Germ cell tumors of the testis (GCTs) provide an ideal tumor model to investigate the cellular versus genetic origin of cancers. In this single institutional study, we evaluated 38 patients with bilateral GCT, including tumors that occurred simultaneously (synchronous) and those occurring at different times (metachronous). For nine of these patients, DNA was isolated from the right and left GCT to determine the genomic and epigenetic differences between tissues using whole-exome sequencing (WES) and reduced representation bisulfite sequencing (RRBS). We found that seminomas and non-seminomas are molecularly distinct based on DNA methylation and not due to synchronous or metachronous disease. In addition, we did not observe conservation of genetic mutations in right and left GCT in either synchronous or metachronous disease. Our data suggest a cellular origin for bilateral GCT.

Objectives: To evaluate the association of preoperative body mass index (BMI) on adverse pathology in peripheral (PZ) and transition zone (TZ) tumors at time of prostatectomy for localized prostate cancer. Methods: Clinical and pathologic characteristics were obtained from up to 100 consecutive prostatectomy patients from 10 prostate surgeons. BMI groups included normal (18.5-24.9), overweight (25-29.9) and obese (> 29.9). "Aggressive" pathology was defined as the presence of Grade Group (GG) 3 or higher and/or pT3a or higher. Pathologic characteristics were evaluated for association with BMI using univariate analyses. Our primary outcome was the association of BMI with adverse pathology, which was assessed using logistic regression accounting for patient age. We hypothesized that obese BMI would be associated with aggressive TZ tumor. Results: Among 923 patients, 140 (15%) were classified as "normal" BMI, 413 (45%) were "overweight", and 370 (40%) were "obese." 474 patients (51%) had aggressive PZ tumors while 102 (11%) had aggressive TZ tumors. "Obese" BMI was not associated with aggressive TZ tumor compared to normal weight. Increasing BMI group was associated with overall increased risk of aggressive PZ tumor (HR 1.56 [95CI 1.04-2.34]; P = 0.03). Among patients with GG1 or GG2, increasing BMI was associated with presence of pT3a or higher TZ tumor (P = 0.03). Conclusions: Increased BMI is associated with adverse pathology in PZ tumors. TZ adverse pathology risk may be increased among obese men with GG1 or GG2 disease, which has implications for future studies assessing behavioral change among men whose tumors are actively monitored. (c) 2023 Published by Elsevier Inc.

BackgroundWe previously reported that increases in circulating sphingolipids are associated with elevated risk of biopsy Gleason grade group (GG) upgrading in men on Active Surveillance (AS) for prostate cancer. Here, we aimed to validate these findings and establish a blood-based sphingolipid biomarker panel for identifying men on AS who are at high-risk of biopsy GG upgrading.MethodsMen diagnosed with low- or intermediate-risk prostate cancer in one of two AS cohorts (CANARY PASS and MDACC) were followed for GG upgrading after diagnostic and confirmatory biopsy. The PASS cohort consisted of 544 patients whereas the MDACC Cohort consisted of 697 patients. The number of patients with GG upgrading during course of study follow-up in the PASS and MDACC cohorts were 98 (17.7%) and 133 (19.1%), respectively. Plasmas collected prior to confirmatory biopsy were used for mass spectrometry-based quantitation of 87 unique sphingolipid species. A neural network layer based on 21 sphingolipids was developed in the CANARY PASS cohort for predicting biopsy GG upgrading. Tertile-based thresholds for low-, intermediate-, and high-risk strata were subsequently developed for the sphingolipid panel as well as a model that combined the sphingolipid panel with PSA density and rate of core positivity on diagnostic biopsy. The resultant models and risk thresholds for GG upgrading were validated in the MDACC cohort. Performance was assessed using Cox proportional hazard models, C-index, AUC, and cumulative incidence curves.ResultsThe sphingolipid panel had a HR (per unit standard deviation increase) of 1.36 (95% CI: 1.07-1.70) and 1.35 (95% CI: 1.11-1.64) for predicting GG biopsy upgrading in the PASS and MDACC cohort, respectively. The model that combined the sphingolipid panel with PSA density and rate of core positivity achieved a HR of 1.63 (95% CI: 1.33-2.00) and 1.44 (1.25-1.66), respectively. Tertile-based thresholds, established in the PASS cohort, were applied to the independent MDACC cohort. Compared to the low-risk group, MDACC patients in the high-risk strata had a GG biopsy upgrade HR of 3.65 (95% CI: 2.21-6.02), capturing 50% of the patients that had biopsy upgrading during study follow-up.ConclusionsThe sphingolipid panel is independently associated with GG biopsy upgrading among men in two independent AS cohorts who have previously undergone diagnostic and confirmatory biopsy. The sphingolipid panel, together with clinical factors, provides a potential means for risk stratification to better guide clinical management of men on AS.

