Survival of Patients With Small Cell Carcinoma of the Prostate During 1973-2003: A Population Based Study

Deorah, Sundeep; Gaitonde, Krishnanath; Raman, R. Ganapathi; Rao, Marepalli B.; Donovan, James F.

doi:10.1016/s0022-5347(09)60186-5

Cited by 20 publications

(28 citation statements)

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“…1,2,[14][15][16] What is surprising is that the distant metastasis rate from SEER database increased from 60.5% to 62% (reported by Deorah between 1973-2003and Wang J between 1973-2004 to the 68% in this study (showed by our results between 2004 and 2015). 14,17 Additionally, we found that most patients showed normal serum PSA levels in contrast to other prostate carcinomas, and these results together with other studies showing prostate SCC patients without elevated PSA, may lead to missed diagnosis in these patients. 1,5,18 Due to the aggressive behavior of SCC and delayed diagnosis at later stage, the median survival time for patients is short, with an average of 8 to 16 months.…”

Section: Discussioncontrasting

confidence: 55%

“…21 To date, previous studies based on SEER dataset lacked the information on chemotherapy and failed to measure the value of chemotherapy in treatment of prostate SCC. 14,17 In this study, we stratified the treatments based on summary stage and found that chemotherapy improved the survival of patients with distant/regional metastasis but not patients with localized tumor. These results agreed with the findings of other studies, in which they demonstrated chemotherapy is beneficial to patients with prostate SCC.…”

Section: Discussionmentioning

confidence: 85%

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Current trend of worsening prognosis of prostate small cell carcinoma: A population‐based study

et al. 2019

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Objective To determine the accurate age‐adjusted incidence of prostate small cell carcinoma (SCC), update the clinical and pathological characteristics, as well as survival data of prostate SCC from Surveillance, Epidemiology, and End Results (SEER) datasets. Methods A total of 260 patients with prostate SCC were selected from the SEER database of the National Cancer Institute between 2004 and 2015. Age‐adjusted incidence (AAI) rates, the observed and relative survival rates were evaluated over time by the SEER*Stat Software version 8.3.5. Overall survival (OS) rates that stratified by summary stage and treatment effects were evaluated by Kaplan‐Meier method. The significant differences were assessed in a log‐rank test. Univariate and multivariate cox hazard regression analysis were performed to determine independent predictors of OS. Results The incidence of prostate SCC has increased over time. The average age of prostate SCC patients was 70.25 years. More than 90% of tumors were poorly differentiated or undifferentiated. The majority of prostate SCC (77.7%) was at stage IV. 49% of patients had lymph node metastases and 68% of patients presented distant metastases (Compared with 60.5% of patients with distant metastases between 1973‐2003). Interestingly only 23.5% patients had high level PSA (>10 ng/mL). 58.8% of patients underwent chemotherapy, 25.4% of patients were treated by surgery, and 31.9% of patients were treated by radiotherapy. The observed survival rates of 1‐year, 2‐year, and 5‐year were 42.1%, 22.1%, and 12.5%, respectively (Compared with 47.9%, 27.5%, and 14.3%, respectively, between 1973 and 2003). Chemotherapy prolonged the OS of patients with regional (distant) metastases from 3 months (2 months) to 12 months (9 months). Multivariate cox regression analysis showed age, race, and stage were independent prognostic factors for prostate SCC patients. Conclusion Prostate SCC is a highly malignant cancer and our analysis of recent data has shown its incidence is increasing. Incidence rate of metastatic prostate SCC has increased and the survival rates have worsened in recent years. However, chemotherapy shows some survival benefit for prostate SCC patients with regional and distant metastasis over other treatment methods. Further work is needed to understand the reason prognosis of this type prostate cancer is worsening.

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 85%

Current trend of worsening prognosis of prostate small cell carcinoma: A population‐based study

et al. 2019

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“…NEPCs show similarities to small-cell carcinoma of the prostate (SCCP), which accounts for 0.5% to 2% of all primary prostatic malignancies (10). Patients diagnosed with SCCP have poor prognosis, with a median survival time ranging from 5 to 17.5 months and the 5-year survival rate of 14.3% (11). Moreover, in patients with locally advanced tumors treated with androgen ablation therapy (alone or in a coadjuvant setting), and in patients with CRPC, the extent of NED has been shown to be an independent prognostic factor (12).…”

Section: Introductionmentioning

confidence: 99%

Proteogenomic Characterization of Patient-Derived Xenografts Highlights the Role of REST in Neuroendocrine Differentiation of Castration-Resistant Prostate Cancer

