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Nadir Prostate-specific Antigen as an Independent Predictor of Survival Outcomes: A Post Hoc Analysis of the PROSPER Randomized Clinical Trial

2023; Lippincott Williams & Wilkins; Volume: 209; Issue: 3 Linguagem: Inglês

10.1097/ju.0000000000003084

1527-3792

Maha Hussain, Cora N. Sternberg, Eleni Efstathiou, Karim Fizazi, Qi Shen, Xun Lin, Jennifer Sugg, Joyce Steinberg, Bettina Noerby, Ugo De Giorgi, Neal D. Shore, Fred Saad,

Cardiovascular Disease and Adiposity

Open AccessJournal of UrologyAdult Urology1 Mar 2023Nadir Prostate-specific Antigen as an Independent Predictor of Survival Outcomes: A Post Hoc Analysis of the PROSPER Randomized Clinical Trial Maha Hussain, Cora N. Sternberg, Eleni Efstathiou, Karim Fizazi, Qi Shen, Xun Lin, Jennifer Sugg, Joyce Steinberg, Bettina Noerby, Ugo De Giorgi, Neal D. Shore, and Fred Saad Maha HussainMaha Hussain *Correspondence: Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 303 E Superior St, Suite 3-107, Chicago, IL 60611 telephone: 312-908-5487; E-mail Address: [email protected] Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois , Cora N. SternbergCora N. Sternberg Englander Institute for Precision Medicine, Meyer Cancer Center, Weill Cornell Medicine, New York, New York , Eleni EfstathiouEleni Efstathiou MD Anderson Cancer Center, Houston, Texas , Karim FizaziKarim Fizazi Institut Gustave Roussy, University of Paris Saclay, Villejuif, France , Qi ShenQi Shen Pfizer Inc., Collegeville, Pennsylvania , Xun LinXun Lin Pfizer Inc., La Jolla, California , Jennifer SuggJennifer Sugg Astellas Pharma, Inc., Northbrook, Illinois , Joyce SteinbergJoyce Steinberg Astellas Pharma, Inc., Northbrook, Illinois , Bettina NoerbyBettina Noerby Sygehus, Lillebaelt, Vejle, Denmark , Ugo De GiorgiUgo De Giorgi IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Italy , Neal D. ShoreNeal D. Shore Carolina Urologic Research Center, Myrtle Beach, South Carolina , and Fred SaadFred Saad University of Montreal Hospital Center, Montreal, Canada View All Author Informationhttps://doi.org/10.1097/JU.0000000000003084AboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Abstract Purpose: This post hoc analysis of PROSPER evaluated the relationship between depth of PSA decline and clinical outcomes in enzalutamide-treated men with nonmetastatic castration-resistant prostate cancer. Materials and Methods: PROSPER was an international, randomized, double-blind, placebo-controlled, phase 3 trial that demonstrated significantly improved metastasis-free survival and overall survival with androgen deprivation therapy plus enzalutamide vs placebo. A total of 905 enzalutamide-treated men were included in this post hoc analysis. Metastasis-free survival (primary endpoint) and overall survival (secondary endpoint) were evaluated for 4 mutually exclusive subgroups defined by PSA decline: <50% (reference); ≥50% to <90%; ≥90%, nadir ≥0.2 ng/mL; and ≥90%, nadir <0.2 ng/mL. Medians and 95% confidence intervals were determined using a 12-month landmark analysis; hazard ratios and P values were based on an unstratified Cox proportional analysis model. Results: In enzalutamide-treated men, PSA declines of <50%, ≥50% to <90%, ≥90% with nadir ≥0.2 ng/mL, and ≥90% with nadir <0.2 ng/mL were associated with median metastasis-free survival in months (95% confidence intervals) of 22.1 (14.8-not reached), 34.2 (29.4-not reached), 36.6 (33.4-not reached), and not reached, respectively, and overall survival in months (95% confidence intervals) of 40.8 (31.7-44.9), 54.4 (49.0-67.0), 64.3 (63.4-not reached), and not reached, respectively. Conclusions: There was a statistically significant correlation between greater depth of PSA decline and improved clinical outcomes, suggesting a previously underappreciated relationship between changes in PSA levels and clinical outcomes in nonmetastatic castration-resistant prostate cancer. In men with prostate cancer (PC), a rising PSA concentration is usually the first sign of disease progression or recurrence and is associated with increased mortality. Those with nonmetastatic castration-resistant prostate cancer (nmCRPC) and a high baseline PSA value or a PSA doubling time (PSADT) of ≤10 months are at higher risk of developing metastasis.1-3 Thus, PSA monitoring is recognized as an established tool