[Treatment costs of localized prostate cancer in Germany : Economic results from the HAROW observational study]. / Behandlungskosten des lokal begrenzten Prostatakarzinoms in Deutschland : Ökonomische Ergebnisse der HAROW-Beobachtungsstudie.

BACKGROUND: Prostate cancer (PCa) is the most common cancer in men. For medical treatment of PCa, a number of therapies are available. The economic consequences associated with these individual treatment options in routine care in Germany are unclear so far. METHODS: The present analysis was based on the Germany-wide HAROW observational study, which was conducted from 2008-2013. During this study, all participating physicians and involved patients reported and documented individual health care resource consumption. These data were evaluated in monetary terms stratified by treatment regime (hormone therapy, HT; active surveillance, AS; radiotherapy, RT; radical prostatectomy, RP; watchful waiting, WW). RESULTS: Overall, the data of 2672 patients were available for analysis. Based on the observational study design, the included patient groups were heterogeneous in their baseline characteristics. The annual total costs from the societal perspective were the largest for patient undergoing RP (9254 €; 95 % CI 8353-10,154), mainly driven by the costs for the initial hospital stay for surgery. HT, AS, RT, and WW seem to be comparable in terms of direct costs, ranging from 805 € (95 % CI 154-1455) for WW up to 1115 € (95 % CI 826-1405) for RT. The highest indirect costs were observed for patients receiving RT (3928 €; 95 % CI 0-10,675), which can be justified by the frequent incapacity to work in this patient group. CONCLUSION: The treatment of prostate cancer can lead to significant economic follow-up costs which vary greatly depending on the type of treatment. The analysis indicates a need for the implementation of a long-term health economic study in the future, which will be more suitable to show treatment-specific differences in the temporal occurrence of costs.

[Transforming growth factor ß in prostate cancer: cellular effects and basic molecular mechanisms]. / "Transforming growth factor ß" im Prostatakarzinom : Zelluläre Wirkungen und molekulare Grundlagen.

The multifunctional cytokine transforming growth factor ß (TGFß) plays a dual role in prostate cancer (PCa), cell growth and tumorigenesis, reflected by its opposing properties of anti-oncogenic (e.g. growth inhibition and apoptosis) and pro-oncogenic effects (e.g. proliferation, cell motility and remodelling of the microenvironment). In the later stages of PCa, TGFß loses anti-proliferative and thereby tumor-suppressive functions and shifts to a tumorigenic phenotype, mainly initiated by cross-talk between TGFß signalling and other proliferation signal transduction pathways, such as mitogen-activated protein kinase (MAPK) and androgen receptor (AR) signalling. Although TGFß plays an important role in tumor progression little is known about the underlying effects of TGFß in the molecular pathology of PCa.

[Second line therapy for castration-resistant prostate cancer (CRPC)]. / Zweitlinientherapie beim kastrationsresistenten Prostatakarzinom (CRPC).

Every year in Germany approximately 12,000 men die of castration-resistant prostate cancer even though early detection using PSA-based diagnostics allows more patients to be diagnosed with a curable cancer. An established first line therapy at this stadium is docetaxel chemotherapy, given in a 3-week regimen, providing an overall survival advantage of 2 months. In 6-9 months, the patients treated primarily with docetaxel will progress to a docetaxel-insensitive phase which requires a secondary systemic therapy. Increasing understanding of molecular signal transduction has permitted a growing variety of promising modern drugs, including cabazitaxel, sipuleucel-T and abiraterone. More prospective clinical data will provide a large variety of different therapy combinations, sequence therapies or other therapy regimens particularly for selected subgroups of patients with castration-resistant prostate cancer.

[Parameters to improve the specificity of the prostate-specific antigen. Early detection of prostate cancer]. / Parameter zur Verbesserung der Spezifität des prostataspezifischen Antigens. Früherkennung des Prostatakarzinoms.

