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Purpose: Castration-sensitive prostate cancer (CSPC) is a complex and heterogeneous condition encompassing a range of clinical presentations. As new approaches have expanded management options, clinicians are left with myriad questions and controversies regarding the optimal individualized management of CSPC., Materials and Methods: The US Prostate Cancer Conference (USPCC) multidisciplinary panel was assembled to address the challenges of prostate cancer management. The first annual USPCC meeting included experts in urology, medical oncology, radiation oncology, and nuclear medicine. USPCC co-chairs and session moderators identified key areas of controversy and uncertainty in prostate cancer management and organized the sessions with multidisciplinary presentations and discussion. Throughout the meeting, experts responded to questions prepared by chairs and moderators to identify areas of agreement and controversy., Results: The USPCC panel discussion and question responses for CSPC-related topics are presented. Key advances in CSPC management endorsed by USPCC experts included the development and clinical utilization of gene expression classifiers and artificial intelligence (AI) models for risk stratification and treatment selection in specific patient populations, the use of advanced imaging modalities in patients with clinically localized unfavorable intermediate or high-risk disease and those with biochemical recurrence, recommendations of doublet or triplet therapy for metastatic CSPC (mCSPC), and consideration of prostate and/or metastasis-directed radiation therapy in select patients with mCSPC., Conclusions: CSPC is a diverse disease with many therapeutic options and the potential for adverse outcomes associated with either undertreatment or overtreatment. Future studies are needed to validate and clinically integrate novel technologies, including genomics, AI, and advanced imaging, to optimize outcomes among patients with CSPC., Competing Interests: CONFLICTS OF INTEREST The authors declare the following competing interests: Alan H. Bryce has received compensation for a consulting or advisory role from Merck, Janssen, Astellas, AstraZeneca, Pfizer, Myovant, and Lantheus; and grant funding from Janssen. Andrew J. Armstrong has received compensation for a consulting or advisory role from Astellas, Epic Sciences, Pfizer, Bayer, Janssen, Dendreon, BMS, AstraZeneca, Merck, Forma, Celgene, Clovis, Exact Sciences, Myovant, Exelixis, GoodRx, and Novartis; and his institution has received research funding from Astellas, Pfizer, Bayer, Janssen, Dendreon, BMS, AstraZeneca, Merck, Forma, Celgene, Amgen, and Novartis. AI has received compensation for a consulting or advisory role from Alpha9Tx, Clarity Pharmaceuticals, Novartis, Progenics, Radionetics, RayzeBio, and Telix; and research/grant funding from GE Healthcare and Novartis. Ana M. Aparicio has received compensation for a consulting or advisory role from Pfizer, Janssen, and Bristol Myers Squibb. Alicia K. Morgans has received compensation for a consulting or advisory role from Astellas, AstraZeneca, AAA, Bayer, Janssen, Exelixis, Myovant, Myriad Genetics, Lantheus, Novartis, Merck, Pfizer, Telix, and Sanofi; and research funding from Bayer, Astellas, Myovant, Pfzer, Sanofi, and Janssen. Brian F. Chapin has received compensation for a consulting or advisory role from Blue Earth Diagnostics, Astellas, Pfizer, and Janssen; and is a clinical trial investigator for Regeneron and Blue Earth Therapeutics. Daniel P. Petrylak has received compensation for a consulting or advisory role from Ada Cap (Advanced Accelerator Applications), Amgen, Astellas, AstraZeneca, Bayer, Bicycle Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Eli Lilly, Exelixis, Gilead Sciences, Incyte, Infinity Pharmaceuticals, Ipsen, Janssen, Merck & Company Inc, Mirati, Monopteros, Pfizer, Pharmacyclics, Regeneron, Roche, Sanofi Aventis Pharmaceuticals, Seattle Genetics, and Urogen; has received grant support from Ada Cap (Advanced Accelerator Applications), Agensys Inc, Arvinas, Astellas, AstraZeneca, Bayer, BioXcel Therapeutics, Bristol Myers Squibb, Clovis Oncology, Daiichi Sankyo Company Limited, Eisai, Eli Lilly, Endocyte, Ferring, Genentech, Gilead Sciences, Innocrin, MedImmune, Medivation, Merck, Mirati, Novartis, Pfizer, Progenics, Replimune, Roche, Sanofi Aventis, and Seattle Genetics; and has owned stock in Bellicum and Tyme. Daniel E. Spratt has received compensation for a consulting or advisory role from AstraZeneca, Bayer, Boston Scientific, Elekta, Janssen, Novartis, Pfizer, and