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Objective: To characterize changes in body composition following cytotoxic chemotherapy for germ cell carcinoma of the testis (GCT) and quantify associations between body composition metrics and chemotherapy-associated adverse events (AEs) and post-retroperitoneal lymph node dissection (RPLND) complications., Materials and Methods: This retrospective multi-center study included 216 men with GCT treated with cytotoxic chemotherapy and/or RPLND (2005-2020). We measured body composition including skeletal muscle (SMI), visceral adipose (VAI,), subcutaneous adipose (SAI), and fat mass (FMI) indices on computed tomography. We quantified chemotherapy-associated changes in body composition and evaluated associations between body composition and incidence of grade 3 + AEs and post-RPLND complications on multivariable logistic regression analyses., Results: One hundred and eighty-two men received a median of 3 cycles of cisplatin-based chemotherapy. Following chemotherapy, median change in SMI was -6% (P = <.0001), while VAI, SAI, and FMI increased by +13% (P = <.0001), +11% (P = <.0001), and +6% (P = <.0001), respectively. Seventy-nine patients (43%) experienced at least one grade 3 + AE. A decrease in SMI following chemotherapy was associated with increased risk of grade 3 + AEs (P = .047). One hundred and 3 men with a median age of 28.5 years (IQR 23-35.5) underwent RPLND of whom 22 (21.3%) experienced at least 1 grade 3 + post-RPLND complication. No baseline body composition metrics were associated with post-RPLND complications., Conclusion: In men with GCT of the testis, chemotherapy was associated with 6% loss of lean muscle mass and gains in adiposity. Lower skeletal muscle was associated with a higher incidence of chemotherapy-associated AEs. Body composition was not associated with the incidence of post-RPLND complications., Competing Interests: Declaration of Competing Interest Sarah Psutka serves on an advisory board for Janssen/Johnson & Johnson, Immunity Bio, CG Oncology, Merck; Research funded by the National Institute on Aging, the Bladder Cancer Advocacy Network; Global PI for SunRISE-4; Janssen; Florian Fintelmann receives research support from Pfizer, serves as a consultant and speaker for Boston Scientific, and has a patent for “patient risk stratification based on body composition derived from computed tomography images sing machine learning” (patent number: WO2019051358A1). The remaining authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Small cell bladder cancer (SCBC) is a rare histologic subtype with relative paucity of data regarding treatment response and outcomes. We reviewed 2 databases to compare outcomes in patients with localized SCBC treated with cystectomy versus concurrent chemoradiotherapy (CCRT). We hypothesized that survival would be similar with these therapy approaches., Methods: We retrospectively reviewed our institutional and SEER-Medicare databases to identify patients with SCBC. Overall survival (OS) was determined from the date of diagnosis to last follow-up/death. For those with nonmetastatic disease, a multivariate Cox analysis was used to compare locoregional therapy with neoadjuvant chemotherapy (NAC) + cystectomy versus CCRT., Results: We identified 53 patients in our institutional database and 1166 patients in SEER-Medicare with localized SCBC. Median OS (mOS) with NAC + cystectomy was 46 months (95% CI, 21-72) and 45 months (95% CI, 0-104) in the institutional and SEER-Medicare databases, respectively, whereas mOS with CCRT was 26 months (95% CI, 5-47) and 23 months (95% CI, 18-28) in the 2 series, respectively. In multivariate analysis, NAC followed by cystectomy was associated with an approximately 30% reduction in mortality compared to CCRT in both institutional and national databases but did not reach statistical significance (Institution HR 0.71, 95% CI, 0.22-2.4, P = .58; SEER HR 0.73, 95% CI, 0.49-1.08; P = .11)., Conclusions: SCBC is very aggressive with limited survival observed in our institutional and SEER-Medicare datasets regardless of locoregional therapy used. There is an unmet need to define the optimal locoregional therapy for nonmetastatic stage and identify novel therapeutic targets., Competing Interests: Disclosure Dimitra Rafailia Bakaloudi: no conflicts to disclose. Elizabeth L. Koehne: no conflicts to disclose. Leonidas N. Diamantopoulos: no conflicts to disclose. Sarah K. Holt: no conflicts to disclose. Rishi R. Sekar: no conflicts to disclose. Fady Ghali: Consulting: Immunitybio Funda Vakar-Lopez: