Unusually large numbers needed to treat for radical prostatectomy in prostate cancer patients with PSA velocity ≤2 ng/ml/year.

BACKGROUND: The numbers needed to treat (NNT) and the corresponding confidence intervals for patients with prostate cancer and defined annual PSA increases (PSA velocity, PSAV) have not been described previously. AIM: The objective of this study is to assess NNT, numbers needed to treat to harm and corresponding confidence intervals for radical prostatectomy (RP) in patients with prostate cancer defined as a PSAV ≤2 ng/ml/year. METHODS: NNT following RP were estimated in risk groups defined by PSAV using mortality statistics and hazard ratios obtained in a noncontrolled trial. As no suited control group and no appropriate randomized trials were available for doing this calculation and as such trials are unlikely to become available in the near future we have calculated our NNTs as published previously by using relative risk reduction from an earlier randomized trial (RCT) comparing RP with watchful waiting (WW) [Can J Urol 2006;13(suppl 1):48-55]. RESULTS: For preoperative PSAV >2 ng/ml/year, NNT for RP were estimated at 25, whereas for preoperative PSAV ≤2 ng/ml/year, the estimate was 618. The lower 95% confidence limits (NNTBl) were 9 and 126, respectively (treatment with benefit). The implications emerging from these findings are discussed by comparison with published NNT values from other RCTs. The lower 95% confidence limit for preoperative PSAV ≤2 ng/ml/year was found to be large in comparison. CONCLUSION: The NNT estimate obtained here for PSAV >2 ng/ml/year and its lower 95% confidence interval is comparable to values in other studies on prostate cancer for therapies considered to be effective, while the estimated NNT for patients with PSAV ≤2 ng/ml/year is large in comparison. We conclude that the benefits of RP for localized prostate cancer with preoperative PSAV ≤2 ng/ml/year may be considered small. There are several limitations to our findings, the most important of which lies in the fact that while PSAV remains significantly associated with outcomes, the predictive value of PSA measurements is low. While PSAV >2 ng/ml/year clearly indicates a need for surgery, a PSAV ≤2 ng/ml/year should imply further decision making.

[LHRH analogues for the treatment of prostate cancer: an evidence level-based analysis]. / LHRH-Analoga zur Androgendeprivation beim Prostatakarzinom. Eine Evidenzlevelanalyse.

In this review the current indications and the options for LHRH analogues are elucidated. For this purpose, a literature search in PubMed and the Cochrane-Database was performed. In addition, the EAU and AUA guidelines as well as actual meeting abstracts up to 2008 were taken into account. Since the first prospective study in 1991 showed the same effectivity for LHRH analogues and orchiectomy in metastasised prostate cancer patients, the use of LHRH analogues increased thereafter. Testosterone levels do not need to be checked regularly, but rather only when PSA rises again under treatment. After cessation of LHRH analogue treatment the time to testosterone level recovery is longer when the treatment time was longer. One must especially recognise the risks of diabetes and osteoporosis after more than 3 years of LHRH analogue treatment. In the case of neoadjuvant and adjuvant LHRH analogue treatment, several points have to be taken into consideration: LHRH analogues before radical prostatectomy lead to a lower positive margin rate and lower rate of lymph node metastasis, but tumour-specific survival is not improved. In contrast, neoadjuvant LHRH analogue treatment before radiation therapy leads to better tumour-specific and overall survival. An increased cardiovascular toxicity was not observed. Intermittent androgen ablation has been proved to be equivalent with a reduction of side effects. Hormonal salvage therapy should be initiated when the PSA doubling time is short or the PSA velocity is > 2 ng / mL / year. The benefit of early initiation (PSA < 10 ng / mL, PSA doubling time < 12 months) is that it can prolong the metastasis-free survival time.

[Primary prevention of bladder cancer. What's new?]. / Primärprävention des Blasenkarzinoms. Was gibt es Neues?