Varian. Emmanuel S. Antonarakis has received compensation for a consulting or advisory role from Sanofi, Dendreon, Janssen Biotech, ESSA, Merck, AstraZeneca, Clovis Oncology, Lilly, Bayer, Amgen, Astellas Pharma, Blue Earth Diagnostics, Bristol Myers Squibb/Celgene, Constellation Pharmaceuticals, Curium Pharma, Exact Sciences, Foundation Medicine, GlaxoSmithKline, InVitae, Ismar Health Care, Medivation, Tempus, Orion, and Alkido Pharma; he has received research funding from Celgene and Clovis Oncology; his institution has received research funding from Janssen Biotech, Johnson & Johnson, Sanofi, Dendreon, Aragon Pharmaceuticals, Exelixis, Millennium, Genentech, Novartis, Astellas Pharma, Tokai Pharmaceuticals, Merck, AstraZeneca, Clovis Oncology, Constellation Pharmaceuticals, Celgene, and Clovis Oncology; and he is co-inventor of a biomarker technology that has been licensed to Qiagen. E. David Crawford has received compensation for a consulting or advisory role from Janssen, Bayer, MDx, Tolmar, Pfizer, and Astellas; has received research/grant funding from the NIH and University of Colorado Cancer Center; and has received compensation for a leadership position from Carden Jennings. Eric Small has received compensation for a consulting or advisory role from Janssen, Fortis, and Deciphera; received honoraria from Janssen and Johnson & Johnson; and owns stock/stock options in Fortis, Harpoon, and Teon. Evan Y. Yu has received compensation for a consulting or advisory role from Aadi Bioscience, Advanced Accelerator Applications, Bayer, Janssen, Merck, and Oncternal; and his institution has received research funding from Bayer, Blue Earth, Daiichi-Sankyo, Dendreon, Lantheus, Merck, Seagen, Surface, Taiho, and Tyra. Felix Y. Feng has received compensation for a consulting or advisory role from Astellas, Bayer, Blue Earth Diagnostics, Janssen, Myovant, Novartis, Roivant, Sanofi, Tempus, Artera, BMS (Tumor Microenvironment Group), ClearNote, and Serimmune, Himisha Beltran has received compensation for a consulting or advisory role from Janssen, Merck, Pfizer, Foundation Medicine, Blue Earth Diagnostics, Amgen, Bayer, Oncorus, LOXO, Daicchi Sankyo, Sanofi, Curie Therapeutics, Fusion Pharma, Astra Zeneca, and Novartis; and her institution has received research funding from Janssen, Bristol Myers Squibb, Circle Pharma, Daicchi Sankyo, and Novartis. Jeremie Calais has received compensation for a consulting, advisory, or blinded image reading role from Advanced Accelerator Applications, Amgen, Astellas, Bayer, Blue Earth Diagnostics Inc., Curium Pharma, DS Pharma, GE Healthcare, Isoray, IBA RadioPharma, Janssen Pharmaceuticals, Monrol, Lightpointmedical, Lantheus, Novartis, Pfizer, POINT biopharma, Progenics, Radiomedix, Sanofi, Siemens-Varian, SOFIE, and Telix Pharmaceuticals; and grant funding from the Prostate Cancer Foundation. John W. Davis has received research funding from Janssen. Katie S. Murray has received compensation for a consulting or advisory role from Curium and Urogen Pharma. Michael S. Cookson has received compensation for a consulting or advisory role from LynxDx, Natera, Bayer, Consulting JW, Remedica Medical Education & Publishing, Pfizer, Lantheus, Nonagen Bioscience Corp, MJH LifeSciences, Pacific Edge Diagnostics USA Ltd, Janssen, Prokarium, BioPharm Communications, Myovant, Merck, Clinical Education Alliance, TesoRx Pharma; and has received research support from Ferring Pharmaceuticald and MDXHealth. Maha H. Hussain has received compensation for a consulting or advisory role from GSK, Novartis, and Bayer; honoraria for educational event or lecture from Merck, Mubarak Mahdi Almansour (Chairman, International Genitourinary Cancer Conference), MJH, and Academic CME; her institution has received research/grant funding from AstraZeneca and Arvinas. Michael Morris has received compensation for a consulting or advisory role from AstraZeneca, Lantheus, Daiichi, Convergent Therapeutics, Pfizer, ITM Isotope Technologies, Clarity Pharmaceuticals, Blue Earth Diagnostics, POINT Biopharma, Telix, and Z-Alpha; he is an uncompensated advisor to Bayer and Novartis; his institution has received research funding from Bayer, Corcept, Roche, Janssen, Celgene, Novartis, and Astellas. Matthew B. Rettig has received compensation for a consulting or advisory role from Myovant, INmune Bio, Bayer, and Johnson & Johnson; is a member of the Speakers’ Bureau for Johnson & Johnson and Bayer; and has received grants/research support from Merck, Lantheus, Progenics, Clovis, ORIC, Pfizer, Novartis, Amgen. Neeraj Agarwal has received compensation for a consulting or