Flores‐Morales

Bergmann

Lavallee

et al. 2019

Clinical Cancer Research

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Purpose: An increasing number of castration-resistant prostate cancer (CRPC) tumors exhibit neuroendocrine (NE) features. NE prostate cancer (NEPC) has poor prognosis, and its development is poorly understood.Experimental Design: We applied mass spectrometrybased proteomics to a unique set of 17 prostate cancer patient-derived xenografts (PDX) to characterize the effects of castration in vivo, and the proteome differences between NEPC and prostate adenocarcinomas. Genome-wide profiling of REST-occupied regions in prostate cancer cells was correlated to the expression changes in vivo to investigate the role of the transcriptional repressor REST in castration-induced NEPC differentiation.Results: An average of 4,881 proteins were identified and quantified from each PDX. Proteins related to neurogenesis, cell-cycle regulation, and DNA repair were found upregulated and elevated in NEPC, while the reduced levels of proteins involved in mitochondrial functions suggested a prevalent glycolytic metabolism of NEPC tumors. Integration of the REST chromatin bound regions with expression changes indicated a direct role of REST in regulating neuronal gene expression in prostate cancer cells. Mechanistically, depletion of REST led to cell-cycle arrest in G 1 , which could be rescued by p53 knockdown. Finally, the expression of the REST-regulated gene secretagogin (SCGN) correlated with an increased risk of suffering disease relapse after radical prostatectomy.Conclusions: This study presents the first deep characterization of the proteome of NEPC and suggests that concomitant inhibition of REST and the p53 pathway would promote NEPC. We also identify SCGN as a novel prognostic marker in prostate cancer.

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“…Prostatic small cell carcinoma (PSCC) is a rare manifestation of prostate cancer, comprising 0.5-2% of all prostatic carcinomas. It is associated with highly aggressive behavior including metastases to visceral organs and other hematogenous sites uncommon for prostate cancer, such as liver, lung, and brain [1][2][3][4][5][6][7][8]. PSCCs often coexist with conventional acinar adenocarcinoma, and shared molecular alterations support the hypothesis that both of these forms of prostate cancer are derived from the same clonal origin [9,10].…”

Section: Introductionmentioning

confidence: 99%

Increased androgen receptor gene copy number is associated with TMPRSS2-ERG rearrangement in prostatic small cell carcinoma

et al. 2014

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Small cell carcinoma of the prostate (PSCC) is a highly aggressive malignancy that often develops in patients previously treated with hormonal therapy for metastatic prostatic acinar adenocarcinoma. The TMPRSS2-ERG gene rearrangement is highly specific for prostate cancer and shared by PSCC; however, the role of androgen receptor (AR) gene alterations and interaction with TMPRSS2-ERG rearrangement are incompletely understood in PSCC. Sixty-one cases of PSCC were examined for AR gene copy number and TMPRSS2-ERG rearrangement by fluorescence in situ hybridization (FISH) and AR protein expression by immunohistochemistry. Of 61 cases of PSCC, 51% (31/61) demonstrated increased AR gene copy number (FISH+), 54% (33/61) were positive for TMPRSS2-ERG gene fusion, and 38% (23/61) showed AR protein expression. Of the 31 AR FISH+ cases, 23 also showed TMPRSS2-ERG gene fusion, and 16 expressed AR protein. Of the 33 cases with TMPRSS2-ERG fusion, 28 were AR FISH+ or expressed AR protein. Statistically significant correlations were observed between AR gene copy number or AR protein expression and TMPRSS2-ERG gene fusion (P = 0.001 and P = 0.03, respectively). In summary, high AR gene copy number emerges during the development of PSCC, often in association with TMPRSS2-ERG rearrangement. This potential mechanism warrants further study. Improvement will come from understanding the biology of the disease and integrating new therapies into the treatment of this rare and aggressive tumor.

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Survival of Patients With Small Cell Carcinoma of the Prostate During 1973-2003: A Population Based Study

Cited by 20 publications

References 0 publications

Current trend of worsening prognosis of prostate small cell carcinoma: A population‐based study

Current trend of worsening prognosis of prostate small cell carcinoma: A population‐based study

Proteogenomic Characterization of Patient-Derived Xenografts Highlights the Role of REST in Neuroendocrine Differentiation of Castration-Resistant Prostate Cancer

Increased androgen receptor gene copy number is associated with TMPRSS2-ERG rearrangement in prostatic small cell carcinoma

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