Germ cell tumor of the testis (GCT) is a curable cancer even when it is widely metastatic; however, outcomes can differ based on tumor histology. Chemo-resistance in certain phenotypes, such as teratoma and yolk sac tumor, contributes to poor clinical outcomes in some patients with GCT. Despite this resistance to S-YSTemic therapy, many of these tumor subtypes remain amenable to surgical resection and possible cure. In this study, we report on a series of seven patients highlighting two chemo-resistant subtypes of nonseminomatous germ cell tumor (NSGCT), sarcomatoid yolk sac tumor (S-YST), and epithelioid trophoblastic tumor (ETT) for which early resection rather than additional salvage chemotherapy or high-dose intense chemotherapy might provide a superior clinical outcome and enhance cure rate.

BACKGROUND AND OBJECTIVE:The feasibility and safety of a robotic approach for postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in testicular cancer have been demonstrated, but data on long-term oncological outcomes of this procedure are limited. Our aim was to evaluate oncological outcomes following robotic PC-RPLND in this setting. METHODS:This retrospective cohort study included consecutive patients with testicular cancer treated with robotic PC-RPLND at 11 academic centers worldwide between 2011 and 2023. Patient characteristics, clinicopathological findings, and oncological outcomes were recorded. Recurrence-free survival (RFS) was estimated via the Kaplan-Meier method. KEY FINDINGS AND LIMITATIONS:A total of 173 patients were included, of whom 159 underwent pure robotic PC-RPLND; 14 cases were converted to open surgery. Among the pure robotic cases, 152 (96%) had nonseminoma, 122 (77%) had International Germ Cell Cancer Collaborative Group good risk, and 120 (76%) had a postchemotherapy mass size ≤5 cm. Salvage chemotherapy was received by ten patients (6%). Median estimated blood loss, operative time, and length of hospital stay were 100 ml, 300 min, and 2 d, respectively. Final pathology revealed necrosis/fibrosis in 64 cases (40%), teratoma in 78 (49%), and viable germ-cell tumor in 17 (11%). At median follow-up of 22 mo (interquartile range 7-50), eight patients had disease recurrence, which was in-field in three cases. One port-site recurrence was identified. The median time to recurrence was 7 mo. The 4-yr RFS rate was 93%. Two cancer-related deaths were recorded. Subgroup analysis revealed that patients with conversion to open surgery were more likely to have a larger preoperative mass and received salvage chemotherapy before RPLND. In addition, conversion to open surgery was associated with a higher rate of perioperative complications; however, oncological outcomes were statistically similar to those for pure robotic PC-RPLND. The main limitation of the study is its retrospective nature. CONCLUSIONS AND CLINICAL IMPLICATIONS:Robotic PC-RPLND in testicular cancer is associated with acceptable intermediate-term oncological outcomes in appropriately selected patients. PATIENT SUMMARY:In this large multicenter study, we investigated the outcomes of robotic surgery after chemotherapy for advanced testicular cancer. We found that robotic surgery yields acceptable cancer control results.

Abstract Purpose: Develop and deploy a robust discovery platform that encompasses heterogeneity, clinical annotation, and molecular characterization and overcomes the limited availability of prostate cancer models. This initiative builds on the rich MD Anderson (MDA) prostate cancer (PCa) patient-derived xenograft (PDX) resource to complement existing publicly available databases by addressing gaps in clinically annotated models reflecting the heterogeneity of potentially lethal and lethal prostate cancer. Experimental Design: We performed whole-genome, targeted, and RNA sequencing in representative samples of the same tumor from 44 PDXs derived from 38 patients linked to donor tumor metadata and corresponding organoids. The cohort includes models derived from different morphologic groups, disease states, and involved organ sites (including circulating tumor cells), as well as paired samples representing heterogeneity or stages before and after therapy. Results: The cohort recapitulates clinically reported alterations in prostate cancer genes, providing a data resource for clinical and molecular interrogation of suitable experimental models. Paired samples displayed conserved molecular alteration profiles, suggesting the relevance of other regulatory mechanisms (e.g., epigenomic) influenced by the microenvironment and/or treatment. Transcriptomically, models were grouped on the basis of morphologic classification. DNA damage response–associated mechanisms emerged as differentially regulated between adenocarcinoma and neuroendocrine prostate cancer in a cross-interrogation of PDX/patient datasets. Conclusions: We addressed the gap in clinically relevant prostate cancer models through comprehensive molecular characterization of MDA PCa PDXs, providing a discovery platform that integrates with patient data and benchmarked to therapeutically relevant consensus clinical groupings. This unique resource supports robust hypothesis generation and testing from basic, translational, and clinical perspectives.