advisory role from Astellas, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, and Seattle Genetics; his institution has received research funding from Arnivas, Astellas, Astra Zeneca, Bavarian Nordic, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, Crispr, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, Glaxo Smith Kline, Immunomedics, Janssen, Lava, Medivation, Merck, Nektar, Neoleukin, New Link Genetics, Novartis, Oric, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, and Tracon. Neal Shore has received compensation for a consulting or advisory role from AbbVie, Alessa Therapeutics, Akido, Amgen, Arquer, Asieris, Astellas, Astra Zeneca, Bayer, BMS, Boston Scientific, Clarity, Clovis, Cold Genesys, Dendreon, Exact Images, Exact Sciences, FerGene, FIZE Medical, GConcology, GenesisCare, Genetech, Guardant, Ferring, Foundation Medicine, ImmunityBio, Incyte, Invitae, Janssen, Lantheus, Lilly, MDX, Merck, Minomic, Myovant, Myriad, NGM, Nonagen, Novartis, NYMOX, Pacific Edge, Photocure, Pfizer, PlatformQ, Profound, Promaxo, Propella, Protara, Sanofi, SesenBio, Speciality Networks, Telix, Tolmar, Urogen, Vaxiion, and Vessi; received payment for expert testimony from Ferring; and is on the board of Photocure. Oliver Sartor has received compensation for a consulting or advisory role from Advanced Accelerator Applications, Amgen, ART BioScience, Astellas Pharma, AstraZeneca, Bayer, Clarity Pharmaceuticals, EMD Serono, Fusion Pharmaceuticals, Isotopen Technologien, Janssen, MacroGenics, Novartis, Pfizer, Point Biopharma, Ratio, Sanofi, Telix Pharmaceuticals, and TeneoBio; he has stock or other ownership interested with AbbVie, Cardinal Health, Clarity Pharmaceuticals, Convergent, Eli Lilly, Fusion Pharmaceuticals, Point Biopharma, Ratio, Telix, and United Health Group; he has patents for Saposin C and receptors as targets for treatment of benign and malignant disorders (U.S. patent awarded January 23, 2007; patent no. 7,166,691); he has provided expert testimony for Sanofi; he has received reimbursement for travel, accommodations, or expenses from AstraZeneca, Bayer, Lantheus, and Sanofi; and his institution has received research/grant funding from Advanced Accelerator Applications, Amgen, AstraZeneca, Bayer, InVitae, Janssen, Lantheus, Merck, and Sanofi. Phillip J. Koo has received compensation for a consulting or advisory role from Lantheus, Blue Earth Diagnostics, Merck, Janssen, Pfizer, Astellas, AstraZeneca, Bayer, Novartis, Sanofi, Telix, and Curium. Scott E. Eggener has received compensation for a consulting or advisory role Candel Therapeutics, A3P Biomedical, Cellvax, MetasTx, Optum-Health, and Janssen. Sandy Srinivas has received compensation for a consulting or advisory role from Novartis and Janssen. Scott T. Tagawa has received compensation for a consulting or advisory role from Sanofi, Medivation, Astellas, Dendreon, Janssen, Genentech, Bayer, Endocyte, Eisai, Immunomedics, Karyopharm, Abbvie, Tolmar, Seattle Genetics, Amgen, Clovis, QED, Pfizer, AAA/Novartis, Clarity, Genomic Health, POINT Biopharma, Blue Earth, AIkido Pharma, Telix Pharma, Convergent Therapeutics, EMD Serono, Myovant, Merck, Daiichi Sankyo, TransThera, and Regeneron; he is an unpaid consultant for Atlab Pharma, Phosplatin Therapeutics, Amgen, and Ambrx; he and his institution hold patents for biomarkers for sacituzumab govitecan therapy (Immunomedics/Gilead); and his institution has received research funding from Sanofi, Medivation, Astellas, Janssen, Amgen, Progenics, Dendreon, Lilly, Genentech, Newlink, BMS, Inovio, AstraZeneca, Immunomedics, Aveo, Rexahn, Atlab, Boehringer Ingelheim, Millennium, Bayer, Merck, Abbvie, Karyopharm, Endocyte, Clovis, Seattle Genetics, Novartis, Gilead, POINT Biopharma, Ambrx, Clarity. Thomas P. Boike has received compensation for a consulting or advisory role from Lantheus, Myovant, Novartis, Pfizer, Janssen, Astellas, Blue Earth, AstraZeneca, Palette Life Sciences, and Boston Scientific. Tanya Dorff has received compensation for a consulting or advisory role from AstraZeneca, Bayer, Janssen, and Sanofi. Tian Zhang has received compensation for a consulting or advisory role from Merck, Exelixis, Sanofi-Aventis, Janssen, Astra Zeneca, Pfizer, Amgen, BMS, Dendreon, SeaGen, Eisai, Aveo, Bayer, and Eli Lilly; honoraria from MJH Associates, Vaniam, Aptitude Health, PlatformQ, IntegrityCE, PeerView, and WJ Weiser; and her institution has received research funding from Novartis, Merck, Janssen, Astra Zeneca, Pfizer, Tempus, and Eli Lilly. Wendy Poage is an employee of Servier Pharmaceuticals; and she has ownership interests in 3D biopsy.