no conflicts to disclose. Yaw A. Nyame: no conflicts to disclose. Sarah P. Psutka: Research Funding: National Institute on Aging; Bladder Cancer Advocacy Network; PRIME Education, Inc; Guidelines Committee: American Urological Association: Upper Tract Urothelial Carcinoma Guidelines 2023 Advisory/Consultancy: Janssen (SunRise-4 Global Co-PI), Immunity Bio, Merck, CG Oncology John L. Gore: Research Grant funding from Ferring Pharmaceuticals. Claire de la Calle: no conflicts to disclose. Daniel W. Lin: DSMB for the POTOMAC study with AstraZeneca; Consulting or Advisory Role—Astellas Pharma, Clovis Oncology, Janssen Oncology, and Lantheus, Research Funding –Veracyte; MDxHealth. George R. Schade: Advisor ImmunityBio, Consultant EDAP. Intellectual property licensed to Petal Surgical. Jay Liao: no conflicts to disclose. Andrew C. Hsieh: Honoraria—Hotspot Therapeutics; Research Funding—eFFECTOR Inc; Patents, Royalties, Other Intellectual Property—MTOR modulators and uses thereof Patent number: 9629843; Use Of Translational Profiling To Identify Target Molecules For Therapeutic Treatment, Publication number: 20140288097. Todd Yezefski: Institutional research funding from AstraZeneca, Astellas, participation in educational programs for Dendreon Jessica E. Hawley: consulting for Seagen, Daiichi-Sankyo, Immunity Bio; institutional research support from AstraZeneca, Bristol-Meyers Squibb, Crescendo Biologics, Macrogenics, Johnson & Johnson Innovative Medicine, PromiCell, Amgen, and Vaccitech. Evan Y. Yu: consulting for Aadi Bioscience, Advanced Accelerator Applications, Bayer, Bristol-Myers Squibb, Janssen, Lantheus, Loxo, Merck, Oncternal; institutional research support from Bayer, Blue Earth, Daiichi-Sankyo, Dendreon, Lantheus, Merck, Oncternal, Seagen, Surface, Taiho, Tyra. Robert B. Montgomery: Research Funding—AstraZeneca, Bayer, Clovis, Janssen Oncology. Petros Grivas (unrelated to this manuscript in the last 2 years): consulting for MSD, Bristol Myers Squibb, AstraZeneca, EMD Serono, Seagen, Pfizer, Janssen, Roche, Astellas Pharma, Gilead Sciences, Silverback Therapeutics, BostonGene, Fresenius Kabi, Lucence Health, PureTech, G1 Therapeutics, Aadi Biosciences, CG Oncology, Strata Oncology, ImmunityBio, Asieris Pharmaceuticals, AbbVie; Institutional research funding: Pfizer, Bristol Myers Squibb, MSD, QED Therapeutics, GlaxoSmithKline, Mirati Therapeutics, EMD Serono, G1 Therapeutics, Gilead Sciences, Acrivon Therapeutics, ALX Oncology, Genentech. Jonathan L. Wright: Royalties—UpToDate; Clinical Trials/Research—Merck, Nucleix, Altor Biosciences, Pacific Edge, Seagen, Janssen, Veracyte; Consulting—ImmunityBio; Pacific Edge., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: While 177 Lu-PSMA-617 (LuPSMA) is an effective therapy for many patients with metastatic castration-resistant prostate cancer (mCRPC), biomarkers associated with outcomes are not well defined. We hypothesized that prostate cancer mutational profile may associate with clinical activity of LuPSMA. We devised a study to evaluate associations between mCRPC mutational profile with LuPSMA clinical outcomes., Methods: This was a multicenter retrospective analysis of patients with mCRPC with next-generation sequencing (NGS) who received LuPSMA. PSA 50 response (ie, ≥50% decline in prostate-specific antigen [PSA]) rate, PSA progression free survival (PSA PFS), and overall survival (OS) were compared between genetically defined subgroups., Results: One hundred twenty-six patients with NGS results who received at least one cycle of LuPSMA were identified. The median age was 73 (IQR, 68-78) years, 124 (98.4%) received ≥1 prior androgen receptor-signaling inhibitor, and 121 (96%) received ≥1 taxane-based chemotherapy regimen. Fifty-eight (46%) patients with a DNA damage repair gene mutation (DNA damage response group) and 59 (46.8%) with a mutation in TP53 , RB1 , or PTEN tumor suppressor genes (TSG group) were identified. After adjusting for relevant confounders, the presence of ≥1 TSG mutation was associated with shorter PSA PFS (hazard ratio [HR], 1.93 [95% CI, 1.05 to 3.54]; P = .034) and OS (HR, 2.65 [95% CI, 1.15 to 6.11]; P = .023). There was improved OS favoring the DNA damage response group (HR, 0.37 [95% CI, 0.14 to 0.97]; P = .044) on multivariable analysis. Univariate analysis of patients with ATM mutations had significantly higher rates of PSA 50 response, PSA PFS, and OS., Conclusion: Outcomes on LuPSMA varied on the basis of mutational profile. Prospective studies to define the clinical activity of LuPSMA in predefined genomic subgroups are justified.

