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GnRH antagonists--a new therapy option for advanced prostate cancer

At present medical castration employing luteinising hormone releasing hormone (LHRH) agonists is the standard of care for patients with advanced prostate cancer. LHRH agonists suppress the synthesis of testosterone to a castration level. In contrast ... expand abstractto surgical castration, medical castration is reversible. However LHRH agonists induce an initial increase of the testosterone level. This so-called testosterone surge leads to tumour growth and increases the disease-specific complaints, known as flare phenomena. It may be possible that the overall survival of these patients is deteriorated. In contrast, gonadotrophin releasing hormone (GnRH) antagonists do not induce a testosterone surge and the level of testosterone decreases as rapidly as that known from a surgical castration. collapse abstract

Can dutasteride delay or prevent the progression of prostate cancer in patients with biochemical failure after radical therapy? Rationale and design of the Avodart after Radical Therapy for Prostate Cancer Study.

OBJECTIVE: To describe the Avodart after Radical Therapy for prostate cancer Study (ARTS), investigating the use of dutasteride (a dual 5alpha-reductase inhibitor that suppresses intraprostatic dihydrotestosterone, reduces tumour volume and improves ... expand abstractother markers of tumour regression in prostate cancer) to prevent or delay disease progression in patients with biochemical recurrence after therapy with curative intent. PATIENTS AND METHODS: An increasing serum prostate-specific antigen (PSA) level after radical prostatectomy (RP) or radiotherapy (RT) is indicative of recurrent prostate cancer and typically pre-dates clinically detectable metastatic disease by several years. ARTS is an ongoing European multicentre trial in which patients are stratified by previous therapy (RP with or without salvage RT vs primary RT) and randomized to double-blind treatment with dutasteride 0.5 mg or placebo once daily for 2 years. Eligible patients will have a PSA doubling time (DT) of 3-24 months. Biochemical recurrence is defined as three increases in PSA level from the nadir, with each increase > or =4 weeks apart and each PSA level > or =0.2 ng/mL, and a final PSA level of > or =0.4 ng/mL (after RP) or > or =2 ng/mL (after primary RT). Study endpoints include time to PSA doubling, time to disease progression, treatment response (PSA decrease or an increase of < or =15% from baseline), changes in PSA and PSADT, and changes in anxiety (Memorial Anxiety Scale for Prostate Cancer). CONCLUSIONS ARTS: will be the first study to evaluate the effects of dutasteride on PSADT, disease progression and treatment response in patients with biochemical failure after RP or RT, and should help to elucidate the potential role of dual 5alpha-reductase inhibition in prostate cancer. collapse abstract

Adjuvant hormone therapy for prostate cancer after local treatment in the context of evidence based medicine

At present, prostate cancer is the most frequent malignant disease in German men. The aims of adjuvant hormone treatment are to increase progression free survival and improve cure rate. Risk factors for progression are a Gleason score > or =8, large ... expand abstracttumor volumes, a high preoperative PSA (>15-29 ng/ml), penetration of the capsule, positive margins and lymph node metastasis. The type of hormone therapy (LHRH-nnalogues, non-steroidal anti-androgens, surgical castration) should be discussed with the patient. Bicalutamide seems to be an alternative for younger patients due to the lack of side effects of testosterone suppression. collapse abstract

Intermittent androgen castration: a biological reality during intermittent treatment in metastatic prostate cancer?

INTRODUCTION: To assess the effects of intermittent maximal androgen blockade (IMAB) on testosterone (T) levels during on- and off-treatment periods. MATERIALS AND METHODS: A total of 51 patients with metastatic prostate cancer underwent a 6-months p... expand abstracteriod of continuous maximal androgen blockade (MAB) consisting of leuprorelin (3.75 mg at monthly intervals) plus flutamide (250 mg t.i.d.) followed by IMAB. During each cycle, the cut-off prostate-specific antigen (PSA) levels to stop and resume treatment were 4 and 10 ng/ml, respectively. IMAB continued until progression under treatment occurred. Monthly PSA and T measurements were performed in central laboratories. RESULTS: From the 51 patients included (mean age 67.6 years), 27, 16, 12, 8 and 5 underwent a second, third, fourth, fifth and sixth cycle, respectively (mean follow up: 17 months). Before treatment, 4 patients had a T lower than normal laboratory value but these recovered all to a normal T value at the end of the first cycle. During the 6 cycles, only 8 patients did not recover a normal T at least once during the off-treatment periods (OTP). The mean T values at the end of each OTP did not change during these 6 cycles (Anova test, p=0.621) with a mean stable recovery delay of 32-43 days (Anova test, p=0.722). CONCLUSION: IMAB protocol with an initial 6-month treatment period can result in an intermittent castration with the recovery of normal T levels in most patients during six consecutive cycles of treatment. collapse abstract