You have accessJournal of UrologyProstate Cancer: Localized: Ablative Therapy I (MP25)1 May 2024MP25-16 FOCAL CRYOTHERAPY FOR LOCALIZED PROSTATE CANCER: INITIAL REPORT FROM THE INTERNATIONAL FOCAL THERAPY SOCIETY (FTS) REGISTRY Ardeshir Rastinehad, Sriram Deivasigamani, Michael J. Schwartz, John F. Ward, Arvin George, Abhinav Sidana, Ezequiel Becher, Aaron E. Katz, Rafael Sanchez-Salas, and Thomas J. Polascik Ardeshir RastinehadArdeshir Rastinehad , Sriram DeivasigamaniSriram Deivasigamani , Michael J. SchwartzMichael J. Schwartz , John F. WardJohn F. Ward , Arvin GeorgeArvin George , Abhinav SidanaAbhinav Sidana , Ezequiel BecherEzequiel Becher , Aaron E. KatzAaron E. Katz , Rafael Sanchez-SalasRafael Sanchez-Salas , and Thomas J. PolascikThomas J. Polascik View All Author Informationhttps://doi.org/10.1097/01.JU.0001008692.26556.39.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Focal cryotherapy was initially utilized to treat low-risk prostate cancer (PCa) as an alternative to active surveillance. The development of imaging and biopsy techniques resulted in the accurate localization of the tumor that allowed focal therapy to be considered in intermediate and carefully selected localized high-risk diseases. This study presents the first report of the oncological and functional outcomes of focal cryotherapy in patients with organ confined PCa, from our prospective, international multicenter Focal Therapy Society (FTS) registry. METHODS: An analysis of consecutive patients who underwent focal cryoablation with >6 months of follow-up between 2005-2023 was conducted. These patient details were prospectively recorded in the FTS registry from the 8 centers (7 US and one South American). The primary outcome was to determine the failure-free survival (FFS), defined as avoidance of salvage therapy including radical prostatectomy, radiation therapy, repeat ablation, systemic therapy, and metastasis/cancer-specific death. The secondary outcomes include cancer-specific survival (CSS), overall survival (OS), and metastasis-free survival (MFS) along with reporting the functional outcomes including urinary continence, defined as strictly no pad usage, and preserved erectile function (patient-reported, with/without pharmacologic intervention, defined as an erection sufficient for sexual intercourse of those patients who were initially potent IIEF 5>17) at 12 months. RESULTS: A total of 282 patients met the study inclusion criteria. The median follow-up was 24 months (interquartile range [IQR] 12-43). The median age was 72 years (IQR, 66-76) and the median preoperative PSA was 6.8 ng/ml (IQR, 5-9.35). A total of 217 (77%) patients and 45 (16%) patients had D'Amico intermediate- and high-risk disease. FFS was 74% (95% confidence interval [CI] 63-80%) at 5 years. The MFS, CSS and OS at 5 years was 97% (95% CI 89-99%), 99% (95% CI 92-99%), and 96% (95% CI 89-98%), respectively. Post-ablation biopsy was performed in 70% (198/282) of patients, showing a clinically significant in-field and out-field PCa recurrence rate of 11% and 18%. Of 212 patients with minimum of 1-year follow-up, 74% (77/104) of patients who were initially potent maintained erections sufficient for sexual intercourse and 98% (209/212) of patients are continent requiring no pad usage at 12-month follow-up. CONCLUSIONS: In this multicenter international study of focal cryoablation for organ-confined prostate cancer, mid-term results appeared to be promising with good oncological control and low rates of treatment-related functional outcomes decline. Further multicenter studies with a larger sample size are required to validate these findings. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e410 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Ardeshir Rastinehad More articles by this author Sriram Deivasigamani More articles by this author Michael J. Schwartz More articles by this author John F. Ward More articles by this author Arvin George More articles by this author Abhinav Sidana More articles by this author Ezequiel Becher More articles by this author Aaron E. Katz More articles by this author Rafael Sanchez-Salas More articles by this author Thomas J. Polascik More articles by this author Expand All Advertisement PDF downloadLoading ...