Introduction: To examine oncologic outcomes and response to neoadjuvant chemotherapy (NAC) in patients with sarcomatoid urothelial carcinoma (SUC) treated with radical cystectomy (RC)., Materials and Methods: We retrospectively queried our institutional database (2003-18) and Surveillance, Epidemiology, and End Results (SEER)-Medicare (2004-2015) for patients with cT2-4, N0-2, M0 SUC and conventional UC (CUC) treated with RC. Clinicopathologic characteristics were described using descriptive statistics (t test, χ2-test and log-rank-test for group comparison). Overall (OS) and recurrence-free-survival (RFS) after RC were estimated with the Kaplan Meier method and associations with OS were evaluated with Cox proportional hazards models., Results: We identified 38 patients with SUC and 287 patients with CUC in our database, and 190 patients with SUC in SEER-Medicare. In the institutional cohort, patients with SUC versus CUC had higher rates of pT3/4 stage (66% vs. 35%, P < 0.001), lower rates of ypT0N0 (6% vs. 35%, P = .02), and worse median OS (17.5 vs. 120 months, P < .001). Further, patients with SUC in the institutional versus SEER-Medicare cohort had similar median OS (17.5 vs. 21 months). In both cohorts, OS was comparable between patients with SUC undergoing NAC+RC vs. RC alone (17.5 vs. 18.4 months, P = .98, institutional cohort; 24 vs. 20 months, P = .56, SEER cohort). In Cox proportional hazards models for the institutional RC cohort, SUC was independently associated with worse OS (HR 2.3, CI 1.4-3.8, P = .001)., Conclusion: SUC demonstrates poor pathologic response to NAC and worse OS compared with CUC, with no OS benefit associated with NAC. A unique pattern of rapid abdominopelvic cystic recurrence was identified., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Bipolar androgen therapy (BAT) results in rapid fluctuation of testosterone (T) between near-castrate and supraphysiological levels and has shown promise in metastatic castration-resistant prostate cancer (mCRPC). Its clinical effects may be mediated through induction of DNA damage, and preclinical studies suggest synergy with PARP inhibitors., Patients and Methods: This was a single-center, Phase II trial testing olaparib plus BAT (T cypionate/enanthate 400 mg every 28 days) with ongoing androgen deprivation. Planned recruitment was 30 subjects (equal proportions with/without homologous recombination repair [HRR] gene mutations) with mCRPC post abiraterone and/or enzalutamide. The primary objective was to determine PSA 50 response (PSA decline ≥50% from baseline) rate at 12-weeks. The primary analysis utilized the entire (intent-to-treat [ITT]) cohort, with those dropping out early counted as non-responders. Secondary/exploratory analyses were in those treated beyond 12-weeks (response-evaluable cohort)., Results: Thirty-six patients enrolled and 6 discontinued prior to response assessment. In the ITT cohort, PSA 50 response rate at 12-weeks was 11/36 (31%; 95% CI 17-48%), and 16/36 (44%, 95% CI 28-62%) had a PSA50 response at any time on-study. After a median follow-up of 19 months, the median clinical/radiographic progression-free survival in the ITT cohort was 13.0 months (95% CI 7-17). Clinical outcomes were similar regardless of HRR gene mutational status., Conclusions: BAT plus olaparib is associated with high response rates and long PFS. Clinical benefit was observed regardless of HRR gene mutational status., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Germline mutations in DNA repair genes are present in approximately 10% of men with metastatic prostate cancer (mPC), and guidelines recommend genetic germline testing. Notable barriers exist, including access to genetic counseling, insurance coverage, and out-of-pocket costs. The GENTleMEN study was designed to determine the feasibility of an Internet-based, patient-driven germline genetic testing approach for men with mPC., Patients and Methods: In this prospective cohort study, men with mPC provided informed consent via an Internet-based platform and completed a questionnaire including demographics and family cancer history. Supporting medical data were also collected. Genetic testing was performed using the Color Genomics 30-gene targeted panel of cancer predisposition genes on a mailed saliva sample. Men whose test results identified a germline pathogenic or likely pathogenic variant received results by phone or telehealth genetic counseling; other participants received results by email with an option for phone-based or telehealth genetic counseling., Results: As of August 18, 2021, 816 eligible men were consented, of whom 68% (551) completed genetic testing, and 8.7% (48 of 551) were found to carry a pathogenic or likely pathogenic variant in a germline DNA repair gene: CHEK2 (17), BRCA2 (15), ATM (6), NBN1 (3), BRCA1 (2), PALB2 (2), PMS2 (2), and MSH6 (1). Participants were more likely to complete the testing process if they were non-Hispanic White, married, highly educated, or from a higher-income bracket., Conclusion: Here, we show the feasibility of delivering germline (inherited) genetic testing by a voluntary, patient-driven, Internet-based platform to men with mPC. Preliminary results show rates of germline DNA repair mutations, consistent with other cohorts. Although feasible for some, reduced steps for participation, more dedicated diverse outreach and participant support, and identification and addressing of additional barriers is needed to ensure equitable access and optimization.

