Impact of treatment on progression to castration‐resistance, metastases, and death in men with localized high‐grade prostate cancer

Miller, Eric T.; Chamie, Karim; Kwan, Lorna; Lewis, Michael; Knudsen, Beatrice S.; Garraway, Isla P.

doi:10.1002/cam4.981

Cited by 15 publications

(13 citation statements)

References 39 publications

(51 reference statements)

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“…Twenty-seven out of 30 NRS described data on OM or PSCM, in favor of RP in the majority of the studies [35,36,43,44,47,49,51,55,59,60,64]. When comparing RP to the combination of EBRT + ADT, the reported benefit in OS and cancer-specific survival (CSS) ranged from 10% to 28% [35,55,60] and 4% to 8% [35,47,51,55] [40].…”

Section: Oncological Outcomesmentioning

confidence: 99%

Benefits and Risks of Primary Treatments for High-risk Localized and Locally Advanced Prostate Cancer: An International Multidisciplinary Systematic Review

et al. 2020

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Context. The optimal treatment for men with high-risk localized or locally advanced prostate cancer (PCa) remains unknown. Objective. To perform a systematic review of the existing literature on the effectiveness of the different primary treatment modalities for high-risk localized and locally advanced PCa. The primary oncological outcome is the development of distant metastases at ≥5 years of follow-up. Secondary oncological outcomes are prostate cancer specific mortality (PCSM), overall mortality (OM), biochemical recurrence and need for salvage treatment with ≥5 years of follow-up. Non-oncological outcomes are quality of life (QoL), functional outcomes and treatment-related side effects reported. Evidence acquisition. Medline, Medline In-Process, Embase, and the Cochrane Central Register of Randomized Controlled Trials were searched. All comparative (randomized and non-randomized) studies published between January 2000 and May 2019 with at least 50 participants in each arm were included. Studies reporting on high-risk localized PCa (ISUP grade 4-5 [GS 8-10] or PSA >20 ng/mL or ≥cT2c) and/or locally advanced PCa (any PSA, cT3-4 or cN+, any ISUP grade/ GS score) or where subanalyses were performed on either group were included. The following primary local treatments were mandated: radical prostatectomy (RP), external beam radiotherapy (EBRT) (≥64 Gy), brachytherapy (BT) or multimodality treatment combining any of the local treatments above (+/-any systemic treatment). Risk of Bias (RoB) and confounding factors were assessed for each study. A narrative synthesis was performed. Evidence synthesis. Overall, 90 studies met the inclusion criteria. RoB and confounding factors revealed high RoB for selection, performance and detection bias and low RoB for correction of initial PSA and biopsy GS. When comparing RP to EBRT, retrospective series suggested an advantage for RP, although with a low level of evidence. Both RT and RP should be seen as part of a multimodal treatment plan with possible addition of (post-operative) RT and/or ADT respectively. High levels of evidence exist for EBRT treatment with several RCTs showing superior outcome for adding long-term ADT or BT to EBRT. No clear cutoff can be proposed for RT dose but higher RT doses by means of dose escalation schemes result in an improved biochemical control. Twenty studies reported data on QoL, with RP resulting mainly in GU toxicity and sexual dysfunction, and EBRT in bowel problems. Conclusion. Based on the results of this systematic review, both RP as part of multimodal treatment and EBRT + long-term ADT can be recommended as primary treatment in high-risk and locally advanced PCa. For high-risk PCa, also EBRT + BT can be offered, despite more grade 3 toxicity. Interesting, for selected patients, e.g. with higher comorbidity, a shorter duration of ADT might be an option. For locally advanced PCa, EBRT + BT shows promising result but still needs further validation. In this setting, it is important that patients are aware that the offered therapy will be mos...

