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      Case Report: Long-term complete response to PSMA-targeted radioligand therapy and abiraterone in a metastatic prostate cancer patient

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          Abstract

          Despite decades of research and clinical trials, metastatic castration-resistant prostate cancer (mCRPC) remains incurable and typically fatal. Current treatments may provide modest increases in progression-free survival but can come with significant adverse effects and are disaggregated from the diagnostic imaging needed to fully assess the spread of metastatic disease. A theranostic approach, using radiolabeled ligands that target the cell surface protein PSMA, simplifies the visualization and disease treatment process by enabling both to use similar agents. Here, we describe an exemplary case wherein a gentleman in his 70s with mCRPC on diagnosis was treated with 177Lu–PSMA-617 and abiraterone, and remains disease-free to date, over five years later.

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          Most cited references37

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          Cancer treatment and survivorship statistics, 2022

          The number of cancer survivors continues to increase in the United States due to the growth and aging of the population as well as advances in early detection and treatment. To assist the public health community in better serving these individuals, the American Cancer Society and the National Cancer Institute collaborate triennially to estimate cancer prevalence in the United States using incidence and survival data from the Surveillance, Epidemiology, and End Results cancer registries, vital statistics from the Centers for Disease Control and Prevention's National Center for Health Statistics, and population projections from the US Census Bureau. Current treatment patterns based on information in the National Cancer Database are presented for the most prevalent cancer types by race, and cancer-related and treatment-related side-effects are also briefly described. More than 18 million Americans (8.3 million males and 9.7 million females) with a history of cancer were alive on January 1, 2022. The 3 most prevalent cancers are prostate (3,523,230), melanoma of the skin (760,640), and colon and rectum (726,450) among males and breast (4,055,770), uterine corpus (891,560), and thyroid (823,800) among females. More than one-half (53%) of survivors were diagnosed within the past 10 years, and two-thirds (67%) were aged 65 years or older. One of the largest racial disparities in treatment is for rectal cancer, for which 41% of Black patients with stage I disease receive proctectomy or proctocolectomy compared to 66% of White patients. Surgical receipt is also substantially lower among Black patients with non-small cell lung cancer, 49% for stages I-II and 16% for stage III versus 55% and 22% for White patients, respectively. These treatment disparities are exacerbated by the fact that Black patients continue to be less likely to be diagnosed with stage I disease than White patients for most cancers, with some of the largest disparities for female breast (53% vs 68%) and endometrial (59% vs 73%). Although there are a growing number of tools that can assist patients, caregivers, and clinicians in navigating the various phases of cancer survivorship, further evidence-based strategies and equitable access to available resources are needed to mitigate disparities for communities of color and optimize care for people with a history of cancer. CA Cancer J Clin. 2022;72:409-436.
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            Epidemiology of Prostate Cancer

            Prostate cancer is the second most frequent cancer diagnosis made in men and the fifth leading cause of death worldwide. Prostate cancer may be asymptomatic at the early stage and often has an indolent course that may require only active surveillance. Based on GLOBOCAN 2018 estimates, 1,276,106 new cases of prostate cancer were reported worldwide in 2018, with higher prevalence in the developed countries. Differences in the incidence rates worldwide reflect differences in the use of diagnostic testing. Prostate cancer incidence and mortality rates are strongly related to the age with the highest incidence being seen in elderly men (> 65 years of age). African-American men have the highest incidence rates and more aggressive type of prostate cancer compared to White men. There is no evidence yet on how to prevent prostate cancer; however, it is possible to lower the risk by limiting high-fat foods, increasing the intake of vegetables and fruits and performing more exercise. Screening is highly recommended at age 45 for men with familial history and African-American men. Up-to-date statistics on prostate cancer occurrence and outcomes along with a better understanding of the etiology and causative risk factors are essential for the primary prevention of this disease.
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              Increased survival with enzalutamide in prostate cancer after chemotherapy.

              Enzalutamide (formerly called MDV3100) targets multiple steps in the androgen-receptor-signaling pathway, the major driver of prostate-cancer growth. We aimed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy. In our phase 3, double-blind, placebo-controlled trial, we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity. We randomly assigned them, in a 2:1 ratio, to receive oral enzalutamide at a dose of 160 mg per day (800 patients) or placebo (399 patients). The primary end point was overall survival. The study was stopped after a planned interim analysis at the time of 520 deaths. The median overall survival was 18.4 months (95% confidence interval [CI], 17.3 to not yet reached) in the enzalutamide group versus 13.6 months (95% CI, 11.3 to 15.8) in the placebo group (hazard ratio for death in the enzalutamide group, 0.63; 95% CI, 0.53 to 0.75; P<0.001). The superiority of enzalutamide over placebo was shown with respect to all secondary end points: the proportion of patients with a reduction in the prostate-specific antigen (PSA) level by 50% or more (54% vs. 2%, P<0.001), the soft-tissue response rate (29% vs. 4%, P<0.001), the quality-of-life response rate (43% vs. 18%, P<0.001), the time to PSA progression (8.3 vs. 3.0 months; hazard ratio, 0.25; P<0.001), radiographic progression-free survival (8.3 vs. 2.9 months; hazard ratio, 0.40; P<0.001), and the time to the first skeletal-related event (16.7 vs. 13.3 months; hazard ratio, 0.69; P<0.001). Rates of fatigue, diarrhea, and hot flashes were higher in the enzalutamide group. Seizures were reported in five patients (0.6%) receiving enzalutamide. Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy. (Funded by Medivation and Astellas Pharma Global Development; AFFIRM ClinicalTrials.gov number, NCT00974311.).
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                28 April 2023
                2023
                : 13
                : 1192792
                Affiliations
                [1] 1 Private Health Management , Los Angeles, CA, United States
                [2] 2 Curanosticum , Frankfurt-Wiesbaden, Germany
                Author notes

                Edited by: Arun Azad, Peter MacCallum Cancer Centre, Australia

                Reviewed by: Nattakorn Dhiantravan, Queensland Health, Australia; Ivan De Kouchkovsky, University of California, San Francisco, United States

                *Correspondence: Eva J. Gordon, egordon@ 123456privatehealth.com ; Richard P. Baum, baumrp@ 123456gmail.com
                Article
                10.3389/fonc.2023.1192792
                10175697
                7bc7ab38-4678-4328-accb-c018f9e770b7
                Copyright © 2023 Parker, Zambelli, Lara, Wolf, McDonald, Lee, Abou-Elkacem, Gordon and Baum

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 23 March 2023
                : 14 April 2023
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 37, Pages: 16, Words: 2565
                Categories
                Oncology
                Case Report
                Custom metadata
                Genitourinary Oncology

                Oncology & Radiotherapy
                case report,psma,radioligand therapy,prostate cancer,metastatic castration resistant prostate cancer,lu-psma-617,theranostics

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