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PubMed2005

Quality of life survey in patients with advanced prostate cancer.

Prostate cancer is a major health concern for Western patients who are facing important decisions, alongside with the physicians, concerning their treatment. Additionally, the physician has to take into account the potential side effects of the disease and the treatment itself. Treatment for advanced prostate cancer produces problematic physical and psychosocial side effects. The patient should be asked by the physician for information concerning daily life activities, overall satisfaction voiding ability, and sexual activity in a standardized questionnaire assessing the quality of life (QoL) of the patient. Many such questionnaires and studies have been evaluated or are still in progress. Modern QoL questionnaires are considered to be more than a necessity nowadays for the improvement of the treatment administered from the physician and the performance and functional status of the patient.

Humans↗

PubMedDate not supplied

[Selected aspects of diagnosis and treatment of prostatic cancer].

Prostatic cancer is one of the most frequent malignant tumours in men. The chronic course of the disease and the opportunity of selecting of one of many available treatment methods make possible adjustment of the management to the individual problems of the patient. This leads, however, to various difficulties connected with the selection of optimal management in various clinical situations. The purpose of the paper was presentation of selected problems in the diagnosis and treatment of prostatic cancer in the light of own clinical experience, in the first place.

Humans↗

PubMed2002

Generalized lymphadenopathy: a rare presentation of disseminated prostate cancer.

Prostate cancer most often metastases to regional lymph nodes and bones by hematogenous or lymphatic spread. Metastases to the supradiaphragmatic nodes are rare. A 56-yr-old male smoker with generalized lymphadenopathy was referred to our center with the complaints of weight loss of 15 kg and severe back and leg pain. On computed tomography of the thorax and abdomen, massive mediastinal, intra-abdominal, retroperitoneal, and inguinal lymphadenopathies with hydroureteronephrosis of the left kidney were noted. Excisional biopsy of left cervical lymph node revealed metastasis of prostatic adenocarcinoma and transrectal biopsy of the prostate disclosed poorly differentiated adenocarcinoma. Bone marrow aspiration biopsy, done for the differential diagnosis of anemia, also showed infiltration with prostate-specific antigen positive neoplastic cells. Supradiaphragmatic spread of prostate cancer has been postulated to be by a hematogenous route via the vertebral venous system, or Batson's plexus, accessible via direct extension from the primary cancer site.

Adenocarcinoma↗

PubMed1993

Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer.

Prostate specific antigen (PSA) in serum has recently been shown to occur in complex with alpha 1-antichymotrypsin and as an approximately 30 kDa. noncomplexed molecular form. We characterized PSA by 3 different assays in samples from 144 patients with benign prostatic hyperplasia (BPH) and 121 with carcinoma of the prostate. One of these noncompetitive assays measured total PSA by detecting PSA complexed to serine proteinase inhibitors and the noncomplexed molecular form, a second measured only PSA in complex with alpha 1-antichymotrypsin, whereas a third detected the noncomplexed form. PSA in complex with alpha 1-antichymotrypsin was the predominant form in all patient sera. Noncomplexed PSA constituted a minor fraction that was significantly smaller in patients with untreated prostate cancer than in those with BPH (p < 0.0001). The proportion of noncomplexed PSA does not correlate to the serum concentration of PSA or that of alpha 1-antichymotrypsin. In men with a serum PSA concentration of less than 10 micrograms./l. the combination of assays measuring total PSA immunoreactivity, the noncomplexed molecular form and PSA in complex with alpha 1-antichymotrypsin may facilitate discrimination between prostate cancer and BPH.

Biomarkers, Tumor↗

PubMed1998

Gene therapy for prostate cancer.

Prostate cancer remains one of the most significant challenges in clinical oncology, yet present therapies provide incomplete treatment in many cases. Innovative and practical gene therapy-based approaches will prove invaluable in filling the gaps that now exist in the treatment of localized and distant disease. Although multiple potential strategies have been developed, early clinical trials in prostate cancer gene therapy are now in the phase I/II stage of development. Novel preclinical and early clinical data should be considered optimistically, yet cautiously, as this field emerges from its infancy.

Clinical Trials as Topic↗

PubMed2004

Changes in extracellular matrix (ECM) and ECM-associated proteins in the metastatic progression of prostate cancer.