PURPOSE: The aim of the study was to improve the case detection rate of prostate cancer for patients who had unremarkable palpation findings and a PSA value in the range of 4 to 10 ng/ml by combination of the parameters total PSA (tPSA), f/tPSA ratio, prostate volume, PSA density, patient's age and transrectal ultrasound findings. METHODS: Sextant biopsy of the prostate was performed for 619 patients aged 45-75 years who had unremarkable palpation findings and PSA values in the range of 4 to 10 ng/ml. The f/tPSA ratio was determined, transrectal ultrasound examination was performed, the prostate volume was measured and the PSA density calculated. The relationship between the various test variables - and their combination - and the histology results was investigated using logistic regression. RESULTS: Prostate cancer was detected in 131 of 619 patients. Analysis of the aforementioned test variables by means of logistic regression revealed that the combination of the parameters f/tPSA ratio, PSA density and patient's age can significantly increase the sensitivity and specificity of PSA in predicting prostate cancer compared with the use of these parameters on an individual basis. With an assumed limit value of 5% for performance of punch biopsy, 31% of biopsies could be avoided in practice. In such a case, only 3% of instances of prostate cancer would have gone undetected. CONCLUSION: The combined use of f/tPSA ratio, PSA density and patient's age can significantly enhance the case detection sensitivity for the PSA range of 4 to 10 ng/ml.

Correlation of pathological and cytological-cytometric grading of transitional cell carcinoma of the urinary tract.

INTRODUCTION: Cystoscopy and cytology are standard procedures for diagnosis and follow-up of patients with bladder cancer. Urinary cytodiagnosis is a descriptive method for tumor characterization. We correlated histopathologic diagnosis of noninvasive urothelial carcinomas with cytological evaluation and, furthermore, we validated cytology by cytometric analysis. PATIENTS AND METHODS: 94 patients with a history of bladder cancer were included in the study. 25 patients were negative for tumors, 22 showed pTa G1 carcinomas, 25 had pTaG2 and 22 patients had G3 carcinomas. All patients underwent cytological and cytometric evaluation. Nuclear diameter and circumference were measured for 15 representative nuclei per specimen. Statistical evaluation was performed using Graph Pad Software. RESULTS: Cytology showed excellent tumor detection for G2 and G3 carcinomas, with a sensitivity of 100% combined with a specificity of 100%. Using cytometry, we can significantly distinguish between unsuspicious patients and G1 carcinomas on the one hand and high-grade carcinomas on the other. Furthermore, in 6 of 25 patients (24%) with noninvasive G2 carcinomas, but G3 cytological evaluation, tumor progression occurred. CONCLUSIONS: Urinary cytology is an excellent instrument for detection of clinically relevant high-grade bladder cancer. Descriptive alterations of the cytopathology can be validated by objective data using cytometric analysis.

[Early detection of prostate cancer: is serum PSA testing alone sufficient?]. / Früherkennung von Prostatakarzinomen : Ist die Untersuchung des Serum-PSA alleine ausreichend?

The euphoria over PSA as an optimal marker for prostate cancer is gone. Measuring PSA levels has several deficiencies in detecting prostate cancer. First results of the randomized studies ERSPC and PLCO were not able to conclusively prove the value of PSA-based screening. Many attempts have been made to optimize early detection of prostate cancer like using modern imaging techniques or new biomarkers. This review deals with PSA isoforms und emerging biomarkers for the diagnosis of prostate cancer. Despite the inadequacies of PSA it is still the most important marker for the early detection of prostate cancer. Modern biomarkers with the ability to reliably predict aggressive prostate cancer are still missing.

[Problems, objective, and substance of early detection of prostate cancer]. / Probleme, Zielsetzung und Inhalt der Früherkennung beim Prostatakarzinom.

The current S3 guideline for early detection of prostate cancer initiates a change to the paradigm in early detection from the detection of all prostate cancers to the identification of aggressive prostate cancers. Early detection is performed annually and starts at the age of 40 years; it should be terminated at a life expectancy of less then 10 years. The choice of the frequency of early detection should be risk adapted. The digital rectal examination is supplemented by determination of PSA. Previous to the first PSA test the patient has to be informed concerning possible consequences such as biopsy recommendation and treatment options. A threshold of 4 ng/ml is defined as an indication for prostate biopsy for the first administration. In the following early detections the PSA velocity should be considered. Today imaging methods do not play a major role in early detection of prostate cancer. Early detection identifies many latent prostate cancers and patients may receive overtreatment. The recent S3 guideline for early detection is discussed against this background on the basis of the recent literature.

[Characterization of the EGF receptor status in penile cancer : retrospective analysis of the course of the disease in 45 patients]. / Charakterisierung des EGF-Rezeptorstatus beim Peniskarzinom : Retrospektive Auswertung der Krankheitsverläufe von 45 Patienten.