Bladder cancer (Bc) with an incidence of 8.6% ranks fourth in males and with an incidence of 3.5% ranks eighth in females in Germany. The study of Cole demonstrating that coffee drinking poses a risk for developing Bc raised interest in primary prevention. In the meantime, however, 42 case-control studies could disprove this finding. Cigarette smoking raises the Bc risk threefold. Responsible are among others arylamines which are activated in the liver, but also detoxified. A genetically caused lack of transferases is responsible for every third Bc. Another risk factor is contributed by permanent hair dyes. Similarly to smoking, an arylamine is taken up by the body and has to be detoxified by transferases in the liver and skin. Furthermore, a chronic urinary tract infection may be related to Bc. Thus, the best prevention is the reduction of risk factors.A high fluid intake--irrespective of its kind--reduces the Bc risk by approximately 50%. Particularly smokers should realize that they can lower their risk of developing Bc by almost 70% with a high fluid intake. A connection between alcohol consumption and Bc development has never been shown. Vitamins A, B, and C were extensively investigated in epidemiological studies. Usefulness for primary prevention of Bc was not convincingly demonstrated. Interestingly, folic acid-containing food may reduce the Bc risk for smokers. Fruits and vegetables possess only a weak preventive efficacy. However, copious fruit consumption may reduce the risk for smokers by almost 50%. The trace element selenium does not possess a proven protection; however, it has been shown that persons with a high selenium plasma level have a lower incidence of Bc. Among probiotics yogurt containing Lactobacillus casei is particularly useful in smokers according to one study. Finally, the preventive action of NSAIDs is controversial. Surprisingly, users of analgetics have a low incidence of Bc.

[Local recurrence of prostate cancer: hormone therapy]. / Das Lokalrezidiv des Prostatakarzinoms: Hormontherapie.

BACKGROUND: The majority of patients receive HT after biochemical progression despite primary therapy of prostate cancer with curative intent. It is difficult to differentiate at a low rise in PSA level, e.g.,

Biphosphonates in advanced prostate and renal cell cancer--current status and potential applications.

OBJECTIVE: This review summarizes recent findings on the therapeutic benefits of biphosphonates in patients with advanced prostate or renal cell carcinoma (RCC). The role of biphosphonates in ADT-induced osteoporosis and delay of skeletal-related events (SREs) in metastatic bone disease is discussed. A brief overview on the proposed modes of action is given. METHODS: Literature search of PubMed documented publications and abstracts from meetings. RESULTS: Among the biphosphonates currently available, zoledronic acid is the only one known to be capable of delaying SREs in RCC and prostate cancer patients. Zoledronic acid counteracts cancer treatment-induced osteoporosis in men with prostate malignancies. The antitumor activity of biphosphonates found in vitro and in vivo is intriguing and has to be further assessed in clinical studies. CONCLUSION: Due to its unique properties, zoledronic acid is a breakthrough in the management of metastatic bone disease in patients with advanced prostate cancer and RCC. It significantly improves the patients' quality of life, drastically prolongs time to first SRE, and showed a positive but not significant effect on survival.

[Fortuitous finding microhematuria]. / Zufällig entdeckte Mikrohämaturie..

The present article describes the procedure to be followed when the rapid urinary test is positive, and identifies possible diffential diagnoses.

Reversible, non-barrier male contraception: status and prospects.

OBJECTIVE: Male, non-barrier, contraceptive options are limited to vasectomy and inadequate methods such as withdrawal and periodic abstinence. Herein we give an overview of current research on male contraception by pharmacological means. METHODS: Literature search of PubMed documented publications and abstracts from meetings. RESULTS: Cross-cultural surveys show men's willingness to carry contraceptive responsibility. Clinical trials substantiate that hormonal contraception involving suppression of gonadotropins holds the best promise to provide a male pharmacological contraceptive. Androgens have been demonstrated to induce reversible infertility particularly in combination with certain progestins and GnRH antagonists. Advances in non-endocrine contraception include intervention with triptolide derivatives, alkylated imino sugars, and immunization by eppin. CONCLUSION: The prospect of a pharmacological, male contraceptive has been considerably advanced in recent years. Long-term studies involving a greater number of subjects may result in a safe, reversible and effective means. Asia is likely to be the first market for male, hormonal contraceptive methods. The clinical evaluation of non-endocrine approaches may ultimately lead to an alternative to hormone-based male contraception.