Background: Management strategies for metastatic castration-resistant prostate cancer (mCRPC) have rapidly shifted in recent years. As novel imaging and therapeutic approaches have made their way to the clinic, providers are encountering increasingly challenging clinical scenarios, with limited guidance from the current literature., Materials and Methods: The US Prostate Cancer Conference (USPCC) is a multidisciplinary meeting of prostate cancer experts intended to address the many challenges of prostate cancer management. At the first annual USPCC meeting, areas of controversy and consensus were identified during a 2-day meeting that included expert presentations, full-panel discussions, and postdiscussion responses to questions developed by the USPCC cochairs and session moderators., Results: This narrative review covers the USPCC expert discussion and perspectives relevant to mCRPC, including neuroendocrine/aggressive-variant prostate cancer (NEPC/AVPC). Areas of broad agreement identified among USPCC experts include the benefits of poly (ADP-ribose) polymerase (PARP) inhibitors for patients with BRCA1/2 mutations, the use of radioligand therapy in patients with prostate-specific membrane antigen (PSMA)-positive mCRPC, and the need for clinical trials that address real-world clinical questions, including the performance of novel therapies when compared with modern standard-of-care treatment. Ongoing areas of controversy and uncertainty included the appropriateness of PARP inhibitors in patients with non- BRCA1/2 mutations, the optimal definition of PSMA positivity, and systemic therapies for patients with NEPC/AVPC after progression on platinum-based therapies., Conclusions: The first annual USPCC meeting identified several areas of controversy in the management of mCRPC, highlighting the urgent need for clinical trials designed to facilitate treatment selection and sequencing in this heterogeneous disease state., Competing Interests: CONFLICTS OF INTEREST The authors declare the following competing interests: Alan H. Bryce has received compensation for a consulting or advisory role from Merck, Janssen, Astellas, AstraZeneca, Pfizer, Myovant, and Lantheus; and grant funding from Janssen. Andrew J. Armstrong has received compensation for a consulting or advisory role from Astellas, Epic Sciences, Pfizer, Bayer, Janssen, Dendreon, BMS, AstraZeneca, Merck, Forma, Celgene, Clovis, Exact Sciences, Myovant, Exelixis, GoodRx, and Novartis; and his institution has received research funding from Astellas, Pfizer, Bayer, Janssen, Dendreon, BMS, AstraZeneca, Merck, Forma, Celgene, Amgen, and Novartis. Andrei Iagaru has received compensation for a consulting or advisory role from Alpha9Tx, Clarity Pharmaceuticals, Novartis, Progenics, Radionetics, RayzeBio, and Telix; and research/grant funding from GE Healthcare and Novartis. Ana M. Aparicio has received compensation for a consulting or advisory role from Pfizer, Janssen, and Bristol Myers Squibb. Alicia K. Morgans has received compensation for a consulting or advisory role from Astellas, AstraZeneca, AAA, Bayer, Janssen, Exelixis, Myovant, Myriad Genetics, Lantheus, Novartis, Merck, Pfizer, Telix, and Sanofi; and research funding from Bayer, Astellas, Myovant, Pfzer, Sanofi, and Janssen. Brian F. Chapin has received compensation for a consulting or advisory role from Blue Earth Diagnostics, Astellas, Pfizer, and Janssen; and is a clinical trial investigator for Regeneron and Blue Earth Therapeutics. Daniel P. Petrylak has received compensation for a consulting or advisory role from Ada Cap (Advanced Accelerator Applications), Amgen, Astellas, AstraZeneca, Bayer, Bicycle Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Eli Lilly, Exelixis, Gilead Sciences, Incyte, Infinity Pharmaceuticals, Ipsen, Janssen, Merck & Company Inc, Mirati, Monopteros, Pfizer, Pharmacyclics, Regeneron, Roche, Sanofi Aventis Pharmaceuticals, Seattle Genetics, and Urogen; has received grant support from Ada Cap (Advanced Accelerator Applications), Agensys Inc, Arvinas, Astellas, AstraZeneca, Bayer, BioXcel Therapeutics, Bristol Myers Squibb, Clovis Oncology, Daiichi Sankyo Company Limited, Eisai, Eli Lilly, Endocyte, Ferring, Genentech, Gilead Sciences, Innocrin, MedImmune, Medivation, Merck, Mirati, Novartis, Pfizer, Progenics, Replimune, Roche, Sanofi Aventis, and Seattle Genetics; and has owned stock in Bellicum and Tyme. Daniel E. Spratt has received compensation for a consulting or advisory role from AstraZeneca, Bayer, Boston Scientific, Elekta, Janssen, Novartis, Pfizer, and Varian. Emmanuel S. Antonarakis has received compensation for a consulting or advisory role from