Optimising the management of bone related effects of androgen deprivation therapy in prostate cancer in the non-castration resistant scenario

Gómez Rivas, J.; Fernandez, L.; Moreno-Sierra, J.

doi:10.1016/j.acuroe.2022.08.010

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Same approach considerations depending on the size of the lesion. *** Excision or ablative treatment of resectable metastases will be considered if the general situation of the patient (ECOG or PS) allows it. Regarding adrenal “conservative” surgery, it has not been introduced in the hospital, but we believe that at this time it could be considered in the case of bilateral lesions or contralateral recurrence after previous adrenalectomy, and after its discussion in the endocrine tumour board." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Araujo-Castro, E. Pascual-Corrales, J. Lorca Álvaro, C. Mínguez Ojeda, H. Pian, I. Ruz-Caracuel, A. Sanjuanbenito Dehesa, A.B. Serrano Romero, T. Alonso-Gordoa, J. Molina-Cerrillo, V. Gómez Dos Santos" "autores" => array:11 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Araujo-Castro" ] 1 => array:2 [ "nombre" => "E." "apellidos" => "Pascual-Corrales" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Lorca Álvaro" ] 3 => array:2 [ "nombre" => "C." "apellidos" => "Mínguez Ojeda" ] 4 => array:2 [ "nombre" => "H." "apellidos" => "Pian" ] 5 => array:2 [ "nombre" => "I." "apellidos" => "Ruz-Caracuel" ] 6 => array:2 [ "nombre" => "A." "apellidos" => "Sanjuanbenito Dehesa" ] 7 => array:2 [ "nombre" => "A.B." "apellidos" => "Serrano Romero" ] 8 => array:2 [ "nombre" => "T." "apellidos" => "Alonso-Gordoa" ] 9 => array:2 [ "nombre" => "J." "apellidos" => "Molina-Cerrillo" ] 10 => array:2 [ "nombre" => "V." 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Gómez Rivas, L. Fernandez, J. Moreno-Sierra" "autores" => array:3 [ 0 => array:4 [ "nombre" => "J." "apellidos" => "Gómez Rivas" "email" => array:1 [ 0 => "juangomezr@gmail.com" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] 3 => array:2 [ "etiqueta" => "1" "identificador" => "fn0005" ] ] ] 1 => array:3 [ "nombre" => "L." "apellidos" => "Fernandez" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "1" "identificador" => "fn0005" ] ] ] 2 => array:3 [ "nombre" => "J." "apellidos" => "Moreno-Sierra" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Urology, Hospital Clínico San Carlos, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Health Research Institute of the Hospital Clínico San Carlos (IdISSC), Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Optimización del manejo de los efectos adversos óseos derivados de la terapia de privación de andrógenos en el escenario del cáncer de próstata no resistente a la castración" ] ] "textoCompleto" => "Androgens function predominantly through their action on the androgen receptor (AR), a member of the steroid hormone receptor family of ligand-activated nuclear transcription factors. Dihydrotestosterone (DHT) binds the AR in a more stable manner, compared with testosterone, leading to a 10-fold increase in transcriptional activation, which makes DHT the primary ligand and effector of AR-mediated signaling at the tissue level. As androgens have a critical role in driving PCa growth, physicians have utilized ADT to achieve drastic reductions in the rates of testicular androgen synthesis and levels of circulating androgens, thereby minimizing AR ligand availability and subsequent AR-mediated proliferative effects on the prostate.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>ADT is archieved either with bilateral orchiectomy or pharmaceutically using use of gonadotropine releasing hormone (GnRH) agonists or antagonists and the final consequence is hypogonadism. ADT, by reducing serum free testosterone levels to castrate range and serum estradiol levels, has become the most common contemporary cause of severe male hypogonadism. It has a negative impact on lipid, glucose, muscle, and bone metabolisms, resulting in a large variety of adverse events, including obesity, metabolic sindrome, osteoporosis, sarcopenia, diabetes mellitus, cardiovascular disease, ginecomastia and sexual dysfunction. These effects may have a significant impact on health and quality of life (QoL). Lipid alterations are common and may occur as early as the first 3 months of treatment. ADT also decreases insulin sensitivity and increases fasting plasma insulin levels, which is a marker of insulin resistance. The prevalence of a metabolic-like syndrome is higher during ADT compared with men not receiving ADT, and cardiovascular mortality is a common cause of death in PCa patients. Several studies showed that ADT after only 6 months was associated with an increased risk of diabetes mellitus, cardiovascular disease, and myocardial infarction.<a class="elsevierStyleCrossRefs" href="#bib0005">1–5</a> Hot flushes are a common side-effect of ADT (prevalence estimated 44–80%). They appear 3 months after starting ADT, usually persist long-term and have a significant impact on QoL. Cessation of sexual activity is very common in people undergoing ADT, affecting up to 93%.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> Bone and muscle health are a major issue in PCa patients. Muscle mass loss might result in a decrease of muscle strenght, increased fragility, decline in the functional performance and loss of independence. These changes are usually more prominent to older men. Currently, there is strong evidence that exercise interventions conducted over 12–24 weeks consisting of two to three days per week were associated with significant improvements in health and disease specific QoL. Bone mass density (BMD) declines within months of the initiation of treatment, with a maximum decrease of 5–10% within the first year. Bone turnover markers are also found to increase within the first 3–6 weeks of treatment. Annual bone loss was found to be 2–8% for the lumbar spine ald 1.8–6.5% for the femoral neck. Testosterone exerts its effects on bone remodelling by stimulating the proliferation of osteoblasts and inhibiting apoptosis of osteoblasts and osteoclasts. In addition, testosterone affects the skeleton indirectly through its conversion by aromatase to estradiol. It is essential to identify patients who are at high risk for bone loss. Evaluation of baseline BMD, as it represents a major risk factor for bone fracture, should be performed by dual emission X-ray absorptiometry before starting long-term ADT and should be repeted 12 months after treatment initiation eith a subsequent individualized monitoring frequency. The World Health Organization FRAX tool is recommended for the evaluation of individual fracture risk, but it has not been validated in these patients. Beneficial lifestyle modifications include smoking cessation, moderating alcohol and caffeine consumption, regular weight bearing and supplementation of calcium (1000−1200 mg/day) and vitamin D (800−1000 mg/day) is recommended by the American Society of Clinical Oncology (ASCO).<a class="elsevierStyleCrossRefs" href="#bib0030">6,7</a>Various drugs have been evaluated for the management of osteopenia and osteoporosis. Biphosphonates (aledronate, pamidronate and zoledronic acid) reduce loss or increase BMD in patients who receive ADT. Zoledronic acid showed the best number needed to treat (NTT), compared with placebo. Denusumab is a human monoclonal antibody against RANKL that blocks the maduration of pre-osteoclasts to osteoclasts. In a large randomized, placebo-controlled phase III trial that enrolled 1468 men receiving ADT and at high risk for fracture, denosumab given subcutaneously every 6 months found to increase significantly lumbar spine BMD at 24 months by 5.6% compared with a 1% loss in the placebo group. Similar results were seen in the total hip, femoral neck, and radius. The selective estrogen receptor modulators raloxifene and toremifene, although they are not currently approved by the US Food and Drug Administration (FDA) for the indication of preventing ADT-related bone loss, have been shown to significantly increase BMD in men on ADT. However, venous thromboembolic events occurred more frequently in the toremifene group. ASCO and the National Comprehesive Cancer Network (NCCN) suggest the addition of an osteoclast inhibitor to reduce the risk of fracture in the setting of osteoporosis (T scores of −2.5 or less in the femoral neck, total hip or lumbar spine) or when the estimated 10-year probability of hip fracture is >3% or the 10-year probability of a major osteoporosis-related fracture is >20%. European Society of Medical Oncology (ESMO) guidelines suggest the addition of a bone targeted agent for individuals with a T-score less than −2 and for those with T score > −2 and any two of the following risk factors: age < 65 years, T-score < −1.5, smoking (current or pasr history), body mass index (BMI) < 24, family history of hip fracture, personal history of fragility fracture above age 50 or oral glucocorticoid use for > 6 months. Men who require drug therapy to prevent bone loss/fractures receive Denusumab 60 mg subcutaneously every six months or zoledronic acid 5 mg by intravenous infusion once per year. The optimal duration is unknown. ESMO guidelines suggest continuation of the bone targeted agent for the duration of endocrine treatment or for up to five years.<a class="elsevierStyleCrossRefs" href="#bib0040">8–10</a>ADT usage has a negative impact on lipid, glucose, muscle, and bone metabolisms, resulting in a large variety of adverse events, including obesity, metabolic sindrome, osteoporosis, sarcopenia, diabetes mellitus, cardiovascular disease, ginecomastia and sexual dysfunction, thus we need to have a comprehensive overview on the management of its adverse effects in order to maintain the QoL of our patients." "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "Both authors contributed equally." 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Terpos" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/J.ANNONC.2020.07.019" "Revista" => array:6 [ "tituloSerie" => "Ann Oncol" "fecha" => "2020" "volumen" => "31" "paginaInicial" => "1650" "paginaFinal" => "1663" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32801018" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735786/0000004700000002/v3_202310271248/S2173578622000853/v3_202310271248/en/main.assets" "Apartado" => array:4 [ "identificador" => "6293" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Editorial" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735786/0000004700000002/v3_202310271248/S2173578622000853/v3_202310271248/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173578622000853?idApp=UINPBA00004N"]

