 ± 8.7 years and mean PSA was 7.1 ± 6.1 ng/mL. Positive biopsies were found in 84 (51.5%) men. The sensitivity and negative predictive value of an OPKO4K score were 86.7% and 72.3%; values for an ExoDx test were 76.5% and 77.1%, respectively. On regression analysis, clinical markers (Age, PSA, DRE) generated an AUC of 0.559. The addition of an OPKO4K score raised the AUC to 0.653. The stepwise addition of an ExoDx score raised the AUC to 0.766. The combined use of both biomarkers, patient characteristics, and MRI yielded an AUC of 0.825. CONCLUSION: This analysis demonstrates the high negative predictive value of both the OPKO4K score and ExoDX IntelliScore independently while demonstrating that the combination of an OPKO4K score, an ExoDX IntelliScore, and MRI increases predictive capability for biopsy confirmed prostate cancer.

Assessing Decision Regret in Patients with Same-Day Discharge Pathway After Robot-Assisted Radical Prostatectomy.

Introduction: After the introduction of same-day discharge (SDD) pathways for various surgeries, these pathways have demonstrated comparable complication rates and a reduced overall cost of care. Outpatient robot-assisted radical prostatectomy (RARP) is introduced in high-volume centers; however, patients' perspectives on the SDD RARP protocol are not well understood. Materials and Methods: A questionnaire consisting of 24 questions, including the Likert Decisional Regret Scale, was distributed to patients who underwent RARP at our center. The overall decision regret score was calculated as described in the literature. We used 15 as a cutoff point for differentiating between high- and low-regret rates. Median and interquartile range were determined for non-normally distributed variables, while mean ± standard deviation was calculated for continuous data. Results: Of the 72 patients who completed the questionnaire, 65.7% (n = 44) of patients felt no regret about their decision of choosing the SDD RARP protocol and 90.3% (n = 65) of men stated that they would have made the same decision. At the same time, 97.1% (n = 68) of patients would also recommend this procedure to others. The median decisional regret score of the cohort (n = 67) was 0 (0-10). Fifty-four of 67 (80.6%) patients were in the low-regret score group, while 13 (19.4%) were in the high-regret group. Patients in the high-regret group were more likely to have low household income (<$30,000 a year) and they experienced postoperative pain more frequently compared with patients in the lower regret group (7.7% vs 1.9%, p = 0.626, and 61.5% vs 38.9%, p = 0.212, respectively). Conclusions: Most patients expressed low regret about choosing the SDD pathway for RARP, underscoring the importance of thorough explanation of the procedure and discharge process to enhance patient experience. However, a subset of patients did express regret, possibly due to an interplay of patient- and procedure-related factors.

MRI-Based Radiomics Analysis of Levator Ani Muscle for Predicting Urine Incontinence after Robot-Assisted Radical Prostatectomy.

BACKGROUND: The exact role of the levator ani (LA) muscle in male continence remains unclear, and so this study aims to shed light on the topic by characterizing MRI-derived radiomic features of LA muscle and their association with postoperative incontinence in men undergoing prostatectomy. METHOD: In this retrospective study, 140 patients who underwent robot-assisted radical prostatectomy (RARP) for prostate cancer using preoperative MRI were identified. A biomarker discovery approach based on the optimal biomarker (OBM) method was used to extract features from MRI images, including morphological, intensity-based, and texture-based features of the LA muscle, along with clinical variables. Mathematical models were created using subsets of features and were evaluated based on their ability to predict continence outcomes. RESULTS: Univariate analysis showed that the best discriminators between continent and incontinent patients were patients age and features related to LA muscle texture. The proposed feature selection approach found that the best classifier used six features: age, LA muscle texture properties, and the ratio between LA size descriptors. This configuration produced a classification accuracy of 0.84 with a sensitivity of 0.90, specificity of 0.75, and an area under the ROC curve of 0.89. CONCLUSION: This study found that certain patient factors, such as increased age and specific texture properties of the LA muscle, can increase the odds of incontinence after RARP. The results showed that the proposed approach was highly effective and could distinguish and predict continents from incontinent patients with high accuracy.

Periprostatic Adipose Tissue MRI Radiomics-Derived Features Associated with Clinically Significant Prostate Cancer.

