Low PSA Metastatic Androgen&amp;ndash; Independent Prostate Cancer

Sella, Avishay; Konichezky, Miriam; Flex, Dov; Sulkes, Aarón; Baniel, Jack

doi:10.1159/000020289

Cited by 84 publications

(65 citation statements)

References 12 publications

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“…13 The presenting symptoms were typical of metastatic prostate carcinoma in general, and most patients presented with symptoms of advanced local disease or symptomatic bone metastases. Despite reported rates of soft tissue metastases of up to 55%, 9 there was a relatively low rate (30%) of non bone disease (either visceral metastases or nonregional lymph node metastases) in this study.…”

Section: Discussioncontrasting

confidence: 75%

“…5 The pattern of metastatic disease is considered to be unlike the pattern observed in tumors with high PSA levels, with increased numbers of visceral and soft tissue metastases (up to 55% of patients) and a nontypical pattern of bone disease seen. 9 However, these latter data were obtained from patients with androgen independent, clinically progressive disease rather than patients who presented with treatment-naïve metastatic prostate carcinoma with low serum PSA levels. The objective of this study was to provide a better description of the clinical features of patients who present with metastatic prostate carcinoma and serum PSA levels Ͻ 10 ng/mL in the largest group of patients characterized to date.…”

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confidence: 99%

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Clinical features of patients who present with metastatic prostate carcinoma and serum prostate‐specific antigen (PSA) levels < 10 ng/mL

Birtle

Freeman

Masters

et al. 2003

Cancer

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BACKGROUNDAlthough < 1% of men present with prostate‐specific antigen (PSA)‐negative prostate carcinoma, in that they have serum PSA levels much lower than the tumor burden would suggest, such patients represent a management dilemma. To the authors' knowledge, little information exists in the literature regarding patterns of disease and response to treatment. The authors wished to define the clinical features of this patient group.METHODSThe British Association of Urological Surgeons Cancer Registry 2000 and 2001 data bases were used to identify the clinical features and outcome of 33 men with metastatic prostate carcinoma who presented with serum PSA levels < 10 ng/mL. Clinical notes and histopathology were reviewed for each patient.RESULTSSeventeen patients (51%) presented with urinary symptoms and/or pelvic pain, 6% with cachexia and 21% with bone pain. Characteristic bone metastases were present in 81% of patients, similar to the presentation of men with high serum PSA levels. Hypercalcemia was a feature in 9% of patients. Visceral metastases were present in two patients. The median response duration to first‐line hormone manipulation was 7 months. No responses were seen in 11 of 13 patients who received second‐line hormones or to any third‐line treatment. Three of 5 patients who received chemotherapy responded but developed recurrent disease within 8 weeks of treatment cessation. The median overall survival was 12 months.CONCLUSIONSThe presentation of patients with treatment‐naïve PSA‐negative metastatic prostate carcinoma is similar to that of patients with high serum PSA levels, but their median survival and response duration to first‐line hormone therapy are of much shorter duration. Second‐line hormone therapy is ineffective, but early chemotherapy may be beneficial. Hypercalcemia is a particular feature in this group of patients. Cancer 2003. © 2003 American Cancer Society.

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Section: Discussioncontrasting

confidence: 75%

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confidence: 99%

Clinical features of patients who present with metastatic prostate carcinoma and serum prostate‐specific antigen (PSA) levels < 10 ng/mL

Birtle

Freeman

Masters

et al. 2003

Cancer

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“…[1][2][3] Despite recent progress in PC detection and treatment, most of the deaths from PC occur in patients with androgen-independent metastatic disease. 1,4 Cancer metastasis is a complex multistep process involving tumor cell proliferation, loss of adhesion, cell migration, invasion, angiogenesis and cell implantation in distant organs. [5][6][7] Once PC becomes metastatic, its treatment options are limited to androgen withdrawal.…”

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confidence: 99%

Calcitonin stimulates the secretion of urokinase‐type plasminogen activator from prostate cancer cells: Its possible implications on tumor cell invasion

