M.W. Kramer

Targeted therapy of urological tumours. Experimental field or established therapeutic approach

ZusammenfassungDer Einsatz der sog. „targeted“ Therapeutika verfolgt das Ziel, gegenüber der konventionellen Chemotherapie nicht allgemeine, im Wesentlichen in die zelluläre Replikation involvierte Mechanismen zu inhibieren, sondern auf molekularer Ebene gezielt die Aktivierung solcher Pathways oder Signaltranduktionswege zu beeinflussen, für die eine wesentliche Beteiligung an der Progression humaner Malignome angenommen wird. Während dieser Ansatz beispielsweise in der Behandlung des Nierenzellkarzinoms aufgrund der gegenüber Zytokin-basierten Therapieformen überlegenen klinischen Effektivität etabliert ist, stehen für andere urologische Malignome wie das Harnblasen- oder Prostatakarzinom lediglich rudimentäre Ergebnisse aus kleineren klinischen Serien zur Verfügung. Ziel der vorliegenden Arbeit ist es, den gegenwärtigen Stellenwert der Target-Therapie in der Behandlung verschiedener Tumorentitäten des urologischen Formenkreises zu beschreiben.AbstractUnlike conventional systemic chemotherapies, the aim of targeted therapeutic approaches is not to address general mechanisms involved in cellular replication. In contrast, they aim at such regulatory pathways that have been identified to be involved in the progression of human malignant disease. Whereas the application of targeted therapeutic modalities is well established for the treatment of metastatic renal cell cancer, only very few data on their clinical efficacy during the treatment of other urological tumours such as prostate and bladder cancer are currently available. The aim of this paper is to reflect on the current status regarding the relevance of targeted therapeutic approaches during the treatment of urological cancers of different origin.Unlike conventional systemic chemotherapies, the aim of targeted therapeutic approaches is not to address general mechanisms involved in cellular replication. In contrast, they aim at such regulatory pathways that have been identified to be involved in the progression of human malignant disease. Whereas the application of targeted therapeutic modalities is well established for the treatment of metastatic renal cell cancer, only very few data on their clinical efficacy during the treatment of other urological tumours such as prostate and bladder cancer are currently available. The aim of this paper is to reflect on the current status regarding the relevance of targeted therapeutic approaches during the treatment of urological cancers of different origin.

Die Target-Therapie urologischer Tumoren

ZusammenfassungDer Einsatz der sog. „targeted“ Therapeutika verfolgt das Ziel, gegenüber der konventionellen Chemotherapie nicht allgemeine, im Wesentlichen in die zelluläre Replikation involvierte Mechanismen zu inhibieren, sondern auf molekularer Ebene gezielt die Aktivierung solcher Pathways oder Signaltranduktionswege zu beeinflussen, für die eine wesentliche Beteiligung an der Progression humaner Malignome angenommen wird. Während dieser Ansatz beispielsweise in der Behandlung des Nierenzellkarzinoms aufgrund der gegenüber Zytokin-basierten Therapieformen überlegenen klinischen Effektivität etabliert ist, stehen für andere urologische Malignome wie das Harnblasen- oder Prostatakarzinom lediglich rudimentäre Ergebnisse aus kleineren klinischen Serien zur Verfügung. Ziel der vorliegenden Arbeit ist es, den gegenwärtigen Stellenwert der Target-Therapie in der Behandlung verschiedener Tumorentitäten des urologischen Formenkreises zu beschreiben.AbstractUnlike conventional systemic chemotherapies, the aim of targeted therapeutic approaches is not to address general mechanisms involved in cellular replication. In contrast, they aim at such regulatory pathways that have been identified to be involved in the progression of human malignant disease. Whereas the application of targeted therapeutic modalities is well established for the treatment of metastatic renal cell cancer, only very few data on their clinical efficacy during the treatment of other urological tumours such as prostate and bladder cancer are currently available. The aim of this paper is to reflect on the current status regarding the relevance of targeted therapeutic approaches during the treatment of urological cancers of different origin.Unlike conventional systemic chemotherapies, the aim of targeted therapeutic approaches is not to address general mechanisms involved in cellular replication. In contrast, they aim at such regulatory pathways that have been identified to be involved in the progression of human malignant disease. Whereas the application of targeted therapeutic modalities is well established for the treatment of metastatic renal cell cancer, only very few data on their clinical efficacy during the treatment of other urological tumours such as prostate and bladder cancer are currently available. The aim of this paper is to reflect on the current status regarding the relevance of targeted therapeutic approaches during the treatment of urological cancers of different origin.