to assess disease progression and recurrence after local, definitive therapy.4-7 In clinical trials, PSA progression is defined as an increase in PSA of ≥25% and an absolute increase of ≥2 ng/mL from the nadir PSA (the lowest level to which PSA declines following treatment) confirmed by a second value ≥3 weeks later.8,9 For men with nmCRPC, it has traditionally been recommended that drug development efforts focus on safe and effective therapies for those with a shorter PSADT, as these men have the greatest risk of metastases and death.2,3,9 Across a number of PC disease states including metastatic castration-sensitive PC and metastatic castration-resistant PC, nadir PSA posttreatment has demonstrated a correlation with clinical outcomes.10-17 However, the relationship between PSA dynamics and survival outcomes in men with nmCRPC has not yet been fully elucidated. The PROSPER study investigated the effects of the second-generation androgen receptor inhibitor, enzalutamide, in men with nmCRPC and rapidly rising PSA levels with a PSADT of ≤10 months.16 In men randomized to enzalutamide plus androgen deprivation therapy (ADT), metastasis-free survival (MFS; 36.6 vs 14.7 months; HR, 0.29 [95% CI 0.24–0.35]; P < .001) and overall survival (OS; 67.0 vs 56.3 months; HR, 0.73; [95% CI 0.61–0.89]) were significantly prolonged vs men taking placebo plus ADT.16,18 A previous post hoc analysis of the PROSPER study found that, regardless of the definition of PSA progression, enzalutamide treatment significantly reduced the risk of metastases or death and concluded that any increase in PSA may warrant closer monitoring.19 The objective of our post hoc analysis was to further explore PSA dynamics (eg, absolute and percent change) and clinical outcomes and to evaluate the relationship between depth of PSA response and both extended MFS and prolonged OS in men with nmCRPC randomized to once-daily enzalutamide plus ADT or placebo plus ADT. Materials And Methods The PROSPER study methodology, including the study design and protocol, has been previously reported in detail16,18 and will be described briefly here. Trial Participants The PROSPER study was an international, randomized, double-blind, placebo-controlled, phase 3 trial conducted at 398 study locations across 32 countries. The PROSPER study was monitored by an independent data and safety committee, conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice guidelines of the International Conference on Harmonisation, and all patients provided written informed consent before participating. Eligible participants were men with a diagnosis of nmCRPC who had been receiving ADT with a gonadotropin-releasing hormone agonist or antagonist or had undergone bilateral orchiectomy and had no evidence of metastatic disease as assessed by CT or MRI for soft tissue disease and by whole-body radionuclide bone scan for osseous metastases. At enrollment, eligible participants had a PSA level ≥2 ng/mL and a PSADT ≤10 months. Study Design All trial participants continued receiving ADT and were randomized 2:1 to receive enzalutamide 160 mg once daily or placebo. The primary endpoint was MFS, defined as the time from randomization to radiographic progression as determined by central review at any time, or as the time to death from any cause during the period from randomization to 112 days after the discontinuation of the trial regimen without evidence of radiographic progression, whichever occurred first. Secondary endpoints included time to PSA progression; PSA response rate, defined as a decrease from baseline of ≥50%; time to first use of a subsequent antineoplastic therapy; quality-of-life assessments; OS, defined as the time from randomization to death from any cause; and safety. After the primary analysis was completed and the trial data were unblinded, patients in the placebo group were given the opportunity to receive open-label enzalutamide. Assessments Scheduled PSA measurements were conducted at screening, at baseline immediately before the first dose of study drug, at week 17, and every 16 weeks thereafter. The PSA level was assessed at a central laboratory, and patients and investigators were blinded to all PSA values during the study (except when local values were obtained; investigators were discouraged from obtaining or making decisions based upon local