Objectives: To quantify changes in body composition during cytotoxic chemotherapy for germ cell carcinoma of the testis (GCT) and evaluate associations between change in skeletal muscle and adipose tissue and chemotherapy-associated adverse events., Materials and Methods: This retrospective single-institution study evaluated men with GCT treated with cytotoxic chemotherapy from 2005 to 2018. We measured skeletal muscle index (SMI [cm 2 /m 2 ]), skeletal muscle density (SMD [Hounsfield Units (HU)]), skeletal muscle gauge (SMG [cm²*HU/m²]), fat mass index (FMI [kg/m 2 ]), visceral adipose index (VAI [cm 2 /m 2 ]), and subcutaneous adipose index (SAI [cm 2 /m 2 ]) on axial computed tomography images at the level of the third lumbar vertebra within 75 days before and after chemotherapy. Chemotherapy-associated adverse events (AE) were graded based on the Common Terminology Criteria for Adverse Events (CTCAE v5.0.) Changes in body composition were quantified. Predictors of change in body composition were evaluated with multivariable linear regression. Associations between baseline or change in body composition and AEs were estimated with multivariable logistic regression adjusting for age, comorbidity, performance status, stage, and number/type of chemotherapy cycles., Results: 141 patients (median age, 30 years [IQR 25-39]) including 86 patients (61%) with non-seminomatous GCT were included. Patients received a median of 3 cycles of cisplatin-based chemotherapy, and 124 patients (88%) completed planned chemotherapy. Median observed changes in SMI, SMD, and SMG were -6% (P<0.0001), -2% (P=0.07), and -7% (P<0.0001), respectively, while FMI increased 5.3% (P<0.0001). Overall, 120 patients (85%) experienced at least one AE including one or more ≥grade 3 AE in 57 patients (48%). Decrease in SMI (OR: 0.89, P=0.02), decrease in SMG (OR: 0.88, P=0.01,) and post-chemotherapy SMG (OR: 0.94, P=0.05) were independently associated with higher incidence of AEs, while pre-chemotherapy skeletal muscle parameters and post-chemotherapy SMI and SMD were not associated with AEs (P>0.05 for all). Preoperative adipose tissue or change in adiposity was not associated with incidence of AEs., Conclusions: In men with GCT receiving cytotoxic chemotherapy, a decrease in skeletal muscle mass and quality during chemotherapy were associated with a higher incidence of chemotherapy-associated AEs. Adipose tissue was not associated with the incidence of AEs., Competing Interests: Disclosures Dr. P Grivas (all unrelated COI in the last 3 years): Consulting: AstraZeneca; Astellas Pharma; Bayer; Bristol-Myers Squibb; Clovis Oncology; Dyania Health, EMD Serono; Exelixis; Foundation Medicine; Genentech/Roche; Genzyme; GlaxoSmithKline; Immunomedics/Gilead, Infinity Pharmaceuticals, Janssen; Merck; Mirati Therapeutics; Pfizer; Seattle Genetics, QED Therapeutics; Regeneron Pharmaceuticals; 4D Pharma PLC; UroGen. Research Funding to Institution: Merck; Mirati Therapeutics; Pfizer, Clovis Oncology, Bavarian Nordic, Immunomedics/Gilead, Debiopharm, Bristol-Myers Squibb, QED Therapeutics, GlaxoSmithKline,G1 Therapeutics. Dr. S. Psutka:Consulting: Merck, Research Funding: Prime Education Inc.; Bladder Cancer Advocacy Network Dr. F. J. Fintelmann, Related patent pending Dr. T. Yezefski, Consulting: Dendreon, Pfizer Dr. M. T. Schweizer, Paid consultant and/or received Honoria from Sanofi, AstraZeneca, PharmaIn and Resverlogix. He has received research funding to his institution from Zenith Epigenetics, Bristol Myers Squibb, Merck, Immunomedics, Janssen, AstraZeneca, Pfizer, Madison Vaccines, Hoffman-La Roche, Tmunity, SignalOne Bio and Ambrx, Inc. Dr. E. Yu: (all unrelated COI in the last 3 years):Consulting: Abbvie, Advanced Accelerator Applications, Bayer, Clovis, Exelixis, Janssen, Merck, Sanofi, Research Funding to Institution: Bayer, Blue Earth, Daiichi-Sankyo, Dendreon, Lantheus, Merck, Seagen, Taiho Dr. B. Montgomery: (all unrelated COI in the last 3 years):Consulting (uncompensated): Propella, Strandsmart, Research Funding to Institution: Astellas, AstraZeneca, Beigene, ESSA, Janssen, Clovis, (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Perioperative blood transfusion (PBT) has been associated with worse outcomes across tumor types, including bladder cancer. We report our institutional experience with PBT utilization in the setting of radical cystectomy (RC) for patients with bladder cancer, exploring whether timing of PBT receipt influences perioperative and oncologic outcomes., Methods: Consecutive patients with bladder cancer treated with RC were