Introduction While active surveillance (AS) is the preferred management strategy for low risk prostate cancer, frequent clinical monitoring and invasive biopsy are associated with costs, discomfort and overtreatment among a group of men at minimal risk of prostate cancer-related mortality. Non-invasive markers may help guide de-escalation strategies, though none are consistently associated with risk of biopsy Gleason grade group (GG) upgrading. Our group previously determined that circulating sphingolipid levels may be associated with biopsy GG upgrading among men on AS. We describe the development and validation of a sphingolipid-based biomarker and its performance with established clinical factors in this population. Methods Men diagnosed with low- or intermediate-risk prostate cancer in one of two AS cohorts (CANARY PASS [N=544] and MDACC [N=238]) were followed for Gleason GG upgrading after diagnostic and confirmatory biopsy. Plasmas collected prior to confirmatory biopsy were used in mass spectrometry-based lipidomic assays, and sphingolipid metabolite levels were quantified. We leveraged machine learning in 8 different models to develop a panel of sphingolipids that was associated with biopsy GG upgrading, and the sphingolipid panel was set. Multivariable cox proportional hazards models were used to determine association between sphingolipid panel and risk of biopsy GG upgrading. Cut points were then established using a combination of panel score and clinical factors. Results Median age was 67 (IQR 58-70) in the CANARY PASS cohort and 63 (IQR 58-68) in the MDACC cohort. 85.5% and 90.0% of patients had GG1 disease, respectively. Median follow-up was 2.1 years (1.4-4.5) and 3.5 years (1.0-5.1) and 98/544 (18%) and 33/238 (14%) had GG upgrading, respectively. A panel of sphingolipids generated using a neural network achieved the best performance, and was independently associated with GG upgrade on multivariable models in the PASS cohort (HR of 1.33, 95% CI 1.05-1.70 per StDev increase) and the MDACC validation cohort (HR 2.51, 95% CI: 1.42-2.4 per unit StDev increase). When combined with clinical factors PSA density and core biopsy positivity, tertile-based cutoffs demonstrated that high risk group stratification was associated with biopsy GG upgrade when compared to the low risk group in both cohorts (HR 3.17, 95% CI 1.84-5.46; and, HR 9.70, 95% CI 2.89-32.5, respectively). Conclusions The sphingolipid panel is independently associated with GG biopsy upgrading among men in two independent AS cohorts who have previously undergone diagnostic and confirmatory biopsy. Use of the sphingolipid panel, along with cut offs that include important clinical factors, may allow for safe de-escalation strategies among men on AS. Future studies are needed to further validate these data and incorporate other clinical factors such as MRI results.

OBJECTIVES:To determine whether 6 months of preoperative apalutamide for intermediate-risk prostate cancer (IRPCa) reduces the aggregate postoperative radiotherapy risk and to evaluate associations of molecular perturbations with clinical outcomes in this study cohort. PATIENTS AND METHODS:Between May 2018 and February 2020, eligible patients with IRPCa (Gleason 3 + 4 or 4 + 3 and clinical T2b-c or prostate-specific antigen level of 10-20 ng/mL) were treated with apalutamide 240 mg/day for 6 months followed by radical prostatectomy (RP) in this single-arm, phase II trial. The primary endpoint was presence of any adverse pathological feature at risk of pelvic radiation (pathological T stage after neoadjuvant therapy [yp]T3 or ypN1 or positive surgical margins). Translational studies, including germline and somatic DNA alterations and RNA and protein expression, were performed on post-apalutamide RP specimens, and assessed for associations with clinical outcomes. RESULTS:A total of 40 patients underwent a RP, and only one patient discontinued apalutamide prior to 6 months. In all, 40% had adverse pathological features at time of RP, and the 3-year biochemical recurrence (BCR) rate was 15%, with 27.5% being not evaluable. Genomic alterations frequently seen in metastatic PCas, such as androgen receptor (AR), tumour protein p53 (TP53), phosphatase and tensin homologue (PTEN), or BReast CAncer associated gene (BRCA1/2) were underrepresented in this localised cohort. Adverse pathological features and BCR at 3-years were associated with increased expression of select cell cycle (e.g., E2F targets: adjusted P value [Padj] < 0.001, normalised enrichment score [NES] 2.47) and oxidative phosphorylation (Padj < 0.001, NES 1.62) pathways. CONCLUSIONS:Preoperative apalutamide did not reduce the aggregate postoperative radiation risk to the pre-specified threshold in unselected men with IRPCa. However, transcriptomic analysis identified key dysregulated pathways in tumours associated with adverse pathological outcomes and BCR, which warrant future study. Further investigation of preoperative therapy is underway for men with high-risk PCa.