values). This post hoc analysis evaluated MFS and OS for 4 mutually exclusive subgroups defined by PSA percent decline and PSA nadir (±0.2 ng/mL for ≥90% decline only) from baseline: <50% (reference group); ≥50% to <90%; ≥90%, PSA nadir ≥0.2 ng/mL; and ≥90%, PSA nadir <0.2 ng/mL. Defining and stratifying PSA concentrations by both percent decline from baseline and actual decline above or below 0.2 ng/mL clarifies the relationship between PSA metrics and clinical outcomes, distinguishing PSA metrics as a potential intermediate biomarker and predictor of survival outcomes. The focus of this post hoc analysis was to evaluate MFS and OS for enzalutamide-treated patients by PSA decline subgroups. For completeness, placebo-treated patients were also analyzed by PSA decline subgroups. Statistical Analysis A 12-month landmark analysis was performed for MFS and OS to address the potential bias given that PSA decline and PSA nadir were determined at various times after randomization. As part of the setup of the landmark analysis, PSA decline and PSA nadir were defined using only PSA results prior to the landmark, ie, ≤12 months. Estimates of medians and 95% CIs for MFS and OS were determined using the Kaplan-Meier method, and HRs were based on an unstratified Cox proportional analysis model using PSA decline <50% as the reference subgroup. P values were based on unstratified Cox proportional analysis and assessed at a nominal significance level of 0.05. In the landmark analysis, the follow-up time started at the 12-month landmark. Patients not known to have died or who had an MFS event at the time of analysis were censored on the date at which they were last known to be alive or the last available scan before the analysis data cutoff date, respectively. The data cutoff date for MFS was June 28, 2017, and for OS October 15, 2019. SAS version 9.4 was used in the analysis. Results Analysis Population A total of 1,401 men with nmCRPC were enrolled in PROSPER and randomized in a 2:1 ratio to enzalutamide plus ADT or matched placebo plus ADT. Nine hundred and thirty patients were treated with enzalutamide and 465 patients were treated with placebo. All patients were included in the analysis except those without post-baseline PSA values who discontinued prior to the first assessment at week 17. Nine hundred and five enzalutamide-treated patients (97% of total enzalutamide-treated patients) and 457 placebo-treated patients (98% of total placebo-treated patients) were included in this analysis. Any PSA data points collected after an MFS event were excluded from the analysis. Median follow-up times for OS in the enzalutamide and placebo groups for patients without an event were 46.7 months and 43.7 months, respectively. A CONSORT diagram (supplementary Figure 1, https://www.jurology.com) and baseline characteristics by subgroup (supplementary Table 1, https://www.jurology.com) can be found in the supplementary Appendix (https://www.jurology.com). PSA Levels and Decline In men treated with enzalutamide, median (range) baseline PSA was 11.1 ng/mL (0.8-1,071). Of 905 men treated with enzalutamide, 65 (7%) had no PSA decline. Eighty-six percent (n=774/905) of men treated with enzalutamide had a PSA decline of ≥50% (Table 1). In men treated with enzalutamide, 90.3% (n=699/774) of PSA responses with a decline of ≥50% occurred within the first 17 weeks of treatment (the time of the first treatment scan). In total, 65% of enzalutamide-treated men achieved a nadir PSA of ≥90% decline from baseline, and median time to nadir PSA (interquartile range) was 227 days (116-449). When patients were grouped by PSA decline, there appears to be a relationship between the time to PSA nadir and magnitude of the decline; however, this relationship was not statistically evaluated (supplementary Table 2, https://www.jurology.com). Table 1. PSA Responses by Nadir (Maximum Recorded Decline From Baseline Prior to Metastasis-free Survival Event)a,b in PROSPER (Intent-to-Treat Population) PSA decline from baseline Enzalutamide No. (%)(n = 905) Placebo No. (%)(n = 457) <50% 131 (14) 442 (97) ≥50% to <90% 189 (21) 12 (3) ≥90%, PSA nadir ≥0.2 ng/mL 242 (27) 2 (0) ≥90%, PSA nadir 6 months after randomization), corresponding to the second postbaseline PSA measurement, a 12-month landmark was chosen to address the potential bias associated with