Neuroendocrine differentiation in prostate cancer: Current and emerging therapy strategies

Conteduca, Vincenza; Aieta, Michele; Amadori, Dino; Giorgi, Ugo De

doi:10.1016/j.critrevonc.2014.05.008

Cited by 77 publications

(92 citation statements)

References 97 publications

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“…Even today, the real frequency and definition of visceral involvement in mCRPC is difficult to establish [3]. Lung, liver and soft tissue metastases occur infrequently and, in the majority of cases, are related to neuroendocrine di fferentiation in mCRPC [4][5][6][7].…”

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confidence: 99%

Impact of Visceral Metastases on Outcome to Abiraterone After Docetaxel in Castration-Resistant Prostate Cancer Patients

et al. 2015

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confidence: 99%

Impact of Visceral Metastases on Outcome to Abiraterone After Docetaxel in Castration-Resistant Prostate Cancer Patients

et al. 2015

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“…Neuroendocrine differentiation is a common feature of prostatic carcinoma, which is usually present in primary high Gleason-grade tumours of the prostate heralding a more aggressive clinical behaviour and requiring a different treatment approach 3 4. However, there is still conﬂicting data reported in the literature regarding the prognostic signiﬁcance of neuroendocrine tissue markers in prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Small-cell neuroendocrine cancer of the prostate: an atypical presentation of a common disease

Alves¹,

Calmeiro²,

Silva³

et al. 2016

BMJ Case Reports

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A 70-year-old man with a history of prostate cancer, previously submitted to surgical castration and trans-urethral resection of the prostate, was admitted to Accident and Emergency department. He had been suffering from osteoarticular and abdominal pain, and recent weight loss. An abdominal and a pelvic CT showed multiple hepatic metastases and a pelvic mass, but his prostate-specific antigen values were low (0.26 n/mL). A biopsy of a hepatic metastasis and of the pelvic mass revealed a small-cell neuroendocrine prostate cancer, a rare and aggressive androgen-independent form of prostate cancer with a poor prognosis. Our purpose was to report a clinical case of a rare and aggressive variant of a common disease. A high index of suspicion is required to make an early diagnosis and to ensure a proper therapeutic approach.

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“…Neuroen- Review docrine markers, CgA and NSE, are often combined for the detection of NEPC in prostate cancer tissue using immunohistochemistry to account for a heterogeneous marker expression [40]. In addition, the combination of these 2 markers is unaffected by different therapeutic interventions [38,41] and proved independent of PSA levels [42]. However, a meaningless result of PFS was found in subgroup analysis in multivariate analysis.…”

Section: Major Study Findings and Research Statusmentioning

confidence: 99%

“…Even if this conclusion was affected by confounding factors, we can still assume that there are potential connections between AR-targeted therapies and serum neuroendocrine markers. Because the prostate neuroendocrine cell usually does not express nuclear AR [33], the novel hormonal therapy of mCRPC mainly acts on the non-neuroendocrine component, which means the patients with NED are almost resistant to hormonal therapies [16]. Clinical data display approximately 25% of patients treated with ENZ, and one third of those treated with abiraterone show primary resistance to these agents [43].…”

Section: Major Study Findings and Research Statusmentioning

confidence: 99%

“…With the application of novel AR-targeted therapies in mCRPC, great importance has been attached to the timely and credible judgment of NED occurrence. Traditional prostate tumor marker PSA proved bad forecast value in NEPC because of histological features of poorly differentiated carcinoma [33]. Therefore, NEDrelated biomarkers CgA and NSE may be considered a potential predictor due to the complexity prognosis of mCRPC.…”

Section: Major Study Findings and Research Statusmentioning

confidence: 99%

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Serum Neuroendocrine Markers Predict Therapy Outcome of Patients with Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis

et al. 2018

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Purpose: To evaluate whether serum neuroendocrine markers could effectively predict treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: The PubMed, Cochrane Library and Embase databases were sought to identify eligible studies concerning serum neuroendocrine markers and the prognosis of post-treatment mCRPC from inception to April 2018. The association between serum neuroendocrine markers, that is, chromogranin A (CgA) and neurone-specific enolase (NSE), levels and the prognosis of post-treatment mCRPC were summarized using a random-effects model and hazard ratio (HR) with 95% CI Sensitivity analyses were conducted to assess potential bias. Results: A total of 234 participants are included in this meta-analysis (mean age = 71.3 years) from 6 studies. The pooled results show that higher markers’ levels at baseline in patients were associated with unfavorable overall survival (OS; univariate analysis: HR 3.775, 95% CI 1.469–9.698, p = 0.006; multivariate analysis: HR 3.838, 95% CI 1.774–8.304, p = 0.001), and a similar situation was observed in progression-free survival (PFS; univariate analysis: HR 2.785, 95% CI 1.315–5.898, p = 0.007; multivariate analysis: HR 1.266, 95% CI 1.017–1.577, p = 0.035). Estimates of the total effects were generally consistent in the sensitivity analysis. Publication bias was observed when performing the univariate analysis of PFS, and we have the explanation accordingly. Conclusions: The results of this pooled analysis confirm serum neuroendocrine markers could be the effective predictor of treatment outcome in patients with mCRPC. In addition, a combination of CgA and NSE is more valuable to predict worse OS. Further randomized case-control trials are required to validate this relationship.

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Neuroendocrine differentiation in prostate cancer: Current and emerging therapy strategies

Cited by 77 publications

References 97 publications

Impact of Visceral Metastases on Outcome to Abiraterone After Docetaxel in Castration-Resistant Prostate Cancer Patients

Impact of Visceral Metastases on Outcome to Abiraterone After Docetaxel in Castration-Resistant Prostate Cancer Patients

Small-cell neuroendocrine cancer of the prostate: an atypical presentation of a common disease

Serum Neuroendocrine Markers Predict Therapy Outcome of Patients with Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis

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