C-reaktives Protein vor radikaler Zystektomie

BACKGROUND Numerous studies have shown a positive correlation between elevated C-reactive protein (CRP) and systemic spread of malignancies. The goal of the current study was to assess the predictive significance of preoperative CRP in patients undergoing radical cystectomy (RC). MATERIAL AND METHODS Preoperative CRP values were measured in 194 patients undergoing RC because of urothelial carcinoma between 1996 and 2005. Elevated CRP level was defined as ≥ 5 mg/l. RESULTS Preoperative increased CRP values were detected in 89 (45.9%) patients and these patients were more likely to have advanced tumor stages (pT3-4), positive resection margins and positive lymph nodes. Advanced urinary diversions were more common in patients with normal CRP values. In multivariate analysis, CRP was identified as an independent prognostic indicator for poor cancer-specific survival. CONCLUSION The results confirm previous reports that showed a prognostic significance of preoperative CRP elevation.

Systemic therapy of metastatic bladder cancer.

This review focuses on current options in the medical therapy of metastasized urothelial carcinoma of the bladder. Standard treatments as well as new, recently published therapeutic approaches are evaluated and discussed.ZusammenfassungIn dieser Übersichtsarbeit werden die aktuellen medikamentösen Therapieoptionen beim metastasierten Urothelkarzinom der Harnblase vorgestellt. Neben den Standardtherapien werden neue Therapieansätze diskutiert und bewertet, die in den letzten Jahren publiziert oder auf Kongressen vorgestellt wurden.AbstractThis review focuses on current options in the medical therapy of metastasized urothelial carcinoma of the bladder. Standard treatments as well as new, recently published therapeutic approaches are evaluated and discussed.

Systemische Therapie des metastasierten Blasenkarzinoms

This review focuses on current options in the medical therapy of metastasized urothelial carcinoma of the bladder. Standard treatments as well as new, recently published therapeutic approaches are evaluated and discussed.ZusammenfassungIn dieser Übersichtsarbeit werden die aktuellen medikamentösen Therapieoptionen beim metastasierten Urothelkarzinom der Harnblase vorgestellt. Neben den Standardtherapien werden neue Therapieansätze diskutiert und bewertet, die in den letzten Jahren publiziert oder auf Kongressen vorgestellt wurden.AbstractThis review focuses on current options in the medical therapy of metastasized urothelial carcinoma of the bladder. Standard treatments as well as new, recently published therapeutic approaches are evaluated and discussed.