comparative survival analyses. In enzalutamide-treated men, PSA declines of ≥50% to <90% (HR, 0.38 [P = .003]), ≥90% with nadir ≥0.2 ng/mL (HR, 0.22 [P < .001]), and ≥90% with nadir <0.2 ng/mL (HR, 0.10 [P < .001]), were associated with a reduced risk of metastasis development vs a decline of <50% (Table 2 and Figure 1). Table 2. Twelve-month Landmark Analysis of Metastasis-free Survival by PSA Decline Subgroup PSA decline subgroup Enzalutamide (n = 905) Placebo (n = 457) No. patients No. events Median MFS (95% CI), mo HRa (95% CI) No. patients No. events Median MFS (95% CI), mo HRa (95% CI) <50% 23 13 22.1 (14.8-NR) Reference 148 62 29.4 (22.1-33.1) Reference ≥50% to <90% 113 38 34.2 (29.4-NR) 0.38b (0.20-0.72) 5 1 NR (18.3-NR) 0.36 (0.05-2.6) ≥90%, PSA nadir ≥0.2 ng/mL 172 33 36.6 (33.4-NR) 0.22c (0.12-0.43) - - - - ≥90%, PSA nadir <0.2 ng/mL 190 19 NR 0.10c (0.05-0.21) - - - - Data cutoff: June 28, 2017. Abbreviations: CI, confidence interval; HR, hazard ratio; MFS, metastasis-free survival; NR, not reached; PSA, prostate-specific antigen. HR and P values were calculated using an unstratified Cox proportional analysis model; PSA decline <50% was used as the reference subgroup for calculation of HR. P = .003. P < .001. Figure 1. Twelve-month landmark analysis of metastasis-free survival (MFS) by prostate-specific antigen (PSA) decline subgroup for enzalutamide-treated men. Data cutoff: June 28, 2017. Similarly, PSA declines of ≥50% to <90% (HR, 0.43 [P < .001]), ≥90% with nadir ≥0.2 ng/mL (HR, 0.25 [P < .001]), and ≥90% with nadir <0.2 ng/mL (HR, 0.11 [P < .001]), were associated with a reduced risk of death vs a decline of <50% (Table 3 and Figure 2). Table 3. Twelve-month Landmark Analysis of Overall Survival by PSA Decline Subgroup PSA decline subgroup Enzalutamide (n = 905) Placebo (n = 457) No. patients No. events Median OS (95% CI), mo HRa (95% CI) No. patients No. events Median OS (95% CI), mo HRa (95% CI) <50% 78 45 40.8 (31.7-44.9) Reference 382 136 58.8 (54.7-NR) Reference ≥50% to <90% 196 79 54.4 (49.0-67.0) 0.43b (0.30-0.62) 10 1 NR (48.9-NR) 0.24 (0.03-1.75) ≥90%, PSA nadir ≥0.2 ng/mL 266 69 64.3 (63.4-NR) 0.25b (0.17-0.37) 2 0 NR 0 ≥90%, PSA nadir <0.2 ng/mL 287 34 NR 0.11b (0.07-0.17) 1 0 NR 0 Data cutoff: October 15, 2019. Abbreviations: CI, confidence interval; HR, hazard ratio; NR, not reached; OS, overall survival; PSA, prostate-specific antigen. HR and P values were calculated using an unstratified Cox proportional analysis model; PSA decline <50% was used as the reference subgroup for calculation of HR. P <.001. Figure 2. Twelve-month landmark analysis of overall survival (OS) by prostate-specific antigen (PSA) decline subgroup for enzalutamide-treated men. Data cutoff: October 15, 2019. Discussion It is well recognized that the risk of developing metastasis in men with nmCRPC is associated with a high baseline PSA value, rising PSA concentrations, and short PSADT,1-3 and the importance of PSA monitoring is well established as a strong indicator of treatment response and progression following local therapy.4-7 Although it has been investigated in men with nmCRPC taking apalutamide,14,20 the relationship between PSA decline, nadir PSA while on treatment, and survival outcomes in men with nmCRPC is not yet fully established. In the PROSPER study, a previous post hoc analysis evaluating PSA dynamics demonstrated a significantly increased risk of metastasis or death in participants with PSA progression vs those without.19 In our analysis, prognostic association with PSA decline increased in relation to depth of PSA nadir in men treated with enzalutamide for both MFS and OS. This suggests potentially improved survival outcomes in the men who attained a PSA nadir of <0.2 vs ≥0.2 ng/mL; however, the number of events in the former subgroup was low, and therefore statistical significance could not be established. The relationship among absolute PSA concentration, percentage decline from baseline, and actual decline below 0.2 ng/mL emphasizes the importance of PSA decline as well as PSA nadir in men with nmCRPC as an intermediate biomarker of risk of disease progression. This relationship between PSA decline, PSA nadir ≥0.2 ng/mL vs 0.1 ng/mL.17 Similarly, an analysis of patients across multiple clinical trials revealed that an early PSA response of >50% from baseline within 4 weeks