identified. PBT was defined as red blood cell transfusion during RC or the postoperative admission. Clinicopathologic and peri and/or postoperative parameters were extracted and compared between patients who did and did not receive PBT using Mann Whitney U Test, chi-square, and log-rank test. Overall (OS) and recurrence-free survival (RFS) were estimated with the Kaplan Meier method. Univariate/multivariate logistic and Cox proportional hazards regression were used to identify variables associated with postoperative and oncologic outcomes, respectively., Results: The cohort consisted of 747 patients (77% men; median age 67 years). Median follow-up was 61.5 months (95% CI 55.8-67.2) At least one postoperative complication (90-day morbidity) occurred in 394 (53%) patients. Median OS and RFS were 91.8 months (95% CI: 76.0-107.6) and 66.0 months (95% CI: 48.3-83.7), respectively. On multivariate analysis, intraoperative, but not postoperative, BT was independently associated with shorter OS (HR: 1.74, 95% CI: 1.32-2.29) and RFS (HR: 1.55, 95%CI: 1.20-2.01), after adjusting for relevant clinicopathologic variables. PBT (intra- or post- operative) was significantly associated with prolonged postoperative hospitalization ≥10 days., Conclusions: Intraoperative BT was associated with inferior OS and RFS, and PBT overall was associated with prolonged hospitalization following RC. Further studies are needed to validate this finding and explore potential causes for this observation., Competing Interests: Conflict of interest Leonidas N. Diamantopoulos: no conflicts to disclose;Rishi R. Sekar: no conflicts to disclose; Sarah K. Holt: no conflicts to disclose; Ali R. Khaki: no conflicts to disclose; Natalie J Miller: no conflicts to disclose; Adam Gadzinski: no conflicts to disclose; Yaw A. Nyame: no conflicts to disclose; Brian R. Winters: no conflicts to disclose; Funda Vakar-Lopez: no conflicts to disclose; Maria S. Tretiakova: no conflicts to disclose; Sarah P. Psutka: Honoraria - Prime; Education; Travel, Accommodations, Expenses - Prime Education. John L. Gore: Research Grant funding from Ferring Pharmaceuticals.Daniel W. Lin: DSMB for the POTOMAC study with AstraZeneca; Consulting or Advisory Role – Astellas Pharma, Clovis Oncology, Dendreon; Research Funding – GenomeDx; Genomic Health; MDxHealth. George R. Schade: Patents, Royalties, Other Intellectual Property - Global Cancer Technology. Andrew C. Hsieh: Honoraria - Hotspot Therapeutics; Research Funding - eFFECTOR Inc; Patents, Royalties, Other Intellectual Property - MTOR modulators and uses thereof Patent number: 9629843; Use Of Translational Profiling To Identify Target Molecules For Therapeutic Treatment, Publication number: 20140288097. John K. Lee: Research Funding - Immunomedics; Todd Yezefski: no conflicts to disclose; Michael T. Schweizer: Paid consultant to  Resverlogix. He has received research funding to his institution from Immunomedics, Janssen, AstraZeneca, Pfizer, Madison Vaccines, Tmunity and Hoffmann-La Roche. Heather H. Cheng: Research Funding - Astellas Medivation, Clovis Oncology, Color Foundation, Janssen, Sanofi. Consulting for AstraZeneca. Royalties – UpToDate. Evan Y. Yu: consulting for Abbvie, Advanced Accelerator Applications, Amgen, AstraZeneca, Bayer, Clovis, Dendreon, Incyte, Janssen, Merck, Pharmacyclics, QED, Sanofi, and Seattle Genetics; institutional research support from Bayer, Blue Earth, Daiichi-Sankyo, Dendreon, Merck, Pharmacyclics, Taiho, and Seattle Genetics (all unrelated in last 3 years).Lawrence D. True: Stock and Other Ownership Interests – Lightspeed Micro Research Funding, Ventana Medical Systems; Patents, Royalties, Other Intellectual Property – Lens on an open-top lightsheet microscope. Robert B. Montgomery: Research Funding – AstraZeneca, ESSA, Ferring, Janssen Oncology. Petros Grivas (all unrelated in the last 3 years): consulting for AstraZeneca, Bayer, Bristol-Myers Squibb, Clovis Oncology, Dyania Health, Driver, EMD Serono, Exelixis, Foundation Medicine, GlaxoSmithKline, Genentech, Genzyme, Heron Therapeutics, Immunomedics, Janssen, Merck, Mirati Therapeutics, Pfizer, Roche, Seattle Genetics, QED Therapeutics; institutional research funding from AstraZeneca, Bavarian Nordic, Bayer, Bristol-Myers Squibb, Clovis Oncology, Debiopharm, Genentech, GlaxoSmithKline, Immunomedics, Kure It Cancer Research, Merck, Mirati Therapeutics, Oncogenex, Pfizer, QED Therapeutics. Jonathan L. Wright: Royalties – UpToDate; Clinical Trials - Movember Foundation, Merck, Nucleix, Altor Biosciences; Consulting – Sanofi Genzyme., (Published by Elsevier Inc.)