Sanofi, Dendreon, Janssen Biotech, ESSA, Merck, AstraZeneca, Clovis Oncology, Lilly, Bayer, Amgen, Astellas Pharma, Blue Earth Diagnostics, Bristol Myers Squibb/Celgene, Constellation Pharmaceuticals, Curium Pharma, Exact Sciences, Foundation Medicine, GlaxoSmithKline, InVitae, Ismar Health Care, Medivation, Tempus, Orion, and Alkido Pharma; he has received research funding from Celgene and Clovis Oncology; his institution has received research funding from Janssen Biotech, Johnson & Johnson, Sanofi, Dendreon, Aragon Pharmaceuticals, Exelixis, Millennium, Genentech, Novartis, Astellas Pharma, Tokai Pharmaceuticals, Merck, AstraZeneca, Clovis Oncology, Constellation Pharmaceuticals, Celgene, and Clovis Oncology; and he is co-inventor of a biomarker technology that has been licensed to Qiagen. E. David Crawford has received compensation for a consulting or advisory role from Janssen, Bayer, MDx, Tolmar, Pfizer, and Astellas; has received research/grant funding from the NIH and University of Colorado Cancer Center; and has received compensation for a leadership position from Carden Jennings. Eric Small has received compensation for a consulting or advisory role from Janssen, Fortis, and Deciphera; received honoraria from Janssen and Johnson & Johnson; and owns stock/stock options in Fortis, Harpoon, and Teon. Evan Y. Yu has received compensation for a consulting or advisory role from Aadi Bioscience, Advanced Accelerator Applications, Bayer, Janssen, Merck, and Oncternal; and his institution has received research funding from Bayer, Blue Earth, Daiichi-Sankyo, Dendreon, Lantheus, Merck, Seagen, Surface, Taiho, and Tyra. Felix Y. Feng has received compensation for a consulting or advisory role from Astellas, Bayer, Blue Earth Diagnostics, Janssen, Myovant, Novartis, Roivant, Sanofi, Tempus, Artera, BMS (Tumor Microenvironment Group), ClearNote, and Serimmune, Himisha Beltran has received compensation for a consulting or advisory role from Janssen, Merck, Pfizer, Foundation Medicine, Blue Earth Diagnostics, Amgen, Bayer, Oncorus, LOXO, Daicchi Sankyo, Sanofi, Curie Therapeutics, Fusion Pharma, Astra Zeneca, and Novartis; and her institution has received research funding from Janssen, Bristol Myers Squibb, Circle Pharma, Daicchi Sankyo, and Novartis. Jeremie Calais has received compensation for a consulting, advisory, or blinded image reading role from Advanced Accelerator Applications, Amgen, Astellas, Bayer, Blue Earth Diagnostics Inc, Curium Pharma, DS Pharma, GE Healthcare, Isoray, IBA RadioPharma, Janssen Pharmaceuticals, Monrol, Lightpointmedical, Lantheus, Novartis, Pfizer, POINT biopharma, Progenics, Radiomedix, Sanofi, Siemens-Varian, SOFIE, and Telix Pharmaceuticals; and grant funding from the Prostate Cancer Foundation. John W. Davis has received research funding from Janssen. Katie S. Murray has received compensation for a consulting or advisory role from Curium and Urogen Pharma. Michael S. Cookson has received compensation for a consulting or advisory role from LynxDx, Natera, Bayer, Consulting JW, Remedica Medical Education & Publishing, Pfizer, Lantheus, Nonagen Bioscience Corp, MJH LifeSciences, Pacific Edge Diagnostics USA Ltd, Janssen, Prokarium, BioPharm Communications, Myovant, Merck, Clinical Education Alliance, TesoRx Pharma; and has received research support from Ferring Pharmaceuticald and MDXHealth. Maha H. Hussain has received compensation for a consulting or advisory role from GSK, Novartis, and Bayer; honoraria for educational event or lecture from Merck, Mubarak Mahdi Almansour (Chairman, International Genitourinary Cancer Conference), MJH, and Academic CME; her institution has received research/grant funding from AstraZeneca and Arvinas. Michael Morris has received compensation for a consulting or advisory role from AstraZeneca, Lantheus, Daiichi, Convergent Therapeutics, Pfizer, ITM Isotope Technologies, Clarity Pharmaceuticals, Blue Earth Diagnostics, POINT Biopharma, Telix, and Z-Alpha; he is an uncompensated advisor to Bayer and Novartis; his institution has received research funding from Bayer, Corcept, Roche, Janssen, Celgene, Novartis, and Astellas. Matthew B. Rettig has received compensation for a consulting or advisory role from Myovant, INmune Bio, Bayer, and Johnson & Johnson; is a member of the Speakers’ Bureau for Johnson & Johnson and Bayer; and has received grants/research support from Merck, Lantheus, Progenics, Clovis, ORIC, Pfizer, Novartis, Amgen. Neeraj Agarwal has received compensation for a consulting or advisory role from Astellas, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, and Seattle Genetics; his institution has received research funding from Arnivas, Astellas, Astra