Sabbisetti

Chigurupati

Thomas

et al. 2006

Intl Journal of Cancer

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Calcitonin (CT) is synthesized and secreted in prostate epithelium, and its secretion from malignant prostates is several folds higher than that in benign prostates. CT receptor (CTR) is expressed in malignant prostate epithelium, and its activation increases invasiveness of prostate cancer (PC) cells via activation of protein kinase A. Since the role of urokinase-type plasminogen activator (uPA) in invasion of PC has been established, we tested the hypothesis that CT increases invasion of PC cells by stimulating uPA secretion from PC cells. Exogenously added CT stimulated the secretion of uPA from PC-3M cells in a dose-dependent manner, which was blocked by Rp.cAMP, a competitive inhibitor of protein kinase A. CT stimulated the secretion of MMP-2 and MMP-9 from PC-3M cells, and also increased their invasiveness. Both these actions of CT were blocked by uPA-neutralizing antibodies. Immunofluorescence studies with PC-3M cells suggest that CT stimulated redistribution of cellular uPA to focal adhesion sites, which was further confirmed by co-immunoprecipitation of uPA with focal adhesion kinase (FAK) in response to CT. These results suggest that CT increases invasiveness of PC cells by stimulating PKA-mediated uPA secretion and by redirecting the secreted uPA to focal adhesion sites. The results also suggest that uPA may, at least in part, mediate proinvasive actions of CT on PC cells by stimulating the secretion of gelatinases and degradation of focal adhesion sites. ' 2005 Wiley-Liss, Inc.

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“…Remains to be defined have minimal PSA production [34,35]. Bone scintigraphy predicts the risk of spinal cord compression, a major cause of morbidity in CRPC [36].…”

Section: Highlight Clinical Benefitmentioning

confidence: 99%

Using Surrogate Biomarkers to Predict Clinical Benefit in Men with Castration-Resistant Prostate Cancer: An Update and Review of the Literature

Armstrong

Febbo

2009

The Oncologist

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Recurrent prostate cancer has a complex molecular etiology and a prolonged disease course. Although initially responsive to androgen ablation, many men eventually become castration resistant, develop skeletal metastases, and are palliatively treated with docetaxel-based chemotherapy, radiation therapy, bisphosphonates, and best supportive care. Given the modest success rates of the current standard of care, clinical trial enrollment is encouraged. Castration-resistant prostate cancer (CRPC) is a heterogeneous disease, both in clinical manifestations and outcomes, requiring an individualized approach to both patient care and trial design. Herein, we review surrogate markers of disease progression and treatment efficacy in advanced prostate cancer in light of recently published guidelines that have redefined eligibility, response criteria, and suitable endpoints in prostate cancer drug development. The guidelines have refined outcome measures to potentially better capture clinical benefit and the ability of novel targeted molecular and biologic agents to impact favorably on this disease. We consider prostatespecific antigen changes, circulating tumor cells, bone scan alterations, markers of bone metabolism (urinary N-telopeptide and bone-specific alkaline phosphatase), pain improvements, and progression-free survival. To illustrate the role and challenges of these potential biomarkers and endpoints in drug development, we discuss a class of novel molecularly targeted agents, the src kinase inhibitors. Given that there are currently no validated surrogate markers of overall survival for assessing early clinical benefit from systemic therapy in metastatic CRPC, incorporation of relevant biomarkers into all phases of clinical development is essential to accelerate drug development in this field. The Oncologist

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Low PSA Metastatic Androgen– Independent Prostate Cancer

Cited by 84 publications

References 12 publications

Clinical features of patients who present with metastatic prostate carcinoma and serum prostate‐specific antigen (PSA) levels < 10 ng/mL

Clinical features of patients who present with metastatic prostate carcinoma and serum prostate‐specific antigen (PSA) levels < 10 ng/mL

Calcitonin stimulates the secretion of urokinase‐type plasminogen activator from prostate cancer cells: Its possible implications on tumor cell invasion

Using Surrogate Biomarkers to Predict Clinical Benefit in Men with Castration-Resistant Prostate Cancer: An Update and Review of the Literature

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