Prostate cancer (PCa) is no exception to the multi-step process of metastasis. As PCa progresses, changes occur within the microenvironments of both the malignant cells and their targeted site of metastasis, enabling the necessary responses that result in successful translocation. The majority of patients with progressing prostate cancers develop skeletal metastases. Despite advancing efforts in early detection and management, there remains no effective, long-term cure for metastatic PCa. Therefore, the elucidation of the mechanism of PCa metastasis and preferential establishment of lesions in bone is an intensive area of investigation that promises to generate new targets for therapeutic intervention. This review will survey what is currently know concerning PCa interaction with the extracellular matrix (ECM) and the roles of factors within the tumor and ECM microenvironments that contribute to metastasis. These will be discussed within the context of changes in expression and functional heterodimerization patterns of integrins, changes in ECM expression and reorganization by proteases facilitating invasion. In this context we also provide a brief summary of how growth factors (GFs), cytokines and regulatory signaling pathways favor PCa metastasis to bone.

Animals↗

PubMed2006

Cholecalciferol (vitamin D3) and the retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) are synergistic for chemoprevention of prostate cancer.

Prostate cancer, the most commonly diagnosed cancer among American men, develops slowly over many years. The long latent period of 20 to 30 years, involved in the multistep process of carcinogenesis, provides an important opportunity to block or reverse progression to a malignant state. Vitamin A (retinoids) and vitamin D not only have the ability to block steps in the process of carcinogenesis but they can also modulate or reverse some malignant characteristics of cancer cells. However, at high levels, vitamins A and D have undesirable side effects, thus, limiting effective dose levels and efficacy. Therefore, combination treatment at low doses, to increase efficacy and avoid toxicity, is of special interest. This study examines the effects of the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) in combination with cholecalciferol (vitamin D3) on growth, and on the expression of vimentin, matrix metalloproteinase-2 (MMP-2), and retinoid and vitamin D receptor expression, using the non-tumorigenic, human prostate epithelial cell line RWPE-1. Treatment with 4-HPR and cholecalciferol resulted in synergistic growth inhibition when compared to that caused by each agent alone. A decrease in vimentin expression and MMP-2 activity, and up-regulation of vitamin D receptor (VDR) and some of the retinoid-X (RXRs) and retinoic acid receptor (RARs) subtypes, was observed. These results suggest that combined treatment with 4-HPR and cholecalciferol, at doses lower than what might be effective with single agents, increases their efficacy and suggest that this may serve as an effective strategy for chemoprevention and treatment of prostate cancer.

Anticarcinogenic Agents↗

PubMedDate not supplied

Vaccines for immunotherapy of breast cancer and prostate cancer: new developments and comparative aspects.

This review summarizes the most recent findings and the newest approaches in the design of vaccines for breast cancer and prostate cancer. The antigens associated with breast cancer and prostate cancer and their use in vaccine development are discussed. We consider the comparative aspects in the new vaccines and focus on their clinical potential. The future directions in designing cancer vaccines are discussed.

Adjuvants, Immunologic↗

PubMed1997

Molecular and cellular biology of prostate cancer.

Prostate cancer is an enigmatic disease. Although prostatic-intraepithelial neoplasia appears as early as the third decade and as many as 80% of 80 year old men have epithelial cells in their prostate that fit the morphological criteria for cancer, only about 10% of men will ever have the clinical disease and less than 3% will die from it. There have been no significant proven interventions which have altered the natural history of the disease since hormone down regulation was introduced in the 1940s and new research has been poorly supported. There is however an urgent need to develop new criteria to distinguish those patients with localised disease who will benefit from intervention from those that do not require it or who will have occult extra prostatic metastases. Similarly, there is an urgent need to develop new treatments for those in whom the disease is extra-prostatic and therefore incurable by conventional treatments. This review covers the latest developments in epidemiology, cellular and molecular biology including new areas such as ion channels in the field of prostate cancer.

Adult↗

PubMed2006

The changing pattern of management for hormone-refractory, metastatic prostate cancer.

