Paragangliomas are neuroendocrine tumors arising from extra-adrenal chromaffin cells within the autonomic nervous system. Primary urogenital disease is rare (6.7% of paragangliomas), with prostatic involvement reported in only a few case studies. Management follows National Comprehensive Cancer Network (NCCN) guidelines for neuroendocrine and adrenal tumors; however, there is limited data to guide systemic therapy in cases that present with metastasis. We describe a report of a 60-year-old man with metastatic pelvic paraganglioma detected after 4 months of gross hematuria and urinary retention. Despite the large tumor burden, the patient has been successfully treated with systemic therapy after an appropriate workup.

e17057 Background: Currently non-specific protein factors (Alkaline Phosphatase-ALK, LDH, albumin) are used for identifying prognostic risk groups in mCRPC. We explored NGS-based proteome sequencing for scalable and high-throughput plasma proteomic profiling for developing an integrated approach of mCRPC tumor-biology associated proteins with existing biomarkers based on patient-centric nomograms that estimate 6-, 12- and 24-months overall survival (OS) probabilities. Methods: Proteomic profiling of plasma for 3,072 proteins using Olink Explore NGS platform was performed in 32 local stage prostate cancer, 123 metastatic hormone-sensitive (mHSPC) and 157 mCRPC state samples (Total N = 312) in a clinically annotated real-world cohort study. Proteins were measured in Normalized Protein eXpression (NPX) units. NPX values of all proteins across all three cancer states were compared to identify Differentially Expressed Proteins (DEPs) exclusively to mCRPC using t-test with multiple corrections. Clinical outcome in the mCRPC was overall survival (OS) and Hazard Ratios (HRs) for mCRPC-DEPs with significant (P<0.05) association with survival at a univariate level were build into an aggregated composite score generated by multiplying each individual DEP’s univariate-level survival HR coefficient with the corresponding NPX value. The “Composite Proteome Prognostic Score (CPPS)” range for the mCRPC cohort (N = 121 pts) was dichotomized above and below the cohort median as “High” and “Low” and evaluated using Cox Proportional Hazard Regression along with current prognostic protein biomarkers (PSA, LDH, Alkaline Phosphatase and Albumin) at the univariate level and included in multi-variable analysis (MVA) for univariate-level significant (P<0.05) variables. Prognostic nomogram integrating MVA significant clinical factors with the CPPS was developed and nomogram performance with and without CPPS for estimating 6-,12- and 24-months survival was determined using Area Under Curve (AUC). Results: Median OS of the mCRPC cohort (N = 157) was 28 months (range: 0.3-45). 866/3072 DEPs were exclusive to mCRPC and 252/866 associated with OS (HR > 1; P < 0.05). 102/252 DEPs were significant after multiple correction (FDR < 0.05). The top 20 DEPs were used to generate CPPS. The CPPS HR value of 3.48 (95% CI: 1.77-6.83) was higher compared to known clinical factors including PSA, LDH , Alkaline Phosphatase, Albumin. AUCs for estimating mCRPC OS probabilities integrating CPPS with clinical factors versus clinical factors alone increased to 0.90 from 0.83 (6-months); 0.86 from 0.72 (12-months) and 0.76 from 0.69 (24-months). Conclusions: A patient-centric nomogram to estimate survival in mCRPC which includes novel protein classifiers can enhance current prognostication models.

225 Background: Currently non-specific clinical factors including non-tumor biology proteins (Alkaline Phosphatase-ALK, LDH, albumin) are used for identifying high, intermediate or low prognostic survival risk in mCRPC. We integrated these biomarkers with plasma proteins overexpressed exclusively in mCRPC to develop patient-centric nomograms for estimating 1,2 and 3-year (yr) overall survival (OS) probabilities. Methods: Proteomic profiling of plasma for 3072 proteins using Olink Explore NGS platform was performed in 32 local stage prostate cancer, 123 metastatic hormone-sensitive (mHSPC) and 157 mCRPC state samples (Total N=312) in a clinically annotated real-world cohort study that enrolled patients (pts) between 2020 and 2024. Protein assays were measured in normalized protein expression (NPX) units through a normalization process. We compared NPX values of all protein assays across all three cancer states to identify Differentially Expressed Proteins (DEPs) exclusively overexpressed in mCRPC using t-test with multiple corrections. Clinical outcome in the mCRPC was OS. A composite score was generated aggregating DEPs overexpressed in mCRPC with OS, by multiplying each individual DEP’s univariate-level survival Hazard Ratio (HR) coefficient with their corresponding NPX value. The composite score range for the mCRPC cohort (N=121 pts) was dichotomized above and below the cohort median as “High” and “Low” and evaluated for survival using Cox Proportional Hazard Regression along with current prognostic protein biomarkers (ALK, LDH, albumin) at the univariate followed by multi-variable analysis (MVA) for variables observed with univariate significance (P<0.05). Prognostic nomograms integrating MVA significant clinical factors with the DEP composite score was developed and performance of the nomogram with and without the composite score for estimating 1,2 and 3-years survival probabilities was determined using ROC curves and Area Under Curve (AUC). All analyses were conducted in RStudio. Results: Median OS of the mCRPC cohort (N=121) was 28 months (range: 0.3-45). There were 353/3072 DEPs exclusive to mCRPC and 19/353 DEPs were associated with OS (univariate P<0.05) (SCRN1, GP2, NFU1, DPY30, SNRPB2, KRT19, FKBP5, PGD, IL6, L3HYPDH, MYDGF, DH1, IQGAP2, TOMM20, YAP1, CLGN, IMMT, PKD2, PALM2). MVA Hazard Ratios (HR) with 95% CIs for nomogram input included: DEP score HR-3.48 (1.77-6.83; P<0.0003); LDH: HR-1.01 (1-1; P=0.13); ALK: HR-1 (1-1; P=0.000035); Albumin: HR-0.61 (0.24-1.51; P=0.28). AUCs for estimating mCRPC OS probabilities integrating the DEP score with current factors versus clinical factors alone increased to 0.87 from 0.85 (1-yr); to 0.78 from 0.73(2-yr) and to 0.79 from 0.70 (3-yr). Conclusions: A patient-centric approach using nomograms to estimate survival in mCRPC which includes novel protein classifiers can enhance current prognostication models.

