[Evaluation of a prostate cancer E­health tutorial : Development and testing of the website prostata-information.ch]. / Evaluation eines Online-Tutorials zum Prostatakarzinom : Entwicklung und Überprüfung der Seite prostata-information.ch.

BACKGROUND: Due to the multitude of therapy options, the treatment decision after diagnosis of localized prostate cancer is challenging. Compared to printed booklets, web-based information technology offers more possibilities to tailor information to patients' individual needs. OBJECTIVES: To support the decision-making process as well as the communication with patients, we developed an online tutorial in a systematic process in the German-speaking part of Switzerland and then tested it in a pilot study. The study investigated users' satisfaction, the coverage of information needs, the preparation for decision making, and the subjective quality of the decision. MATERIALS AND METHODS: Based on already existing information material, the online tutorial was developed in an iterative process using focus groups with patients and urologists. For the following evaluation in eight clinics a total of 87 patients were invited to access the platform and participate in the study. Of these patients, 56 used the tutorial and 48 answered both surveys (the first one 4 weeks after the first login and the second one 3 months after treatment decision). The surveys used the Preparation for Decision Making Scale (PDMS), the Decisional Conflict Scale (DCS), and the Decisional Regret Scale (DRS). RESULTS AND CONCLUSION: Satisfaction with the tutorial is very high among patients with newly diagnosed localized prostate cancer. Users find their information needs sufficiently covered. Three months after the decision they felt that they were well prepared for the decision making (mean PDMS 75, standard deviation [SD] 23), they had low decisional conflict (mean DCS 9.6, SD 11), and almost no decisional regret (mean DRS 6.4, SD 9.6). Based on these findings, further use of the tutorial can be recommended.

Experiencia inicial con una serie de adrenalectomía laparoscópica asistida por robot / Initial experience of a series of robotic-assisted laparoscopic adrenalectomy

Objetivos: Presentamos nuestra experiencia inicial utilizando la adrenalectomía laparoscópica robótica en el tratamiento quirúrgico de las masas suprarrenales. Material y métodos: Entre octubre de 2009 y octubre de 2011 fueron operados en nuestra institución un total de 18 pacientes (11 mujeres y 7 hombres) con diagnóstico de masa tumoral adrenal funcionante o no funcionante. Evaluamos variables quirúrgicas, el tiempo de recuperación intrahospitalario, los hallazgos patológicos y las complicaciones peri y postoperatorias. Resultados: La edad media de la población intervenida fue 51,2 años (rango: 18-81), el promedio de puntuación ASA 2,11 (rango: 1-4) y el IMC 27,0 (rango: 18,8-36,1). De los 18 pacientes 11 fueron operados del lado izquierdo y 7 del derecho. El tiempo medio de cirugía fue 150 minutos (rango: 84-329) y el sangrado intraoperatorio 121 ml (rango: 10-1.500), con una pérdida media de hemoglobina y de hematocrito de 2,11g/dl y 6,33%, respectivamente. Dos pacientes fueron convertidos a cirugía convencional. Los factores que influyeron en la conversión quirúrgica fueron: tamaño tumoral (>10cm), peso tumoral (>100 g), feocromocitoma activo y localización izquierda del tumor. Se extirparon 7 adenomas corticales funcionantes, 6 tumores suprarrenales metastásicos, 3 feocromocitomas y 2 tumores incidentales. El tamaño medio del tumor fue 5,39 cm (rango: 3-15). La mediana de la estancia hospitalaria fue de 6 días (rango: 4-14). Un total de 5 pacientes presentaron complicaciones perioperatorias. De éstos solo uno (5%) tuvo complicaciones mayores (Clavien III). El seguimiento medio fue de 6 meses (rango: 2-24). Conclusiones: La tecnología robótica para la realización de adrenalectomías laparoscópicas es una opción válida para el tratamiento de los tumores suprarrenales. En nuestra experiencia, con una curva de aprendizaje relativamente corta, permite reducir los tiempos de tratamiento hospitalario, así como las complicaciones intra y postoperatorias, sin afectar los resultados oncológicos y funcionales postoperatorios (AU)