Background: Altered systemic and cellular lipid metabolism plays a pivotal role in the pathogenesis of prostate cancer (PCa). In this study, we aimed to characterize T1-magnetic resonance imaging (MRI)-derived radiomic parameters of periprostatic adipose tissue (PPAT) associated with clinically significant PCa (Gleason score ≥7 [3 + 4]) in a cohort of men who underwent robot-assisted prostatectomy. Methods: Preoperative MRI scans of 98 patients were identified. The volume of interest was defined by identifying an annular shell-like region on each MRI slice to include all surgically resectable visceral adipose tissue. An optimal biomarker method was used to identify features from 7631 intensity- and texture-based properties that maximized the classification of patients into clinically significant PCa and indolent tumors at the final pathology analysis. Results: Six highest ranked optimal features were derived, which demonstrated a sensitivity, specificity, and accuracy of association with the presence of clinically significant PCa, and area under a receiver operating characteristic curve of 0.95, 0.39 0.82, and 0.82, respectively. Conclusion: A highly independent set of PPAT features derived from MRI scans that predict patients with clinically significant PCa was developed and tested. With future external validation, these features may provide a more precise scientific basis for deciding to omit biopsies in patients with borderline prostate-specific antigen kinetics and multiparametric MRI readings and help in the decision of enrolling patients into active surveillance.

Impact of Obstructive Sleep Apnea Syndrome on Time to Complete Recovery of Continence After Robot-Assisted Radical Prostatectomy: A Propensity Score Matching Analysis.

Background: Postoperative urinary incontinence after robot-assisted radical prostatectomy (RARP) represents a bothersome side effect, which may permanently affect patient's quality of life. Several studies have demonstrated that obstructive sleep apnea syndrome (OSAS) is associated with urinary symptoms such as urge incontinence, overactive bladder, and nocturia. In this study, we sought to further explore the effect of OSAS on urinary continence after RARP. Methods: We queried our prospectively collected institutional RARP database and identified 82 patients with OSAS and 131 controls, which were matched for age and body mass index (BMI), with available follow-up data for continence. To minimize selection bias, we conducted a propensity score-matched analysis. Patient's characteristics and urinary continence outcomes were compared between the two groups before and after propensity-score matching. Kaplan-Meier curves were constructed to assess the difference in continence between the two groups. Results are presented as means with standard deviations and percentages with 95% confidence intervals (CIs). Results: A total of 213 patients were included in the analysis, of whom 82 with OSAS and 131 with non-OSAS (control group). The mean age of the total cohort was 61.7 ± 6.96 years, the mean BMI was 30.4 ± 5.36, and 52% of the cohort were classified as obese (BMI ≥30). In post-propensity score-matched analyses, there was no significant difference in baseline demographics and tumor characteristics between the two groups (included 82 cases in each group). The median time to continence was 6.6 months for the control group as compared with 13.0 months for the OSAS group (p < 0.001). At 12 months the continence rate for the OSAS group was 41.2% (95% CI: 28.9%-51.4%) as compared with 61.7% (95% CI: 28.5%-71.5%) for the control group. At 24 months the continence rate for the OSAS group was 68.7% (95% CI: 56%-77.7%) as compared with 90.8% (95% CI: 79%-96%) for the control group. Conclusion: On matched analysis, we found that patients with OSAS tended to demonstrate worse urinary continence recovery as compared with patients without OSAS. Additional investigation will be necessary to confirm these initial findings.

Single-Port Robotic Applications in Urology.

Objective: The da Vinci single-port (SP) platform represents the latest innovation in minimally invasive urologic surgery, and the adoption of this technology by urologists is increasing. In this article, we briefly describe the evolution of minimally invasive and single-site surgery, and offer a comprehensive review of the current literature on the SP platform. Materials and Methods: For relevant articles, three electronic databases, including PubMed, Scopus, and Web of Science, were searched from their inception until August 15, 2022. The published literature to date within SP robotic surgery in urology will be discussed. Evidence Synthesis: There are relatively few high-quality studies on the SP system, but there are multiple case series describing unique indications and surgical approaches with the SP robot, demonstrating safety and feasibility in the hands of experienced robotic surgeons. There also are an increasing number of prospective, larger cohort studies comparing outcomes between SP and multiport (MP) approaches that show benefits of the SP system regarding improved cosmesis, postoperative pain control, and decreased length of stay. Conclusions: Multiple prospective studies have shown benefits regarding cost and pain control for SP platform procedures compared to the traditional MP robotic approach. While its high cost and learning curve represent barriers to adoption, the SP platform represents a critical development in minimally invasive surgery. As this technology is further implemented at more institutions, long-term, high-quality data should accrue that will demonstrate its true value.

