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)

Screening for prostate cancer represents a clinical dilemma with no clear evidence to suggest decreased mortality from any diagnostic test. We now possess new knowledge regarding optimal combinations of DRE, TRUS, and PSA. While DRE and TRUS may be too subjective and PSA too nonspecific, their combined predictive values identify not only men at high risk but also those for whom continued frequent screening may not be cost effective. A monoclonal PSA decision level of no more than 4.0 ng/ml should be used, since 40 percent of cancers detected from 4.0 to 10.0 ng/ml already have extracapsular extension. Assuming that DRE is performed by experienced examiners, the combination of PSA and DRE should produce cost-effective early detection and minimize missed cancers below 4.0 ng/ml. TRUS should be reserved for those patients with either PSA elevations and/or DRE abnormalities. The use of TRUS gland volume data to further modify PSA decision levels, such as the "predicted" PSA concept, may also improve TRUS biopsy criteria and predictive values. Prostate cancer detection can then be objectively limited to a small percentage of the population and better selected for earlier, more localized disease. The ultimate decrease in mortality from screening remains to be demonstrated in randomized trials or observed only after decades of increased public awareness about prompt early detection combined with effective, definitive therapy.
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PMID:Prostate cancer screening: current trends and future implications. 137 79

The role of free (F) and complexed serum PSA is now under investigation. In the present study, we evaluated the clinical significance of F-PSA and F/Total (T) PSA ratio in a preliminary series of samples from 88 patients with prostate cancer (PC), 113 with benign prostatic disease (BPD), and 98 with non-prostatic disease (NP). We used the F-PSA and third generation T-PSA (DPC, Los Angeles, USA) chemiluminescent enzyme immunometric assays with the IMMULITE automated system. At the 10 ng/ml cutoff for T-PSA levels, we obtained a sensitivity of 83% with a specificity of 100% in NP and 80% in BPD. The addition of the F/T ratio--rather than F-PSA levels--was useful to better discriminate PC and BPD in the cases erroneously classified by T-PSA alone: 44/68 samples (65%) were correctly diagnosed. Moreover, the F/T ratio was particularly effective in the critical T-PSA range between 4.1-9.9 ng/ml; 26/40 cases (65%) were correctly evaluated. In conclusion, the F/T ratio seems to be an interesting auxiliary test to T-PSA, to be reserved for selected cases where additional diagnostic information is necessary.
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PMID:Preliminary clinical evaluation of free/total PSA ratio by the IMMULITE system. 874 Jun 38

This work deals with our experience of a programme of early diagnosis of prostate cancer carried out on patients suffering from dysuria through rectal-digital examination (EDR), hematic dosage of PSA (IRMA COAT-A-COUNT DPC) and transrectal echtomography. We have also quantified the costs and verified which methods, either single or combined with other methods, are most advantageous as regards costs/benefits. From Jan 1991 to Jan 1995 306 of 1185 patients (25.8%) underwent prostate biopsy by means of transperineal echograph with gauge 18 needles as in Hodge's technique. Histologic examination revealed prostate adenocarcinoma in 81 (26.5%) cases, benign prostate hypertrophy in 196 (64%), acute and/or chronic phlogosis in 26 (8.5%) and granulomatosic prostatitis in 3 (1%). The diagnostic sensitivity, preciseness and accuracy were, respectively, 92.5%, 78.3%, 79.3% for the EDR, 80.2%, 93.3% and 90% for PSA with cut-off 10 ng/ml, 91% 78.3%, and 90% for the PSA with cut-off 4 ng/ml, 100%, 30.3% and 48.6% for the echograph, 98.8%, 60% and 77% for EDR+PSA (cut-off 4 ng/ml), 98.8%, 65.8 and 79.9% for EDR+PSA (cut-off 10 ng/ml), 100%, 22% and 64.2% for EDR+echograph, 100%, 20% and 62.9% for echograph+PSA (cut-off 4 ng/ml), 100%, 26.6% and 64.9% for echograph+PSA (cut-off 10 ng/ml). We calculated that a programme of early diagnosis using the three methods, if completely at the patient's expense, would cost 207.000-437.000 lire (average 322.000) per patient for a total of 245,295,000-517,845,000 (average 381,570,000). An eco-guided prostate biopsy with a histologic examination would cost 250.000-500.000 lire (average 375.000) per patient with a total cost for 306 patients of 76,500,000-153,000,000 (average 114,750,000). We also quantified, in the light of the results reported here, the number of biopsied which would have been necessary if we had used only two methods in the screening and we also estimated the costs. The results reveal that the echograph is not to be considered as a first approach method as it gives a high number of false positive results; in fact if we had excluded it from the screening we would not have ignored any diagnosis of prostate neoplasia and we would have avoided about 141 (46.2%) biopsied with a reduction in health expenditure of 62.1%. On the contrary the EDR and the PSA have a better cost/benefit result: setting the cut-off of the PSA at 4 ng/ml or at 10 ng/ml without varying the diagnostic accuracy, the sensitivity and/or specificity of the method increase respectively. To conclude, we consider the EDR and the serum dosage of PSA necessary and adequate methods in the programme of early diagnosis and screening of prostate neoplasy. The prostate echography should be reserved for cases of doubt (hematic PSA between 4-10 ng/ml etc.) and for the exclusion of needle biopsy. These measures also result in an optimization of health expenditure.
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PMID:[Screening for prostatic carcinoma in dysuric patients: diagnostic protocols and cost-benefit analysis]. 927 88