PURPOSE:We hypothesized that treatment with Radium223 (Ra223) and Stereotactic ablative radiotherapy (SABR) in patients with bone-only metachronous oligometastastic hormone-sensitive prostate cancer (moHSPC) could safely delay the start of androgen deprivation therapy (ADT) and maintain quality of life (QoL). METHODS AND MATERIALS:This prospective trial included 20 men with moHSPC and ≤5 bone-only metastases who previously had definitive treatment to the prostate and pelvic lymph nodes. Eligibility criteria were testosterone ≥ 100 ng/dL and metastases validated by conventional imaging. Exclusion criteria were postinitial treatment (LHRH) therapy or N1 disease at bone metastasis diagnosis. Treatment included 6 cycles of Ra223 and SABR (30 Gy in 5 fractions). Bone scans and Prostate Specific Antigen (PSA) levels were monitored regularly. The primary endpoint was freedom from ADT use at 15 months in ≥20% of patients. Patients were followed for 2 years, with clinically significant patient-reported outcome changes defined as >1/2 standard deviation from baseline. Statistical analyses used Wilcoxon rank sum, Pearson's χ2 tests, and univariate Cox regression, with significance set at P < .05 RESULTS: The median number of Ra223 cycles was 6. Freedom from ADT at 15 and 24 months was 50.0% and 40.0%, respectively (P < .001). Eleven (55%) and 5 (25%) patients had PSA declines exceeding 50% and 90%, respectively, with 2 patients achieving undetectable PSA levels (<0.01) at 2 years. No significant changes were observed in any patient-reported outcome QoL domains. Two patients had grade 3 skeletal-related events, and grade 2+ events attributed to Ra223 and SABR were observed in 4 and 2 patients, respectively. CONCLUSIONS:In this phase 2 trial, the initial use of Ra223 and SABR for moHSPC significantly delayed ADT use compared with historical controls. The therapy is well tolerated, preserves QoL, and can lead to undetectable PSA levels at 2 years.

38 Background: In a subset of patients with molecular-imaging defined recurrent oligometastatic prostate cancer (PCa), salvage oligometastatectomy with surgery and/or radiation may provide improved androgen deprivation therapy (ADT)-free survival. Methods: This is a phase II trial with oligorecurrent PCa after primary prostatectomy or radiation therapy detected on Axumin (n=11) or Prostate-Specific Membrane Antigen (PSMA) (n=9) positron emission tomography. Oligometastatic disease was defined as ≤ 10 total sites, either of lymph node (LN) only (Group A), bone only (Group B), or LN and bone (Group C). Surgical intervention for patients with LN disease included extended pelvic and/or retroperitoneal LN dissection, depending on the location of the LNs. Groups A and C received adjuvant IMRT without ADT if PSA response was ≥ 1/3 decrease but remained ≥ 0.2 ng/dL. The primary outcome was a reduction in PSA by ≥ 50% at 6 months. Secondary objectives included PSA progression free-survival (PSA-PFS), ADT-free survival, and safety. Results: We accrued a total of 20 patients. The median age was 65 years (IQR 61-70), 95% (19/20) had an ECOG of 0, and 10% (2/20) were Hispanic. All patients had a prior prostatectomy, after which 45% (9/20) received adjuvant/salvage RT, with 33% (3/9) including the pelvis/ prostate bed. 30% (6/20) had exposure to ADT before trial treatment. The median time from definitive prostate cancer treatment to trial treatment was 2.8 years (IQR: 0.9-6.0). Oligorecurrent disease occurred as lymph nodes only (18/20; 90%) or bony (2/20; 10%). Within Group A, one patient completed adjuvant RT. The average number of imaging-identified positive LNs was 1.8 (range 1-6). The primary endpoint of reduction in PSA by ≥ 50% at 6 months was 40% (95%CI 19-64%) (Table 1). The secondary endpoint of PSA-PFS at 12 months was 84.4% (95%CI 66.6-100%). ADT-free survival at 12-months was 71.4% (95% CI 52.7% - 96.6%). There were no Clavien Grade III-IV complications. Conclusions: Salvage treatment of oligometastatic disease after prostatectomy or radiation identified on molecular imaging is feasible and safe. Nearly half the cohort had a good response to salvage treatment, demonstrated by a ≥ 50% reduction in PSA at 6 months. Ongoing analyses include comparing imaging and pathology correlations, and comparing complete/ partial responders and treatment failure. Further research is needed to identify ideal candidates for salvage treatment. Clinical trial information: NCT03796767 . PSA progression-free survival at 6- and 12-months (PFS). Time Estimate 95% Confidence Interval 6 months 100% --- 12 months 84.4% 66.6-100%