When to order genomic tests: development and external validation of a model to predict high-risk prostate cancer at the genotypic level.

PURPOSE: The aim of this study was to develop a model to predict high-genomic-risk prostate cancer (PCa) according to Decipher score, a validated 22 gene prognostic panel. By doing so, one might select the individuals who are likely to benefit from genomic testing and improve pre-op counseling about the need for adjuvant treatments. METHODS: We retrospectively reviewed IRB-approved databases at two institutions. All patients had preoperative magnetic resonance imaging (MRI) and Decipher prostate radical prostatectomy (RP), a validated 22 gene prognostic panel. We used binary logistic regression to estimate high-risk Decipher (Decipher score > 0.60) probability on RP specimen. Area under the curve (AUC) and calibration were used to assess the accuracy of the model in the development and validation cohort. Decision curve analysis (DCA) was performed to assess the clinical benefit of the model. RESULTS: The development and validation cohort included 622 and 185 patients with 283 (35%) and 80 (43%) of those with high-risk Decipher. The multivariable model included PSA density, biopsy Gleason Grade Group, percentage of positive cores and MRI extracapsular extension. AUC was 0.73 after leave-one-out cross-validation. DCA showed a clinical benefit in a range of probabilities between 15 and 60%. In the external validation cohort, AUC was 0.70 and calibration showed that the model underestimates the actual probability of the outcome. CONCLUSIONS: The proposed model to predict high-risk Decipher score at RP is helpful to improve risk stratification of patients with PCa and to assess the need for additional testing and treatments.

Single-port and multiport robot-assisted radical prostatectomy: A meta-analysis.

Objective: To compare the perioperative, oncological, and functional outcomes between single-port robot-assisted radical prostatectomy (SP-RARP) and multiport robot-assisted radical prostatectomy (MP-RARP) via a meta-analysis. Methods: For relevant articles, three electronic databases, including PubMed, Scopus, and Web of Science, were searched from their inception until January 15, 2022. A meta-analysis has been reported in line with PRISMA 2020 and AMSTAR Guidelines. The risk ratio and weighted mean difference (MD) were applied for the comparison of dichotomous and continuous variables with 95% confidence intervals (CI). Results: Of the 368 retrieved abstracts, 41 underwent full-text review, and seven studies were included in the final analysis, comprising a total cohort of 1,934 cases of RARP (355 SP-RARP cases and 1,579 MP-RARP cases). Compared to MP-RARP, the SP-RARP group had less postoperative pain score (MD = -0.7, 95% CI -1 to -0.4, P<0.001), morphine milligram equivalents usage (MD = -3.8, 95% CI -7.5 to -0.1, P=0.04), hospital stay (MD = -1, 95% CI -1.8 to -0.1, P=0.019), and urinary catheterization time (MD = -1.1, 95% CI -1.9 to -0.3, P=0.008). However, the SP-RARP group had a longer console time than the MP-RARP group (MD = 5.3, 95% CI 2.6 to 7.9, P<0.001). Conclusions: Our study demonstrated that early results were mostly equivalent with the single-port approach. This technology may help to reduce the hospital stay and postoperative pain for patients undergoing radical prostatectomy compared to MP-RARP, without compromising the functional and early oncological outcomes.

Fluorescence-guided radical prostatectomy.

Robotic-assisted laparoscopic radical prostatectomy represents one of the most common operations in urologic oncology and involves several critical technical steps including pelvic lymph node dissection, cavernous nerve sparing and vesicourethral anastomosis. The quality of performing these steps is linked to functional and oncological outcomes. Indocyanine green [ICG] is a non-radioactive, water-soluble compound which allows for enhanced visualization with near-infrared fluorescence of both anatomical structures and vasculature during complex abdominal operations such as prostatectomy. During the last decade, several investigators have examined the value and role of ICG fluorescence during prostatectomy. In this review, we sought to evaluate the body of evidence for fluorescence-guided robotic prostatectomy as well as assess potential future areas of investigation with this technology.

Does Perioperative Testosterone Predict Post-Prostatectomy Genomic Risk Score?