Background: Localized prostate cancers (PCs) may resist neoadjuvant androgen receptor (AR)-targeted therapies as a result of persistent intraprostatic androgens arising through upregulation of steroidogenic enzymes. Therefore, we sought to evaluate clinical effects of neoadjuvant indomethacin (Indo), which inhibits the steroidogenic enzyme AKR1C3, in addition to combinatorial anti-androgen blockade, in men with high-risk PC undergoing radical prostatectomy (RP)., Methods: This was an open label, single-site, Phase II neoadjuvant trial in men with high to very-high-risk PC, as defined by NCCN criteria. Patients received 12 weeks of apalutamide (Apa), abiraterone acetate plus prednisone (AAP), degarelix, and Indo followed by RP. Primary objective was to determine the pathologic complete response (pCR) rate. Secondary objectives included minimal residual disease (MRD) rate, defined as residual cancer burden (RCB) ≤ 0.25cm 3 (tumor volume multiplied by tumor cellularity) and elucidation of molecular features of resistance., Results: Twenty patients were evaluable for the primary endpoint. Baseline median prostate-specific antigen (PSA) was 10.1 ng/ml, 4 (20%) patients had Gleason grade group (GG) 4 disease and 16 had GG 5 disease. At RP, 1 (5%) patient had pCR and 6 (30%) had MRD. Therapy was well tolerated. Over a median follow-up of 23.8 months, 1 of 7 (14%) men with pathologic response and 6 of 13 (46%) men without pathologic response had a PSA relapse. There was no association between prostate hormone levels or HSD3B1 genotype with pathologic response., Conclusions: In men with high-risk PC, pCR rates remained low even with combinatorial AR-directed therapy, although rates of MRD were higher. Ongoing follow-up is needed to validate clinical outcomes of men who achieve MRD., (© 2021 Wiley Periodicals LLC.)

Background: Micropapillary urothelial carcinoma (MPC) is a rare urothelial carcinoma variant with conflicting data guiding clinical practice. In this study, we explored oncologic outcomes in relation to neoadjuvant chemotherapy (NAC) in a retrospective cohort of patients with MPC, alongside data from Surveillance, Epidemiology, and End Results (SEER)-Medicare., Patients and Methods: We retrospectively identified patients with MPC or conventional urothelial carcinoma (CUC) without any variant histology undergoing radical cystectomy (RC) in our institution (2003-2018). SEER-Medicare was also queried to identify patients diagnosed with MPC (2004-2015). Clinicopathologic data and treatment modalities were extracted. Overall survival (OS) was estimated with the Kaplan-Meier method. Mann-Whitney-Wilcoxon and chi-square tests were used for comparative analysis and Cox regression for identifying clinical covariates associated with OS., Results: Our institutional database yielded 46 patients with MPC and 457 with CUC. In SEER-Medicare, 183 patients with MPC were identified, and 63 (34%) underwent RC. In the institutional cohort, patients with MPC had significantly higher incidence of cN+ (17% vs. 8%), pN+ stage (30% vs. 17%), carcinoma-in-situ (43% vs. 25%), and lymphovascular invasion (30% vs. 16%) at RC versus those with CUC (all P < .05). Pathologic complete response (ypT0N0) to NAC was 33% for MPC and 35% for CUC (P = .899). Median OS was lower for institutional MPC versus CUC in univariate analysis (43.6 vs. 105.3 months, P = .006); however, MPC was not independently associated with OS in the multivariate model. Median OS was 25 months in the SEER MPC cohort for patients undergoing RC, while NAC was not associated with improved OS in that group., Conclusion: Pathologic response to NAC was not significantly different between MPC and CUC, while MPC histology was not an independent predictor of OS. Further studies are needed to better understand biological mechanisms behind its aggressive features as well as the role of NAC in this histology variant., (Published by Elsevier Inc.)