Locally advanced prostate cancer patients comprise those with iatrogenic capsular injury, extracapsular extension resulting in positive surgical margins following radical prostatectomy, and tumors with lymph node metastases, thus representing stage T3,N0,M0 or T1-4,N1-2,M0 disease. Parameters can be combined, as shown below, in a nomogram to predict advanced prostate cancer: if, for example, stage T2c is coupled with a PSA of 16 ng/ml and a high Gleason grade, the patient will have an approximately 70% likelihood of having extracapsular extension; then again, if the Gleason score is known from biopsies and a PSA of 10-20 ng/ml is given, then a stage T2c prostate cancer patient with a Gleason of 7 will have a 39% probability of having positive lymph nodes. The following therapeutic considerations may be used to enhance the chance of eradicating advanced disease through radical prostatectomy: (1) Neoadjuvant hormonal therapy helps downsize the tumor and may eventually reduce the number of positive margins by almost 50%. However, it is a moot point if this will lead to a prolonged survival period. (2) Technical refinements on radical prostatectomy may be achieved through the principle of wide extension excision, a modification of current apical dissection procedures, which involves the use of panoramic magnifying loupes, and an examination of resection margins during surgery using repetitive frozen sections. (3) If positive (not simply 'equivocal' as defined by Epstein) margins are found, radical prostatectomy alone is not curative. Among the various options available is postoperative irradiation with or without adjuvant hormonal therapy. The latter should probably be reserved for patients with extracapsular extension, a high Gleason score or positive lymph nodes. Hormonal therapy may be used continuously or intermittently. The value of adjuvant treatment is currently being tested in phase-III trials. (4) Hormonal therapy may be commenced at the time of biochemical or clinical progression, although it is not clear whether this modality is inferior to adjuvant forms of treatment. Technical expertise in radical prostatectomy accumulated at major institutions can be used to the advantage of patients with locally advanced prostate cancer. In this regard, results of ongoing phase-III trials testing various options including this procedure are eagerly awaited.
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PMID:Enhancing the efficacy of radical prostatectomy in locally advanced prostate cancer. 960 52