PURPOSE: The role of endogenous testosterone in de novo prostate cancer pathogenesis in humans remains unclear. The effect of testosterone on the tumor genome is not explored. We sought to explore the correlation between perioperative testosterone level and genomic risk score in a cohort of men who underwent radical prostatectomy. MATERIALS AND METHODS: We included patients who underwent radical prostatectomy (2013-2018) and had adverse pathological features in their final surgical specimens (positive margin, and/or pT3a or higher). The outcome of interest was the genomic risk score: low (<0.45), intermediate (0.45-0.6) and high (>0.6). The associations between serum testosterone level and 188 gene expression-based signatures were examined. Secondary outcomes of interest included biochemical recurrence and receipt of secondary treatment. RESULTS: The median genomic risk score was lower in the low testosterone group compared to the intermediate and normal testosterone groups (0.38 vs 0.52 vs 0.53, respectively; p=0.049). There was no difference in biochemical recurrence-free survival between the 3 testosterone groups (p=0.9). Patients with low testosterone levels had higher odds of receiving secondary treatment (OR: 2.27; 95% CI: 1.14-4.50; p=0.02) than those with normal levels. A total of 43 (of 188) gene expression signatures were associated with testosterone level (p <0.05). In total, 33 signatures were positively associated with serum testosterone levels, including 12 signatures involved in DNA repair pathways. CONCLUSIONS: This is the first study to assess the correlation of preoperative testosterone level on the tumor transcriptome and showed no clinical correlation between pre-defined genomic risk score groups and testosterone groups. This study adds to the notion of the limited role of endogenous testosterone on the development of de novo high-risk localized prostate cancer.

Oncological and Functional Outcomes of Robot-Assisted Radical Prostatectomy in Kidney Transplant Recipients.

OBJECTIVE: Management of prostate cancer in kidney transplant recipients presents a unique surgical challenge due to the risk of direct or indirect injury to the transplanted kidney. Herein, we report the largest single center study of Robot-assisted Radical prostatectomy (RARP) in kidney transplant recipients. METHODS: Between Jan 2014-2019, 14 kidney transplant recipients with prostate cancer underwent RARP. Clinical and pathological features, perioperative and postoperative complications were retrospectively evaluated. Continence was defined as by patient utilization of zero urinary pads postoperatively. RESULTS: The median (IQR) age at RARP was 60.2 (57.8-61.3) years, the interval between kidney transplant and RARP was 8.1 ± 7.5 years. The median (IQR) PSA was 6.9 (4-8.6); 10 of 14 patients had intermediate or high-risk prostate cancer. The median ASA score was 3, the mean (SD) operative time was 129.7 (26.3) minutes, and mean (SD) blood loss was 110 (44.6) ml. All cases were completed robotically, there was no graft loss or injury to transplanted ureter, and the mean length of stay was 1 (0.26) day.Final pathology demonstrated that 42.8% (6/14) of the patients had nonorgan confined disease (pT3a/T3b). 50% (7/14) of the patients were upgraded to higher risk Gleason disease on final surgical pathology. Post-RARP continence rate at 3 months, and 12 months were 45.5% (5/11) and 87.5% (7/8), respectively. CONCLUSION: RARP following kidney transplantation represents a safe and feasible operation which does not appear to compromise oncological or transplant outcomes.

Measuring Quality of Life Following Robot-Assisted Radical Prostatectomy.

BACKGROUND: Prostate cancer (PCa) represents the most common solid organ malignancy in men. Fortunately, at the time of diagnosis, the majority of cases are staged as localized or regional disease, conferring excellent 5- and 10-year cure rates. There are several first line treatment options including surgical approaches such as robot-assisted radical prostatectomy (RARP) and radiation therapy (RT) available to patients with localized disease that offer similar PCa oncologic outcomes but are associated with potentially significant side effects which may impact health-related quality of life (HRQOL) domains. Recently, clinicians and investigators have sought to better understand these changes in HRQOL metrics with the utilization of patient-reported outcomes (PRO). Given that RARP represents the most common surgical treatment for PCa in the United States, there has been a particular interest in assessing these outcomes derived by patient perspectives to more fully appreciate treatment-related impact on quality of life following RARP. OBJECTIVE: This narrative review sought to explore the instruments available to measure quality of life after RARP, a review of the PRO data after RARP, and future directions for assessing and improving quality of life outcomes following this surgery. CLINICAL USE: There are several treatment options for men diagnosed with local and regional prostate cancer with similar oncologic outcomes but differing patterns of side effects affecting post-treatment quality of life. Understanding data reported directly by patients following RARP about their side effects and quality of life gives providers additional information for appropriate preoperative counseling for patients choosing between treatment options for their prostate cancer.

Family history in patients who would have been candidates for active surveillance.