Background: Plasmacytoid urothelial carcinoma is a rare bladder cancer variant with scarce data on outcomes and prognostic factors., Objective: We report our institutional experience with this histology to determine response to neoadjuvant chemotherapy, definitive surgery and survival., Methods: We conducted a retrospective chart review of consecutive patients with plasmacytoid, as well as conventional urothelial carcinoma (for comparison) seen in our institution (2007 - 2018). Baseline characteristics, clinicopathologic and treatment data were captured. T-test, chi-squared and log-rank test was used for group comparison. Kaplan Meier method was used for estimation of overall survival and Cox regression for identification of prognostic factors., Results: 64 patients with plasmacytoid and 418 with conventional urothelial histology were identified; 53% of those with plasmacytoid presented with cT3/4 stage and 67% underwent extirpative surgery. Patients with plasmacytoid histology had higher rates of pT3/4 (65% vs. 28%), nodal disease (37% vs. 16%) and positive surgical margins (23% vs. 5%) compared to urothelial group (p < 0.01), as well as higher incidence of post-operative recurrence (47% vs. 29%, p = 0.05) and lower ypT0N0 rates after neoadjuvant chemotherapy (10% vs. 33%, p = 0.03). Plasmacytoid histology was associated with lower median overall survival compared to conventional urothelial (24 vs. 154 months, p < 0.01)., Conclusions: Plasmacytoid urothelial carcinoma frequently presented with advanced stage at diagnosis and extirpative surgery, poor pathologic response to neoadjuvant chemotherapy, and inferior outcomes, when compared to conventional urothelial. Prospective trials evaluating upfront cystectomy versus preoperative chemotherapy and/or novel treatments should be considered., Competing Interests: Conflict of Interest Statement Leonidas Nikolaos Diamantopoulos No Relationships to Disclose Ali Raza Khaki Stock and Other Ownership Interests - Pfizer; Procter & Gamble; Walgreens Boots Alliance Petros Grivas: personal fees and other from Genentech, personal fees and other from Bayer, personal fees and other from Merck & Co., personal fees and other from Mirati Therapeutics, other from Oncogenex, personal fees and other from Pfizer, personal fees and other from Bristol-Myers Squibb, personal fees, non-financial support and other from Astra Zeneca, personal fees from Biocept, personal fees, non-financial support and other from ClovisOncology, personal fees from EMD Serono, personal fees from Seattle Genetics, personal fees from Foundation Medicine, personal fees from Driver Inc., personal fees from QED Therapeutics, personal fees from Heron Therapeutics, personal fees from Janssen, other from Bavarian Nordic, other from Immunomedics, other from Debiopharm, personal fees from GlaxoSmithKline, personal fees from Roche, personal fees from Genzyme, personal fees from Exelixis. John L. Gore Research Funding – Ferring Pharmaceuticals George R Schade Patents, Royalties, Other Intellectual Property - Global Cancer Technology Andrew Caleb Hsieh Honoraria - Hotspot Therapeutics Research Funding - eFFECTOR Inc Patents, Royalties, Other Intellectual Property - MTOR modulators and uses thereof Patent number: 9629843; USE OF TRANSLATIONAL PROFILING TO IDENTIFY TARGET MOLECULES FOR THERAPEUTIC TREATMENT Publication number: 20140288097 John Kyung Lee Research Funding - Immunomedics Todd Yezefski No Relationships to Disclose Evan Y. Yu Consulting or Advisory Role - Amgen; AstraZeneca; Bayer; Churchill Pharmaceuticals; Dendreon; EMD Serono; Incyte; Janssen; Merck; QED; Seattle Genetics; Tolmar Research Funding - Agensys; Astellas Pharma; Bayer; Dendreon; Genentech/Roche; Merck; Seattle Genetics Michael Thomas Schweizer Consulting or Advisory Role - Janssen Research Funding - AstraZeneca; Janssen; Madison Vaccines, Inc.; Pfizer; Roche; Zenith Epigenetics Heather H. Cheng Research Funding - Astellas Medivation; Clovis Oncology; Color Foundation; Inovio Pharmaceuticals; Janssen; Sanofi Sarah P. Psutka Honoraria - Prime Education Travel, Accommodations, Expenses - Prime Education Daniel W. Lin Consulting or Advisory Role - Astellas Pharma; Clovis Oncology; Dendreon Research Funding - GenomeDx; Genomic Health; MDxHealth Maria S. Tretiakova No Relationships to Disclose Funda Vakar-Lopez No Relationships to Disclose Robert B. Montgomery Research Funding - AstraZeneca; ESSA; Ferring; Janssen Oncology Jonathan L. Wright Speakers’ Bureau - Foundation Health Partners Carroll Cancer Center; OncLive; Seattle Cancer Care Alliance Research Funding - Altor BioScience; Merck; Nucleix Other Relationship - Movember; UpToDate

