Prevalence of Skeletal Complications and Their Impact on Survival of Hormone Refractory Prostate Cancer Patients in Japan

Inoue, Takamitsu; Segawa, Tomio; Kamba, Tomomi; Yoshimura, Koji; Nakamura, Eijiro; Nishiyama, Hiroyuki; Ito, Noriyuki; Habuchi, Tomonori; Ogawa, Osamu

doi:10.1016/j.urology.2008.07.062

Cited by 48 publications

(41 citation statements)

References 13 publications

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“…9 SREs are common in metastatic prostate cancer due to frequent occurrence of bone metastasis. 25,26,27 SREs have a considerable impact on patients' quality of life as they affect patients' general well-being and the ability to perform basic functions of daily living. 5,28,29 In the present study, we found that 44% of men with possible bone metastasis had an SRE.…”

Section: Discussionmentioning

confidence: 99%

Mortality following bone metastasis and skeletal-related events among men with prostate cancer: a population-based analysis of US Medicare beneficiaries, 1999–2006

Sathiakumar

Delzell

Morrisey

et al. 2011

Prostate Cancer Prostatic Dis

191

148

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Information on the impact of bone metastasis and skeletal-related events (SREs) on mortality among prostate cancer patients is limited. Using the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified men aged 65 years or older diagnosed with prostate cancer between July 1 1999 and December 31 2005 and followed to determine deaths through December 31 2006. We classified subjects as having bone metastasis and SREs as indicated by Medicare claims. Using Cox regression, we estimated mortality hazards ratios (HR) among men with bone metastasis with or without SRE, compared with men without bone metastasis. Among 126 978 men with prostate cancer (median follow-up, 3.3 years), 9746 (7.7%) had bone metastasis at prostate cancer diagnosis (1.7%) or during follow-up (5.9%). SREs occurred in 4296 (44%) men with bone metastasis. HRs for risk of death were 6.6 (95% CI ¼ 6.4-6.9) and 10.2 (95% CI ¼ 9.8-10.7), respectively, for men with bone metastasis but no SRE and for men with bone metastasis plus SRE, compared with men without bone metastasis. Bone metastasis was associated with mortality among prostate cancer patients. This association appeared to be stronger for bone metastasis plus SRE than for bone metastasis without SRE.

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Section: Discussionmentioning

confidence: 99%

Mortality following bone metastasis and skeletal-related events among men with prostate cancer: a population-based analysis of US Medicare beneficiaries, 1999–2006

Sathiakumar

Delzell

Morrisey

et al. 2011

Prostate Cancer Prostatic Dis

191

148

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“…As a consequence, bone metastases are highly prevalent in patients with prostate cancer (PCa). Whereas bone metastases are infrequent in newly diagnosed PCa, very high levels of frequency ( > 65%) have been reported in hormone-refractory PCa accompanied by a high mortality rate [ 1,2 ] . The formation of bone metastases requires traffi cking of malignant cells via the circulatory or lymphatic system in a multistep process [ 3 ] .…”

Section: Introductionmentioning

confidence: 99%

Molecular phenotyping of circulating tumour cells in patients with prostate cancer: prediction of distant metastases