Zeneca, Bavarian Nordic, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, Crispr, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, Glaxo Smith Kline, Immunomedics, Janssen, Lava, Medivation, Merck, Nektar, Neoleukin, New Link Genetics, Novartis, Oric, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, and Tracon. Neal Shore has received compensation for a consulting or advisory role from AbbVie, Alessa Therapeutics, Akido, Amgen, Arquer, Asieris, Astellas, Astra Zeneca, Bayer, BMS, Boston Scientific, Clarity, Clovis, Cold Genesys, Dendreon, Exact Images, Exact Sciences, FerGene, FIZE Medical, GConcology, GenesisCare, Genetech, Guardant, Ferring, Foundation Medicine, ImmunityBio, Incyte, Invitae, Janssen, Lantheus, Lilly, MDX, Merck, Minomic, Myovant, Myriad, NGM, Nonagen, Novartis, NYMOX, Pacific Edge, Photocure, Pfizer, PlatformQ, Profound, Promaxo, Propella, Protara, Sanofi, SesenBio, Speciality Networks, Telix, Tolmar, Urogen, Vaxiion, and Vessi; received payment for expert testimony from Ferring; and is on the board of Photocure. Oliver Sartor has received compensation for a consulting or advisory role from Advanced Accelerator Applications, Amgen, ART BioScience, Astellas Pharma, AstraZeneca, Bayer, Clarity Pharmaceuticals, EMD Serono, Fusion Pharmaceuticals, Isotopen Technologien, Janssen, MacroGenics, Novartis, Pfizer, Point Biopharma, Ratio, Sanofi, Telix Pharmaceuticals, and TeneoBio; he has stock or other ownership interested with AbbVie, Cardinal Health, Clarity Pharmaceuticals, Convergent, Eli Lilly, Fusion Pharmaceuticals, Point Biopharma, Ratio, Telix, and United Health Group; he has patents for Saposin C and receptors as targets for treatment of benign and malignant disorders (U.S. patent awarded January 23, 2007; patent no. 7,166,691); he has provided expert testimony for Sanofi; he has received reimbursement for travel, accommodations, or expenses from AstraZeneca, Bayer, Lantheus, and Sanofi; and his institution has received research/grant funding from Advanced Accelerator Applications, Amgen, AstraZeneca, Bayer, InVitae, Janssen, Lantheus, Merck, and Sanofi. Phillip J. Koo has received compensation for a consulting or advisory role from Lantheus, Blue Earth Diagnostics, Merck, Janssen, Pfizer, Astellas, AstraZeneca, Bayer, Novartis, Sanofi, Telix, and Curium. Scott E. Eggener has received compensation for a consulting or advisory role Candel Therapeutics, A3P Biomedical, Cellvax, MetasTx, OptumHealth, and Janssen. Sandy Srinivas has received compensation for a consulting or advisory role from Novartis and Janssen. Scott T. Tagawa has received compensation for a consulting or advisory role from Sanofi, Medivation, Astellas, Dendreon, Janssen, Genentech, Bayer, Endocyte, Eisai, Immunomedics, Karyopharm, Abbvie, Tolmar, Seattle Genetics, Amgen, Clovis, QED, Pfizer, AAA/Novartis, Clarity, Genomic Health, POINT Biopharma, Blue Earth, AIkido Pharma, Telix Pharma, Convergent Therapeutics, EMD Serono, Myovant, Merck, Daiichi Sankyo, TransThera, and Regeneron; he is an unpaid consultant for Atlab Pharma, Phosplatin Therapeutics, Amgen, and Ambrx; he and his institution hold patents for biomarkers for sacituzumab govitecan therapy (Immunomedics/Gilead); and his institution has received research funding from Sanofi, Medivation, Astellas, Janssen, Amgen, Progenics, Dendreon, Lilly, Genentech, Newlink, BMS, Inovio, AstraZeneca, Immunomedics, Aveo, Rexahn, Atlab, Boehringer Ingelheim, Millennium, Bayer, Merck, Abbvie, Karyopharm, Endocyte, Clovis, Seattle Genetics, Novartis, Gilead, POINT Biopharma, Ambrx, Clarity. Thomas P. Boike has received compensation for a consulting or advisory role from Lantheus, Myovant, Novartis, Pfizer, Janssen, Astellas, Blue Earth, AstraZeneca, Palette Life Sciences, and Boston Scientific. Tanya Dorff has received compensation for a consulting or advisory role from AstraZeneca, Bayer, Janssen, and Sanofi. Tian Zhang has received compensation for a consulting or advisory role from Merck, Exelixis, Sanofi-Aventis, Janssen, Astra Zeneca, Pfizer, Amgen, BMS, Dendreon, SeaGen, Eisai, Aveo, Bayer, and Eli Lilly; honoraria from MJH Associates, Vaniam, Aptitude Health, PlatformQ, IntegrityCE, PeerView, and WJ Weiser; and her institution has received research funding from Novartis, Merck, Janssen, Astra Zeneca, Pfizer, Tempus, and Eli Lilly. Wendy Poage is an employee of Servier Pharmaceuticals; and she has ownership interests in 3D biopsy.

