UMLS:C0027627 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

At the present time, there are three radiolabeled antibodies that have been approved by the US Food and Drug Administration (FDA) for imaging of cancer, a fourth commercially sponsored product recommended for approval (as of 10/29/96, cap romab pendetide (ProstaScint; Cytogen Corp., Princeton, NJ) was upgraded from recommended for approval to approved), and several additional agents in FDA-monitored trials. The majority of antibodies studied to date have been whole or fragmented murine monoclonals whereas the first of the human and humanized immunoglobulins are now entering clinical trials. While no antibody has behaved as a perfect imaging agent, they have consistently been shown to contribute to diagnosis, complementing and often exceeding the diagnostic ability of conventional modalities. Many promising new trends in antibody imaging, relating to the radiolabeled immunoglobulin, its route and manner of administration, and mode of detection, are under development. Because of the requisite several-year delay inherent in the (FDA) testing process, there is a lag before the most-promising of these innovations will achieve (FDA) approval and be incorporated into routine imaging studies. In spite of this effective performance, as "new kid on the block," radioimmunoscintigraphy may have often been expected to perform in an unrealistic manner, considering the great variation in biological behavior of primary and metastatic cancer and the consequent limitation of all diagnostic tests. Nonetheless, because radioimmunoscintigraphy identifies antigens on a cellular level, differing fundamentally from anatomic imaging modalities such as computed tomography and ultrasound which identify gross morphological changes, it has potential to impact significantly on patient care. With adequate resources focused on radioimmunoscintigraphy, this technology will continue to emerge as an important and unique diagnostic tool in the care of cancer patients, with demonstrable clinical efficacy and cost effectiveness.
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PMID:Trials and tribulations: oncological antibody imaging comes to the fore. 912 20

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

Diagnostic methods are limited for detecting microscopic soft tissue metastases in patients with prostate cancer. Previous studies using (111)Indium Capromab Pendetide (ProstaScint scan) analyzed patients with extensive localized tumor (prostate specific antigen (PSA) >20 ng/ml) not optimal for surgical therapy. We evaluated the role of the ProstaScint trade mark scan in a preoperative population to provide histological documentation and to assess its utility in a surgical population. A total of 22 preoperative patients, underwent a ProstaScint scan. The mean preoperative PSA was 16.0 ng/ml (range 3.9-33 ng/ml). The mean Gleason score at biopsy was 6.9 (range 6-9). Each patient underwent a radical retropubic prostatectomy and bilateral pelvic lymph node dissection, which included resection of both obturator and common iliac lymph nodes. Histologic analysis of the resected lymph nodes provided the standard of comparison with the ProstaScint scan. The results of the scan and pathology for all 22 patients were compared with the bilateral obturator and iliac nodes, creating 88 data points. Nine areas (10%) were positive on the scan. One of these (11%) was a true positive while the other eight (89%) were false positives. Seventy-nine areas (90%) were negative on scan results. Of these, five areas (6%) were false negatives and 74 areas (94%) were true negatives. The scan yielded a sensitivity of 17%, specificity of 90%, negative predictive value (NPV) of 94% and a positive predictive value (PPV) of 11%. The high false positive rate and low PPV of ProstaScint scans overestimates metastatic lymph nodes disease, and is not useful when used preoperatively.
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PMID:Evaluation of preoperative ProstaScint scans in the prediction of nodal disease. 1249 3

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

ProstaScint (CYT-356 or capromab pendetide, Cytogen) is an 111In-labeled monoclonal mouse antibody specific for prostate-specific membrane antigen, a prostate transmembrane glycoprotein that is upregulated in prostate adenocarcinoma. ProstaScint scans are US Food and Drug Administration approved for pretreatment evaluation of metastatic disease in high-risk patients. They are also approved for post-prostatectomy assessment of recurrent disease in patients with a rising prostate-specific antigen level. This review explores the literature on ProstaScint and its use in guiding the treatment of prostate cancer. A novel technique for identifying areas of cancer within the prostate using ProstaScint images fused with pelvic computed tomography scans is also described. The identification of areas of high antibody signal provides targets for radiotherapeutic dose escalation, with the overall goals of improving treatment outcome while preserving adjacent tissue structures and decreasing treatment morbidity.
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PMID:Role of ProstaScint for brachytherapy in localized prostate adenocarcinoma. 1522 91