Background Muscle-invasive urothelial cancer (UC) has a high risk of recurrence after definitive treatment. Nivolumab adjuvant to radical surgery improves disease-free survival in patients with UC with a high risk of recurrence; however, its role adjuvant to chemoradiation therapy (CRT) is unknown.Methods The NEXT trial is a single-arm, phase-2 study evaluating the efficacy and tolerability of nivolumab adjuvant to CRT in patients with localized or locoregional UC. The primary endpoint is failure-free survival (FFS) at 2 years. Secondary endpoints include patterns of recurrence, toxicity and quality of life (QoL). Plasma cell-free DNA (cfDNA) was subjected to shallow whole-genome sequencing to correlate with outcomes.Results 28 patients were enrolled and received 480 mg of nivolumab intravenously every 4 weeks for up to 12 cycles adjuvant to CRT. The FFS at 2 years was 33.2% (95% CI 18.5% to 59.6%). Nine (32%) patients had localized progression, and eight (29%) had distant progression. 25 (89%) had one or more high-risk features (ie, plasmacytoid differentiation, T4, N+, multiple tumors, tumors >5 cm, residual disease before CRT, carcinoma in situ, and hydronephrosis). Patients with ≤2 high-risk features had a median FFS of 45.2 months (95% CI 14.56 to not reached (NR)) compared with 8.2 months (95% CI 7.1 to NR) in those with three or more risk features (p=0.0024). Nivolumab-associated treatment-related adverse events occurred in 18 (64.3%) patients, only 3 had grade 3 TRAEs, with significant changes in QoL. Plasma cfDNA copy number instability (CNI) scores ≤25 before the first dose of adjuvant nivolumab and at cycle 4 were associated with better overall survival compared with CNI scores ≥26 (49.6 months vs 20.5 months, p=0.0024). Genome copy number changes indicated chromatin remodeling and tyrosine kinase pathways, among others, as oncogenic drivers implicated in progression.Conclusion Nivolumab adjuvant to CRT in localized or locally advanced UC is well tolerated. Stratification by risk factors and correlation with plasma cfDNA analyses generate hypotheses for potential patient selection and putative therapeutic targets for future study.Trial registration number NCT03171025.

INTRODUCTION:Obesity in prostate cancer survivors may increase mortality. Better characterization of this effect may allow better counseling on obesity as a targetable lifestyle factor to reduce mortality in prostate cancer survivors. The purpose of this study was to determine whether pre- and post-diagnostic obesity and weight change affect all-cause mortality, cardiovascular disease specific mortality, and prostate cancer specific mortality in patients with nonmetastatic prostate cancer. PATIENTS AND METHODS:We performed a retrospective cohort analysis of 5,077 patients diagnosed with localized prostate cancer from 1997 to 2017 with median follow-up of 15.5 years. The Utah Population Database linked to the Utah Cancer Registry was used to identify patients at a variety of treatment centers. RESULTS:Pre-diagnosis obesity was associated with a 62% increased risk of cardiovascular disease specific mortality and a 34% increased risk of all-cause mortality (HR 1.62, 95% CI 1.05-2.50; HR 1.34, 95% CI 1.07-1.67, respectively). Post-diagnosis obesity increased the risk of cardiovascular disease specific mortality (HR 1.83, 95% CI 1.31-2.56) and all-cause mortality (HR 1.37, 95% CI 1.16-1.64) relative to non-obese men. We found no association between pre-diagnostic obesity or post-diagnostic weight gain and prostate cancer specific mortality. CONCLUSION:Our study strengthens the conclusion that pre-, post-diagnostic obesity and weight gain increase cardiovascular disease and all-cause mortality but not prostate cancer specific mortality compared to healthy weight men. An increased emphasis on weight management may improve mortality for prostate cancer survivors who are obese.