Objectives: We present our initial experience using robotic-assisted laparoscopic adrenalectomy in the surgical treatment of adrenal masses. Material and methods: A total of 18 patients (11 women and 7 men) diagnosed of a functioning or non-functioning adrenal tumor mass were operated on in our facilities between October 2009 and October 2011. Surgical variables, intra-hospital recovery time, pathological findings and peri- and post-operatory findings were evaluated. Results: Mean age of the population intervened was 51.2 years (range 18-81), average ASA score 2.11 (range 1-4) and BMI 27.0 (range 18.8-36.1). Of the 18 patients, 11 were operated on the left side and 7 on the right. Mean surgery time was 150 (range 84-329) min and intra-operatory bleeding 121 (range 10-1500) ml, with a mean loss of hemoglobin and hematocrits of 2.11g/dl and 6.33%, respectively. Two patients were converted to conventional surgery. The factors influencing surgical conversion were: normal size (>10cm), tumor weight (>100g.), active pheochromocytoma and left localization of the tumor. Seven functioning cortical adenomas, 6 metastatic adrenal tumors, 3 pheochromocytoma and 2 incidental tumors were excised. Mean tumor size was 5.39 (range 3-15) cm. Median hospital stay was 6 days (range 4-14). Five patients had peri-operatory complication. Of these, only one (5%) had major complications (Clavien III). Mean follow-up was 6 months (range 2-24). Conclusions: Robotic technology for laparoscopic adrenalectomies is a valid option for adrenal tumor treatment. In our experience with a relatively short learning curve, it makes it possible to reduce hospital treatment times and the intra- and post-operatory complications, without affecting the oncological and post-operatory functional results (AU)

[Initial experience of a series of robotic-assisted laparoscopic adrenalectomy]. / Experiencia inicial con una serie de adrenalectomía laparoscópica asistida por robot.

OBJECTIVES: We present our initial experience using robotic-assisted laparoscopic adrenalectomy in the surgical treatment of adrenal masses. MATERIAL AND METHODS: A total of 18 patients (11 women and 7 men) diagnosed of a functioning or non-functioning adrenal tumor mass were operated on in our facilities between October 2009 and October 2011. Surgical variables, intra-hospital recovery time, pathological findings and peri- and post-operatory findings were evaluated. RESULTS: Mean age of the population intervened was 51.2 years (range 18-81), average ASA score 2.11 (range 1-4) and BMI 27.0 (range 18.8-36.1). Of the 18 patients, 11 were operated on the left side and 7 on the right. Mean surgery time was 150 (range 84-329) min and intra-operatory bleeding 121 (range 10-1500) ml, with a mean loss of hemoglobin and hematocrits of 2.11g/dl and 6.33%, respectively. Two patients were converted to conventional surgery. The factors influencing surgical conversion were: normal size (>10cm), tumor weight (>100g.), active pheochromocytoma and left localization of the tumor. Seven functioning cortical adenomas, 6 metastatic adrenal tumors, 3 pheochromocytoma and 2 incidental tumors were excised. Mean tumor size was 5.39 (range 3-15) cm. Median hospital stay was 6 days (range 4-14). Five patients had peri-operatory complication. Of these, only one (5%) had major complications (Clavien III). Mean follow-up was 6 months (range 2-24). CONCLUSIONS: Robotic technology for laparoscopic adrenalectomies is a valid option for adrenal tumor treatment. In our experience with a relatively short learning curve, it makes it possible to reduce hospital treatment times and the intra- and post-operatory complications, without affecting the oncological and post-operatory functional results.

[Nephron-sparing surgery 2012]. / Organerhaltende Nierenchirurgie 2012.

Nephron-sparing surgery is considered to be the standard surgery for small renal masses. There is a large socioeconomic and oncological relevance in such a decision, especially since tumour incidence as well as average life expectancy increases, also triggered by better diagnostic quality. The present review highlights the current state of nephron sparing-surgery, evaluates different surgical approaches and gives perspectives on the future developments and scientific investigations required. In conclusion, nephron-sparing surgery has been well studied and different approaches have shown high safety profiles with oncological results comparable to those of radical nephrectomy. Nephron -sparing surgery provides decisive advantages in long-term survival and patient morbidity, especially concerning chronic renal failure rates. Therefore, whenever feasible, a renal mass should be considered for nephron-sparing surgery.