Adolescent young adult (AYA) cancer survivors continue to have substantive unmet needs. Literature and insights from a task force of survivors, caregivers, and survivor advocates convened by Servier Pharmaceuticals indicate desires for peer created and provided support. This secondary data analysis of information from the task force identified unmet needs in five domains and solutions explored for four prioritized needs. Ultimately, four actionable solution concepts were selected by the task force for further development. Through their work, many key insights about including survivors in creating solutions and the many approaches for best serving AYAs with cancer were revealed.

Purpose: Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services., Methods: A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider)., Results: Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing-initial testing of priority genes followed by expanded testing-was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included BRCA2, BRCA1, and mismatch repair genes, with broader testing, such as ATM , for clinical trial eligibility. BRCA2 was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for BRCA2 carriers, with consideration in HOXB13, BRCA1, ATM , and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches., Conclusion: This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.

Background: The 4Kscore is a new commercially available blood-based diagnostic test which predicts risk for aggressive, clinically significant prostate cancer on prostate biopsy. The 4Kscore is currently restricted to patients who have not had a digital rectal exam (DRE) in the previous 96 h, owing to prior mixed data suggesting that prostate specific antigen (PSA) isoforms may increase by a statistically significant-if not necessarily clinically significant-amount shortly after DRE. Our primary objective was to determine if 4Kscore test results are affected by a preceding DRE., Methods: Participants at a Prostate Cancer Awareness Week screening event sponsored by the Prostate Conditions Education Council filled out clinical history questionnaires and had blood samples for 4Kscore testing drawn prior to DRE, then 15-45 min following DRE. Patients with prior cancer diagnosis, 5-alpha reductase inhibitor medication use, or lower urinary tract procedures in the prior 6 months were excluded, resulting in a population of 162 participants for analysis. Values were then compared to determine if there was a significant difference in 4Kscore following DRE., Results: A statistically significant increase was seen in levels of 3 kallikreins measured (total PSA, free PSA, and intact PSA; median <0.03 ng/mL for all). This resulted in a small but statistically significant decrease in post-DRE 4Kscore (median absolute score decrease 0.43%). Using a 4Kscore cutoff of 7.5% resulted in reclassification of 10 patients (6.2%), nine of whom were "downgraded" from above the cutoff to below., Conclusions: If the blood draw for the 4 K score is performed after a screening DRE, there is a statistically significant difference in the 4 K score results, but in the vast majority of cases it would not affect clinical decision making., (© 2018 Wiley Periodicals, Inc.)

Purpose Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling, testing, and genetically informed management. Methods An expert consensus conference was convened including key stakeholders to address genetic counseling and testing, PCA screening, and management informed by evidence review. Results Consensus was strong that patients should engage in shared decision making for genetic testing. There was strong consensus to test HOXB13 for suspected hereditary PCA, BRCA1/2 for suspected hereditary breast and ovarian cancer, and DNA mismatch repair genes for suspected Lynch syndrome. There was strong consensus to factor BRCA2 mutations into PCA screening discussions. BRCA2 achieved moderate consensus for factoring into early-stage management discussion, with stronger consensus in high-risk/advanced and metastatic setting. Agreement was moderate to test all men with metastatic castration-resistant PCA, regardless of family history, with stronger agreement to test BRCA1/2 and moderate agreement to test ATM to inform prognosis and targeted therapy. Conclusion To our knowledge, this is the first comprehensive, multidisciplinary consensus statement to address a genetic evaluation framework for inherited PCA in the multigene testing era. Future research should focus on developing a working definition of familial PCA for clinical genetic testing, expanding understanding of genetic contribution to aggressive PCA, exploring clinical use of genetic testing for PCA management, genetic testing of African American males, and addressing the value framework of genetic evaluation and testing men at risk for PCA-a clinically heterogeneous disease.

