Chemical or Surgical Castration—Is This Still an Important Question?

Kolinsky, Michael; Rescigno, Pasquale; Bono, Johann S. de

doi:10.1001/jamaoncol.2015.4918

Cited by 12 publications

(11 citation statements)

References 14 publications

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“…Actually, the question is not just to provide a tool to modify dosing schedule to obtain an economical bene t. The question is to be able to discontinue the treatment when the patient will probably remain castrated in order to avoid the adverse effects of ADT with LHRH agonists themselves [6].…”

Section: Resultsmentioning

confidence: 99%

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Testosterone recovery after androgen deprivation therapy in prostate cancer: building a predictive model

Borque‐Fernando

Estrada-Domínguez

Esteban

et al. 2021

Preprint

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Purpose: To analyze variability, associated factors, and the design of nomograms for individualized testosterone recovery after androgen deprivation therapy (ADT) withdrawal.Methods: A longitudinal study was performed on 208 patients in 2003-2019 period. The castrate and normogonadic levels were defined as testosterone, 0.50 and 3.50 ng/ml respectively. Cumulative incidence curve describes testosterone recovery. A univariate and multivariate analysis was performed to predict testosterone recovery with the candidate prognostic factors: PSA at diagnosis, Clinical stage, biopsy Gleason score, age at cessation of ADT, duration of ADT, primary therapy for patients, and LHRH agonist. Results: The median followup of the study was 80 months, interquartile range (49,99). The 25% and 81% of patients did not recover the castrate and normogonadic level, respectively. Months of ADT and age at ADT withdrawal were significant predictors for testosterone recovery. We built two nomograms of testosterone estimation recovery at 12, 24, 36 and 60 months. The castration recovery model shows good calibration. The c-index was 0.677, with areas under the ROCcurve (AUC) of 0.74, 0.78, 0.78 and 0.78, at 12, 24, 36 and 60 months, respectively. The normogonadic recovery model had an overestimation of high probabilities. The cindex was 0.683, with AUC values of 0.81, 0.71, 0.71 and 0.70 at 12, 24, 36 and 60 months, respectively.Conclusion: Depending on the age of patients and time of treatment, clinicians can discontinue ADT to maintain castrate levels without treatment with enough confidence, or even recover testosterone to normogonadic levels in short courses of treatment with high probabilities.

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Section: Resultsmentioning

confidence: 99%

“…On the other hand, there is mounting evidence that ADT is linked to signi cant adverse effects, such as cardiovascular events, diabetes, acute kidney injury, and bone loss [4][5] and these dangerous effects could be related not to the absence of testosterone but to the drug used for obtaining the chemical castration [4,6].…”

Section: Introductionmentioning

confidence: 99%

Testosterone recovery after androgen deprivation therapy in prostate cancer: building a predictive model

Borque‐Fernando

Estrada-Domínguez

Esteban

et al. 2021

Preprint

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“…Another approach to inhibit androgen synthesis and subsequently PCa growth is to inhibit the HPG axis [ 58 ]. The hypothalamus synthesizes gonadotropin-releasing hormones (luteinizing-hormone releasing hormone [LHRH] and follicle-stimulating hormone releasing hormone [FSHRH]), which in turn stimulates the pituitary gland to release gonadotropins, leutinizing and follicle-stimulating hormones (LH and FSH) [ 59 ].…”

Section: Treatments Targeting the Ar Signaling Pathway For Androgen-dmentioning

confidence: 99%

Therapeutic targeting of the androgen receptor (AR) and AR variants in prostate cancer

Narayanan

2020

Asian Journal of Urology

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Prostate cancer (PCa) accounted for over 300 000 deaths world-wide in 2018. Most of the PCa deaths occurred due to the aggressive castration-resistant PCa (CRPC). Since the androgen receptor (AR) and its ligands contribute to the continued growth of androgen-dependent PCa (ADPCa) and CRPC, AR has become a well-characterized and pivotal therapeutic-target. Although AR signaling was identified as therapeutic-target in PCa over five-decades ago, there remains several practical issues such as lack of antagonist-bound AR crystal structure, stabilization of the AR in the presence of agonists due to N-terminus and C-terminus interaction, unfavorable large-molecule accommodation of the ligand-binding domain (LBD), and generation of AR splice variants that lack the LBD that impede the discovery of highly potent fail-safe drugs. This review summarizes the AR-signaling pathway targeted therapeutics currently used in PCa and the approaches that could be used in future AR-targeted drug development of potent next-generation molecules. The review also outlines the discovery of molecules that bind to domains other than the LBD and those that inhibit both the full length and splice variant of ARs.

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“…A recent study found that orchiectomy was associated with a lower risk of fracture, peripheral arterial disease, and cardiac-related complications, and a similar risk of diabetes, thromboembolism, and cognitive decline. 15 and clinical disease-free survival in patients with intermediate-and high-risk prostate cancer. Five-year biochemical disease-free survival was 82.6% in the combination group compared with 69.8% in the RT group (hazard ratio [HR], 0.52; P<.001).…”

Section: Intermittent Versus Continuous Adtmentioning

confidence: 99%

Evolving Use of Androgen Deprivation Therapy in Prostate Cancer Management

Mohler

2016

J Natl Compr Canc Netw

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Since its introduction more than 70 years ago, the use of androgen deprivation therapy (ADT) for prostate cancer has evolved to become part of a multimodal management approach. In this presentation from the NCCN 21st Annual Conference, James L. Mohler, MD, reviewed data that inform these strategies and gave his bottom-line recommendations on issues such as ADT plus radiotherapy, continuous versus intermittent ADT, ADT for positive nodes, and ADT plus docetaxel. He suggested that ADT plus radiation therapy should be used in patients at high risk, intermittent ADT is more appropriate for most patients than continuous ADT, and docetaxel should be given with ADT for high-volume metastatic disease.

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Chemical or Surgical Castration—Is This Still an Important Question?

Cited by 12 publications

References 14 publications

Testosterone recovery after androgen deprivation therapy in prostate cancer: building a predictive model

Testosterone recovery after androgen deprivation therapy in prostate cancer: building a predictive model

Therapeutic targeting of the androgen receptor (AR) and AR variants in prostate cancer

Evolving Use of Androgen Deprivation Therapy in Prostate Cancer Management

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