Differential diagnosis and evaluation of the clinical course of transurethrally resected T1G3 urothelial carcinoma of the bladder by DNA image cytometry.

The value of DNA image cytometry in the differential diagnosis of 106 T1G3 urothelial carcinomas of the bladder and the long-term prognosis (recurrence-free interval, survival) of the patients was tested in comparison with Ta/T1G1 (n=30) and Ta/T1G2 carcinoma (n=54). Monolayer smears were prepared from three 50-microm-thick sections by a cell separation technique and were stained according to Feulgen. The DNA content of 250 epithelial cells, chosen at random, was determined using a TV-image analysis system CM-1 (Hund, Wetzlar, Germany). The DNA content of 30 lymphocytes served as an internal standard for the normal diploid value in every individual case. Different DNA cytometric parameters and the mean nuclear area were calculated. In comparison with G1- and G2-cases, the mean values of all DNA cytometric variables were markedly increased in the group of T1G3 cases, most obviously for the 5cEE, the mean ploidy and the ploidy imbalance (0.0006 > or = p > or = 0.0001). However, a remarkable overlay of the data distribution had to be considered. An aneuploid DNA stemline ploidy was highly characteristic for T1G3 urothelial carcinoma (sensitivity: 92%), but not sufficiently specific (57%). However, if increased values for the mean ploidy, the 2cDI, the 5cEE or the 9cEE (specificity: 86%-89%) were present additionally, the diagnosis of a T1G3 urothelial carcinoma could be made cytometrically. Follow-up data for survival (recurrence) analysis was available for 90 (82) patients of the T1G3 group. Using the median value as threshold, significant differences in survival were found for the mean ploidy only (p=0.0353). The length of the recurrence-free interval was significantly different for the entropy (p=0.0205), the 2cDI (p=0.0309) and the mean ploidy (p=0.0442). In conclusion, DNA single cell cytometry represents a highly relevant tool in the objective identification of T1G3 urothelial carcinoma of the bladder, with a sufficient sensitivity and specificity. Further, this method enables prediction of tumor recurrence if suitable variables are chosen. The long-term survival of patients with T1G3 urothelial carcinoma can be estimated by DNA cytometry only in a limited manner, possibly due to the fact that the causes of death in the mostly elderly patients will be independent from the limited tumor disease.

[Long-term outcome of radical prostatectomy in an observation period of at least 10 years]. / Langzeitergebnisse der Radikalen Prostatektomie mit einer Nachbeobachtungszeit von mindestens 10 Jahren.

PURPOSE: To evaluate the long-term outcome of radical prostatectomy in unselected patients with prostate cancer of relatively poor prognosis. MATERIALS AND METHODS: Between 1977 and 1989, 293 patients underwent radical retropubic prostatectomy. We analyzed 224 patients with a minimum follow-up of 10 years (mean 14 years, range 10.5 to 24 years). RESULTS: The pathological stage distribution of these 224 patients was pT1 in 14.3 %, pT2 43.6 %, pT3 39.1 % and pT4 3 %. Of these patients, 50 (22.3 %) had positive lymph nodes and 45 (20.1 %) positive margins. At 10 years after surgery, the actuarial survival rate for all patients was 67.1 % and the cancer-specific survival rate 85 %. Once progression of the disease developed, the median actuarial time to death was 5.5 years. Since PSA measurements were not introduced in the follow-up after radical prostatectomy until 1986, PSA data were available in only 84 (37.5 %) patients. In a survival analysis, preoperative PSA (< 10 ng/ml vs. > or = 10 ng/ml) was a significant predictor of the probability of positive margins (22 % vs. 78 %) and cancer-specific survival (87 % vs. 69 %) after 10 years. CONCLUSIONS: Long-term survival can be expected even in patients with locally advanced prostate cancer treated with radical prostatectomy.