The role of PSA in diagnosis of prostate cancer and its recurrence

Prostate specific antigen is the most important tumor marker of prostate cancer. PSA, in conjunction with digital rectal examination, is the first-line clinical tool for detection of prostate cancer. To improve its specificity PSA-density, PSA-ratio ... expand abstract(fPSA/tPSA), PSA-velocity, and complexed PSA have been introduced into clinical praxis. The treatment of lower stage disease in younger men has resulted in a longer period of post-treatment cancer surveillance. Biochemical recurrence is an early indicator for clinical disease recurrence. PSA doubling time allows to distinguish between local and systemic progression and is also a valid predictor for distant metastasis and death of disease. collapse abstract

The aftercare principle for metastasizing prostate cancer. Few diagnostics, much support

For advanced prostate cancer - not including intermittent strategies - the patient is in continual treatment. The effect of the therapy must be controlled so that its failure can be determined as soon as possible and a new regimen started. As in most... expand abstract cases the progression of the disease can not be stopped, the aim of the therapy is to provide the patient with the best possible quality of life. In order to carry out therapy, if possible in the patient's usual environment, supportive therapies should be used, such as compensation for anaemia or pain therapy as required. Skeletal complications can be prophylactically treated by the use of biphosphonates. collapse abstract

Urological illnesses in the elderly

Urological illnesses in the elderly are a growing clinical problem because as life expectancy increases so does the prevalence of such illnesses. However, sufficient data for judging the various possible therapies are lacking for patients over the ag... expand abstracte of 70. Age itself does not have enough predictive value for the determination of the best treatment. It seems more important to estimate the functional and socio-economic status, comorbidity, and the cognitive and emotional abilities of elderly patients as well as their nutritional intake. collapse abstract

Chemotherapy of the hormone-refractory prostate cancer

The scepticism dominating the chemotherapy of the hormone-refractory prostate cancer (HRPC) has been replaced by a wave of enthusiasm. Phase II studies with taxane-containing combination therapies could achieve high response rate in some cases, and H... expand abstractRPC can not longer be deemed resistant to chemotherapy. It remains to be seen whether the combinations offer a survival advantage. This will be tested in phase III studies. Palliative chemotherapy should be considered in patients with HRPC if the initial hormone therapy was effective for a short time only and after several hormone therapies have been completed. Since chemotherapy is not yet an established standard therapy of HRPC, patients should be, if possible, included in clinical studies. collapse abstract

Significance of docetaxel in the chemotherapy of hormone-refractory prostate cancer

Docetaxel (Taxotere) is a taxoid derived from the European yew tree, taxus baccata. In 4 phase-II studies docetaxel has important single agent activity with an overall prostate-specific antigen response rate of 42% in hormone refractory prostate canc... expand abstracter. Other phase-II studies suggest that the addition of estramustine to docetaxel results in a higher response rate but also in an increased toxicity. At present Docetaxel with and without estramustine is being evaluated in phase-III studies that will provide definitive information about its role in hormone refractory prostate cancer. collapse abstract

Urological complications of renal transplantation: a series of 900 cases.

Intermittent androgen ablation as a treatment for prostate cancer.

Urologic tumors and organ transplantation. Recommendations of the Kidney Transplantation Working Group of the Ongoing Graduate and Continuing Education Committee of the German Society of Urology

Interleukin-6: a potential inflammatory marker after total joint replacement.

In a prospective study C-reactive protein (CRP) and interleukin-6 (IL-6) measurements were taken serially in 30 patients before and after 20 total hip arthroplasties (THR) and 10 total knee arthroplasties (TKR). There were no peri- and postoperative ... expand abstractcomplications. Postoperatively the IL-6 serum concentration increased rapidly and peaked 6 h postoperatively at maximum levels (399+/-140 pg/ml). There was a mean half-life of 15 h and thereafter a rapid return to normal concentrations. In comparison, the postoperative CRP concentration rose more slowly and reached maximum levels (138+/-54 mg/l) on the second postoperative day. There was thereafter a slow descent with a mean half-life of 62 h. There was no significant difference between the patients with THR and those with TKR (P>0.05). IL-6 is therefore a superior marker for the inflammatory phase after THR and TKR. collapse abstract

Altered prostate specific antigen reference range after transurethral resection of the prostate.