Lower urinary tract symptoms (LUTS) are common in older men and are frequently associated with benign prostatic hyperplasia (BPH). The relationship between BPH and endogenous total testosterone (TT) levels has been widely studied. The aim of this post hoc analysis was to determine the association between LUTS and endogenous TT levels in a subset of men participating in the 2013 Prostate Cancer Awareness Week, a U.S. community-based prostate cancer screening program. Men completed the International Prostate Symptom Score (I-PSS) questionnaire, prostate size was estimated by a digital rectal examination, and serum TT and prostate-specific antigen levels were measured. Mean TT levels (ng/dl) did not significantly correlate with prostate size category (r = +.03, p = .69): normal, 419.2 (n = 106); enlarged, 394.7 (n = 71); abnormal, 416.4 (n = 7); and abnormal/suspicious, 515.2 (n = 19). Mean TT levels (ng/dl) did not significantly correlate with I-PSS category (r = -.06, p = .40): none, 468.5 (n = 15); mild, 414.0 (n = 138); moderate, 397.4 (n = 66); and severe, 437.9 (n = 7). Mean TT levels (ng/dl) did not significantly correlate with I-PSS quality of life rating (r = -.13, p = .055): delighted, 474.5 (n = 43); pleased, 424.6 (n = 65); mostly satisfied, 361.2 (n = 63); mixed, 448.2 (n = 29); mostly dissatisfied, 337.2 (n = 17); and unhappy, 435.8 (n = 6). Adjustment for prostate size or prostate-specific antigen levels yielded similar findings. In conclusion, endogenous TT levels did not correlate with LUTS or prostate size, and these findings support the saturation theory in which TT is not able to induce further androgen-stimulated prostate tissue growth due to receptor saturation. Any worsening of LUTS following testosterone replacement therapy in hypogonadal men may be related to stimulation of prostatic cells previously deprived of testosterone., (© The Author(s) 2015.)

Cancer care is costly, particularly when chemotherapy and its supportive costs are considered. Yet, chemotherapy is not the right course for every patient. Patients with cancer need appropriate treatment that will give them the best possible outcome. Personalized medicine has become an important area of oncology. In addition to genetic testing, genomic testing has become a useful tool in diagnostics. For genomic assays to be viable, they must have clinical validity, analytic validity, and clinical utility. Stakeholders are willing to provide coverage for such testing through medical policy when there is strong evidence the tests are effective. Genomic testing can be used in decision making to rule out chemotherapy or other treatment options that would not be effective for the care of an individual patient. The use of genomic testing to help eliminate ineffective or possible harmful treatment options and determine appropriate care will benefit the patient while reducing healthcare utiliztion and costs.

Objective: Since testosterone levels exhibit a circadian variation with peak levels in the morning, evidence-based guidelines recommend measuring morning total testosterone (TT) levels as the initial diagnostic test for androgen deficiency. However, it has been suggested that morning blood draw may not be necessary in older men due to a blunted circadian rhythm. We sought to determine whether it is possible to expand the morning sampling window for measurement of TT., Research Design and Methods: TT levels were measured in a subset of men (mean age of 61 years) participating in the 2013 Prostate Cancer Awareness Week., Results: TT levels measured in blood drawn from 8 to 11 AM (n = 229) differed significantly from those drawn outside this window (n = 442) (411.7 vs 368.3 ng/dl; p = 0.0003). Differences in TT levels were evident across five blood draw time windows (p = < 0.0001) and persisted after adjustment for age and BMI. TT levels in blood drawn from 2 to 5 PM (344.3 ng/dl) and 5 to 8 PM (334.4 ng/dl) differed significantly from that drawn from 8 to 11 AM (p < 0.05), while TT levels from 11 AM to 2 PM (396.5 ng/dl) and 8 PM to 8 AM (373.4 ng/dl) did not (p = 0.90 and 0.73, respectively)., Conclusion: Based on these findings, it may be possible to expand the blood draw time window for measurement of serum TT. This community-based study was not prospectively design to determine the most appropriate blood draw window for TT measurement. Only a single TT measurement was made without consideration for day-to-day variability, and TT levels were not measured in the same men at different blood draw times.