Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1519176 (PSA)
 5,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostate cancer is the most common cancer and the second leading cause of cancer-related death among men. New prostatic markers are needed to increase diagnostic and prognostic effectiveness. One such new marker is prostate-specific membrane antigen (PSMA). PSMA is a highly prostate-restricted membrane glycoprotein that is expressed in normal prostatic epithelial cells and elevated in prostate cancers, especially in poorly differentiated, metastatic, and hormone refractory carcinomas. It has been measured in serum with immunocompetitive and Western blot assays, and its levels have been found to be correlated with the prediction of treatment failure and disease prognosis. Reverse transcriptase-polymerase chain reaction (RT-PCR) assays with primers specific for PSMA have been shown to be more effective than PSA-specific primers in detecting hematogenous circulating prostate cancer cells; however, no clear benefit in patient staging or utility as a predictor of clinical outcome or response to treatment has so far been obtained using RT-PCR methods. PSMA is currently utilized as an immunoscintigraphic target using the antibody conjugate CYT-356 (ProstaScint; Cytogen, Princeton, NJ) and has been shown to have clinical value, particularly in detecting occult prostate cancer. Another current application of PSMA is in immunotherapy of prostate cancer, in which promising results have been obtained in a phase I trial, and a phase II trial is underway. The research summarized in this article indicates that PSMA is an excellent target for diagnostic and therapeutic applications in prostate cancer.
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PMID:Prostate-specific membrane antigen: current and future utility. 950 77

Capromab Pendetide imaging illustrates the successful translation of monoclonal antibody technology from the laboratory to the clinic. It provides a means of identifying otherwise occult soft tissue metastases in patients with adenocarcinoma of the prostate. When utilized with other clinical, pathological and laboratory findings, Capromab Pendetide imaging enables more accurate disease staging and monitoring than is afforded by other imaging modalities such as CT and MRI. In the primary disease setting Capromab Pendetide imaging should be reserved for use in patients with negative bone scans who are at high risk for metastatic disease based on such factors as advanced clinical stage, high Gleason score and significantly elevated serum PSA or alkaline phosphatase. Due to low sensitivity for small-volume disease, a negative Mab scan may not eliminate the need for a staging lymph node dissection but should encourage further consideration of local treatment options. Capromab Pendetide should be used with caution in patients at low risk for metastatic disease. Positive scan findings in low risk patients should be confirmed before altering the treatment plan since some false positive scans should be anticipated in a population with low disease prevalence. Capromab Pendetide imaging has not been shown to be reliable in determining the local extent of the primary tumor but new techniques involving co-registration of SPECT and CT images show promise in this regard. In the patient with recurrent disease following primary therapy, the predictive value of Capromab Pendetide imaging of the prostate or prostate fossa is limited, particularly following RT. Its more important role in this setting is to identify lymph node metastases in the high risk patient with a negative bone scan who might otherwise be a candidate for local salvage therapy. A large prospective study is needed for confirmation, but preliminary data suggest that Capromab Pendetide imaging is helpful in identifying those patients with PSA elevation after radical prostatectomy who are most likely to benefit from salvage RT. As with any imaging technique, Capromab Pendetide has strengths and weaknesses that must be understood to maximize patient benefit by utilizing the scan in clinical settings where it is most likely to be useful and least likely to be misleading. Capromab Pendetide is a technically demanding procedure best performed and interpreted at sites with experience and expertise.
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PMID:Capromab Pendetide imaging of prostate cancer. 1080 17

For the typical patient who has newly diagnosed prostate cancer, clinically organ-confined disease of moderate grade, and a PSA less than 10 ng/mL, the current role of imaging studies and molecular biomarkers is limited. Bone scans are not necessary for newly diagnosed men with a PSA less than 10 ng/mL in the absence of bone pain. Similarly, abdominal and pelvic CT scanning rarely provides any useful diagnostic or staging information when the PSA is less the 20 ng/mL and is indicated rarely. Endorectal coil MR imaging adds staging information for patients with a PSA between 10 and 20 ng/mL, a Gleason score of 7 or less, and 50% or more positive biopsies on a sextant sampling. Indium 111 capromab pendetide scanning (ProstaScint) is FDA-approved to evaluate newly diagnosed patients at high risk for metastases. These patients have a Gleason score of 7 or greater and a PSA greater than 20 ng/mL, a Gleason score of 8 to 10 regardless of the PSA value, or clinical stage T3 disease and a Gleason score of 6 or greater. RT-PCR testing of blood or bone marrow for prostate-specific or prostate cancer-specific gene expression, or "molecular staging," is a promising technique whose current use is still investigational. Much useful information may be gained by careful study of prostate needle biopsy material. Aside from current Gleason grading and the number or percentage of cores involved with cancer, no molecular biomarker is approved for clinical use. p27, p53, bcl-2, Ki-67 (MIB-1), and the assessment of neovascularity hold promise, but prospective multicenter studies are needed. In the long-term, multiple gene expression profiling of biopsy material using gene chips may revolutionize the care of patients with prostate cancer and those who elect radical prostatectomy.
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PMID:The role of imaging studies and molecular markers for selecting candidates for radical prostatectomy. 1159 Aug 6