[Early detection of cancer of the prostate. Pros and cons]. / Leitlinien fordern zur Vorsorge beim Prostatakarzinom: Bestimmen Sie auch den PSA-Wert.

Since the introduction of PSA determination for the detection of cancer of the prostate, there have been discussions of the pros and cons of PSA screening for early detection of this cancer. The PSA test used in combination with digital rectal examination has proven to be a superior diagnostic instrument for the diagnosis of malignant prostate disease at an early stage. The German Guideline Catalog for the early detection of carcinoma of the prostate recommends measurement of the PSA from the age of 45 onwards in patients who have first been comprehensively informed about the further proceedings in the event of a positive result. To date, PSA screening has not been shown to lower the disease-specific mortality rate. Two ongoing randomized, multicentre studies (ERSPC and PLCO) are expected to throw more light on the matter.

Erectile dysfunction (ED) is prevalent, bothersome and underdiagnosed in patients consulting urologists for benign prostatic syndrome (BPS).

OBJECTIVES: The aim of the present study was to determine the prevalence of erectile dysfunction (ED) in patients visiting office-based urologists in Germany because of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), and to evaluate the impact of ED on quality of life (QoL) in these patients. METHODS: 500 office-based urologists in Germany were invited to evaluate 20 consecutive patients for erectile dysfunction, who presented because of BPH-related LUTS. Physicians provided information on demographic factors, duration and treatment history of BPH, severity of LUTS, ED risk factors, and assessed the patient for the clinical diagnosis of ED. Patients were asked to complete the German version of the IPSS to measure LUTS severity. ED-patients quantified erectile dysfunction and impact on quality of life with validated German questionnaires (Cologne assessment of male erectile dysfunction KEED, and Qol-Med). RESULTS: Office-based urologists were aware of ED in 37.3% of 8768 patients presenting for LUTS before the study, 14.7% of patients were treated for ED. After the study-related assessment, physicians diagnosed ED in 62.1% of these patients and planned treatment in 46.9%. Severity of LUTS and ED prevalence correlated significantly after age-stratification. The incidence of ED was increased in patients with established ED risk factors. Mean QoL-Med score (best QoL: 100, worst QoL: 0) was 53.8 in patients with ED and 50.1 in ED-patients considering treatment. CONCLUSION: ED is highly prevalent in LUTS patients visiting an office-based urologist and is accompanied by a profound impact on the quality of life. Apparently, even during an urological consultation many ED-patients are hesitant to actively ask for treatment. Sexual issues should become key considerations for physicians managing patients with LUTS, especially since effective and well established oral treatment for ED is available.

The probiotic approach: an alternative treatment option in urology.

OBJECTIVE: The prophylactic and therapeutic use of probiotic microorganisms is a wide and still controversial field. The review paper is aimed to summarize recent findings on the health-benefiting effects of probiotics in urological diseases. The use of certain beneficial strains against urogenital infections, bladder cancer recurrence and renal stone formation is discussed. METHODS: Literature search of PubMed documented publications and abstracts from meetings. RESULTS: Various clinical trials have now been performed which substantiate the beneficial effects of the probiotic strains L. rhamnosus GR-1, L. fermentum RC-14 and L. crispatus CTV-05 against urogenital infections, such as urinary tract infections and bacterial vaginosis. The potential of L. casei Shirota to reduce the recurrence rate of bladder cancer is one of the most intriguing examples for the use of probiotics in medical practice. The use of O. formigenes in the prevention of calcium oxalate stone disease was only recently suggested and needs to be further investigated. CONCLUSION: Clinical trials increasingly provide a profound scientific basis for the use of probiotics in medicinal practice including urology. Efforts to make probiotic products available which are validated according to the guidelines recommended by the WHO and FAO and produced according to Good Manufacturing Practice will contribute to the acceptance of probiotic therapy by both the physicians and the patients.