of treatment was prognostic for OS and radiographic progression-free survival (both P < .001).25 In our analysis, we established that in men treated with enzalutamide, 90.3% of cases with a PSA decline of ≥50% occurred within the first 4 months of treatment; however, further investigation is required to establish a potentially prognostic relationship between PSA kinetics and clinical outcomes specifically in men with nmCRPC. Our analysis includes a large, global cohort of men with nmCRPC and builds upon previous assessments of PSA levels in the PROSPER study.19 Additionally, we have investigated the relationship between PSA decline and enzalutamide only. A post hoc analysis of men with nmCRPC treated with apalutamide plus ADT in the SPARTAN trial demonstrated similar results with rapid, deep, and durable PSA responses at 6 months posttreatment being significantly associated with improved survival outcomes, independent of molecular prognostic marker assessment.20,26 However, as these analyses are post hoc in nature and not prespecified, the results are exploratory and should be interpreted with caution. Even with this caveat, these analyses add to the validity of PSA response as a prognostic factor, although further study is required to establish PSA nadir as a true surrogate of survival outcomes, as well as to investigate the relationship between PSA decline and other available therapies in men with nmCRPC. Defining PSA dynamics by both percent change and actual decreased concentration reveals a previously underappreciated relationship between these measures, and further underscores the value of PSA as an intermediate biomarker for treatment benefit and risk of disease progression in patients with nmCRPC. We believe this information adds substantially to evaluating treatment choices for these patients and advising them on timing and expectations of efficacy. PSA dynamics have powerful implications for future study design decisions and will potentially inform future consensus criteria. A summary infographic of the analysis (supplementary Figure 2, https://www.jurology.com) has been included. Conclusions The principal finding from this post hoc analysis of the PROSPER study was that in enzalutamide-treated men with nmCRPC and a rapidly rising PSA, greater depth of posttreatment PSA decline was associated with improved MFS and OS outcomes. Defining PSA response as both a relative decline from baseline and an absolute decline below 0.2 ng/mL suggests a previously underappreciated relationship between changes in PSA levels and clinical outcomes in men with nmCRPC. For clinicians, these findings may help to personalize frequency of clinical follow-up and imaging of patients. Acknowledgments We thank the patients, their families, and all investigators and their teams involved in this study. Medical writing and editorial support funded by the sponsors was provided by Kirstie Anderson, Adam Anazim, and Julie B. Stimmel, PhD of Onyx (a Prime Global agency). References 1. . Disease and host characteristics as predictors of time to first bone metastasis and death in men with progressive castration-resistant nonmetastatic prostate cancer. Cancer. 2011; 117(10):2077-2085. Crossref, Medline, Google Scholar 2. . Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. 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Crossref, Medline, Google Scholar Support: This study was sponsored by Pfizer Inc (New York, New York) and Astellas Pharma, Inc (Northbrook, Illinois), the co-developers of enzalutamide. Role of the Funder/Sponsor: The sponsors were involved in the study design, collection, analysis, and interpretation of data, and review of the manuscript; employees of the sponsor companies are coauthors. Ultimate responsibility for opinions, conclusions, and data interpretation lies with the authors. Conflict of Interest: MH: Consultant: Bristol-Myers Squibb, Daiichi Sankyo, Janssen, Pfizer; Speaker's bureau: Astellas Pharma, AstraZeneca, MLI PeerView, OncLive, PER, Philips Gilmore Oncology, Projects in Knowledge, Research to Practice, Sanofi Genzyme, UroToday, Precisca, Merck, Reach MD, Web MD; Research funding: AstraZeneca, Bayer, Genentech, PCCTC, Pfizer (UM-Inst), Arvinas; Intellectual property/Royalties holder: Exelexis. CNS: Consultant: Janssen-Cilag, Astellas Pharma, Sanofi–Genzyme, Bayer, Pfizer, Merck, Merck