Prostate cancer responds initially to hormonal manipulation by androgen withdrawal and peripheral androgen blockade. The inevitable progression to a hormone-refractory state is accompanied by an exacerbation of local symptoms and metastatic spread, principally to the bones, which has a considerable impact on quality of life and survival. Treatment of hormone-refractory prostate cancer is palliative, and surgery and radiotherapy are used for the relief of lower urinary tract symptoms and localized painful bony metastases. Systemic treatments are not widely accepted in this setting, but clinical trials have demonstrated the potential for bone targeting agents such as strontium-89 and the bisphosphonates to palliate painful bone metastases and to delay progression in certain settings. Chemotherapy with mitozantrone in combination with steroids has previously been shown to have palliative benefits and to delay progression. The additional costs incurred by the use of chemotherapy or bone-targeting therapies may be offset by gains in overall care with fewer in-patient admissions compared with steroid monotherapy. Recent clinical trials have demonstrated that docetaxel significantly improves patient quality of life, and importantly, increases survival. Future studies investigating the timing of chemotherapy, combinations with existing treatments or other novel therapies are underway.

Androgen Antagonists↗

PubMed2006

New techniques and management options for localized prostate cancer.

Prostate cancer is diagnosed in younger men who want treatment that does not compromise their quality of life, take time away from work, or cause worrisome side effects. Laparoscopic radical prostatectomy, robot-assisted laparoscopic radical prostatectomy, and third-generation cryotherapy are modifications of previously used techniques in the treatment of prostate cancer and are presented in this article. Although some or all of the outcomes might be expected to change in the future, the urologic surgeon is left to select an approach, presumably on the basis of the experience, level of training, and care pathways at his or her institution.

Journal Article↗

PubMed1999

Paclitaxel in the treatment of hormone-refractory prostate cancer.

Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in men in the United States. In 1997 it was estimated that more than 41,000 men died of this disease. Treatment of metastatic disease remains palliative, with androgen ablation used as first-line therapy. After failure of androgen ablation, chemotherapy can now be used to induce a remission in many men. Treatment regimens that include paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) have been particularly successful in treating hormone-refractory prostate cancer in the phase II setting. We have conducted a trial of estramustine 280 mg orally three times per day for 14 days combined with etoposide 50 mg/m2/d (in general, one 50-mg tablet twice a day) for 14 days, with paclitaxel 135 mg/m2 over 1 hour on day 2. This regimen is repeated every 21 days for a maximum of six cycles. Patients responding to therapy are then given a break and re-treated at physician discretion. On preliminary analysis, 24 of 38 patients demonstrated a decline in pretreatment prostate-specific antigen of more than 50% (63%). The regimen was well-tolerated and only seven patients demonstrated grade 3 or 4 neutropenia. Further analysis is ongoing.

Antineoplastic Agents, Phytogenic↗

PubMed1999

Malignant ascites as only manifestation of metastatic prostate cancer.

Prostate cancer is the most common malignancy in men in the US. Both at diagnosis and throughout the disease progression it can metastasize to multiple organs (bone and lymph being the most common). Effusions (either pleural or abdominal) are relatively uncommon, but usually occur as a result of soft tissue lesions. Herein we report on a patient with androgen independent prostate cancer and an elevated PSA with disease confined to ascites of the abdomen.

Journal Article↗

PubMed2004

Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer.

Prostate specific membrane antigen (PSMA), is a unique membrane bound glycoprotein, which is overexpressed manifold on prostate cancer as well as neovasculature of most of the solid tumors, but not in the vasculature of the normal tissues. This unique expression of PSMA makes it an important marker as well as a large extracellular target of imaging agents. PSMA can serve as target for delivery of therapeutic agents such as cytotoxins or radionuclides. PSMA has two unique enzymatic functions, folate hydrolase and NAALADase and found to be recycled like other membrane bound receptors through clathrin coated pits. The internalization property of PSMA leads one to consider the potential existence of a natural ligand for PSMA. In this review we have discussed the regulation of PSMA expression within the cells, and significance of its expression in prostate cancer and metastasis.

Alternative Splicing↗

PubMed1993

Incorporating tumor biology into therapy for prostate cancer.

