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.

[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.,

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.

[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.

Postpuberal castration and prostatic carcinoma.

The occurrence of prostatic carcinoma after postpuberal castration is rather unique since only one other case has been reported. However, there was no lack of androgens in the patient in this report, because the testicular ablation was compensated by nodular hyperplasia of the adrenal cortex maintaining a normal plasma testosterone.

Prostatic carcinoma: plasma kinetics and intraprostatic metabolism of testosterone in low-dose estrogen-treated patients in vivo.

Plasma kinetics, in vivo uptake, and intraprostatic metabolism of 3H testosterone was investigated in 9 patients with advanced carcinoma of the prostate. The metabolic effect of low-dose ethinyl estradiol was studied (estrogen suppressed testosterone, luteinizing hormone, and follicle-stimulating hormone). The production rate of testosterone was lowered, the elimination of androgen from plasma delayed. The uptake of testosterone and metabolites by the prostatic carcinoma was suppressed. Estrogen did not alter significantly the intraprostatic androgen turnover.

Stage T1A carcinoma of prostate.

When presented with a post-TURP patient with pathologically confirmed Stage T1a disease, several points should be considered (Fig. 1). Is the patient's anticipated longevity and quality-of-life likely to be affected by the confirmed diagnosis? From current knowledge, men over the age of seventy or with co-morbid risk factors probably will not be adversely affected, and no treatment is required apart from expectant follow-up with semiannual DRE and serum PSA determinations. The group at risk seems to be the young patient with a Stage T1a tumor who is likely to survive more than ten years after the diagnosis. Data showing progression rates without treatment as high as 16-25 percent at eight to ten years seem to indicate the need for additional therapy. If the patient belongs to this category and is ready to pursue more aggressive treatment, reestablishing the diagnosis might be suggested, as well as an evaluation of the pre- and post-TUR PSA levels. This can be done by TRUS-guided biopsies of the prostate (or repeat TURP, which we regard as less preferable). If residual tumor is not found, we would counsel a "wait and see" approach. If subsequent tissue sampling identifies other than well-differentiated cancer or indicates the likelihood of more extensive cancer than the T1a staging, treatment would be suggested. If the restaging reveals some residual well-differentiated disease that would not alter the initial staging of T1a, the patient should be offered the alternatives of close monitoring, radical prostatectomy, or radiation therapy. Until prognostic factors such as DNA ploidy and nuclear roundness are better studied, we are unable to counsel the patient on the biologic significance/aggressiveness of his Stage T1a disease.

The combination of LH-RH analogues with other treatment modalities in prostate cancer.

Androgen deprivation is the mainstay of therapy for prostate cancer. LHRH agonists are an essential part of this form of treatment and may be employed as the only endocrine manipulation, or in combination with antiandrogens, i.e., maximal androgen blockade. In patients with bone metastases, maximal androgen blockade prolongs life for 3-6 months. The patient with minimal metastatic spread, however, may benefit much longer from this combination. In addition to being used permanently, maximal androgen blockade may be given intermittently. In locally advanced prostate cancer, LH-RH analogues, alone or together with antiandrogens, are presently being studied in conjunction with radical surgery or definitive irradiation. Whether such a neoadjuvant or adjuvant use postpones the time to progression has not yet been decided. The patient with lymph node metastases seems to benefit from early androgen deprivation in conjunction with radical prostatectomy, if the primary tumor is diploid.

[Megacaliosis--diagnosis and differential diagnosis (author's transl)]. / Die Megakaliose. Diagnose und Differentialdiagnose

Megacaliosis is a renal dysplasia which is characterised by rudimentary papillae. The pathogenesis, clinical features and radiological appearances in fire cases are described and the differential diagnosis from other types of calyceal ectasia is discussed, In typical cases the diagnosis of megacaliosis can be made from the excretion urogram. We regard divided renal function studies as essential before making the diagnosis. Where the renal changes are not quite typical, it is necessary to exclude obstructive and inflammatory disease, vesico-ureteric reflux and renal tuberculosis.

[Percutaneous nephro-pyelostomy applications and results (author's transl)]. / Perkutane Nephropyelostomie- Anwendungsmöglichkeiten und Ergebnisse.

The use of percutaneous nephro-pyelostomy with a fine needle is described after 90 examination in 70 patients. Fine needle pyelography is used for antegrade demonstration of suspected ureteric obstruction when there is no renal excretion. Percutaneous nephro-pyelostomy can be used to assess the recovery of renal function after decompression, as well as for pressure measurements pre-operatively before carrying out plastic operations (Whitaker). Percutaneous nephropyelostomy offers the possibility of temporary or permanent urinary diversion in the presence of obstruction. In our own experience, the percutaneous method has almost totally replaced operative nephrostomy whenever supravesical drainage is necessary. In addition, it can be used for treating fistulas, antegrade splinting of the ureter or percutaneous removal of stones. Complications of renal puncture consisted of two small perirenal haematomas and two patients with short-lived haematuria, as well as one case of septicaemia with rapid recovery.

[Fine needle puncture for antegrade pyelography and percutaneous nephropyelostomy (author's transl)]. / Feinnadelpunktion zur antegraden Pyelographie und perkutanen Nephropyelostomie.