Sharp & Dohme, AstraZeneca, Clovis, Immunomedics (now Gilead), Bristol-Myers Squibb, Foundation Medicine, UroToday, Medscape, NCI; Institutional funding: Cougar Biotechnology (now Janssen), Medivation (now Pfizer), Clovis Oncology, Roche-Genentech. EE: Research funding: Janssen-Cilag, Sanofi, ORIC Pharma, Astellas Pharma; Speaker's bureau: Janssen-Cilag, Sanofi, Takeda; Consultant: Janssen-Cilag, Genentech, Sanofi, Astellas Pharma, Bayer, AstraZeneca, Merck Sharp & Dohme, Innocrin Pharma, Takeda, Tolmar, ORIC Pharma, Myovant. KF: Consultant: Janssen Oncology, Bayer, Astellas Pharma, Sanofi, Orion Pharma GmbH, CureVac, AstraZeneca, ESSA, Roche-Genentech, Clovis Oncology, Amgen; Travel/accommodation expenses: Amgen; Speaker's bureau: Janssen, Sanofi, Astellas Pharma, Merck. QS: Employment/Stock ownership: Pfizer Inc. XL: Employment/Stock ownership: Pfizer Inc. JSu: Employee: Astellas Pharma; Stock ownership: AstraZeneca. JSt: Employment: Astellas Pharma; Immediate family member has stock ownership in Amgen. BN: no disclosures. UDG: Consultant: Janssen, Astellas Pharma, Sanofi, Bayer, Pfizer, Bristol-Myers Squibb, Novartis, Ipsen, Merck; Institutional funding: Roche, Sanofi, AstraZeneca. NDS: Consultant and grant support: AbbVie, Amgen, Astellas Pharma, Bayer, Dendreon Pharmaceuticals, Ferring Pharmaceuticals, Janssen Oncology, Pfizer, Sanofi–Genzyme, Tolmar Pharmaceuticals. FS: Consultant: Astellas Pharma, Janssen Oncology, Sanofi, AstraZeneca/MedImmune; Speaker's bureau: Astellas Pharma, Janssen Oncology, Sanofi, Bayer, AstraZeneca; Institutional funding: Astellas Pharma, Bayer, Janssen Oncology, Sanofi, AstraZeneca. Ethics Statement: The PROSPER study was monitored by an independent data and safety committee, conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice guidelines of the International Conference on Harmonization, and all patients provided written informed consent before participating. Author Contributions: All Authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All Authors: Acquisition, analysis, or interpretation of data. QS, XL: Administrative, technical, or material support. MH, FS: Concept and design. All Authors: Critical revision of the manuscript for important intellectual content. MH, CNS, EE, KF, BN, UDG, NDS, FS: Drafting of the manuscript. QS, XL, JSu, JSt: Obtained funding. XL: Statistical analysis. MH, FS: Supervision. Data Sharing Policy: Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions, and exceptions, Pfizer may also provide access to the related individual de-identified participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information. Trial Registration: ClinicalTrials.gov identifier: NCT02003924. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.© 2023 The Author(s). Published on behalf of the American Urological Association, Education and Research, Inc.FiguresReferencesRelatedDetailsCited bySiemens D (2022) This Month in Adult UrologyJournal of Urology, VOL. 209, NO. 3, (457-458), Online publication date: 1-Mar-2023. Volume 209Issue 3March 2023Page: 532-539Supplementary Materials Advertisement Copyright & Permissions© 2023 The Author(s). Published on behalf of the American Urological Association, Education and Research, Inc.Keywordssurvival analysisprostatic neoplasmsprostate-specific antigenclinical trialenzalutamideAcknowledgmentsWe thank the patients, their families, and all investigators and their teams involved in this study. Medical writing and editorial support funded by the sponsors was provided by Kirstie Anderson, Adam Anazim, and Julie B. Stimmel, PhD of Onyx (a Prime Global agency).MetricsAuthor Information Maha Hussain Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois *Correspondence: Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 303 E Superior St, Suite 3-107, Chicago, IL 60611 telephone: 312-908-5487; E-mail Address: [email protected] More articles by this author Cora N. Sternberg Englander Institute for Precision Medicine, Meyer Cancer Center, Weill Cornell Medicine, New York, New York More articles by this author Eleni Efstathiou MD Anderson Cancer Center, Houston, Texas More articles by this author Karim Fizazi Institut Gustave Roussy, University of Paris Saclay, Villejuif, France More articles by this author Qi Shen Pfizer Inc., Collegeville, Pennsylvania More articles by this author Xun