Patients whose only sign of recurrence after local therapy for prostate cancer is a rising prostate-specific antigen level (PSA-only recurrence) have become more common. We have developed two models to predict PSA-only recurrence after radical prostatectomy, one using traditional factors (race, sigmoidal transformation of PSA, postoperative Gleason sum, and organ confinement) and a second using traditional clinical and pathologic variables combined with molecular biomarker levels. Treatment options for patients with PSA-only recurrence include observation, radiation therapy for patients who have undergone surgery, salvage surgery or cryotherapy for patients who have received radiotherapy, and traditional or nontraditional hormonal therapy. Radiation for PSA-only recurrence is likely to benefit men who have no adverse pathology, a low PSA level at recurrence, and PSA recurrence after the first year. Salvage radical prostatectomy and cryotherapy pose a relatively high risk of incontinence and other morbidity and should be reserved for carefully selected patients with a high likelihood of organ-confined disease. Hormonal therapy is probably the single most beneficial treatment for PSA-only recurrence. Nontraditional low-dose oral hormonal therapy and intermittent hormonal therapy are gaining in popularity, although their long-term efficacy is unknown. More clinical trials are needed to fine-tune prognostic models and to determine the best treatments, alone or in combination, for PSA-only recurrence.
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PMID:Rising PSA after local therapy failure: immediate vs deferred treatment. 1044 45

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

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

There is compelling evidence that early hormonal therapy prolongs life in many stages of prostate cancer. Large-scale trials to answer this question have not yet been conducted in surgically treated patients or in patients with PSA-only relapse. Thus, many physicians and patients use early hormone therapy in PSA-only relapse. Many unique new agents are being tested in this population and may offer benefits. Patients and physicians are encouraged to participate in such trials, with hormone therapy reserved for subsequent use. Following failure of primary hormone therapy, a standard algorithm of care exists: antiandrogen withdrawal, use of alternative or first-line anti-androgens. ketoconazole. and chemotherapy. At each interval, clinical trials should be offered since none of these maneuvers are proven to prolong life.
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PMID:Selecting a secondary treatment. 1273 14

Bone scans of 64 patients with newly diagnosed prostate cancer were retrospectively analysed. Metastases were present in 29 patients (45%). In 75% of these cases, the pattern was manifeastly metastatic. The third threshold has high negative and positive predictive values. The topography of metastatic lesions is in favour of a systemic spread. There were no metastatic cases with a PSA level under 10 ng/ml. Multiple IAU and intense IAU are the most specific patterns of metastatic lesions. Also, focal lesions on sacroiliacs are also in favour of metastatic origin. The distribution of metastases is globally similar to that of the bone marrow in adult and systemic spread is the most probable. Staging bone scan must be reserved to patients with PSA level greater than 10 ng/ml, poorly degree of differentiation and advanced clinical stage.
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PMID:Bone scan in initial staging of prostate cancer. 1453 46

5-Methyltetrahydrofolate, (R)-flurbiprofen; Ad5CMV-p53, adalimumab, alefacept, alemtuzumab, Alequel, alicaforsen sodium, almotriptan, anakinra, aprepitant, aripiprazole, armodafinil; Bevacizumab, bortezomib, bosentan; Canfosfamide hydrochloride, ciclesonide, clofarabine, Cypher; Darbepoetin alfa, diclofenac potassium, drotrecogin alfa (activated), duloxetine hydrochloride; Eel calcitonin, eletriptan, eplerenone, everolimus, ezetimibe; Frovatriptan; Gefitinib, gamma-hydroxybutyrate sodium; HKI-272, HYB-165; Ibutamoren mesylate, imatinib mesylate, interleukin-21, ixabepilone; KRN-951; L-Arginine hydrochloride, levodopa/carbidopa/entacapone; Micafungin sodium, motexafin gadolinium, mycophenolic acid sodium salt; Nesiritide; Peginterferon alfa-2a, pitavastatin calcium, pralatrexate, pregabalin, pVAX/L523S-Ad.L523S; Rasagiline mesylate, recombinant human nerve growth factor, regadenoson, rF-PSA, rimonabant, rizatriptan, rofecoxib, rosuvastatin calcium, rV-B7.1, rV-PSA; Sipuleucel-T, sirolimus-eluting stent, solifenacin succinate, sorafenib, sunitinib malate; Talactoferrin alfa, Taxus, tegaserod maleate, teriparatide, tipifarnib; Valdecoxib, vandetanib, vatalanib succinate; WT1-peptide vaccine; Xaliproden hydrochloride. (c) 2006 Prous Science. All rights reserved.
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PMID:Gateways to clinical trials. 1720 Jul 30


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