[Mistletoe extract for treatment of urological tumors]. / Mistelpräparate zur Behandlung urologischer Tumoren.

In Germany misteltoe extract is one of the most commonly used complementary therapeutic strategies in oncology. There are anthroposophical as well as phytotherapeutic concepts to explain the potential mechanism of action; however, the oncological and uro-oncological literature lacks definitive proof to support recommendations on which is the most effective drug, the optimal dose, a clear indication or its efficacy. Weighting the current data, potential side effects and contraindications, the application of mistletoe extract in daily uro-oncological practice requires careful consideration of the indications in the context of a detailed patient informed consent and request for this unique therapeutic modality.

[Radical cystectomy - pro robotic]. / Radikale Zystektomie - pro robotisch.

The standard therapy for muscle invasive bladder cancer is radical cystectomy and urinary diversion. For open surgery this procedure has notable perioperative morbidity. Performing laparoscopic cystectomy can reduce this morbidity. So far it remains unclear, whether the oncologic outcome of the laparoscopic approach is comparable to open surgery or not due to a lack of long-term follow-up data. Important surgical steps, such as extended lymphadenectomy, sparing of the neurovascular bundle for preservation of potency, preparation of the urethra for orthotopic neobladder and intracorporeal construction of a urinary diversion can be achieved much more easily with a robot-assisted approach than with conventional laparoscopy. Furthermore, the learning curve for robot-assisted cystectomy is much steeper. Therefore, if a laparoscopic cystectomy is performed, it should be performed using a robot-assisted approach.

[Third generation anti-androgen therapy of advanced prostate cancer]. / Antihormonelle Therapie des Prostatakarzinoms der 3. Generation.

The identification of intracellular androgen synthesis by prostate cancer cells has led to the identification of new targets and the development of third generation drugs for the therapy of castration-resistant prostate cancer. Inhibitors of androgen synthesis and more potent androgen receptor antagonists, such as abiraterone acetate, MDV3100, TAK-700 and TOK-001, will improve treatment by prolongation of survival and palliation. A significant reduction of tumor-associated pain and a survival advantage of 4.6 months compared to placebo following docetaxel-based chemotherapy has already been shown for abiraterone in a phase III study. Further phase III studies with abiraterone, MDV3100 and TAK-700 before and after docetaxel-based chemotherapy are currently running. TOK-001 is the first of the new drugs which combines the therapeutic use of androgen synthesis inhibition and androgen receptor antagonism in a single drug. The first clinical studies with this therapy are currently being carried out and it remains to be seen whether this combination leads to increased effectiveness. With an increase in therapy options for prostate-resistant cancer, one of the projects in the coming years will be to integrate the present therapies into therapy concepts. In addition to an effective sequence of the individual medications, a combination with already established therapies, such as cytostatic agents, could also prove to be useful. Altogether, the development of new antihormonal therapies is a considerable expansion of the therapy options for patients which could contribute to an improvement of the quality of life and the prognosis of patients.

[Current developments in the diagnostics and therapy of bladder carcinoma]. / Aktuelle Entwicklungen in der Diagnostik und Therapie des Harnblasenkarzinoms.

Considerable progress has been made in nearly all clinical scenarios of bladder carcinoma. Nevertheless early detection of bladder carcinoma using urine markers is still difficult so that none of the available tests can be recommended as a screening test. Photodynamic diagnostics and resection has now been shown for the first time to improve recurrence-free survival of patients but this impact on survival has to be confirmed in a phase III clinical trial before being regarded as standard of care. In pT1G3 tumors early cystectomy seems to improve the prognosis compared to organ preserving strategies. The value of adjuvant chemotherapy is becoming more and more evident, as, apart from several retrospective analyses it has been shown to improve survival in a clinical phase III trial. Furthermore, molecular markers are gaining importance and in the future can be used for identifying patients who may benefit from systemic chemotherapy of bladder carcinoma.

[From tumor tissue via primary cultures to xenograft models: a functional approach in prostate cancer research]. / Vom Gewebe über die Primärzellkultur zum Xenograftmodell : Patientennahe und funktionelle Prostatakarzinomforschung.