Abstract Introduction and Objectives: Von Hippel-Lindau (VHL) is an autosomal dominant genetic disease. The type of VHL alteration has been shown to impact downstream VHL expression and clinical phenotype. However, current screening practices do not differ based on VHL genetic subtype. We aim to define the genotype-phenotype association among an institutional cohort of VHL patients. Methods: We conducted a retrospective cohort study of 69 patients (27 families) with von Hippel-Lindau at the Huntsman Cancer Institute from 1998-2023. 55% (38/69) patients have documented VHL variants for review. We evaluated the association of VHL type with risk of pheochromocytoma (Pheo), renal cancer (RCC), and hemangioblastoma (HB). t test and Fisher’s exact test were used to assess differences in clinicopathologic characteristics by VHL Type. P-value < 0.05 was considered significant. Results: We identified 24 unique VHL alterations among 38 patients. 66% (25/38) of patients had missense mutations, 10% (4/38) nonsense mutations, 21% (8/38) splice mutations, and 3% (1/38) deletion/duplication (Table 1). The median age at VHL diagnosis was 31 years old (range 4-76). VHL Type 2 was more common, 87% (33/38). All VHL Type 1 patients (5/5) developed RCC and HB. No patients with VHL Type 1 developed PheoPara. Of the VHL Type 2 patients, 39% (13/33) have not developed any VHL-associated clinical manifestations. Of the 33 patients diagnosed with VHL Type 2, 18% (6/33) were diagnosed with PheoPara, 30% (10/33) with RCC, and 48% (16/33) with HB. Conclusion: VHL type 2 comprised the majority of VHL diagnoses in our cohort with a notable absence of PheoPara phenotype. VHL Type 1 had higher penetrance and a higher prevalence for RCC and hemangioblastoma. With validation in larger cohorts, this cohort supports utilizing VHL genetic subtypes to personalize surveillance. Additional VHL testing for the remainder of the cohort is ongoing. Clinicopathologic characteristics of von Hippel-Lindau Syndrome cohort with known genetic mutations All (n=38) Type 1 (n=5) Type 2 (n=33) p-value AgeMean (Median) 33.1 (31) 42 (28) 31.7 (31) 0.38 White, n (%) 92% (n=35) 5 (100%) 30 (91%) 1 Hispanic, n (%) 8% (n=3) - 3 (9%) 1 VHL alteration, n (%) - Missense 25 (66%) - 25 (76%) Nonsense 4 (10%) 4 (80%) - Splice site 8 (21%) - 8 (24%) Deletion/Duplication 1 (3%) 1 (20%) - Penetrance, n (%) 25 (66%) 5 (100%) 20 (61%) 0.14 Phenotype, n (%) PheoPara 6 (16%) - 6 (18%) 0.57 RCC 15 (39%) 5 (100%) 10 (30%) 0.006 Hemangioblastoma 21 (55%) 5 (100%) 16 (48%) 0.26 Citation Format: Nicole Murray, Colton Leavitt, Noah Shepard, Zera Gonzales, Jiaming Li, Brock O'Neil, Christopher Dechet, Bogdana Schmidt, Benjamin L. Maughan, Kristen Pauley, Anne Naumer, Wendy Kohlmann, Alejandro Sanchez. Genotype-phenotype associations in von hippel-lindau syndrome: Implications for screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2559.

156 Background: We hypothesized that treatment with Radium-223 (Ra223) and to ≤5 sites of bony metastases (mets) could safely delay the time to start androgen deprivation therapy (ADT) and maintain quality of life (QoL). Methods: 20 men previously treated with surgery, radiation, or both for M0 PCa later developed ≤5 bone-only mets were eligible for this prospective trial. Inclusion: testosterone ≥ 100 ng/dL and mets on conventional bone scan, validated by a CT, MRI, or PET/CT. Exclusion: LHRH therapies after initial treatment, or N1 disease at diagnosis of bone mets. Therapy was 6 cycles of Ra223 and SBRT (30 Gy in 5 fractions between cycles 1-2). Bone scan was performed at baseline and q3 months. PSA was evaluated monthly during the Ra223 course, and q3 months after. Therapeutic effectiveness was defined as ≥20% of patients meeting the primary endpoint of freedom from ADT (FFAdt) use at 15 months. Discontinuation of study therapy occurred if: PSA rise > 10% if baseline PSA >20ng/ml, PSA>20 if baseline PSA <20 ng/ml, radiographic progression or a skeletal-related event (SRE). All endpoints were timed from the Cycle 1 radium date. Patients were followed for 2 years. Clinically significant changes in patient-reported outcome (PRO) measures were defined as >1/2 standard deviation from the mean baseline value and were censored after the time of ADT use. Continuous and categorical covariates were compared using the Wilcoxon rank sum and Pearson’s Chi2 tests, respectively, and univariate Cox regression. Statistical significance was considered at P<0.05. Results: The median number of Ra223 cycles was 6. 6 patients had <6 cycles (range 2-5) due to progression. FFAdt at 15 and 24 Months was 49.5% and 38.5%, respectively (p<0.001). The median time to ADT was 14.8 months. There were no significant changes from baseline in any PRO QoL domain (physical functioning, anxiety, depression, fatigue, satisfaction with participation in social roles, sleep disturbance, and pain interference). There were 2 patients with Grade 3 SREs (bone fracture, pain). Grade 2+ events attributed as possible or likely to Ra-223 were seen in 4 patients (bone pain, fatigue, fracture, decreased WBC count, and other). Grade 2+ events attributed as possible or likely to EBRT were seen in 2 patients and included fatigue and other pain. were noted for age, baseline PSA, days from primary treatment, NCCN risk group, TNM stage, ISUP grade group, BMI, or # of lesions in those who met or failed the primary endpoint (all p>0.05). Conclusions: First-line use of Ra223 and SBRT to oligomets in hormone-naïve men in this prospective pilot study resulted in a significant delay in ADT use compared to historical control, is well tolerated, and maintains QoL. Clinical trial information: NCT03304418 .