INTRODUCTION: Therapeutic success in metastasized squamous cell carcinoma is poor. Some entities, such as head-and-neck tumors or non-small-cell lung cancer, show an over expression of the EGF receptor. In latest studies target-specific substances against the EGF receptor have already been combined with chemotherapy or radiotherapy. Some studies showed a clear advantage of this combination concerning remission rates as well as survival. EGF receptor status has not yet been examined in penile cancer, therefore, a retrospective analysis of the receptor status was performed in patients treated over the last 14 years and correlations with the clinical course were investigated. PATIENTS AND METHODS: The analysis included 45 patients, who underwent primary or secondary treatment at the Department of Urology of the University of Essen during 1990 to 2004. Histological preparations existed for 44 patients. Using immunohistochemistry the expression of EGF receptors was determined. RESULTS: A total of 25 patients were primarily without positive lymph nodes (6 times cN0 and 19 times pN0), while 20 patients had pathologically proven lymph node metastases and 3 of them also had hematogeneous metastases. Out of 42 patients with follow-up 18 are still living of whom only 3 primarily had positive lymph nodes. These patients received adjuvant chemotherapy after resection. Out of the remaining 15 patients, 4 primarily N0 patients developed a lymphogenic recurrence, which was also resected and 3 patients also received adjuvant chemotherapy. Of the patients 24 died, 22 because of penile cancer. Of these 22 patients 16 primarily had positive lymph nodes and 5 of them also had an extensive primary tumor. Surgery was the treatment of choice in these cases and 10 patients also received chemotherapy. Nevertheless, 15 patients developed several recurrences. Distinguishing primarily node-negative and node-positive patients, the Kaplan-Meyer survival curves showed a significant difference (p<0.001). Median overall survival was 55.5 compared to 34 months and median 5-year survival was 76.9% compared to 15.8%. Of the tumors 40 out of 44 (91%) showed a positive or strong positive EGF receptor expression of the primary tumor as well as of the metastases. A correlation between EGF receptor expression and survival could not be shown. CONCLUSION: Clinical data underline the prognostic value of the primary lymph node status as well as the therapeutic value of an ileoinguinal lymphadenectomy and adjuvant chemotherapy. It could also be shown that inductive chemotherapy is not very successful. EGF receptor expression was high and comparable to other squamous cell carcinomas, but there was no correlation to survival.

[The value of urinary cytology in the diagnosis of high grade urothelial tumors]. / Stellenwert der Urinzytologie in der Diagnostik von High-grade-Urotheltumoren.

Urinary cytology is a non-invasive adjunct to cystoscopy in the diagnosis of bladder cancer. In order to assess the diagnostic accuracy of urinary cytology as an office-based method for clinically relevant high grade (G3) bladder cancer, three nationwide cytology survey tests were performed. Urine specimens from seven patients, three patients with high grade (G3) bladder cancer and four patients with urinary tract infections, were collected. A total of 1,000 cytology slides were produced from each urine specimen. Each set contained five slides (two malignant, three benign) which were sent to all participating German urologists. Three nationwide tests were performed from 1998-2000. The specimen sets were kept the same for the first and second test and in the third test two new slides were introduced. In addition to validity, the reliability was calculated for the first and second test as interobserver and intraobserver reliability according to Cohen's kappa statistics. Due to the change of two specimens in the third test in 2000 only sensitivity and specificity were calculated. A total of 335 urologists took part in the first survey test, 329 in the second and 292 in the third The sensitivity for G3 cytologies was 81.34% in the first, 87.08% in the second and 85.1% in the third survey test and the specificity was 85.87%, 83.58% and 89.15%, respectively. Interobserver reliability showed a weighted kappa value of 0.58 for the first and 0.59 for the second survey test. Calculation of intraobserver reliability was possible for 169 urologists taking part in the first and second survey test and showed a mean kappa value of 0.62. The results of the three nationwide urinary cytology tests indicate that urinary cytology has a high sensitivity in the detection of clinically relevant high grade bladder cancer. The kappa values achieved demonstrate a clear agreement of cytological diagnoses.

[PSA--Quo vadis?]. / PSA--Quo vadis?