The clinical course of prostate cancer, the most common cancer in men, is very variable. Despite intense research activities over the years and besides histopathological criteria, prognostic markers that reliably predict tumor behavior and the necessity for treatment are still missing. A likely explanation for this fact is the lack of good tumor models, mimicking the in vivo situation. These models are not only essential for a better understanding of the pathogenesis of prostate cancer but also play an important role in the development of new therapeutic strategies. Since results of permanent cell culture experiments reflect only in part real tumor behavior and primary cultures from patient material cannot be grown indefinitely, novel approaches need to be developed to achieve reliable and clinically relevant prostate cancer research.In this work the development of several approaches for culturing primary prostate cancer tissue is illustrated and a forecast of future research plans utilizing xenograft models in mice is made.

Cistectomía radical laparoscópica asistida por robot: evaluación de los resultados funcionales y oncológicos / Robotic-Assisted Laparoscopic Radical Cystectomy: Evaluation of Functional and Oncological Results

Objetivo: presentamos nuestra experiencia en cistectomía radical robótica informando sobre los resultados quirúrgicos, tanto desde el punto de vista oncológico como funcional. Material y método: entre enero de 2007 y agosto de 2010 fueron operados en nuestra institución un total de 84 pacientes (70 hombres y 14 mujeres) con diagnóstico histopatológico de cáncer de vejiga invasor no metastásico. Evaluamos variables quirúrgicas, el tiempo de recuperación intrahospitalario, los hallazgos patológicos y las complicaciones peri y postoperatorias. Resultados: la edad media de la población en estudio fue 65,6 años (rango: 28-82). En 62 pacientes se realizó derivación urinaria con ureteroileostomía tipo Wallace, los 22 pacientes restantes recibieron una neovejiga ileal tipo Studer. El tiempo promedio de cirugía fue de 261 minutos (rango: 243-618) y la pérdida promedio de sangre intraoperatoria fue de 298ml (rango 50-2.000). Un 29, 38, 26 y 7% presentaron estadios histopatológicos postoperatorios pT1, pT2, pT3 y pT4, respectivamente. El 15% de los pacientes operados presentó metástasis locales a nivel ganglionar. El número de ganglios linfáticos resecados por procedimiento quirúrgico fue de 14,47 (rango: 1-33). En dos casos (2,4%) se registraron márgenes quirúrgicos positivos. El tiempo promedio de aparición de flatos fue 2,12 días, evacuación intestinal postoperatoria 2,87 y alta médica 17,710-33. Un total de 45 pacientes presentaron complicaciones perioperatorias. De estos sólo un 11,9% tuvo complicaciones mayores (Clavien III o mayor) que necesitaron de un tratamiento más invasivo. El tiempo promedio de seguimiento fue de 16,7 meses. Durante ese período 10 pacientes (11%) presentaron recidiva del tumor vesical, de los cuales dos (2,38%) fallecieron. Conclusión: nuestra experiencia con cistectomía radical robótica en el tratamiento del cáncer de vejiga sugiere que en manos adecuadas este procedimiento proporciona resultados quirúrgicos y patológicos aceptables (AU)

Purpose: radical cystectomy remains the most effective treatment for patients with localized, invasive bladder cancer and recurrent noninvasive disease. We report our experience with 84 consecutive cases of robotic assisted laparoscopic radical cystectomy with regard to perioperative results, pathological outcomes and surgical complications. Materials and methods: a total of 84 consecutive patients (70 male and 14 female) underwent robotic radical cystectomy and urinary diversion at our institution from January 2007 to August 2010 for clinically localized bladder cancer. Outcome measures evaluated included operative variables, hospital recovery, pathological outcomes and complication rate. Results: mean age of this cohort was 65.5 years (range 28 to 82). Of the patients 62 underwent ileal conduit diversion, 22 received a neobladder. Mean operating room time for all patients was 261min. (range: 243-618min.) and mean surgical blood loss was 298ml (range: 50-2000ml). 29% of the cases were pT1 or less disease, 38% were pT2, 26% and 7% were pT3 and T4 disease respectively, 15% were node positive. Mean number of lymph nodes removed was 15 (range 1 to 33). In 2 cases (2.4%) there was a positive surgical margin. Mean days to flatus were 2.12, bowel movement 2.87 and discharge home 17.7 (range: 10-33). There were 45 postoperative complications with 11.9% having a major complication (Clavien grade 3 or higher). At a mean followup of 16.7 months 10 patients (11%) had disease recurrence and 2 died of disease. Conclusions: our experience with robotic radical cystectomy for the treatment of bladder cancer suggests that in proper hands this procedure provides acceptable surgical and pathological outcomes (AU)