[Prevention and complementary medicine in aging]. / Prävention und komplementärmedizinische Massnahmen beim Altern.

The subsequent brief review is based on a systematic literature search (Medline, http://www.lef.org and books under the topic Antiaging from 2001). Among the preventive and complementary measures against aging, caloric restriction with an adequate diet is in first place. If the energy supply is reduced by 17%, cardiovascular mortality drops to 31-41%. Among the mechanisms of aging, impaired formation of reactive oxygen species (oxidative stress) plays an important role. Moreover, antioxidants (vitamins A and B as well as selenium) provide protection. If obesity is complicated by a metabolic syndrome, a formula diet should be employed under the supervision of the urologist. The hormonal changes involved in the male climacteric should be treated by hormone replacement therapy. Testosterone given as a gel, plaster, or injection compensates for the secondary hypogonadism and treats osteoporosis. The muscle function can be improved by physical activity only. Sexual dysfunction, however, is not corrected with androgen hormone replacement therapy, whereas an appropriate physical training program may even improve potency by inducing a reactive penile hyperemia. In his office the urologist may implement a program specifically for the "aging male." If he diagnoses a metabolic syndrome, effective countermeasures are required to prevent early onset of arteriosclerosis.

[Early detection and follow-up of prostatic carcinoma. Responsibilities of the general practitioner]. / Früherkennung und Nachbetreuung des Prostatakarzinoms. Aufgaben für den Hausarzt.

Apart from digital rectal examination, the determination of prostate specific antigen is essential for the early detection of cancer of the prostate. The combination of these two examinations significantly improves screening efficacy. With the aid of a well-tested algorithm, the family doctor can establish the need for a urological investigation, and thus help to ensure early, curative treatment. Preventive measures can be rendered more effective by providing individual advice on such matters as lifestyle (risk factors, diet). It now appears that dietary measures are capable of slowing the increase in PSA following definitive treatment. Schematic disease-specific aftercare is usually the domain of the urologist. The general practitioner, however, is confronted by such problems as logistical considerations, documentation, palliative management (e.g. treatment of pain) and the problems associated with concomitant symptoms, the relevance of which needs to be assessed. Overall, however, the main concern of the general practitioner is with aspects of rehabilitation.

Oral treatment of erectile dysfunction with apomorphine SL.

Apomorphine SL (Ixense, Uprima) is a new oral medication shown to be effective in the treatment of erectile dysfunction. This compound is a dopaminergic agonist with affinity for dopamine receptor sites - mostly D(2) - within the brain known to be involved in sexual function. Apomorphine induces selective activation in the nucleus paraventricularis leading to erectogenic signals. More than 5,000 men with erectile dysfunction participated in phase II/III clinical trials assessing the safety and efficacy of doses ranging from 2 to 6 mg. The most favorable risk/benefit ratio is seen with a dose-optimization regimen of 2-3 mg: the 3-mg dose provides efficacy comparable to that of 4 mg but with fewer side effects. Consequently, review of clinical studies focuses on data with the 2- to 3-mg dose, the registered dose for use in clinical practice. The primary efficacy endpoint in most clinical trials with apomorphine SL was the percentage of attempts resulting in erections firm enough for intercourse - one of the most rigorous endpoints used in ED trials to date. These data were collected from both patients and their partners by reviewing entries in patient diaries and partner BSFI questionnaires. Secondary endpoints included percentage of attempts resulting in intercourse and improvement in ED severity based on the International Index of Erectile Function (IIEF). The proportion of attempts resulting in erections firm enough for intercourse was 49.4% with 3 mg compared with the baseline value of 24.3%. Partner evaluations corresponded with those of the patients. Erections occurred between 18 and 19 min after taking apomorphine SL 2 or 3 mg. The most common side effect was nausea which declined with continued use. Vasovagal syncope was reported in <0.2% of men, and was preceded by clear prodromal symptoms. Thus, apomorphine SL is an effective, well-tolerated drug for erectile dysfunction.