Prostate cancer is the most frequent cancer in males. Because of the high cure rates, early detection of prostate cancer should identify organ-confined prostate cancers. An early detection examination should be performed annually starting at the age of 50 years and ending when life expectancy is less than 10 years. Digital rectal examination is supplemented by determination of prostate-specific antigen (PSA). Before the first PSA test, the patient must be informed of possible consequences such as biopsy recommendation and treatment options. A threshold of 4 ng/ml is defined as the indication for prostate biopsy. Imaging methods do not play a major role in early detection of prostate cancer today. Early detection identifies many latent prostate cancers, and patients may receive overtreatment. A possible solution is to change the early detection paradigm from detection of all prostate cancers to identification of aggressive ones. In this article, early detection is discussed based on the recent literature.

[Informed consent for patients on early recognition of prostate carcinoma is insufficient]. / Die Patientenaufklärung zur Prostatakarzinomfrüherkennung ist unzureichend.

Men that undergo an early detection investigation should be informed of the advantages and disadvantages as well as of the therapeutic consequences. In this study the quality of information was checked using the state of scientific knowledge of the patients.An informative consultation was carried out before the early detection investigation using a clarification brochure and an examination by a urologist. A questionnaire was also filled out after the investigation. A total of 1,536 men were questioned. Although 47% of the men had previously undertaken a PSA at least once, only 55% knew their own test result. Subjectively 82% of men felt well informed. In contrast one-third did not know the significance of an increased PSA level. In the field of patient clarification for the early detection for prostate cancer there are considerable deficits but the information received was considered adequate by the participants. However, more than one-third did not understand the significance of the PSA level.

[Free/total PSA ratio in clinical and ambulatory application. Are different cutoffs justified?]. / Der Quotient f/t-PSA in klinischer und ambulanter Anwendung. Sind unterschiedliche Grenzwerte gerechtfertigt?

Especially in the setting of total prostate-specific antigen (PSA) in the intermediate range of 4-10 ng/ml and a negative digital rectal examination, the use of the free/total (F/T) PSA ratio has proved to be an effective tool in prostate cancer screening. Whole blood should be analyzed as soon as possible after venipuncture to ensure optimal effectiveness of the F/T PSA ratio. If an immediate serum analysis is not possible, the serum should be frozen or stored at a maximum of 4 degrees C for a short period. Otherwise, when applying the F/T PSA cutoffs as recommended in the literature to a cohort with delayed analysis, a lack of specificity arises, and the initial advantage of reducing biopsies is minimized. To prevent loss of quality in a setting with delayed F/T PSA measurement, we recommend that physicians compare their own data critically with presented results and eventually adapt the cutoffs individually.

The f/t-PSA ratio in diagnosis of in-patients and out-patients: a unitary cutoff value is not useful!

PURPOSE: In the prostate specific antigen (PSA) range of 4-10 ng/ml after a negative digital rectal examination, the PSA value indicates a lack of specificity with a carcinoma detection rate of roughly 20%. To improve the biopsy/carcinoma ratio, the interdisciplinary consensus recommends free PSA (fPSA) measurement. This does not take into account the pre-analysis when the cutoff value is established for biopsy indication. METHODS: In the present study, an in-patient cohort whose blood samples were immediately analysed was compared with an out-patient cohort whose sample processing was delayed by between 24 and 48 h. RESULTS: The in-patient cohort comprises 382 patients with 99 prostate carcinomas, the out-patient cohort 987 patients with 235 carcinomas. In the in-patient cohort a sensitivity of 90% with a cutoff value of 25% for the f/t-PSA ratios is achieved with the theoretical possibility of reducing the number of punch biopsies by 34.6%. A sensitivity of 90% in the out-patient cohort necessitates a cutoff value of 18% for the f/t-PSA ratios. The specificity is 35.3% with a possible biopsy reduction of 29.1%. CONCLUSIONS: The cutoff values from cohorts with an immediate fPSA measurement cannot be adopted for a typical out-patient cohort whose analyses are delayed. On the contrary, an individual adjustment is necessary which corresponds to the pre-analysis.

[Role of lymphadenectomy in patients with invasive urothelial carcinoma of the bladder]. / Rolle der Lymphadenektomie bei Patienten mit invasivem Urothelkarzinom der Harnblase.

High-grade urothelial carcinomas of the bladder represent high-risk tumors and despite radical surgery and pelvic lymph node dissection patients have a lifelong risk for tumor progression and metastases. Since extended lymph node dissection detected metastases outside the fields of normal pelvic lymphadenectomy, it was concluded that all patients undergoing radical cystectomy should receive extended lymph node dissection. The article reviews published data discussing the question of whether lymph node dissection has prognostic or therapeutic relevance.