[Robotic-assisted laparoscopic radical cystectomy: evaluation of functional and oncological results]. / Cistectomía radical laparoscópica asistida por robot: evaluación de los resultados funcionales y oncológicos.

PURPOSE: radical cystectomy remains the most effective treatment for patients with localized, invasive bladder cancer and recurrent noninvasive disease. We report our experience with 84 consecutive cases of robotic assisted laparoscopic radical cystectomy with regard to perioperative results, pathological outcomes and surgical complications. MATERIALS AND METHODS: a total of 84 consecutive patients (70 male and 14 female) underwent robotic radical cystectomy and urinary diversion at our institution from January 2007 to August 2010 for clinically localized bladder cancer. Outcome measures evaluated included operative variables, hospital recovery, pathological outcomes and complication rate. RESULTS: mean age of this cohort was 65.5 years (range 28 to 82). Of the patients 62 underwent ileal conduit diversion, 22 received a neobladder. Mean operating room time for all patients was 261min. (range: 243-618min.) and mean surgical blood loss was 298ml (range: 50-2000ml). 29% of the cases were pT1 or less disease, 38% were pT2, 26% and 7% were pT3 and T4 disease respectively, 15% were node positive. Mean number of lymph nodes removed was 15 (range 1 to 33). In 2 cases (2.4%) there was a positive surgical margin. Mean days to flatus were 2.12, bowel movement 2.87 and discharge home 17.7 (range: 10-33). There were 45 postoperative complications with 11.9% having a major complication (Clavien grade 3 or higher). At a mean followup of 16.7 months 10 patients (11%) had disease recurrence and 2 died of disease. CONCLUSIONS: our experience with robotic radical cystectomy for the treatment of bladder cancer suggests that in proper hands this procedure provides acceptable surgical and pathological outcomes.

[Complete resection of urothelial cancer metastases with curative intent]. / Metastasenchirurgie in kurativer Absicht beim Urothelkarzinom.

BACKGROUND: Recent publications suggest that a subgroup of patients can benefit from surgical removal of transitional cell carcinoma (TCC) metastases in addition to systemic chemotherapy. We report the combined experience and outcome of patients undergoing resection of TCC metastases at 15 uro-oncologic centers in Germany. MATERIALS AND METHODS: Forty-four patients with distant metastatic TCC of the bladder or upper urinary tract underwent resection of all detectable metastases in 15 different German uro-oncological centers between 1991 and 2008 in an attempt to be rendered free of disease. RESULTS: The resected metastatic sites consisted of retroperitoneal lymph nodes (56.8%), distant lymph nodes (11.3%), lung (18.2%), bone (4.5%), adrenal gland (2.3%), brain (2.3%), small intestine (2.3%), and skin (2.3%). The treatment sequence included systemic chemotherapy in 35/44 (79.5%) patients before and/or after surgery. Median survival times from initial diagnosis of metastatic TCC and subsequent resection were as follows: overall survival, 35 and 27 months, respectively; cancer-specific survival, 38 and 34 months, respectively; and progression-free survival, 19 and 15 months, respectively. Overall 5-year survival from metastasectomy for the entire cohort was 28%. Seventeen patients were still alive without progression at a median follow-up time of 8 months. Seven patients without disease progression survived for more than 2 years and remain free from tumor progression at a median of 63 months. CONCLUSION: The results in this selected cohort confirm that long-term cancer control and possibly cure can be achieved in a subgroup of patients following surgical removal of TCC metastases. However, prospective data to identify patients most likely to benefit from this aggressive therapeutic approach are lacking. Therefore, metastasectomy in patients with disseminated TCC remains investigational and should be offered only to those with limited disease as a combined-modality approach with systemic chemotherapy.