ISSN: 2173-5786

Actas Urológicas Españolas is an international journal dedicated to urological diseases and renal transplant. It has been the official publication of the Spanish Urology Association since 1974 and of the American Urology Confederation since 2008. Its articles cover all aspects related to urology. Actas Urológicas Españolas, governed by the peer review system (double blinded), is published online in Spanish and English. Consequently, manuscripts may be sent in Spanish or English and bidirectional free cost translation will be provided. It has high visibility and accessibility and is found in the most important data bases, Medline/Pubmed, Emabase, JCR, Ïndice Médico Español, Índice bibliográfico Español en Ciencias de la Salud (IBECS), Cuiden, Dialnet, Hinari, Scopus, Google Scholar.

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Science Citation Index Expanded, Journal of Citation Reports, Index Medicus/MEDLINE, Scopus, EMBASE/Excerpta Medica, IBECS

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Impact factor

The Impact Factor measures the average number of citations received in a particular year by papers published in the journal during the two preceding years.

© Clarivate Analytics, Journal Citation Reports 2022

Impact factor 2023

1.2

Citescore

CiteScore measures average citations received per document published.

Citescore 2023

1.9

SJR

SRJ is a prestige metric based on the idea that not all citations are the same. SJR uses a similar algorithm as the Google page rank; it provides a quantitative and qualitative measure of the journal's impact.

SJR 2023

0.332

SNIP

SNIP measures contextual citation impact by wighting citations based on the total number of citations in a subject field.

SNIP 2023

0.557

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Vol. 47. Issue 2.