[Impact of surgery for residual tumors after chemotherapy]. / Bedeutung der Operation von Residualtumoren nach Chemotherapie beim Nierenzell- und Urothelkarzinom.

Metastases are a feature not only of local tumor manifestation but also of systemic disease. Thus, the question arises regarding the extent to which local therapy contributes to a systemic state of disease. With renal cell carcinoma, resection of pulmonary metastases is a common operation. Other sites should be considered individually. Only a well-defined subset of patients with metastasized urothelial carcinoma benefit from the resection of their metastases.

[Role of lymph node dissection in prostate cancer]. / Stellenwert der Lymphadenektomie beim Prostatakarzinom.

We present a comprehensive literature review and critical discussion of the diagnostic and therapeutic value of lymph node dissection in prostate cancer. Lymph node dissection is currently the most reliable staging procedure for detecting lymph node metastases in prostate cancer. Accuracy increases with the extent of the procedure. Overall, in patients with positive lymph nodes after radical prostatectomy and lymph node dissection, a favorable long-time cancer-specific survival can be observed. These data seem to be independent of the extent of the lymph node dissection and also independent of the administration of adjuvant therapy. It can be suspected that patients with lymph node metastases present different prognostic groups based on the extent of lymph node involvement. However, these risk groups might reflect only a lead-time bias, so the therapeutic value of lymph node dissection remains unclear. In conclusion, the therapeutic value of lymph node dissection in prostate cancer must be sufficiently evaluated in prospective clinical trials. Each patient should be individually counseled regarding his individual tumor features and the use of statistical prognostic tools such as nomograms.

[From marker expression to individual therapy of patients with bladder cancer]. / Von der Markerexpression zur individuellen Prognoseabschätzung urothelialer Neoplasien.

Urothelial carcinoma of the bladder is a tumor entity with a heterogenous clinical course. At one end of the spectrum, patients are treated for low-grade carcinomas, which are likely to reccur but show low rates of tumor progression. At the other end, patients suffer from noninvasive or early invasive high-grade carcinomas. In these cases, risk-adapted treatment decisions are more complicated. The following article gives an overview of research activities on bladder cancer with the aim to individualize treatment of patients with bladder cancer.

[Value of targeted therapy for prostate cancer]. / Der Stellenwert der Targeted-Therapie beim Prostatakarzinom.

Prostate cancer is the most frequent malignancy of the male population. Every year in Germany approximately 12,000 patients die of their hormone-refractory prostate cancer even though early detection is able to find more curable prostate cancers. In a hormone-refractory stage we only have limited options for treatment. Although docetaxel is currently the standard of care in most hormone-refractory prostate cancers, it is not the magic therapy that will dramatically change the patient's poor survival. This drug provides an overall survival advantage of 2 months. During recent years, significant progress has been made in the field of molecular therapy in urologic oncology. Targeted therapy leads to an inhibition of angiogenesis and proliferation in malignant tumors. Even if there is a great theoretical potential, mono- and combination therapies with target substances are not relevant in the clinical routine.

[Targeted therapy for metastatic bladder cancer]. / Targeted-Therapie des metastasierten Urothelkarzinoms.

The current therapy concept for metastatic bladder cancer is chemotherapy with gemcitabine and cisplatin as the first line protocol. Within the last 20 years no real progress could be achieved; the median survival is 14 months, though many different protocols have been tested. Expression analyses of growth factor receptors in human tumor tissue showed that expression of certain receptors is correlated with a severe clinical course.For many of these growth factor receptors pharmacological inhibitors are available in order to perform targeted therapy. The following review gives a survey of current studies on targeted therapy of metastatic bladder carcinoma.

[Differential therapy of prostate cancer]. / Differenzialtherapie des Prostatakarzinoms.

Prostate cancer has become the most common malignancy in males worldwide. Standard therapy in local confined prostate cancer with curative intent is a radical ablation of the gland. Brachytherapy seems to be an alternative treatment but long-term results are not yet available. In cases of advanced disease androgen deprivation is applied to eliminate testosterone which is the natural stimulator of tumor growth. The application of chemotherapy is limited to androgen-independent disease without curative intention. Standard chemotherapy is Docetaxel. Both early detection and aftercare are based on measurement of prostate-specific antigen.