[Extending the limits of lymphadenectomy during radical cystectomy: pitfalls in the interpretation of contemporary study results]. / Das Ausmass der Lymphadenektomie im Rahmen der radikalen Zystektomie: Fallstricke bei der Interpretation aktueller Studienergebnisse.

The optimal extent of lymphadenectomy performed during radical cystectomy for transitional cell carcinoma of the bladder is currently under intensive debate. Extending the limits of lymphadenectomy has been hypothesized to add further diagnostic and therapeutic benefit. However, our current knowledge is based exclusively on results from retrospective studies that are hampered by several statistical shortcomings. This article provides a critical analysis of the contemporary data on the subject and outlines typical statistical pitfalls that must be considered when interpreting such research results.

[Development of a three-dimensional primary prostate cancer cell culture model]. / Entwicklung eines dreidimensionalen Prostatakarzinomzellkulturmodells.

Much prostate cancer research is based on cell culture results. Recent genomic studies found major differences between primary prostate cancer tissue and established prostate cancer cell lines, which calls into question the clinical relevance of study results based on cell cultures.Using primary cultures of prostate cancer cells from prostatectomy specimens seems to be a reasonable solution, but primary cell cultures are much more difficult to establish. In this study, a primary cell culture model was combined with an invasion assay. With this combination it was possible not only to select invasive cell clones from the primary culture but also to culture these cells in a three-dimensional model, forming spheroids. A further characterization of this cell population was done by comparative genomic hybridization, showing numerous genetic alterations. The presented cell culture model offers, for the first time, an opportunity to isolate invasive growing cells from primary prostate cancer tissue and cultivate these cells for further analyses.

An improved in vitro model to characterize invasive growing cancer cells simultaneously by function and genetic aberrations.

Invasion into the surrounding tissue and bone metastasis is a common feature of advanced prostate cancer. Chromosomal and other genetic or epigenetic abnormalities were aligned to this behaviour mostly by using permanent cell lines, paraffin embedded tissue or primary tumour samples. Both attempts fail to reflect either the original situation or functional information in the patient's tissue. Thus, we developed an improved in vitro assay to follow invasion of prostate cancer cells derived from fresh samples of radical prostatectomy specimens. Fresh tumour samples were applied onto Matrigeltrade mark-coated invasion chambers using a cocultivation model. Invasive growing cells were harvested from the bottom of the membrane or from the underlying gel and further characterized using comparative genomic hybridization. Prostate cancer cells have the capability to invasively grow through the barrier of a Matrigeltrade mark and could easily be sampled in a pad of Matrigeltrade mark. Comparative genomic hybridization revealed characteristic chromosomal aberrations of the invasive growing cells. Noteworthy is their ability to spheroid formation, which allows for further cell propagation by standard cell culture methods. Thus, our improved invasion model is a tool for the sampling of invasive growing cancer cells from fresh human tumour material allowing for functional as well as genetic studies.

Adrenal metastases in 1635 patients with renal cell carcinoma: outcome and indication for adrenalectomy.

PURPOSE: Routine removal of the ipsilateral adrenal gland in patients with renal cell carcinoma who undergo nephrectomy has been a matter of dispute. In a retrospective study we screened for subgroups of patients with renal cell carcinoma from a large single center patient population who may have benefited from ipsilateral adrenalectomy. MATERIALS AND METHODS: Radical nephrectomy was performed in 1635 patients at a single institution between 1980 and 2000. A total of 1010 patients underwent radical nephrectomy plus ipsilateral adrenalectomy, whereas in 625 no simultaneous adrenalectomy was performed. Numerous clinical and histopathological parameters were investigated by univariate and multivariate statistical methods for their predictive value in regard to cancer specific survival. RESULTS: Metastases in the adrenal gland were found in 5.5% of patients (56 of 1010) undergoing nephrectomy with adrenalectomy. Of 30 patients with adrenal metastasis and preoperative computerized tomography/magnetic resonance imaging 23 were found to have histological evidence of cancer, approaching a false-negative rate of 23.3%. All patients with false-negative computerized tomography/magnetic resonance imaging had a primary tumor of greater than 4 cm. Patients with adrenal metastases predominately had pT3 or greater tumor stage (82%). Cancer specific survival rates (75% vs 73% for adrenalectomy vs no adrenalectomy) and postoperative complications rates (7% vs 8%) did not differ significantly between the 2 groups. The prognosis in patients with a solitary adrenal metastasis (18 of 56) was more favorable than in patients with additional metastatic sites (38 of 56). CONCLUSIONS: Adrenal metastases from primary renal cell carcinoma were found significantly more often in patients with advanced tumor stages. Ipsilateral adrenalectomy should be recommended for all resectable renal cell carcinoma with a primary tumor of greater than 4 cm or with nonorgan confined tumor stages (T3 or greater) since a false-negative rate of about 20% can be expected with current imaging techniques.