612 Background: Definitive chemoradiation (CRT) is the preferred bladder preservation treatment for non-metastatic urothelial cancer (nmUC). The NEXT trial (NCT03171025) evaluated the efficacy of adjuvant nivolumab to definitive CRT in pts with nmUC. Methods: This multicenter study enrolled nmUC pts who received standard-of-care CRT. Nivolumab 480 mg was administered every 4 weeks for up to 12 doses. Primary endpoint: failure-free survival (FFS) at 2 years (yrs). Secondary endpoint: safety. This is the first efficacy and safety analysis after completion of enrollment, and correlation of disease risk features, and changes in plasma cell-free DNA (cfDNA) with outcomes. Shallow whole genome sequenced data from plasma cfDNA was mapped to the human reference genome (HG19), and copy number instability (CNI) Score (Oncocyte) was derived from statistically significant altered regions. Results: From 8/03/2017 to 1/25/2023, 28 pts were enrolled. The median age was 72 yrs (range 54-86 yrs). Ten patients (36%) had ≥ T3 and/or N+ disease. At time of data cut-off (9/14/23), median nivolumab cycles were 8.5 (range 1-12), and median follow-up was 11 months (range 6 - 45). FFS at 2 yrs (n=24) was 38.7 % (95% CI 23%-65.2%). Disease relapse occurred in 16 pts, of which 9 had local recurrences. Grade ≥3 treatment-related adverse events (AEs) occurred at a frequency of 10.7%. These were elevated transaminases, diarrhea, and polymyalgia rheumatica. Grade 3 radiation therapy oncology group (RTOG) AEs occurred in 2 pts. One or more high-risk disease features (ie. plasmacytoid differentiation, T4, N+, multiple tumors, tumors > 5 cm, residual disease before CRT, CIS, and hydronephrosis) were present in 22 pts (79%). In a Cox proportional hazards model, the number of high-risk features was a significant predictor of progression (p = 0.006). Each additional high-risk feature was associated with a hazard ratio for progression of 1.77 (95% CI 1.17-2.67). Median CNI (mCNI) on C1D1 of nivolumab in relapsed pts was 31 (range 3-232) vs. 24 (range 3-109) in pts with ongoing response. The mCNI on C4D1 for pts who progressed was 15.5 (range 6-371) vs. 9 (range 3-65) in pts with ongoing response. Oncogenic gene copy number changes and the associated pathways associated with progression are listed in the table. Conclusions: Adjuvant nivolumab to CRT for nmUC has promising efficacy with tolerable AEs, even in pts with high-risk disease. Disease relapse correlates with high-risk clinical features and CNI in plasma cfDNA. Oncogenic copy number changes in genes involved in DNA repair, RTK-RAS-PI3K, WNT, and cell cycle pathways are present in cfDNA of those who progressed (Table). Clinical trial information: NCT03171025 . [Table: see text]

237 Background: We performed plasma-based high-plex proteomic profiling for identifying classifiers of clinical outcomes in metastatic prostate cancer (PC). Olink Explore NGS-based proteome profiling platform was used for high-precision analysis of 736 cancer associated plasma proteins in plasma samples from non-metastatic stage prostate cancer (PC), metastatic hormone-sensitive PC (mHSPC) and metastatic castrate resistant PC (mCRPC) states. Methods: Plasma was collected prospectively in a cohort of 108 PC patients (24 with non-metastatic PC; 28 mHSPC; 56 mCRPC of which 37 patients were collected before starting any mCRPC treatments). Proteomic data were generated with Proximity Extension Assay (PEA) on the Olink platform from 100 µL plasma per sample. Levels of 736 cancer-associated protein assays were denoted as normalized protein expression (NPX) units through a QC and normalization process developed and provided by Olink. Data generation of NPX consists of normalization to the extension control, log2 -transformation, and level adjustment using the plate control (plasma sample). Temporal trends of differentially expressed assays in non-metastatic PC, mHSPC and mCRPC states were identified using linear mixed effects model (FDR with Benjamini-Hochberg (BH) adjustment; q-value<0.05, R version 4.1.2.). Clinical outcomes included in mCRPC state overall survival (calculated as time from turning mCRPC to death) and in mHSPC early failure of ADT-based therapies defined as progression within 12.5 months. Cox proportional hazard regression was performed for proteins associated with mHSPC and mCRPC states and clinical endpoint of interest. Results: After BH adjustments, 105 protein assays were differentially expressed across non-metastatic, mHSPC and mCRPC states of which 73 assays differed between non-metastatic and metastatic states (q<0.05). 83/105 assays differed between mHSPC and mCRPC states (q<0.05). Of the 83 plasma proteins, 77 were over-expressed in mCRPC. 19/37 mCRPC patients who had collections performed before mCRPC treatments had died. The median time to death was 29 months (Range: 1.9-119 mths). After adjustment for serum Alkaline phosphatase (ALP) levels in these 37 mCRPC patients 32/77 were significantly associated with overall survival. After performing an enrichment analysis the oxidative phosphorylation pathway with specific proteins assays (IMMT, COX5B and FXN, p = 5.1e-4, FDR = 2.55 e-2) were significantly overexpressed in patients with poor survival. Conclusions: A global plasma proteomic profiling of cancer related proteins revealed significant differences in expression in different states of cancer progression. Overexpressed proteins related to oxidative phosphorylation pathway in mCRPC in specific are associated with poor survival.