Lin Pfizer Inc., La Jolla, California More articles by this author Jennifer Sugg Astellas Pharma, Inc., Northbrook, Illinois More articles by this author Joyce Steinberg Astellas Pharma, Inc., Northbrook, Illinois More articles by this author Bettina Noerby Sygehus, Lillebaelt, Vejle, Denmark More articles by this author Ugo De Giorgi IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Italy More articles by this author Neal D. Shore Carolina Urologic Research Center, Myrtle Beach, South Carolina More articles by this author Fred Saad University of Montreal Hospital Center, Montreal, Canada More articles by this author Expand All Support: This study was sponsored by Pfizer Inc (New York, New York) and Astellas Pharma, Inc (Northbrook, Illinois), the co-developers of enzalutamide. Role of the Funder/Sponsor: The sponsors were involved in the study design, collection, analysis, and interpretation of data, and review of the manuscript; employees of the sponsor companies are coauthors. Ultimate responsibility for opinions, conclusions, and data interpretation lies with the authors. Conflict of Interest: MH: Consultant: Bristol-Myers Squibb, Daiichi Sankyo, Janssen, Pfizer; Speaker's bureau: Astellas Pharma, AstraZeneca, MLI PeerView, OncLive, PER, Philips Gilmore Oncology, Projects in Knowledge, Research to Practice, Sanofi Genzyme, UroToday, Precisca, Merck, Reach MD, Web MD; Research funding: AstraZeneca, Bayer, Genentech, PCCTC, Pfizer (UM-Inst), Arvinas; Intellectual property/Royalties holder: Exelexis. CNS: Consultant: Janssen-Cilag, Astellas Pharma, Sanofi–Genzyme, Bayer, Pfizer, Merck, Merck Sharp & Dohme, AstraZeneca, Clovis, Immunomedics (now Gilead), Bristol-Myers Squibb, Foundation Medicine, UroToday, Medscape, NCI; Institutional funding: Cougar Biotechnology (now Janssen), Medivation (now Pfizer), Clovis Oncology, Roche-Genentech. EE: Research funding: Janssen-Cilag, Sanofi, ORIC Pharma, Astellas Pharma; Speaker's bureau: Janssen-Cilag, Sanofi, Takeda; Consultant: Janssen-Cilag, Genentech, Sanofi, Astellas Pharma, Bayer, AstraZeneca, Merck Sharp & Dohme, Innocrin Pharma, Takeda, Tolmar, ORIC Pharma, Myovant. KF: Consultant: Janssen Oncology, Bayer, Astellas Pharma, Sanofi, Orion Pharma GmbH, CureVac, AstraZeneca, ESSA, Roche-Genentech, Clovis Oncology, Amgen; Travel/accommodation expenses: Amgen; Speaker's bureau: Janssen, Sanofi, Astellas Pharma, Merck. QS: Employment/Stock ownership: Pfizer Inc. XL: Employment/Stock ownership: Pfizer Inc. JSu: Employee: Astellas Pharma; Stock ownership: AstraZeneca. JSt: Employment: Astellas Pharma; Immediate family member has stock ownership in Amgen. BN: no disclosures. UDG: Consultant: Janssen, Astellas Pharma, Sanofi, Bayer, Pfizer, Bristol-Myers Squibb, Novartis, Ipsen, Merck; Institutional funding: Roche, Sanofi, AstraZeneca. NDS: Consultant and grant support: AbbVie, Amgen, Astellas Pharma, Bayer, Dendreon Pharmaceuticals, Ferring Pharmaceuticals, Janssen Oncology, Pfizer, Sanofi–Genzyme, Tolmar Pharmaceuticals. FS: Consultant: Astellas Pharma, Janssen Oncology, Sanofi, AstraZeneca/MedImmune; Speaker's bureau: Astellas Pharma, Janssen Oncology, Sanofi, Bayer, AstraZeneca; Institutional funding: Astellas Pharma, Bayer, Janssen Oncology, Sanofi, AstraZeneca. Ethics Statement: The PROSPER study was monitored by an independent data and safety committee, conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice guidelines of the International Conference on Harmonization, and all patients provided written informed consent before participating. Author Contributions: All Authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All Authors: Acquisition, analysis, or interpretation of data. QS, XL: Administrative, technical, or material support. MH, FS: Concept and design. All Authors: Critical revision of the manuscript for important intellectual content. MH, CNS, EE, KF, BN, UDG, NDS, FS: Drafting of the manuscript. QS, XL, JSu, JSt: Obtained funding. XL: Statistical analysis. MH, FS: Supervision. Data Sharing Policy: Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions, and exceptions, Pfizer may also provide access to the related individual de-identified participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information. Trial Registration: ClinicalTrials.gov identifier: NCT02003924. Advertisement Advertisement PDF downloadLoading ...