INTRODUCTION It is unknown whether a family history of prostate cancer confers additional risk among men who are candidates for active surveillance (AS). MATERIALS AND METHODS: Using a prospectively maintained database of men who underwent radical prostatectomy (RP) (2010- 2018), candidates for AS were identified according to the expanded criteria. Pathological upgrading was defined as a pathologic Gleason score (pGS) of 3+4 or higher for patients with a biopsy GS of 3+3 and a pGS of 4+3 or higher for patients with a biopsy GS of 3+4. Major upgrading was defined as a pGS of 4+4 or higher. The ₓ2 test was used for comparisons. RESULTS: Of 1,320 men who were candidates for AS, 288 (21.8%) had a family history of prostate cancer. There were no differences in terms of the age, number of positive cores, or number of patients with a GS of 7 between the two groups. Pathological upgrading was observed in 61.1% of the total cohort, with no difference observed between the two groups (60.7% versus 62.5%; p = 0.5). CONCLUSION: In men who are eligible for AS according to the expanded criteria, a family history of prostate cancer does not appear to be associated with adverse pathology at RP.

Correlative analysis between two commercially available post-prostatectomy genomic tests.

BACKGROUND: Multiple genomic tests are available following radical prostatectomy (RP), however, there is a lack of head-to-head evidence for these tests. We sought to compare the performance of two genomic tests in predicting post-RP oncological outcomes. METHODS: A cohort of 16 post-RP patients with adverse pathological features who had obtained both Decipher (D) and Prolaris (P) testing. The Pearson correlation was used to compare scores from D and cell cycle progression (CCP) from P. Then, we derived a microarray CCP (mCCP) from D and correlated with P-CCP. The associations of D and mCCP with biochemical recurrence (BCR) and metastasis (M) was evaluated in multivariable survival analysis (MVA) in a large cohort of RP patients treated at Johns Hopkins University (1992-2010). In addition, we characterized the expression of the 31 P-CCP genes and mCCP scores in a cohort of 17,967 RP samples from Decipher platform. RESULTS: There was significant correlation between the D score and P-CCP (r = 0.67, p = 0.004), and between the 10-year probability of BCR reported by P and 5-year probability of M reported by D (r = 0.69, p = 0.003). In this cohort, mCCP derived from the D platform was highly correlated to the reported P-CCP scores from the P platform (r = 0.88, p = 6.7e-6). In a comparative retrospective RP cohort, both mCCP and D were significantly associated with M outcome (p < 0.01 for both). On MVA, D was a predictor of M (HR 1.3, 95% CI [1.12-1.52], p = 0.0005), while mCCP was not a predictor of M (p = 0.62). In the D platform cohort, the 31 P-CCP genes were correlated to each other, and TOP2A was the most correlated to mCCP (r = 0.7). CONCLUSIONS: We found that P and D scores post-RP were correlated and help in identifying patients who at high risk of BCR in this cohort. In a larger cohort with longer follow-up, D was predictor of M, whereas mCCP was not.

External validation of genomic classifier-based risk-stratification tool to identify candidates for adjuvant radiation therapy in patients with prostate cancer.

OBJECTIVE: To externally validate a Genomic Classifier (GC) based risk-stratification nomogram identifying candidates who would benefit from adjuvant radiation (aRT) therapy after radical prostatectomy (RP). METHODS: We identified 350 patients who underwent RP, between 2013 and 2018, and had adverse pathological features (positive margin, and/or pT3a or higher) on final pathology. Genomic profile was available for all these men. The clinical recurrence-free survival was estimated using the Kaplan-Meier method. The external validity of the nomogram was tested using the concordance index (c-index), calibration plot, and decision curve analysis. RESULTS: The median follow-up of the cohort was 26.5 months. Overall, 14% of the patients received aRT. During the follow-up period, 3.4% of the patients developed metastasis. Overall 3-year metastasis-free survival was 95% (95% CI 0.92-0.98). The c-index of the nomogram was 0.84. The calibration of the model was favorable. Decision-curve analysis showed a positive net benefit for probabilities ranging between 0.01 and 0.09, with the highest difference at threshold probability around 0.05. At that threshold, the net benefit is 0.06 for the model and 0 for treating all the patients. CONCLUSION: Our report is the first to confirm the validity of this genomic-based risk-stratification tool in identifying men who might benefit from aRT after RP. As such, it can be a useful instrument to be incorporated in shared decision making on whether administration of aRT will lead to a clinically meaningful benefit. Such a model can also be useful for patients' classification in future clinical trials.