OBJECTIVES: We investigated how transurethral resection of the prostate (TURP) affected the serum concentration of prostate specific antigen (PSA) and whether the reference range for PSA has to be altered in these patients following TURP. METHODS: 55... expand abstract patients were retrospectively analysed. All had undergone TURP for bladder outlet obstruction due to benign prostatic hyperplasia which was confirmed by histopathological amination. PSA was determined pre-operatively and postoperatively every 6 months for 48 months. These patients were compared to 12 patients who had undergone radical perineal prostatectomy (RPP) for prostate cancer (CaP). In the latter group, in all patients a TURP had been performed up to 7 years before CaP was diagnosed. RESULTS: The median PSA concentration was 4.9 ng/ml before TURP and was subsequently reduced to 0.6 ng/ml after 48 months. There was a steady decrease of the PSA concentration during the observation period. In contrast in patients who subsequently developed a CaP, the median PSA concentration before TURP was 6.8 ng/ml and was reduced to only 2.2 ng/ml after 48 months. PSA levels started to rise before CaP was diagnosed. CONCLUSION: After a TURP with a benign histopathologic specimer) PSA levels decrease steadily to values below 2 ng/ml. In case these patients demonstrate a rising PSA in the follow-up after partial prostatectomy, a CaP should be ruled out. collapse abstract

Are age-specific reference ranges for prostate specific antigen population specific?

INTRODUCTION: At present PSA is Considered to be the leading screening test for prostate cancer. We determined whether in men 60 to 79 year old with a serum prostate specific antigen (PSA) within age specific PSA reference ranges prostate biopsy coul... expand abstractd be safely eliminated. METHODS: We retrospectively analysed all 60-79 year old men who had undergone radical perineal prostatectomy (RPP) for prostate cancer (CaP) at our institution. All patients had undergone prostate biopsy following an abnormal rectal examination and/or PSA greater than 4.0 ng/ml. We compared our results using the standard reference range of 0 to 4.0 ng/ml with those we had obtained using the age specific PSA reference ranges of Oesterling et al. RESULTS: 204 men between 60-69 years and 67 men between 70-76 years had undergone RPP for CaP. Applying age specific PSA reference ranges 56 CaP would have been overlooked. Of those 46% had a favourable histology. Taken together 54% of the cancers overlooked had an unfavourable histology. CONCLUSION: In contrast to previous reports of unfavourable histological characteristics in only 5-24% of missed cancers, applying age specific PSA reference ranges, 54% of missed cancers in our patients exhibited an unfavourable histology. We therefore conclude that age specific PSA reference ranges did not safely eliminate the need for prostate biopsy in our study population. collapse abstract

Serum-to-urinary prostate-specific antigen ratio in patients with benign prostatic hyperplasia and prostate cancer.

BACKGROUND: Prostate-specific antigen (PSA) is the single most important tumor marker in early detection and monitoring of prostate cancer (CaP). However, routine analysis of serum PSA concentrations does not allow differentiation between CaP and pro... expand abstractstatic diseases. The aim of the present study was to evaluate the usefulness of the serum-to-urinary PSA ratio in a clinical setting. MATERIALS AND METHODS: In a retrospective clinical study, we determined serum and urine PSA concentrations in 48 patients with benign prostatic hyperplasia (BPH) and 57 patients with histologically confirmed CaP. RESULTS: The serum-to-urinary PSA ratio is able to discriminate BPH from CaP. CONCLUSIONS: Determination of the serum-to-urinary PSA ratio enhances the specificity of PSA in screening for CaP and monitoring of patients with CaP under androgen deprivation therapy. collapse abstract

Tissue polypeptide specific antigen serum concentrations in patients with newly diagnosed prostatic diseases.

Recently, tissue polypeptide specific antigen (TPS), a cytokeratin 18 marker, was described to be discriminative between cancer of the prostate (CaP) and benign prostatic hyperplasia (BPH). In our study we investigated the ability of the TPS serum co... expand abstractncentration as a staging marker in patients with newly diagnosed CaP. METHODS: Serum levels of TPS and PSA were determined in patients with newly diagnosed, untreated CaP (pT1-3pNoMo: n = 71; T1-4NxM+: n = 39) and BPH (n = 30). The TPS serum concentration was correlated to the PSA serum concentration. RESULTS: Median TPS concentration was 33.6 U/L in the pT1-3pNoMo-group; 113.5 U/L in the Tl-4NxM(+)-group and 59.7 U/L in the BPH-group. Although the TPS concentration failed to discriminate between patients with localized CaP and BPH, it discriminated very well between patients with (M+) and without (Mo) bone metastases (p < 0.001). Furthermore no correlation with PSA levels could be established. CONCLUSION: The TPS serum concentration seems to provide additional information in the initial staging of patients with newly diagnosed untreated CaP. collapse abstract

Serum levels of prostate specific antigen in men on hemodialysis.