You have accessJournal of UrologyCME1 Apr 2023V05-10 ROBOTIC BILATERAL PARTIAL ADRENALECTOMY FOR TREATMENT OF VON HIPPEL-LINDAU ASSOCIATED BILATERAL PHEOCHROMOCYTOMA Kassandra Dindinger-Hill, Kristen Pauley, Benjamin Maughan, Bogdana Schmidt, Brock O'Neil, Christopher Dechet, and Alejandro Sanchez Kassandra Dindinger-HillKassandra Dindinger-Hill More articles by this author , Kristen PauleyKristen Pauley More articles by this author , Benjamin MaughanBenjamin Maughan More articles by this author , Bogdana SchmidtBogdana Schmidt More articles by this author , Brock O'NeilBrock O'Neil More articles by this author , Christopher DechetChristopher Dechet More articles by this author , and Alejandro SanchezAlejandro Sanchez More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003263.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Partial adrenalectomy is an essential approach for patients with von Hippel-Lindau (VHL) associated pheochromocytoma. One key benefit of partial adrenalectomy is avoidance of lifelong hormone replacement therapy. The purpose of this report is to demonstrate one case of robotic bilateral partial adrenalectomy for treatment of bilateral pheochromocytoma in a patient with VHL. METHODS: The patient was an 18-year-old male with a history of VHL diagnosed at birth who did not follow surveillance. The patient presented for hypertensive crisis leading to partial loss of vision in one eye, at which time plasma free metanephrines and normetanephrines were found to be significantly elevated. Patient was stabilized but continued to have persistent hypertension in the 130’s to 150’s systolic despite doxazosin and lisinopril therapy. Computed tomography (CT) of the abdomen and pelvis showed multiple bilateral large heterogeneously enhancing adrenal lesions consistent with bilateral pheochromocytomas (4 cm and 3 cm lesions on the right and 3.3 cm lesion on the left). The patient then underwent robotic bilateral partial adrenalectomy after adequate pre-operative adrenergic blockade. RESULTS: Robotic bilateral partial adrenalectomy was successfully performed with approximately 30% sparing of the adrenal glands bilaterally. Patient was hemodynamically stable with no post-operative complications. Pathology report showed complete excision of pheochromocytomas bilaterally. Patient has not required continued hydrocortisone replacement since time of surgery. CONCLUSIONS: This case demonstrates that bilateral partial adrenalectomy can be an effective management for bilateral pheochromocytoma to prevent the need for lifelong hormone replacement that would occur as a result of total adrenalectomy. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e427 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kassandra Dindinger-Hill More articles by this author Kristen Pauley More articles by this author Benjamin Maughan More articles by this author Bogdana Schmidt More articles by this author Brock O'Neil More articles by this author Christopher Dechet More articles by this author Alejandro Sanchez More articles by this author Expand All Advertisement PDF downloadLoading ...

68 Background: Germline genetic testing criteria for individuals with prostate cancer (PCa) are expanding. Alternative genetic service models are needed to meet increased need for genetic testing. Studies have shown no difference in genetic testing uptake, satisfaction, or knowledge when patients undergo face-to-face genetic counseling compared to pre-test video genetic education (VGE). Data is limited comparing options for how video genetic education is delivered. This study evaluated the impact of pre-test VGE when facilitated by a genetic counseling assistant (assistant-led) or self-completed by the patient (patient-led). Methods: Individuals with PCa referred for genetic counseling received pre-test VGE. Patients were randomized so that this process involved meeting with a genetic counseling assistant or completed at the patient’s convenience via email instructions. Pre-test VGE included family history completion via electronic software and viewing of informational video. VGE completion and genetic testing uptake were measured for all participants. Questionnaires regarding satisfaction, and knowledge were optional for participants after VGE completion. Data was analyzed using t-test and Fisher’s exact. Results: Eighty-one individuals referred for genetic counseling from October 2020-March 2021, and 78 individuals were randomized (1:1) to assistant-led or patient-led VGE, with 39 individuals in each arm. After removing patients for technological limitations, loss to follow up, and procedural withdrawals, there were 18 patients in the assistant-led arm, and 16 patients in the patient-led arm. The primary reason for discontinuing the process was lack of response to phone and electronic contacts to schedule their genetics visit (n = 22). The median age was 64.5 years, with no difference between the two arms (p = 0.698). Participants identified primarily as white/Caucasian (n = 32, 94%). In the assistant-led group, all participants elected to undergo germline genetic testing and 13 (81%) opted for genetic testing in the patient-led group. There was no difference in genetic testing uptake between the two arms (p = 0.094). Nine patients in the patient-led group and eight patients in the assistant-led group completed the questionnaires. There was no difference in satisfaction with their VGE experience (p = 0.815) or knowledge using the KnowGene scale (p = 0.120). Conclusions: Preliminary data suggests there is no difference in genetic testing uptake when pre-test VGE is facilitated by a genetic counseling assistant or self-led by the patient. Given no preliminary differences in satisfaction and knowledge, patient-led pre-test VGE may serve as a viable option prior to germline testing in PCa patients. Additional research is needed with larger sample size. Furthermore, evaluation of the facilitators and barriers of VGE is needed as there was significant drop off in completion of video pre-test VGE.