Giesing¹,

Driesel²,

Molitor³

et al. 2012

BJU International

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What's known on the subject? and What does the study add?The role of circulating cancer cells in metastogenesis is generally accepted. Two forms of these cells have been reported in a number of studies, cancer cell clusters (CCCs) and individual epithelial cancer cells. Clusters appear at higher frequencies in the blood. CCCs have been reported to be rich in vimentin and poor in E‐cadherin expression The resulting epithelial to mesenchymal transition, a prerequisite for metastasis formation, occurs in CCCs. We have developed a new set of biomarkers, namely the antioxidant genes GPX1, SOD2 and TXNRD1, specific to cell trafficking in the blood.Firstly, the study shows that diagnosis of distant metastases is feasible by applying molecular phenotyping with a five gene test that has 94% sensitivity and 81% accuracy. Again SOD2 and GPX1 showed the highest sensitivities. Secondly, the study shows the efficacy of palliative chemotherapy in clearing the blood of CCCs overexpressing diagnostic genes. Clinically the overall lifespan ranged from 5 to 99 months under taxotere. We aimed to investigate the molecular reasons and found that MDR1 overexpression worsened survival by 31%. To the best of our knowledge, this is the first study to show the clinical impact of drug targeting and the counter‐effect of drug resistance in CCCs on overall survival. The findings may, therefore, add a novel tool for clinicians in tailoring therapies individually.OBJECTIVES To find the molecular phenotype in circulating cancer cells from patients with prostate cancer (PCa) in order to predict distant metastases. To determine genes affecting the study endpoints of overall survival and time to progression. PATIENTS AND METHODS Twenty‐five urologists in several clinics participated in the study, with 51 patients with metastatic and 77 with non‐metastatic PCa. Molecular analysis was carried out in two forms of circulating cancer cells, cancer cell clusters (CCCs) and individual epithelial cancer cells (CECs). Gene expression was studied using real‐time reverse‐transcriptase PCR. Cycle threshold values were normalized with glyceraldehyde 3‐phosphate dehydrogenase in cancer cells and mononucleated cells, yielding comparative specific expression values from the relative quantification method with the help of the standard curve method for each patient and each gene locus. RESULTS Preclinical validation was performed using aggregated and non‐aggregated SW480 cells showing the independence of CCCs and CECs. Prediction of metastases was achieved with five genes showing the highest sensitivity, SOD2, GPX1, AR, cyclin B and bFGF. The following results were obtained: 94% sensitivity, 65% specificity, 76% positive predictive value and 89% negative predictive value. The prevalence was 63%. Test accuracy was 81% with an odds ratio of 32 (P < 0.001). Overall survival was worsened by preceding chemotherapies when leaving insufficient GPX1 clearance in blood. Drug resistance genes were found to worsen the endpoints, among them MDR1 (P = 0.003; hazard ratio: 1.31; 95% CI: 1.09–1.58). CONCLUSIONS SOD2, GPX1 and AR represent a novel biomarker set for circulating cancer cells (clusters and scattered individual cells) in PCa. The clinical usefulness of these biomarkers ranges from the prediction of clinical tumours to disease prognostication, therapy monitoring and therapy outcome prediction (hormonal therapies, chemotherapies). The presence of CCCs and CECs after batch isolation allows the addition of genes for intensive studies, e.g. drug resistance.

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“…Patients who presented pathologic fractures during the trial had a more than 20% increased risk of death 11 . A recent retrospective study on patients with castrateresistant pca demonstrated reduced overall survival when patients presented bone pain [hazard ratio (hr): 2.1; p = 0.007] or higher scores on bone disease extension (hr: 1.7; p = 0.033) 12 .…”

Section: Clinical Manifestations and Diagnosis Of Skeletal Metastasesmentioning

confidence: 99%

Preventing Bone Complications in Advanced Prostate Cancer

Luz

Aprikian

2010

Current Oncology

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The diagnosis and treatment of prostate cancer have steadily been improving since the late 1980s. However, clinicians still confront a large group of men developing disease metastatic to bone. Adequate control of bone complications plays a fundamental role in achieving control of symptoms and quality of life in this group. Androgen deprivation therapy, the standard treatment for advanced prostate cancer, increases the risk of various complications, including bone disease. This review addresses the prevention of bone complications related not only to prostate cancer metastases but also to impaired bone integrity caused by androgen deprivation therapy. KEY-WORDSProstate cancer, bone metastases, skeletal complications

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Prevalence of Skeletal Complications and Their Impact on Survival of Hormone Refractory Prostate Cancer Patients in Japan

Cited by 48 publications

References 13 publications

Mortality following bone metastasis and skeletal-related events among men with prostate cancer: a population-based analysis of US Medicare beneficiaries, 1999–2006

Mortality following bone metastasis and skeletal-related events among men with prostate cancer: a population-based analysis of US Medicare beneficiaries, 1999–2006

Molecular phenotyping of circulating tumour cells in patients with prostate cancer: prediction of distant metastases

Preventing Bone Complications in Advanced Prostate Cancer

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