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

During the last decade, there has been a significant advancement in imaging of urologic diseases. Transrectal ultrasound (TRUS), computerized tomography (CT), magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET) are still experiencing new developments in urology. Despite these many technological advances, the initial diagnostic procedure for a patient with suspected prostate cancer (PC) is multiple site blind prostate biopsies. There is a need for a noninvasive metabolic imaging modality to direct the site of biopsy to decrease the sampling error. MRS seems promising but as it is a costly and more time-consuming test, further studies are needed to evaluate its clinical utility. Currently, PET does not play any role to direct biopsy. Acetate and choline appear to be better tracers than FDG for the detection of a prostate lesion, however, further well-organized studies are needed before any of these agents can be used clinically. Incidental detection of intense focal uptake in the prostate during whole body PET scanning should be evaluated with prostate-specific antigen (PSA) and TRUS-guided biopsy. Although FDG is inferior to other tracers for primary staging, it may be useful in selected patients with suspected high-grade cancer. The role of ProstaScint scan is still controversial for detection of recurrent PC. This study may be helpful for evaluating nodal metastases when PSA is elevated and bone scan is negative. Bone scan remains the study of choice when bone metastases are suspected (PSA>15-20 ng/mL+/-bone pain). Acetate and choline provide better accuracy than FDG in the detection of local soft tissue disease, nodal involvement, and distant metastases. High FDG uptake may be indicative of more aggressive and possibly androgen-independent disease. PET/CT with any of the above PET tracers will most likely be preferred to the PET scan alone due to better localization of a hot lesion in PET/CT. Nuclear medicine studies also have been used to evaluate acute scrotum and testicular neoplasms. Scrotal scintigraphy has lost its popularity to Doppler ultrasound in the evaluation of the acute scrotum. In testicular tumors, FDG-PET appears to be superior to conventional imaging modalities in initial staging, detection of residual/recurrence, and monitoring treatment response. Tumor markers after treatment occasionally are elevated and cannot locate the site of recurrence, FDG-PET can play a very important role in this regard. Nuclear medicine studies also have been used to evaluate diseases of the urinary bladder. Radionuclide cystography is more sensitive and has less than 1/20 the radiation exposure of the conventional contrast enhanced micturating cystourethrogram (MCU). However, the utility of FDG-PET in the evaluation of bladder cancer seems to be limited to the evaluation of distant metastases. 11C-Methionine and choline may be a better option for local and nodal disease due to their negligible excretion in the urine.
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PMID:Nuclear medicine studies of the prostate, testes, and bladder. 1635 96

Cancer of the prostate is the most common cancer in males accounting for 33% of newly diagnosed cases. It is the second leading cause of cancer death in American males. The prevalence of prostate cancer increases most rapidly with age and the incidence (unlike other cancers) continues to rise with advancing age. Death due to this cancer is almost invariably the result of failure to control metastatic disease. In addition, several studies have demonstrated that over 30% of patients will experience biochemical recurrence after surgery with long-term (more than 10 years) follow-up. Information regarding the location of the cancer is critical to the success of initial therapy when deciding between local versus systemic treatment options in the newly diagnosed patient. For patients who have already undergone definitive treatment, the localization of recurrent tumor, evidenced by an elevation of prostate-specific antigen, is difficult unless the tumor burden is large enough to be detected on conventional radiographic studies or digital rectal examination and prostatic fossa biopsy. ProstaScint is a diagnostic tool used to detect metastatic prostate cancer in lymph nodes or other sites. This article provides an overview on the uses of ProstaScint in the assessment of patients with recurrent or metastatic prostate cancer.
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PMID:ProstaScint and its role in the diagnosis of prostate cancer. 1762 43

Accurate lymph node staging in genitourinary (GU) malignancies is important for planning an appropriate treatment and establishing an accurate prognosis. This article discusses the novel imaging techniques for detection of metastases in various GU malignancies, including prostate, bladder, penile, and testicular cancers. Discussion includes nuclear medicine techniques of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT), (11)C-choline and (18)F-choline PET/CT, and ProstaScint scanning, as well as sentinel lymph node mapping. Magnetic resonance (MR) techniques include lymphotropic nanoparticle-enhanced MR imaging and diffusion-weighted MR imaging.
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PMID:Novel imaging modalities for lymph node imaging in urologic oncology. 2204 78

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