CONTEXT:Whole-gland ablation is a feasible and effective minimally invasive treatment for localized prostate cancer (PCa). Previous systematic reviews supported evidence for favorable functional outcomes, but oncological outcomes were inconclusive owing to limited follow-up. OBJECTIVE:To evaluate the real-world data on the mid- to long-term oncological and functional outcomes of whole-gland cryoablation and high-intensity focused ultrasound (HIFU) in patients with clinically localized PCa, and to provide expert recommendations and commentary on these findings. EVIDENCE ACQUISITION:We performed a systematic review of PubMed, Embase, and Cochrane Library publications through February 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. As endpoints, baseline clinical characteristics, and oncological and functional outcomes were assessed. To estimate the pooled prevalence of oncological, functional, and toxicity outcomes, and to quantify and explain the heterogeneity, random-effect meta-analyses and meta-regression analyses were performed. EVIDENCE SYNTHESIS:Twenty-nine studies were identified, including 14 on cryoablation and 15 on HIFU with a median follow-up of 72 mo. Most of the studies were retrospective (n = 23), with IDEAL (idea, development, exploration, assessment, and long-term study) stage 2b (n = 20) being most common. Biochemical recurrence-free survival, cancer-specific survival, overall survival, recurrence-free survival, and metastasis-free survival rates at 10 yr were 58%, 96%, 63%, 71-79%, and 84%, respectively. Erectile function was preserved in 37% of cases, and overall pad-free continence was achieved in 96% of cases, with a 1-yr rate of 97.4-98.8%. The rates of stricture, urinary retention, urinary tract infection, rectourethral fistula, and sepsis were observed to be 11%, 9.5%, 8%, 0.7%, and 0.8%, respectively. CONCLUSIONS:The mid- to long-term real-world data, and the safety profiles of cryoablation and HIFU are sound to support and be offered as primary treatment for appropriate patients with localized PCa. When compared with other existing treatment modalities for PCa, these ablative therapies provide nearly equivalent intermediate- to long-term oncological and toxicity outcomes, as well as excellent pad-free continence rates in the primary setting. This real-world clinical evidence provides long-term oncological and functional outcomes that enhance shared decision-making when balancing risks and expected outcomes that reflect patient preferences and values. PATIENT SUMMARY:Cryoablation and high-intensity focused ultrasound are minimally invasive treatments available to selectively treat localized prostate cancer, considering their nearly comparable intermediate- to long term cancer control and preservation of urinary continence to other radical treatments in the primary setting. However, a well-informed decision should be made based on one's values and preferences.

Active surveillance (AS) is an established clinical strategy for the management of prostate cancer (PCa) exhibiting low to intermediate risk. In AS, treatment is delayed until progression to higher-risk disease is detected during the close monitoring of patients via longitudinal multiparametric magnetic resonance imaging (mpMRI) scans, biopsies, and Prostate Specific Antigen (PSA) tests. Thus, AS has been regarded as a promising strategy to address the current rates of overtreatment and undertreatment in PCa. However, current AS protocols rely on an observational paradigm, which may delay the detection of tumor progression, and the testing frequency is largely fixed according to population studies, which impedes the design of personalized monitoring plans. To address these issues, we propose to advance AS towards a predictive patient-specific paradigm by leveraging computational tumor forecasts obtained with a biomechanistic model informed by the imaging and clinical data collected during standard AS for each individual patient. Here, we present a preliminary study in a cohort of eight PCa patients who enrolled in AS and had three mpMRI scans over a period of 2.6 to 5.6 years. Our model describes PCa growth in terms of the dynamics of tumor cell density as a combination of tumor cell mobility and net proliferation, which are formulated as a diffusion process and logistic growth, respectively. The model is implemented in each patient’s prostate geometry, which is segmented on T2-weighted MRI data. Tumor cell density estimates are derived from Apparent Diffusion Coefficient (ADC) maps obtained from diffusion-weighted MRI data. To facilitate modeling, the longitudinal imaging datasets are non-rigidly co-registered for each patient. We initialize the model with the tumor cell density map obtained from the ADC map of the first mpMRI scan. Then, the model is parameterized by minimizing the model-data mismatch in tumor cell density at the date of a second mpMRI scan. Finally, we perform a tumor forecast up to the date of a third mpMRI scan, which we use to assess the model-data agreement of our predictions of PCa growth. We obtained a concordance correlation coefficient (CCC) for tumor volume and global tumor cell count of 0.87 and 0.95 during model calibration and of 0.91 and 0.87 at forecasting horizon, respectively. For each patient, the spatial fit of tumor cell density yielded a median Dice score and CCC of 0.77 and 0.50 at the second mpMRI date, respectively. Likewise, the tumor cell density predictions at the third scan date resulted in a median Dice coefficient and CCC of 0.74 and 0.51 across the patient cohort, respectively. Thus, while further model development and performance assessment over lager cohorts are required, these results suggest that our forecasting technology is a promising tool to predict PCa progression in AS and, hence, identify patients who require treatment early during the course of AS. Citation Format: Guillermo Lorenzo Gomez, Chengyue Wu, Joshua P. Yung, John F. Ward, Hector Gomez, Alessandro Reali, Thomas E. Yankeelov, Aradhana M. Venkatesan, Thomas J. Hughes. Patient-specific, organ-scale forecasting of prostate cancer growth in active surveillance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 850.