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Section: Oncological Outcomesmentioning

confidence: 99%

Benefits and Risks of Primary Treatments for High-risk Localized and Locally Advanced Prostate Cancer: An International Multidisciplinary Systematic Review

et al. 2020

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“…However, for patients with metastatic disease or recurrent cancer with locoregional and distant metastases, androgen-deprivation therapy (ADT) or castration therapy is considered the primary line of treatment [ 12 ]. Unfortunately, despite the initial outstanding therapeutic response, most PCa patients treated with ADT eventually have the relapse of PCa in a highly aggressive and therapy-resistant form leading to poor clinical outcomes [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Cellular and Molecular Progression of Prostate Cancer: Models for Basic and Preclinical Research

Saranyutanon

Deshmukh

Dasgupta

et al. 2020

Cancers

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We have witnessed noteworthy progress in our understanding of prostate cancer over the past decades. This basic knowledge has been translated into efficient diagnostic and treatment approaches leading to the improvement in patient survival. However, the molecular pathogenesis of prostate cancer appears to be complex, and histological findings often do not provide an accurate assessment of disease aggressiveness and future course. Moreover, we also witness tremendous racial disparity in prostate cancer incidence and clinical outcomes necessitating a deeper understanding of molecular and mechanistic bases of prostate cancer. Biological research heavily relies on model systems that can be easily manipulated and tested under a controlled experimental environment. Over the years, several cancer cell lines have been developed representing diverse molecular subtypes of prostate cancer. In addition, several animal models have been developed to demonstrate the etiological molecular basis of the prostate cancer. In recent years, patient-derived xenograft and 3-D culture models have also been created and utilized in preclinical research. This review is an attempt to succinctly discuss existing information on the cellular and molecular progression of prostate cancer. We also discuss available model systems and their tested and potential utility in basic and preclinical prostate cancer research.

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“…Androgen deprivation therapy (ADT) is commonly used for metastatic prostate cancer patients. ADT is initially effective in hormone-naïve prostate cancer, but around half of patients progress to castration-resistant prostate cancer (CRPC) following ADT [2,3]. Several drugs for CRPC have been developed over the past decade [4].…”

Section: Introductionmentioning

confidence: 99%

CD44v8-10 mRNA contained in serum exosomes as a diagnostic marker for docetaxel resistance in prostate cancer patients

Kato

Mizutani

Kawakami

et al. 2020

Heliyon

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Background: Docetaxel is first-line chemotherapy for castration-resistant prostate cancer (CRPC), but most patients acquire docetaxel resistance. CD44 has been shown to be involved in drug resistance of cancers including prostate cancer. We hypothesized that CD44 in serum exosomes could be a diagnostic marker for docetaxel resistance in CRPC patients. In this study, we examined CD44 protein and mRNA expression in cell lysates and exosomes isolated from prostate cancer cells, evaluated the effect of CD44v8-10 knockdown on docetaxel sensitivity and measured CD44 mRNA copy numbers contained in serum exosomes in prostate cancer patients. Materials and methods: Docetaxel-sensitive PC-3 prostate cancer cells and docetaxel-resistant PC-3R cells established previously from parental PC-3 cells were used. CD44v8-10 knockdown was performed by siRNA transfection. Blood was collected from 50 docetaxel-naïve and 10 docetaxel-resistant patients and 15 control males. CD44 protein expression was evaluated by Western blotting. CD44 mRNA expression was measured by RT-digital PCR.Results: The levels of CD44v8-10 protein and mRNA in cell lysates and exosomes were higher in PC-3R cells than in PC-3 cells. CD44v8-10 knockdown significantly increased docetaxel sensitivity of PC-3R cells. The CD44v8-10 mRNA copy numbers in serum exosomes were higher in docetaxel-resistant patients than in docetaxel-naïve patients and control males (median 46, 12 and 17 copies/mL serum, respectively, P ¼ 0.032). In contrast, the serum exosomal mRNA copy numbers of CD44 standard isoform (CD44s) were not different among 3 groups (median 25, 14 and 13 copies/mL serum, respectively, P ¼ 0.150). Conclusions: CD44v8-10 may be involved in docetaxel resistance in prostate cancer and serum exosomal CD44v8-10 mRNA could be a diagnostic marker for docetaxel-resistant CRPC.

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Impact of treatment on progression to castration‐resistance, metastases, and death in men with localized high‐grade prostate cancer

Cited by 15 publications

References 39 publications

Benefits and Risks of Primary Treatments for High-risk Localized and Locally Advanced Prostate Cancer: An International Multidisciplinary Systematic Review

Benefits and Risks of Primary Treatments for High-risk Localized and Locally Advanced Prostate Cancer: An International Multidisciplinary Systematic Review

Cellular and Molecular Progression of Prostate Cancer: Models for Basic and Preclinical Research

CD44v8-10 mRNA contained in serum exosomes as a diagnostic marker for docetaxel resistance in prostate cancer patients

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