BCR is the most clinically used endpoint for identification of treatment failure. Approximately 15% to 53% of patients undergoing primary curative therapy will develop BCR. BCR often precedes clinically detectable recurrence by years. It does not necessarily translate directly into PCa morbidity and mortality, nor does it always reflect the desired endpoint. Furthermore, it has not been validated as a surrogate endpoint, in that interventions that have been shown to alter the PSA level have not been shown to also alter survival. The utility of PSA level as a surrogate endpoint is brought into question by the knowledge that the overall survival rate of patients at 10 years is similar in patients with and without BCR, and that in a significant proportion of men, the only evidence of disease during their lifetime will be a detectable PSA level. The likelihood of developing BCR post-therapy can be predicted by using multiple clinical and pathologic variables. With the development of nomograms that incorporate several markers, the accuracy of prediction has improved. Until recently, the natural history of BCR post-RRP has not been well understood. Pound et al showed the heterogenous and prolonged natural history of BCR. In this large series of men with BCR following RRP, only 34% of men developed metastatic disease. The median time from development of BCR to identification of metastases was 8 years, and the median time from the development of metastatic disease to death was just under 5 years. These data highlight the extremely variable and potentially indolent nature of BCR. The risk of metastatic disease following BCR has been relatively well defined and relates to PSADT and time to PSA recurrence. It generally is accepted that a PSADT of less than 6 to 10 months and a time to PSA recurrence of less than 1 to 2 years relates to a higher risk of developing metastatic disease. Local recurrence, however, remains poorly understood with respect to its true incidence, clinical significance, and natural history. The significance of BCR post-RT remains unclear due to the lack of data on its natural history. Attempts have been made to identify patients at high risk for metastatic progression by looking at time to PSA recurrence and PSADT. A PSADT of less than 6 to 12 months and a time to PSA recurrence of less than 12 months reflects a higher risk of developing metastatic disease. Accurate risk stratification by means of an algorithm similar to that produced by Pound et al has not been performed on a large cohort, thus making risk assessment for an individual patient difficult. The major dilemma for clinicians in the management of BCR is the identification of the site of disease recurrence, which ultimately guides therapy decisions. Clinicopathologic features allow for risk stratification for recurrence, and multiple investigations have attempted to localize the site of recurrence. Time to biochemical progression, Gleason score, and PSADT are predictive of the probability and time to development of metastatic disease, and allow for stratification of patients into different risk groups (see Table 2). TRUS, CT, PET, and DRE all have limited utility in the identification of local recurrence. ProstaScint and MRI have demonstrated encouraging initial results: however, they require further investigation. Bone scintigraphy is of little value for the initial investigation of BCR. In patients with a PSA level of less than 10 ng/mL, the risk of having a positive bone scan is less than 1% and, until the PSA level rises above 40 ng/mL, the risk of having a positive bone scan is less than 5%. Therefore, bone scintigraphy should be reserved for patients with a PSA level greater than 10 to 20 ng/mL or patients with a rapidly rising PSA level. Using new MRI sequences, there is some evidence that MRI is better for the detection of bony metastatic disease; however, this technique requires further investigation. BCR causes anxiety for the patient and the treating doctor, because the best way to manage patients with PSA-only progression is unknown. Currently, there are no validated treatment recommendations for the management of BCR. The information in this review provides the framework for assignment of patients into clinical trials based on different risk categories. Patients at high risk for metastatic progression could be identified early and thus entered into appropriate clinical trials for systemic therapies. Similarly, patients with a low risk of progression could be placed into observation protocols, potentially sparing them from exhaustive and inappropriate investigations.
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PMID:Markers and meaning of primary treatment failure. 1273 13

Prostate cancer is the most common malignant disease and second in causes of cancer death among men in Western Europe and North America. Despite improved surgical and irradiation techniques tumor relapse after curatively intended therapy is not uncommon. Due to the difficulty in discriminating local and systemic progression, it is often difficult to decide what this means for the patient and what kind of second-line treatment has to be given. Modern imaging techniques (MRI with endorectal coil, Choline-PET-CT, ProstaScint-Scan) are used for diagnosis of prostate cancer relapse. Nevertheless, early detection of local tumor relapse and likewise the detection of disseminated tumor cells often fails. To differentiate between local and systemic progression, prognostic factors of the primary tumor (grading, surgical margins, infiltration of the seminal vesicles, lymph node metastases) and PSA kinetics are used. The time from initial treatment to biochemical relapse and PSA doubling time are of highest prognostic relevance. Local progression allows second-line local treatment with potentially curative results (local irradiation after radical prostatectomy, salvage-surgery / cryotherapy / HIFU after irradiation), while in the case of systemic progress a palliative systemic therapy (hormonal treatment, chemotherapy, bisphosphonates) is indicated. Before deciding on the most appropriate therapy, prognostic factors and the patient's individual situation (co-morbidity, life expectancy, individual wishes) should be taken into account.
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PMID:Prostate cancer relapse after therapy with curative intention: a diagnostic and therapeutic dilemma. 1593 26