BACKGROUND:The prostate tumor microenvironment (TME) is immunosuppressive, with few effector T cells and enrichment of inhibitory immune populations, leading to limited responses to treatments such as immune checkpoint therapies (ICTs). The immune composition of the prostate TME differs across soft tissue and bone, the most common site of treatment-refractory metastasis. Understanding immunosuppressive mechanisms specific to prostate TMEs will enable rational immunotherapy strategies to generate effective antitumor immune responses. Daratumumab (anti-CD38 antibody) and edicotinib (colony-stimulating factor-1 receptor (CSF-1R) inhibitor) may alter the balance within the prostate TME to promote antitumor immune responses.HYPOTHESIS:Daratumumab or edicotinib will be safe and will alter the immune TME, leading to antitumor responses in localized prostate cancer.PATIENTS AND METHODS:In this presurgical study, patients with localized prostate cancer received 4 weekly doses of daratumumab or 4 weeks of daily edicotinib prior to radical prostatectomy (RP). Treated and untreated control (Gleason score ≥8 in prostate biopsy) prostatectomy specimens and patient-matched pre- and post-treatment peripheral blood mononuclear cells (PBMCs) and bone marrow samples were evaluated. The primary endpoint was incidence of adverse events (AEs). The secondary endpoint was pathologic complete remission (pCR) rate.RESULTS:Twenty-five patients were treated (daratumumab, n=15; edicotinib, n=10). All patients underwent RP without delays. Grade 3 treatment-related AEs with daratumumab occurred in 3 patients (12%), and no ≥grade 3 treatment-related AEs occurred with edicotinib. No changes in serum prostate-specific antigen (PSA) levels or pCRs were observed. Daratumumab led to a decreased frequency of CD38+ T cells, natural killer cells, and myeloid cells in prostate tumors, bone marrow, and PBMCs. There were no consistent changes in CSF-1R+ immune cells in prostate, bone marrow, or PBMCs with edicotinib. Neither treatment induced T cell infiltration into the prostate TME.CONCLUSIONS:Daratumumab and edicotinib treatment was safe and well-tolerated in patients with localized prostate cancer but did not induce pCRs. Decreases in CD38+ immune cells were observed in prostate tumors, bone marrow, and PBMCs with daratumumab, but changes in CSF-1R+ immune cells were not consistently observed with edicotinib. Neither myeloid-targeted agent alone was sufficient to generate antitumor responses in prostate cancer; thus, combinations with agents to induce T cell infiltration (eg, ICTs) will be needed to overcome the immunosuppressive prostate TME.

You have accessJournal of UrologyCME1 May 2022MP55-03 USING MAGNETIC RESONANCE IMAGING TO DEFINE FOCAL THERAPY TEMPLATES IN PATIENTS WITH INTERMEDIATE-RISK PROSTATE CANCER Alberto Pieretti, Hyunseon Kang, Haesun Choi, Miao Zhang, Brian Chapin, John Ward, Patricia Troncoso, and Justin Gregg Alberto PierettiAlberto Pieretti More articles by this author , Hyunseon KangHyunseon Kang More articles by this author , Haesun ChoiHaesun Choi More articles by this author , Miao ZhangMiao Zhang More articles by this author , Brian ChapinBrian Chapin More articles by this author , John WardJohn Ward More articles by this author , Patricia TroncosoPatricia Troncoso More articles by this author , and Justin GreggJustin Gregg More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002634.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Focal therapy has emerged as a possible treatment option in well-selected patients with localized prostate cancer. However, currently, there is a paucity of data on the long-term oncologic outcomes of focal therapy and on the risk of undertreating patients by using biopsy results and prostate magnetic resonance imaging (MRI) with PI-RADS 3-5 lesions to define focal therapy treatment templates. This study compared focal therapy templates with final pathology results after radical prostatectomy. METHODS: We retrospectively reviewed our institutional database and identified all patients with a biopsy-confirmed MRI lesion with grade group (GG)2 or GG3, and systematic biopsies or other targeted biopsies with

Progress in understanding prostate cancer (PCa) metastasis and therapy resistance has been hampered by the lack of models, representative of the clinical spectrum and biologic complexity of the disease. Our laboratory is home to one of the largest worldwide repositories of PCa patient-derived xenografts (PDXs), the MDA PCa PDX series, a collection of clinically annotated PDXs reflecting the full spectrum of potentially lethal disease, that includes tumors that are not end stage and not castration-resistant PCa. We performed whole genome sequencing, targeted sequencing and RNA sequencing of 46 MDA PCa PDX models derived from biopsy and surgical specimens from 39 patients, selected in order to reflect the clinicopathological PCa subtypes (data available in cBioPortal). MDA PCa PDXs genomic characterization shows that the cohort recapitulates the mutational landscape found in PCa, highlighting the clinical relevance of these models. Interestingly and consistently with the clinic, certain models lack the typical PCa driver alterations, thus providing a suitable tool for discovery of novel drivers. Our cohort also includes PDXs derived from different areas of the same tumor and longitudinal samples, allowing to study disease heterogeneity and progression. Finally, we have developed a procedure to grow organoids from PDXs, thus providing a powerful in vitro platform that supports hypothesis generation, and testing of clinically relevant observations. Genomic and transcriptomic characterization of MDA PCa PDXs together with the ability to grow them as organoids for in vitro experimentation, provides a unique resource to address the existing clinical gap in PCa, helping to better understand mechanisms of response and resistance. One Sentence Summary MDA PCa PDX series is a dynamic resource capturing the molecular landscape of prostate cancer; a platform for discovery and personalized medicine