You have accessJournal of UrologyCME1 May 2022V07-12 ROBOTIC PROSTATECTOMY WITH WIDE EXCISION FOR LOCALLY ADVANCED PROSTATE CANCER Jeffrey Vehawn, Mouneeb Choudry, Austen Slade, Jacob Ambrose, Alejandro Sanchez, and Christopher Dechet Jeffrey VehawnJeffrey Vehawn More articles by this author , Mouneeb ChoudryMouneeb Choudry More articles by this author , Austen SladeAusten Slade More articles by this author , Jacob AmbroseJacob Ambrose More articles by this author , Alejandro SanchezAlejandro Sanchez More articles by this author , and Christopher DechetChristopher Dechet More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002598.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Locally advanced prostate cancer (PCa) is considered as high-risk disease with a poor prognosis. In this setting, the European Association of Urology (EAU) and the National Compressive Cancer Network (NCC) guidelines recommend radical prostatectomy as part of multimodal therapy. In recent years several variations of the standard robotic-assisted radical prostatectomy (RARP) approach have been described. Our aim was to describe our modified RARP technique for locally advanced PCa patients and report perioperative and long-term oncological outcomes. METHODS: Our cohort was derived from a prospectively maintained institutional prostate cancer database. We identified 117 men with high-risk or locally advanced PCa treated with RARP (wide excision) and pelvic lymph node dissection between 2008-2018 by a single expert robotic surgeon at the Huntsman Cancer Institute. Only patients with a minimum of 2 years follow-up were included. Post-operative outcomes were analyzed in patients with complete follow-up data. Post-operative outcomes were measured using univariate cox-proportional hazard models, modeling for BCR survival in wide local excision patients. RESULTS: The median age of men was 66 (IQR: 60.1-69.9) with a median follow-up of 2.8 years (IQR: 2-5.53). Overall, 41% of men had a pathological T-stage of ≥pT3 and 38.5% of men had a N-stage of pN1. 81.2% and 73.5% of patients had capsular extension and capsular invasion, respectively, on preoperative MRI. 69.2% of patients had negative surgical margins. At 5-year follow-up, 64.1% of men achieved BCR-free survival. From our univariate analysis, grade group, pathologic T- and N-stage, and margin status were all independent predictors of BCR. CONCLUSIONS: In this study we presented a revised RARP approach for patients with locally advanced or high-risk prostate cancer. This technique is associated with good post-operative oncological outcomes and may assure biochemical control of the disease in complex PCa patients. Source of Funding: This research was funded by the Huntsman Cancer Institute at the University of Utah © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e662 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jeffrey Vehawn More articles by this author Mouneeb Choudry More articles by this author Austen Slade More articles by this author Jacob Ambrose More articles by this author Alejandro Sanchez More articles by this author Christopher Dechet More articles by this author Expand All Advertisement PDF downloadLoading ...

506 Background: Nivolumab has known efficacy as adjuvant therapy after radical cystectomy in localized muscle invasive bladder cancer (MIBC). We are evaluating the efficacy of nivolumab adjuvant to definitive chemo-radiation therapy (CRT) in MIBC. Methods: In the NEXT study, we are currently enrolling patients with localized MIBC undergoing standard CRT. Participants are started on nivolumab 480 mg IV every 4 weeks (up to 12 doses) within 90 days of completion of CRT. Cystoscopic and scan-based assessments are done every 3 months for the first two years (yrs). The primary endpoint is failure-free survival (FFS) at 2 yrs from the start of CRT, with failure defined as local or systemic disease recurrence. Secondary endpoints include toxicity and quality of life (QOL) assessments. We have planned correlative studies on peripheral blood and tumor tissue. We performed a protocol-defined interim safety and efficacy analysis to assess the 6-month FFS rate with CRT and adjuvant nivolumab. Results: From 8/03/2017 to 9/28/2021, 20 patients were enrolled at two centers; median age is 76 yrs, clinical stage range is T2-T4b, N0-N+, M0; the median number of nivolumab cycles is 6.5, and the median follow-up is 8.9 months. The estimated 6-month FFS rate is 88.2% (95% CI 74.2% - 100%). Disease has progressed in 9 patients, of which 4 have local bladder recurrence (T1 in 3/4) and 5 have distant metastases. The estimated median FFS is 17.1 months (95% CI 8.71 months - infinity). Grade ≥3 treatment-related adverse events (AEs) are noted in 3/20 patients (15%): elevated transaminases, diarrhea, and polymyalgia rheumatica. Grade 3 radiation therapy oncology group (RTOG) AEs occurred in 2 patients. QOL measures are serially evaluable in 13 patients for the first 3 months of adjuvant nivolumab, and are stable in the domains of disease-related physical symptoms, treatment side effects, and function/well-being, while are significantly improved (p=0.023) in the domain of disease-related emotional symptoms. Conclusions: In this first report of the role of immunotherapy adjuvant to CRT for localized bladder cancer, adjuvant nivolumab is well tolerated and has promising efficacy. Clinical trial information: NCT03171025.

A 29-year-old patient presented to his primary care provider complaining of a painful right inguinal swelling. He was referred for inguinal hernia repair, but during surgery, an enlarged necrotic-appearing testicle was observed and removed. Pathology demonstrated a mixed non-seminomatous germ cell tumor (NSGCT) with evidence of tumor violation. After receiving BEPx3 for elevated post-operative AFP his tumor markers normalized. On surveillance, he was found to have several palpable masses around his inguinal incision. On soft tissue excision he was found to have residual teratoma within his soft tissues. We review the literature on germ cell tumor seeding and atypical recurrences.

