EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer

Mottet, Nicolas; Bellmunt, Joaquim; Bolla, M.; Joniau, Steven; Mason, Malcolm David; Матвеев, В. Б.; Schmid, Hans‐Peter; Kwast, Theo van der; Wiegel, Thomas; Zattoni, Fabio; Heidenreich, Axel

doi:10.1016/j.acuroe.2012.01.001

Cited by 66 publications

(77 citation statements)

References 85 publications

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“…We demonstrated that LNCaP‐B1 cells were significantly more resistant to docetaxel than LNCaP‐V1 cells; this was abolished following siRNA Bcl‐2 treatment. These results are of clinical significance as docetaxel is one of the drugs used in patients who relapse with a castrate‐resistant tumour after bicalutamide treatment 27. A more comprehensive analysis of gene expression may highlight other changes in gene expression that are associated with the development of bicalutamide resistance and thus generate further novel targets for combination therapy with ADT.…”

Section: Discussionmentioning

confidence: 99%

Androgen deprivation results in time‐dependent hypoxia in LNCaP prostate tumours: Informed scheduling of the bioreductive drug AQ4N improves treatment response

Ming

Byrne

Camac

et al. 2012

Intl Journal of Cancer

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Androgen withdrawal induces hypoxia in androgen-sensitive tissue; this is important as in the tumour microenvironment, hypoxia is known to drive malignant progression. Our study examined the time-dependent effect of androgen deprivation therapy (ADT) on tumour oxygenation and investigated the role of ADT-induced hypoxia on malignant progression in prostate tumours. LNCaP xenografted tumours were treated with anti-androgens and tumour oxygenation measured. Dorsal skin fold (DSF) chambers were used to image tumour vasculature in vivo. Quantitative PCR (QPCR) identified differential gene expression following treatment with bicalutamide. Bicalutamide-treated and vehicle-only-treated tumours were re-established in vitro, and invasion and sensitivity to docetaxel were measured. Tumour growth delay was calculated following treatment with bicalutamide combined with the bioreductive drug AQ4N. Tumour oxygenation measurements showed a precipitate decrease following initiation of ADT. A clinically relevant dose of bicalutamide (2 mg/kg/day) decreased tumour oxygenation by 45% within 24 hr, reaching a nadir of 0.09% oxygen (0.67 6 0.06 mmHg) by Day 7; this persisted until Day 14 when it increased up to Day 28. Using DSF chambers, LNCaP tumours treated with bicalutamide showed loss of small vessels at Days 7 and 14 with revascularisation occurring by Day 21. QPCR showed changes in gene expression consistent with the vascular changes and malignant progression. Cells from bicalutamide-treated tumours were more malignant than vehicle-treated controls. Combining bicalutamide with AQ4N (50 mg/kg, single dose) caused greater tumour growth delay than bicalutamide alone. Our study shows that bicalutamide-induced hypoxia selects for cells that show malignant progression; targeting hypoxic cells may provide greater clinical benefit.

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Section: Discussionmentioning

confidence: 99%

Androgen deprivation results in time‐dependent hypoxia in LNCaP prostate tumours: Informed scheduling of the bioreductive drug AQ4N improves treatment response

Ming

Byrne

Camac

et al. 2012

Intl Journal of Cancer

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“…Patients with mCRPC can be divided into three main risk categories (high, intermediate, low) based on the presence or absence of specifi c prognostic factors (pain, visceral metastases, anaemia, bone scan progression) that predict PSA progression and survival [ 44 -46 ] . Current European Association of Urology guidelines indicate that in asymptomatic patients with high serum PSA levels or a rapid PSA doubling time ( < 6 months), chemotherapy should be initiated early and that prognostic factors should also be considered before initiating chemotherapy [ 47 ] . It may be that patients with a high risk of progression are candidates for earlier initiation of fi rst-and second-line chemotherapy.…”