The measurement of prostate specific antigen (PSA) is widely used for the early detection of prostate cancer. However the influence of renal failure on the serum levels of the PSA molecular forms is still a matter of investigation. We therefore exami... expand abstractned the serum concentration of total and free PSA in patients undergoing hemodialysis and discuss the influence of renal failure on both types. MATERIALS AND METHODS: Serum concentrations of total PSA, free PSA and the free-to-total PSA ratio were measured in 48 men undergoing hemodialysis. Total and free PSA levels were measured employing a chemiluminescent enzyme immunoassay. RESULTS: Serum levels of total PSA, free PSA as well as the free-to-total PSA ratio did not change significantly in uremic patients after hemodialysis. Median total PSA concentration was 1.1 ng/mL before and 1.15 ng/mL after hemodialysis (p = 0.24); median free PSA concentration was 0.29 ng/mL before and 0.32 ng/mL after hemodialysis (p = 0.14). Median free-to-total PSA ratio was 0.29 ng/mL before and 0.31 ng/mL after hemodialysis (p = 0.66). CONCLUSION: Serum free PSA as well as total PSA is not eliminated by hemodialysis and the slightly elevated levels of free PSA and the free-to-total PSA ratio in uremic patients after hemodialysis may be caused by the concomitant decrease in binding proteins. We therefore conclude that the reference ranges for total PSA, free PSA and the f-/t-PSA ratio are applicable undergoing chronic hemodialysis. collapse abstract

Reverse transcriptase polymerase chain reaction and immunocytochemistry of bone marrow aspiration specimen and peripheral blood for detection of microdisseminated prostatic carcinoma. A comparative analysis

Reverse transcriptase-polymerase chain reaction (RT-PCR) assay for prostate-specific antigen and immunocytochemistry for cytokeratin-18 (CK-18) are tests for the detection of microdisseminated carcinoma of the prostate. Bone marrow aspirates and peri... expand abstractpheral venous blood from 50 patients with clinically organ-confined prostate cancer were examined. The rate of positive results was independent of the pT stage, serum PSA, and previous antiandrogen treatment. RT-PCR and immunocytochemistry have to be tested under standardized conditions in prospective trials, and the results have to be compared to the serum PSA follow-up. collapse abstract

Second malignancies in melanoma patients in Thuringia.

OBJECTIVE: The incidence of melanoma is increasing. Melanoma patients are at risk for the development of second neoplasias. Data for the new German Bundesländer are not available, but would be suitable to define frequency, site and type of secondary ... expand abstractmalignancies and conclusions for follow-up of melanoma patients. DESIGN: Retrospective study at the Melanoma Outpatient Clinic of the Department of Dermatology and Allergology at the University of Jena (Germany) for patients seen between June 1966 and June 1999. To investigate the impact of second malignancies on survival a case-comparison study of mortality was performed. The log-rank test and chi2-test were used to investigate statistical significance. There were 554 patients with malignant melanoma, 237 male and 317 female, with an age at time of diagnosis between 17.0 and 90.1 years (mean 53.7 years). The mean follow-up was 5.6 years. RESULTS: Sixty-one patients (11.0%) developed a second tumour. The total number of tumours was 83. Forty-five patients developed one, 16 developed > or = 2 second tumours. Basal cell carcinoma (BBC) was the most frequent neoplasia (17 patients, 22 tumours; mean age 64.9 years). A second melanoma was found in 15 patients, while two developed a third melanoma. The mean tumour thickness was 0.81 mm (in second or third melanomas) compared with 1.92 mm of primary melanomas. Seven female patients developed breast cancer (eight cancers; mean age 57.3 years). The other second tumours included skin cancer (eight), gastrointestinal tract tumours (four), genital cancers (19), brain tumours (two), lung cancer (two) and other tumours (six). The difference in survival of patients with second tumours was not statistically significant from age-, sex- and melanoma thickness-matched controls. CONCLUSIONS: Second malignancies were seen in 11.0% of melanoma patients. Most important are second skin tumours such as second melanomas and BCC, recommending follow-up by the dermatologist. In a group of patients with regular follow-up examinations, no negative impact of second tumours (BCC, melanoma, breast cancer) on overall survival could be detected. collapse abstract

Intermittent androgen blockade in prostate cancer: rationale and clinical experience.