Active surveillance (AS) is a safe management strategy for men with low-risk prostate cancer; however, nearly 35% of men on AS will undergo definitive treatment within 4 years, most commonly due to disease progression. Determining a non-invasive means of limiting disease progression would allow men to avoid quality of life issues associated with radical prostate treatment. Some modifiable factors, such as obesity and lipid levels, are associated with prostate cancer risk, though no behavioral intervention has been shown to affect prostate cancer outcomes. Using a prospective study of men on active surveillance, our group recently demonstrated that higher quality diets were associated with a significantly lower risk of disease progression. The Mediterranean diet (MD) specifically may be beneficial for men with localized prostate cancer (PCa) on active surveillance (AS) because of its anti-inflammatory, antilipidemic, and chemopreventive properties. Furthermore, recent evidence supports that dietary interventions can induce modulation of the gut microbiome, and consequently, immune function and inflammatory pathways, which warrants further investigation of the microbiome’s role in the context of prostate cancer. Here, we describe a novel dietary intervention among a group of men with localized prostate cancer who are electing to undergo prostatectomy for prostate cancer treatment. The intervention is a feeding study involving the provision of an isocaloric, high quality diet based on the lipid-lowering and anti-inflammatory parameters of the Mediterranean diet, including a strong focus on fiber-rich plant foods and healthy sources of mono and poly-unsaturated fatty acids. The primary outcome in this pilot study is the feasibility of a neoadjuvant dietary intervention. Secondary outcomes include studying the effects of the diet on metabolic parameters, the fecal microbiome, and changes in circulating metabolites shown to be associated with progression on active surveillance. Furthermore, by focusing on African-American and non-Hispanic White males, this study may provide insights into the key differences in inflammatory, immune and microbiome signatures, which may underly the prominent cancer-racial disparity seen in African-American men. Therefore, this study will gain preliminary data needed to inform further dietary interventions that may impact risk of progression in select men with prostate cancer enrolled on active surveillance. Citation Format: Samuel Cass, Jennifer Wargo, Curtis Pettaway, Louis Pisters, John Davis, Brian Chapin, John Ward, Carrie Daniel, Justin Gregg. A novel Mediterranean dietary intervention for 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 3495.

of (DOACs) in the oncology post-discharge setting. In anticipation of a departmental practice change from enoxaparin to apixaban, tested the hypothesis that apixaban was non-inferior to enoxaparin for post-operative EDP. patients discharged with days of EDP following urologic oncologic the and de fi on Thrombosis estimated events in 6.5% of enoxaparin and 4.0% of apixaban patients. Testing the null hypothesis that apixaban was non- inferior to with a pre-speci fi ed non-inferiority margin of (cid:1) 4%, required 145 patients per group. The baseline period was set at six months based on previous discharge data. Our intervention period was de fi ned to last until at least 145 patients were discharged on apixaban with an option to stop at 6 months for futility. RESULTS: 160 patients were discharged with enoxaparin during the baseline period and 158 with apixaban during the interven- tion period. Major complications occurred in 3.5% of the enoxaparin group (2 [1.2%] major bleeds; 3 [1.8%] DVTs) and 0.0% for apixaban (p [ 0.06), meeting the pre-speci fi ed non-inferiority threshold. Minor bleeding complications occurred in 4.3% (7/160) and 4.4% (7/158) for enoxaparin and apixaban respectively (p [ 1.0). CONCLUSIONS: Apixaban is non-inferior to enoxaparin for EDP after urologic oncology surgery. Apixaban may have a more favorable safety pro fi le than enoxaparin and should be offered to patients who need EDP. Based on these results, apixaban is now our departmental standard. the initial visit to deter-mine if prescriptions were picked up from the pharmacy and started. For patients who did not initiate treatment, we catalogued if they informed the physicians' of fi ce of these barriers to care and the obstacles encountered to initiating therapy. Obstacles were grouped using the- matic analysis. Additional information, including age, medication prescribed, insurance plan, and treatment indications were abstracted. RESULTS: Of 91 new female urogynecology patients prescribed at least one medication during their initial visit, only 50 (55%) were able to initiate all medications prescribed , 6 of whom were given samples free of charge. Thirteen (14%) of those who obtained their medications reported apprehension regarding high copays, inadequate drug ef fi cacy, or safety that either led to discontinuation of treatment within the fi rst two weeks or presented obstacles in obtaining future re fi lls. Forty-one patients (45%) did not pick up thier prescriptions due to pending prior authorizations (4.4%), high copays (7.7%), concerns about drug safety, ef fi cacy, or indication (15%), or failure to recall treatment plan (9.9%). Only 16 (39%) of the 41 patients contacted the of fi ce within 2 weeks of the prescription to report these concerns, while the remaining 25 (61%) did not inform the of fi ce until after they were contacted. CONCLUSIONS: A large proportion of urogynecology patients never initiate prescribed therapy for voiding dysfunction and pelvic fl oor disorders. Signi fi cant obstacles to obtaining and initiating pharmacologic therapy may comprise a larger contribution to poor medication compliance than previously recognized. characterize current of operating-related musculoskeletal and during training. 57% and 49% of respondents reported “ never ” performing micropauses or stretching between surgeries, respectively. 56.9% of respondents take NSAIDs for work related pain. CONCLUSIONS: Most survey responders report an increase in neck and lower back pain after performing surgery. Many did not have formalized ergonomics training and do not employ preventative strate- gies to optimize ergonomics. This survey study identi fi es a gap in urology training and a potential area of focus to promote career well- ness and longevity. an indicator for cancer prognosis and should be considered in the clinical assessment of bladder cancer patients receiving a radical cystectomy. Additional strategies to maximize health care assess for bladder cancer patients must be developed.