Section: Use Of Predictive Factors and Nomograms In Guiding Treatmentmentioning

confidence: 99%

Advances in the management of high‐risk localised and metastatic prostate cancer

Bellmunt

Attard

Bahl³

et al. 2012

BJU International

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At the third annual Interactive Genitourinary Cancer Conference, held in Budapest from 30 April to 1 May 2011, the latest developments in the management of patients with high-risk localised and metastatic prostate cancer were discussed. Prostate cancer is the most common cancer in Western men and, for advanced disease, no curative agents are available. For men with high-risk localised disease there is debate about the best treatment approaches, with both radical prostatectomy and radiation therapy shown to improve outcomes. These approaches have started to be augmented as new techniques and therapies are developed. For instance, radiation therapy combined with androgen deprivation therapy has been shown to be more efficacious than radiation therapy alone, and there may also be a role for adjuvant/neoadjuvant chemotherapy. Ultimately a multidisciplinary approach will most probably result in the best outcomes for patients. The use of androgen deprivation therapy in men with prostate cancer needs to be monitored carefully, given that it results in adverse alterations in several metabolic parameters and an increased risk of further coronary events in men with cardiovascular disease in some studies. Until recently there were limited options for the management of men with advanced prostate cancer, but new agents for use in the post-docetaxel setting have recently been approved. These are cabazitaxel and abiraterone acetate, which have both shown a significant survival benefit in patients who have progressed on docetaxel. Additional agents, for these patients and for patients at other stages of disease, are in the later stages of development. The development of new agents has been aided by a greater understanding of the molecular mechanisms of resistance to current therapies and the recognition of new pathophysiological pathways. As the number of available therapeutic options increases, it will become increasingly important to tailor treatments to the individual patient. This may require the development of novel biomarkers or the use of existing or new predictive tools based on prognostic factors. To ensure optimal patient care, early and continuous involvement of the multidisciplinary team will be required.

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“…PSADT can be used to monitor the effi cacy of therapy and thus guide therapeutic timing and strategy [ 11 ] . European Association of Urology (EAU) guidelines recommend early initiation of chemotherapy in patients with high PSA levels or a PSADT of < 6 months, as it results in signifi cant improvement in survival compared with patients for whom chemotherapy is delayed [ 2 ] .…”

Section: Prognostic Factors In Mcrpcmentioning

confidence: 99%

“…Despite the success of androgen deprivation therapy (ADT) in the treatment of locally advanced or metastatic prostate cancer, progression ultimately occurs in most patients as the disease becomes refractory to such treatment [ 1,2 ] . At this stage the disease is termed ' castration-resistant ' [ 2 ] .…”

Section: Introductionmentioning

confidence: 99%

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Practical aspects of metastatic castration‐resistant prostate cancer management: patient case studies

Bahl¹,

Bellmunt

Oudard

2012

BJU International

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Interactive case studies formed a key feature of the third annual Interactive Genitourinary Cancer Conference held in April/May 2011 in Budapest, Hungary. These cases were used to discuss the practical aspects of the management of metastatic castration‐resistant prostate cancer (mCRPC). Particular emphasis was placed on audience participation with potential management options posed as interactive questions to the delegates. This paper summarises these case studies and the related discussion. Docetaxel is the standard first‐line chemotherapeutic agent for patients with mCRPC and, until recently, second‐line therapeutic options were limited. Results from the recently completed TROPIC trial showed a statistically and clinically significant improvement in overall survival with the microtubule inhibitor cabazitaxel compared with mitoxantrone. Cabazitaxel has been shown to be well tolerated and has been approved in Europe and the USA as second‐line chemotherapy for mCRPC. Prognostic factors have a potential benefit in individualised patient management in mCRPC. Pretreatment prognostic factors, including PSA doubling time, pain, visceral metastases, anaemia and progression of osseous metastases, have been shown to predict survival outcomes and can be used to guide treatment strategies, including appropriate timing of chemotherapy. Multiple treatment options and significant heterogeneity among patients with advanced prostate cancer necessitate multidisciplinary team management in addition to patient education, as part of a patient‐centred approach. The development of second‐line chemotherapeutic agents together with the use of prognostic factors and a patient‐centred multidisciplinary team approach provide encouraging new management prospects for patients with mCRPC.

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EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer

Cited by 66 publications

References 85 publications

Androgen deprivation results in time‐dependent hypoxia in LNCaP prostate tumours: Informed scheduling of the bioreductive drug AQ4N improves treatment response

Androgen deprivation results in time‐dependent hypoxia in LNCaP prostate tumours: Informed scheduling of the bioreductive drug AQ4N improves treatment response

Advances in the management of high‐risk localised and metastatic prostate cancer

Practical aspects of metastatic castration‐resistant prostate cancer management: patient case studies

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