Prostate cancer remains the most common and the second leading cause of cancer death in men. Despite the frequency of the disease, controversies in management continue for all stages. For patients with localized tumors, deciding whether any treatment is indicated and, if so, selecting the appropriate modalities for an individual patient are at issue. For more advanced local tumors, although definitive data showing a survival benefit are lacking, several groups have been using androgen deprivation prior to surgery or radiation therapy in the hopes of improving local control rates. For patients with established metastases, the timing of androgen ablation is still debated, as is the optimal way to integrate treatments aimed at the androgen-independent cell population--the ultimate cause of death from prostatic cancer. In addition, several groups are focusing on methods to try to predict the natural history of the disease in an individual patient, while reserving the final recommendation on treatment based on the biologic behavior in that individual.

Humans↗

PubMed1997

Observations on the early detection of prostate cancer from the American Cancer Society National Prostate Cancer Detection Project.

BACKGROUND: The American Cancer Society National Prostate Cancer Detection Project (ACS-NPCDP) was established in 1987. The experience of the ACS-NPCDP demonstrates the yield and impact of periodic examinations for the early detection of prostate cancer. METHODS: A cohort of 2999 well men ages 55-70 years was tested annually at 10 clinical centers by prostate specific antigen (PSA), transrectal ultrasound (TRUS), and digital rectal examination (DRE). Biopsies were performed on men with suspicious findings. Pathologic findings were reviewed. The initial study outcomes were the detection yield of multimodality testing and the comparative sensitivity and specificity of the different tests employed. Longer term outcomes included patient quality of life and survival. RESULTS: The cancer detection rate declined significantly across the years of intervention. DRE had lower sensitivity than TRUS or PSA, particularly in later years of follow-up. The specificity of TRUS was lower than that of DRE. Fewer than 9% of the cancers detected in this study were clinically advanced at the time of diagnosis. Ninety-four percent of patients in whom cancer was detected are alive after an average follow-up of 54 months. In one case, death occurred after surgery. Two deaths were attributed to prostate cancer, and eleven other deaths were unrelated to prostate cancer or its treatment. CONCLUSIONS: Results of the ACS-NPCDP indicate that a combined-modality approach to prostate cancer detection yields high levels of early detection with infrequent adverse outcomes. Continued follow-up is required to evaluate long term morbidity and mortality.

Aged↗

PubMedDate not supplied

Rhenium-186-HEDP palliative treatment in disseminated bone metastases due to prostate cancer.

Prostate carcinoma is the most commonly associated with osseous metastases malignancy in males. The lesions, being usually of a mixed sclerotic/lytic variety and less often of the pure sclerotic type, need to be treated by a bone seeking radioactive element with an as low as possible radiobiological burden on the surrounding (peritumoral) tissues. Rhenium-186-HEDP was used to treat these osseous metastatic lesions due to its bone seeking kinetics attractive radiochemical properties. Of a total of 16 prostate cancer patients. 3 experiment loss of pain, 8 experienced obvious and 2 some improvement. No change was observed in 3 patients. Ten patients manifested a flare syndrome increasing pain approximately 2 to 6 days, after Re-186-HEDP i.v. application. Six patients showed a definite and 9 a slight decrease in platelet levels and absolute number of polymorphonuclear white blood cells, up to fourth week following treatment. One patient underwent a whole blood transfusion and in 2 peripheral neuropathy was observed lasting about 9 to 12 days. Re-186-HEDP appears to be a promising new metal ion complex for the palliation of painful bone metastases in prostate cancer. Compared to Sr-89 therapy, it shows a longer analgetic efficacy and has the advantage of emitting gamma rays, a fact which facilitates dosimetric calculations.

Aged↗

PubMed1994

[Screening test for prostate cancer].

Prostate specific antigen (PSA), digital rectal examination (DRE) and transrectal ultrasonography (TRUS) are widely used for the detection of prostate cancer. The sensitivity and positive predictive value of PSA are most excellent among these modalities. However, the sensitivity of PSA was 73% when the cut off value was 6ng/ml. In the general clinical practice the use of three screening modalities must be recommended to improve the detection rate. However, the mass screening which has to diagnose many subjects during a short period should be mainly conducted by PSA, because blood sampling for PSA was performed with other kind of mass screening without any specialists (urologists). We are now investigating the effects of age specific PSA and PSA velocity to improve the sensitivity of PSA. It is estimated that the prostate cancer death and the prevalence will rapidly increase in Japan. Therefore, we had better start the preventative research including mass screening. To prove the significance of mass screening program, pilot studies in well executed randomized prospective protocols are urgently needed.

Adult↗