Focal therapy is growing as an alternative management options for men with clinically localized prostate cancer. Parallel to the increasing popularity of active surveillance (AS) as a treatment for low-risk disease, there has been an increased interest towards providing focal therapy for patients with intermediate-risk disease. Focal therapy can act as a logical “middle ground” in patients who seek treatment while minimizing potential side effects of definitive whole-gland treatment. The aim of the current review is to define the rationale of focal therapy in patients with intermediate-risk prostate cancer and highlight the importance of patient selection in focal therapy candidacy.

BACKGROUND:With the advancement of imaging technology, focal therapy (FT) has been gaining acceptance for the treatment of select patients with localized prostate cancer (CaP). We aim to provide details of a formal physician consensus on the utilization of FT for patients with CaP who are discontinuing active surveillance (AS). METHODS:A 3-stage Delphi consensus on CaP and FT was conducted. Consensus was defined as agreement by ≥80% of physicians. An in-person meeting was attended by 17 panelists to formulate the consensus statement. RESULTS:Fifty-six respondents participated in this interdisciplinary consensus study (82% urologist, 16% radiologist, 2% radiation oncology). The participants confirmed that there is a role for FT in men discontinuing AS (48% strongly agree, 39% agree). The benefit of FT over radical therapy for men coming off AS is: less invasive (91%), has a greater likelihood to preserve erectile function (91%), has a greater likelihood to preserve urinary continence (91%), has fewer side effects (86%), and has early recovery post-treatment (80%). Patients will need to undergo mpMRI of the prostate and/or a saturation biopsy to determine if they are potential candidates for FT. Our limitations include respondent's biases and that the participants of this consensus may not represent the larger medical community. CONCLUSIONS:FT can be offered to men coming off AS between the age of 60 to 80 with grade group 2 localized cancer. This consensus from a multidisciplinary, multi-institutional, international expert panel provides a contemporary insight utilizing FT for CaP in select patients who are discontinuing AS.

Abstract Objective This study aimed to identify factors associated with surgeon perception of robot‐assisted radical prostatectomy (RARP) difficulty. Patients and Methods This study surveyed surgeons performing RARP between 2017 and 2018 and asked them to rate operative conditions and difficulty as optimal, good, acceptable, or poor. These answers were stratified as optimal or suboptimal for this study. Associations between surgeon responses and variables hypothesized to affect surgical difficulty, including anatomic factors such as pelvic diameter and prostate volume:pelvic diameter ratio, were assessed. Results Between November 2017 and September 2018, a total of 100 patients were prospectively enrolled in the study of which 58 cases were rated as optimal and 42 were rated as suboptimal. Of the evaluated variables, only increasing clinical T stage (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.03–2.15, p = 0.03) and increasing body mass index (BMI) (OR 1.14, 95% CI 1.03–1.26, p = 0.01) were associated with increased difficulty; 90‐day complication rates were similar between the optimal and suboptimal cohorts (17.3% vs. 23.8%, respectively; p = 0.5). The number of patients with previous surgery, pelvic diameter, and prostate size:pelvic diameter ratio were not significantly different between cohorts (p > 0.05 for all). Operative time (ρ = 0.23, p = 0.02) and estimated blood loss (EBL) (ρ = 0.38, p = 0.0001) were correlated with suboptimal difficulty. Conclusion The factors associated with surgeon‐reported RARP difficulty were patient BMI and clinical T stage among surgeons with significant RARP experience. These data should be incorporated into surgical decision making and patient counseling prior to performing a RARP.