Cancer of the prostate continues to be one of the most common malignancies in men in Europe, with a large number of patients presenting with advanced disease. The current standard treatment for metastatic cancer of the prostate, permanent androgen wi... expand abstractthdrawal, is palliative. Patients treated with permanent androgen blockade usually relapse and die secondary to prostate cancer's ability to progress to an androgen-independent state of growth. Based on experimental and preclinical studies, intermittent androgen blockade appears to be a potential alternative to permanent androgen blockade. Through the cycling of reversible androgen suppression, there appears to be recovery of apoptosis and subsequent slower progression to an androgen-independent state. In this paper experimental and preclinical studies concerning intermittent androgen blockade are reviewed. At present several prospective randomized trials are under way to test intermittent androgen blockade as an alternative treatment in various stages of cancer of the prostate. However, until the results of these trials are available, this approach remains experimental. collapse abstract

Expanded, radical perineal prostatectomy

One hundred and twenty-five consecutive patients with prostate cancer underwent an extended, radical perineal prostatectomy according to the technique described by VE Weldon. This technique was modified by an initial complete mobilization of the post... expand abstracterior aspect of the prostate and seminal vesicles from the rectum and pelvic wall, incision of the endopelvic fascia, and partial resection of the dorsal vein complex after suture ligature. The perioperative morbidity was low. An operative revision was necessary in four (3.2%) patients because of arterial bleeding from a drainage channel (n = 1), wound infection (n = 2), and rectocutaneous fistula (n = 1). The in-dwelling catheter was removed on day 4-8 in 104 (83%) patients. Positive surgical margins were diagnosed in 22 (17.6%) patients only. These patients had pT3 (n = 17) and pT4 (n = 5) tumors with a Gleason score > or = 7 (n = 17) mostly; extensive, multifocal capsular penetration (n = 18); seminal vesicle invasion (n = 11); and lymph node metastases (n = 4). The unifocal positive margins were localized at the apex (n = 3), dorsolateral (n = 6) aspect, and bladder neck (n = 4). In nine patients, multifocal positive surgical margins were noted. The risk for a positive surgical margin depends on the serum PSA level, Gleason score, and tumor volume. In case potency preservation is not considered, the extended, radical perineal prostatectomy with the above mentioned modifications should be considered to guarantee a low rate of surgical margins. collapse abstract

Phenol sulphotransferase SULT1A1 polymorphism in prostate cancer: lack of association.

Preliminary evidence suggests that genetic polymorphisms in certain enzymes involved in xenobiotic metabolism and chemical defense could modify a susceptibility to prostate cancer. In the present study, two recently described phenol sulphotransferase... expand abstract SULT1A1 alleles (SULT1A1*1, SULT1A1*2) were investigated using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. Genotyping was performed on DNA isolated from white blood cells from 134 patients with prostate cancer and 184 healthy control subjects. Both the prostate cancer patients and the controls demonstrated similar frequencies of the variant allele SULT1A1*2 (35.1% vs 39.1%). Homozygosity for the variant allele was slightly less frequent in cancer patients than controls (12.7% vs 17.4%). Our study does not support the hypothesis that the phenol sulphotransferase variant allele SULT1A1*2 with a G/A transition at nucleotide 638 is a risk modifier for prostate cancer in the Caucasian population. collapse abstract

Intermittent androgen deprivation

Interstitial fluid pressure is increased in renal cell carcinoma xenografts.

The purpose of this study was to test the hypothesis that renal cell carcinoma (RCC) exhibits an increased intratumoral interstitial fluid pressure (IT-IFP). Therefore, resected tumors from human primary (n = 23) or metastatic RCC (n = 3) were xenogr... expand abstractafted in SCID mice. The IFP of single tumor nodules (n = 65) and normal mouse tissue (n = 195) was measured by means of the "wick-in-needle" technique. Data demonstrate that the mean IT-IFP at neoplasia was 35 times greater than in normal tissue, and decreased precipitously at the tumor boundary. IT-IFP values tended to increase with the grade of malignancy of the tumor cells and tumor size. The mean IT-IFP of xenografts derived from primary RCC was twice as high as that from metastatic RCC tissue. These findings indicate a biophysical barrier to drug delivery in RCC; this may, in concert with cellular-based drug resistance mechanisms, be an additional explanation for resistance of the tumor to certain blood-borne anticancer therapies. collapse abstract