A method for antegrade pyelography and pyelonephrostomy is described using a long, thin needle with a shorter, wider Seldinger cannula. Puncture with a thin needle reduces the risk during antegrade demonstration of the upper urinary tract and can also be used for puncturing collecting systems which are only slightly dilated. When necessary, the Seldinger cannula can be advanced over the needle; subsequently, with the aid of a J-wire, a nephropyelostomy can be performed. The method has been used in 20 patients. In one case of intended bilateral nephropyelostomy the puncture was successful on only one side. There were no serious complications. In only one patient a small perirenal haematoma was found at operation.

[Problems of interpretation of urethral configurations on the micturition cystourogram in young girls]. / Zur Interpretationsproblematik der Urethrakonfiguration im Miktionszysturogramm (MZU) beim jungen Mädchen.

The aim of the investigation was to classify urethral variability as seen on micturating cystograms of 193 young girls and to study the physiological and pathological significance of the various shapes. It was shown that significant abnormalities were associated with all types of urethral configuration. Comparison of urethral shapes and clinical symptoms (dysuria, enuresis) did not show any particular appearance. Differentiation of urethral shapes into those that were dilated, and therefore suggested a stenosis, and those that were not dilated, showed no significant correlation between clinical and radiological findings.

[Selective arteriography of the internal pudendal artery in posttraumatic erectile dysfunction]. / Selektive Arteriographie der A. pudenda interna bei posttraumatischer erektiler Dysfunktion.

102 patients with erectile dysfunction were evaluated by a multidisciplinary approach including measurement of the bulbocavernous reflex (BCR)-latency, cystometry, dynamic cavernosography and bilateral selective arteriography of the pudendal arteries. Seven patients had a posttraumatic source of their erectile failure. Three patients showed a mixed neurogenic-arteriogenic aetiology of erectile dysfunction, two patients had evidence of isolated arterial damage, one patient had a venous and one an isolated neurogenic cause of erectile dysfunction. The passage of pudendal-penile vessels and nerves through the urogenital diaphragm is the most vulnerable portion of its way through the pelvis. Ruptures of the prostatomembranous urethra are frequently accompanied by injury to the pudendal-penile vessels and nerves, thus causing erectile dysfunction.

Multidisciplinary evaluation in erectile dysfunction after radical prostatectomy.

Radical prostatectomy is associated with a postoperative impotence rate of 90%, a sequel that is the least acceptable to the patient. The use of the nerve-sparing procedure according to Walsh (1) with 70% restoration of sexual power postoperatively is limited considering the prevalence of periprostatic tumour invasion. A method is described which satisfies the demand for both a radical surgical procedure and postoperative restoration of sexual power.

[Lymph node positive prostate carcinoma. A case for primary hormone therapy]. / Das Lymphknoten-positive Prostatakarzinom. Ein Fall für die primäre Hormontherapie.

At the present time, lymph node metastases may be nomographically predicted or histologically proven. As a rule, this indicates a systemic disease. Unimodal local therapy (radical prostatectomy/irradiation) does not alter the outcome. Occasionally, this appeared to be the case, if lymph nodes were diagnosed in a very early stage (diagnostic lead-time). This phenomenon disappears, when the follow-up time is long. A comparable situation is encountered, if one relies on the bimodal local therapy, i.e. radical prostatectomy plus adjuvant irradiation. Similarly, there is a diagnostic lead-time effective. However, patients with minimal lymph node metastases (also known as pN1.1) may probably not need immediate endocrine therapy. The combination of tele- and brachy-therapy in the presence of positive nodes appears to be not useful. Unimodal systemic therapy following radical prostatectomy has never been tested in a phase III-trial. If one weighs the arguments pro immediate versus delayed hormone therapy, the following trends can be found: The time-to-progression is prolonged, however, that does not translate in a longer cause-specific survival. In the results of a phase III-trial of irradiation plus primary versus delayed androgen deprivation in stage N1/pN1 prostate cancer the above trends were noticed. Neoadjuvant hormone therapy in N1 prostate cancer has not been tested in a phase III-trial, however, it is very unlikely that patients benefit more than from a similar treatment in the presence of locally advanced, but node-negative prostate cancer. An interesting concept in these potentially long surviving patients is the intermittent hormone therapy, among the benefits is the reduced number of side-effects.

[Complete androgen blockade versus monotherapy]. / Komplette Androgenblockade versus Monotherapie.

In a comparative analysis of 29 studies, maximal androgen deprivation (MAD) was not found to be superior to partial androgen deprivation. Thus, MAD cannot be regarded as the new gold standard. Most trials focus on quality of life which--given the palliative aim of the treatment--deserves special attention. This aspect has not yet been evaluated, however, in the largest multicenter study, intergroup study 0105. In patients with advanced bone metastasis or severe pain, MAD treatment should be begun because of the flare phenomenon. The synergistic effects of LHRH agonists on the prostate are currently being investigated. Since no clear prognostic factors exist and reduction of serum-PSA levels under MAD does not delay progression, the patient must help to make the decision of whether or not MAD should be begun.

[Chemotherapy of prostatic carcinoma]. / Chemotherapie beim Prostatakarzinom.

The overall results of chemotherapy of hormone-refractory prostate carcinomas are disappointing. In practical terms, only partial remissions are observed. Complete remissions are very rare. Prospective randomized studies revealed no advantage of primary chemotherapy over standard hormone therapy with regard to survival time of patients with metastasized prostate carcinoma. Furthermore, superiority of a combination therapy over therapy with a single cytostatic agent for prostate carcinoma has so far not been proved. These results indicate that chemotherapy of prostate carcinoma should only be applied within controlled studies, and that new substances or combination preparations should preferably be tested in such studies.