High out-of-pocket (OOP) spending on cancer drugs is a known contributor to "financial toxicity" among cancer patients. Many predict that this problem will only worsen as patients continue to bear more responsibility for the cost of their medical care and as the use of oral chemotherapeutic agents increases. Although foundations and pharmaceutical companies offer patient assistance programs (PAPs) to improve drug affordability, the degree to which these programs are used is poorly understood. There are several barriers to the use of PAPs that not only affect access to patients who may benefit but also create limitations on the research and study of these programs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Patients with cancer often face financial hardships, including loss of productivity, high out-of-pocket (OOP) costs, depletion of savings, and bankruptcy. By providing financial guidance and assistance through specially trained navigators, hospitals and cancer care clinics may be able mitigate the financial burdens to patients and also minimize financial losses for the treating institutions., Study Design: Financial navigators at 4 hospitals were trained through The NaVectis Group, an organization that provides training to healthcare staff to increase patient access to care and assist with OOP expenses. Data regarding financial assistance and hospital revenue were collected after instituting these programs., Methods: Amount and type of assistance (free medication, new insurance enrollment, premium/co-pay assistance) were determined annually for all qualifying patients at the participating hospitals., Results: Of 11,186 new patients with cancer seen across the 4 participating hospitals between 2012 and 2016, 3572 (32%) qualified for financial assistance. They obtained $39 million in total financial assistance, averaging $3.5 million per year in the 11 years under observation. Patients saved an average of $33,265 annually on medication, $12,256 through enrollment in insurance plans, $35,294 with premium assistance, and $3076 with co-pay assistance. The 4 hospitals were able to avoid write-offs and save on charity care by an average of $2.1 million per year., Conclusions: Providing financial navigation training to staff at hospitals and cancer centers can significantly benefit patients through decreased OOP expenditures and also mitigate financial losses for healthcare institutions.

Purpose: High-throughput profiling experiments have linked altered expression of microRNAs (miRNA) to different types of cancer. Tumor tissues are a heterogeneous mixture of not only cancer cells, but also supportive and reactive tumor microenvironment elements. To clarify the clinical significance of altered miRNA expression in solid tumors, we developed a sensitive fluorescence-based in situ hybridization (ISH) method to visualize miRNA accumulation within individual cells in formalin-fixed, paraffin-embedded tissue specimens. This ISH method was implemented to be compatible with routine clinical immunohistochemical (IHC) assays to enable the detection of miRNAs and protein markers in the same tissue section for colocalization and functional studies., Experimental Design: We used this combined ISH/IHC assay to study a subset of cancer-associated miRNAs, including miRNAs frequently detected at low (miR-34a and miR-126) and high (miR-21 and miR-155) levels, in a panel of breast, colorectal, lung, pancreas, and prostate carcinomas., Results: Despite the distinct histopathologic alterations of each particular cancer type, general trends emerged that pinpointed distinct source cells of altered miRNA expression. Although altered expressions of miR-21 and miR-34a were manifested within cancer cells, those of miR-126 and miR-155 were predominantly confined to endothelial cells and immune cells, respectively. These results suggest a heterogeneous participation of miRNAs in carcinogenesis by intrinsically affecting cancer cell biology or by modulating stromal, vascular, and immune responses., Conclusions: We described a rapid and sensitive multicolor ISH/IHC assay and showed that it could be broadly applied as an investigational tool to better understand the etiologic relevance of altered miRNA expression in cancer.

The level of survivin was reported to be scarce in mouse megakaryocytes (MKs) compared with erythroid cells. Considering this finding and previously reported in vitro data showing decreased MK ploidy upon retroviral-mediated overexpression of survivin, we sought to examine whether ectopic survivin expression in the MK lineage might alter ploidy level in vivo. Here we report the generation of 2 tissue specific hematopoietic transgenic mouse models, one expressing survivin in both the erythroid and MK lineages and the other expressing survivin solely in the MK lineage. Survivin protein overexpression was confirmed in MKs and erythrocytes. Surprisingly, analysis of both transgenic mouse lines showed no detectable changes in MK number, ploidy level, and platelet and erythrocyte counts, as compared with control mice. We conclude that elevated survivin expression does not alter MK/erythroid lineage development and that elevated survivin, alone, does not interfere with MK ploidy in vivo.