e18614 Background: To examine the relationship between neoadjuvant chemotherapy (NAC) clinical risk factors, and patient reported quality of life in patients with MIBC undergoing cystectomy. Methods: cT2-T4, N0, M0 MIBC patients who underwent radical cystectomy were identified from a prospectively maintained institutional outcomes database. PROMIS-Ca surveys (physical function (PF), pain interference, fatigue, depression, and anxiety domains) were administered at consultation and follow-up as part of routine clinical care. Patients were stratified as receiving NAC vs. none and surveys were anchored to date of cystectomy. Non-parametric kernel regressions with variance-covariance matrix bootstrapping were used to estimate the mean effect of covariates on each domain T-score with 95% confidence intervals. Covariates were: body mass index, smoking history, age, Charlson comorbidity score, pT and pN stage, urinary diversion-type, and survey time relative to the cystectomy date. T-score changes over time were modeled by including univariable parameters with a P<=0.1 in a multivariable model (MVA) for each domain and predicting the marginal means at date of cystectomy, 6 and 12 months postop. Results: The median age was 68 (IQR 60-73) years. NAC was received by 69/134 patients (40 Gem/Cis, 24 MVAC, 5 unknown). On univariate analyses NAC significantly reduces PF (mean change in t-score, 95%CI; -2.4, -3.7 to -0.8, p=0.001), trends toward more pain (0.94, -0.20 to 1.78, p=0.074), but does not influence fatigue, depression or anxiety. Other covariates with p<0.05 reducing PF were BMI (-0.31, -0.53 to -0.03), pT4 vs pT1-2 (-0.31, -0.53 to -0.03), Charlson 1 vs 0 (-0.31, -0.53 to -0.03), age (-0.31, -0.53 to -0.03), and days from surgery (-0.31, -0.53 to -0.03). Table shows how t-scores predicted from the MVA change over time. Conclusions: MIBC patients have mild to moderate impairment in physical function, fatigue, and pain before and after cystectomy, suggesting a need for increased focus on rehabilitation and wellness programs. Although the univariable analysis implies there may be differences in PF and Pain for those receiving NAC vs none, future studies with increased power are needed to properly adjust for the interplay of other significant covariates.[Table: see text]

You have accessJournal of UrologyProstate Cancer: Markers (MP60)1 Sep 2021MP60-08 DEEP TRANSCRIPTOMIC PROFILING OF PROSTATE CANCER WITH QUANTITATIVE MEASURES: A SPECTRA APPROACH Heidi Hanson, Jacob Ambrose, Brock O'Neil, Greg Lee, Claire Leiser, Rosalie Waller, Joemy Ramsay, Michael Madsen, Rupam Das, Christopher Dechet, Brian Avery, and Nicola Camp Heidi HansonHeidi Hanson More articles by this author , Jacob AmbroseJacob Ambrose More articles by this author , Brock O'NeilBrock O'Neil More articles by this author , Greg LeeGreg Lee More articles by this author , Claire LeiserClaire Leiser More articles by this author , Rosalie WallerRosalie Waller More articles by this author , Joemy RamsayJoemy Ramsay More articles by this author , Michael MadsenMichael Madsen More articles by this author , Rupam DasRupam Das More articles by this author , Christopher DechetChristopher Dechet More articles by this author , Brian AveryBrian Avery More articles by this author , and Nicola CampNicola Camp More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002095.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Methods that embrace the complexity of prostate cancer (CaP) gene expression are necessary for accurate phenotypic characterization. We previously presented a novel agnostic computational framework, SPECTRA, to describe RNA sequencing (RNAseq) data using multiple quantitative expression variables, or transcriptomic spectra (TrS). Here, we implement this technique to derive a set of TrS variables for CaP tumors from The Cancer Genome Atlas (TCGA). We compare the identified TrS with clinical and sample characteristics, progression-free interval, and previously established CaP subtypes. METHODS: Gene-level RNAseq data were downloaded from the Genomic Data Commons (GDC) Data Portal. Data were preprocessed using the SPECTRA protocol (nsamples=480, ngenes = 10,438) and matrix factorization was used to derive quantitative measures for each TrS. Linear, logistic, multinomial logistic, and Cox regression were used to assess the relationship between TrS and age, Gleason Risk Score, tumor stage, and progression free interval. Two approaches were used to select TrS associated with demographic, clinical, and molecular features of the tumors; “hard-thresholding” (Bonferonni corrected p-value) and lasso regularization. We compare model fit statistics to determine the difference in predictive power between our TrS and previously defined molecular subtypes defined by fusion of ETS family genes. RESULTS: We identified 21 TrS in our data that together explain 65.5% of the variance in global gene expression across CaP tumors in TCGA. Many of the TrS were associated with demographic and clinical characteristics of the patients and progression-free interval, with TrS3 having the strongest associations (Figure 1). The difference in predictive power of the TrS vs the previously identified molecular subtypes was substantial, with the difference in pseudo R-square in the range of 30% on average. This suggests that more information can be gained from quantitative vs. qualitative measures of gene expression. CONCLUSIONS: This approach had substantially better model fit than traditional qualitative tumor classifications and could lead to innovative ways to understanding gene expression patterns driving individual risk, treatment response and survival. Source of Funding: 5K07CA230150-03 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1044-e1044 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Heidi Hanson More articles by this author Jacob Ambrose More articles by this author Brock O'Neil More articles by this author Greg Lee More articles by this author Claire Leiser More articles by this author Rosalie Waller More articles by this author Joemy Ramsay More articles by this author Michael Madsen More articles by this author Rupam Das More articles by this author Christopher Dechet More articles by this author Brian Avery More articles by this author Nicola Camp More articles by this author Expand All Advertisement Loading ...