[Molecular diagnostics of prostate cancer]. / Molekulare Diagnostik beim Prostatakarzinom.

Although a number of studies have identified molecular markers for prostate cancer, their clinical utility remains mainly unclear. Markers, which allow improved determination of the biological aggressiveness of individual prostate cancers, may help to optimize therapeutic management of this heterogeneous tumor type. Here, a subset of molecular markers, which are intensively discussed in the literature or which are supposed to gain clinical utility in the future, are described in more detail. For a better survey, the markers are divided into (a) susceptibility markers, (b) malignancy markers, and (c) aggressiveness markers. The number of markers described as well as the inconsistency across studies in assessing their clinical utility reflect the heterogeneity of prostate cancer also on a genetic level so that it is unlikely that a single marker will gain clinical relevance. Future research must include systematic analysis of the clinical utility of not only single markers but rather of marker profiles in appropriate studies.

Treatment of androgen-independent prostate cancer using antimicrotubule agents docetaxel and estramustine in combination: an experimental study.

BACKGROUND: Estramustine in combination with other chemotherapeutic agents has demonstrated synergy in hormone-refractory prostate cancer. Docetaxel has demonstrated antineoplastic activity in a variety of chemotherapeutic-unresponsive tumors. We evaluated the effects of estramustine and docetaxel in preclinical models of prostate cancer. METHODS: Cell viability of PC-3 and MAT-LyLu (MLL) cells were assessed 48 hr after drug treatment. For in vivo studies, each flank of five animals in six groups was injected with 1 x 10(6) MLL cells: control, estramustine, docetaxel (low- and high-dose), and low- and high-dose docetaxel with estramustine. Animals were treated on days 4 and 11, and sacrificed on day 14. RESULTS: The IC(50) value for docetaxel was 2 nM in the PC-3 cells and 40 nM in the MLL cells. The addition of 100 nM of estramustine did not alter the IC(50) value for PC-3 cells. In the MLL cells, however, the IC(50) value was lowered to 15 nM. In vivo, low-dose docetaxel with estramustine demonstrated antineoplastic activity similar to that of high-dose docetaxel alone, suggesting additive activity between the drugs. CONCLUSIONS: These results demonstrate that when used in combination, docetaxel and estramustine can be more effective at lower dosages than when the individual drugs are used alone.

Etoposide in prostate cancer.

Hormone refractory prostate cancer is a disease that kills approximately 39,000 people per year. No single chemotherapeutic agent or regimen has been demonstrated to provide a survival advantage in this disease. Etoposide as a single agent, both in i.v. and oral formulations has not proven to be effective. In the 1990s, however, etoposide has been combined with several agents to create novel treatment regiments for patients with hormone refractory disease. Several of these regimens, all involving oral etoposide, have demonstrated promising results in Phase II trials and early results suggest that they may increase survival for hormone refractory patients, although this remains to be tested in a Phase III trial setting.

Novel molecular targets for prostate cancer therapy.

The treatment options available for advanced prostate cancer are increasing. These improved therapies are the result of research involving cellular targets other than DNA proliferation. For example, therapy directed against the intracellular matrix has yielded clinical responses in patients. Other novel targets are being investigated. This review examines both laboratory and clinical advances using cell structure, growth factors, differentiating agents, angiogenesis, metastasis, and the cell cycle in the treatment of prostate cancer.