Transurethrale En-bloc-Resektion nicht muskelinvasiver Harnblasenkarzinome

ZusammenfassungDas Harnblasenkarzinom entwickelt sich aufgrund verschiedener Faktoren zu einer zunehmenden sozioökonomischen Herausforderung. Einerseits kann die im Alter nachgewiesene gesteigerte Inzidenz auf eine längere Wirkung potentiell kanzerogener Noxen mit weitreichenden Auswirkungen auf eine alternde Gesellschaft zurückgeführt werden, andererseits stellt gerade eine alternde Population vor dem Hintergrund zunehmender Komorbiditäten eine Herausforderung unter Beeinflussung der chirurgischen Indikationsstellung an die behandelnde Ärzteschaft dar.Das Standardverfahren zur histologischen Sicherung und Behandlung nicht muskelinvasiver Urothelkarzinome ist die transurethrale Resektion (TURB). Mit dem Holmiumlaser (Ho:YAG), Thuliumlaser (Tm:YAG) sowie mit dem HybridKnife® stehen modifizierte Alternativverfahren insbesondere für En-bloc-Resektionen zur Verfügung. Als Vorteile dieser modifizierten Verfahren sind eine verbesserte Schnittpräzision sowie eine sofortige Hämostase beschrieben worden. Ziele sind eine Reduktion peri- und postoperativer Risiken, eine bessere pathohistologische Aufarbeitung des entnommenen Gewebes sowie ein verlängertes rezidivfreies Überleben.Diese Übersichtsarbeit gibt eine Zusammenfassung hinsichtlich der aktuellen Datenlage zu En-bloc-Resektionen von Harnblasentumoren, der dabei zur Verfügung stehenden technischen Möglichkeiten sowie der peri- und postoperativen Komplikationsraten. Ferner werden die Vorteile eines pathohistologischen Aufarbeitens en bloc resezierten Gewebes diskutiert. Vor dem Hintergrund fehlender randomisierter, prospektiver, TURB vergleichender Studien ist eine onkologische Bewertung der Studienergebnisse zum aktuellen Stand nicht möglich.AbstractBladder cancer of the urothelium is the second most common malignancy among urological tumors. In view of a worldwide aging population and the fact that increased incidence rates are associated with higher age, new socioeconomic challenges will appear. Even nowadays the treatment of bladder cancer bears the highest lifetime treatment costs per patient among all forms of cancer. In conjunction with higher comorbidity rates among older patients urologists are facing new challenges in the treatment and care of patients with bladder cancer. The standard treatment for non-muscle invasive bladder cancer (NMIBC) is monopolar transurethral resection using resection loops (TURB). Based on experience in the surgical treatment of benign prostatic hyperplasia, different concepts of en bloc resection of bladder tumors using alternative energy resources (e.g. holmium laser, thulium laser and the water-jet HybridKnife®) have been developed. Goals of new treatment modalities are reduction of perioperative and postoperative comorbidities, better pathological work-up of the specimens and increased recurrence-free survival. Postulated advantages using laser devices are a more precise cutting line as well as better hemostasis. The evidential value of this review is limited due to the lack of randomized, prospective studies. However, there is a tendency towards a limitation of perioperative and postoperative morbidities as well as higher chance of well-preserved tissues for better pathohistological evaluation using en bloc resection methods. More studies with long-term follow-up periods and better randomization are needed to clarify whether en bloc strategies provide better long-term oncological survival.Bladder cancer of the urothelium is the second most common malignancy among urological tumors. In view of a worldwide aging population and the fact that increased incidence rates are associated with higher age, new socioeconomic challenges will appear. Even nowadays the treatment of bladder cancer bears the highest lifetime treatment costs per patient among all forms of cancer. In conjunction with higher comorbidity rates among older patients urologists are facing new challenges in the treatment and care of patients with bladder cancer. The standard treatment for non-muscle invasive bladder cancer (NMIBC) is monopolar transurethral resection using resection loops (TURB). Based on experience in the surgical treatment of benign prostatic hyperplasia, different concepts of en bloc resection of bladder tumors using alternative energy resources (e.g. holmium laser, thulium laser and the water-jet HybridKnife) have been developed. Goals of new treatment modalities are reduction of perioperative and postoperative comorbidities, better pathological work-up of the specimens and increased recurrence-free survival. Postulated advantages using laser devices are a more precise cutting line as well as better hemostasis. The evidential value of this review is limited due to the lack of randomized, prospective studies. However, there is a tendency towards a limitation of perioperative and postoperative morbidities as well as higher chance of well-preserved tissues for better pathohistological evaluation using en bloc resection methods. More studies with long-term follow-up periods and better randomization are needed to clarify whether en bloc strategies provide better long-term oncological survival.

Systemic and surgical management of metastatic renal cell carcinoma

Several targeted therapies have become available for first-line (sunitinib, bevacizumab, pazopanib, temsirolimus) and second-line (sorafenib, pazopanib, everolimus) use in recent years. The superior outcomes achieved with these targeted agents have led to replacement of the formerly administered cytokines. New developments have raised the question of whether patients benefit from sequential therapies with tyrosine kinase inhibitors and/or whether combination regimes can improve clinical outcomes. This review gives an overview of the current therapeutic options for first- and second-line treatment in metastatic RCC as well as sequential and combination therapies. Adjuvant and neoadjuvant treatment options are being discussed. Furthermore, this review addresses surgical alternatives in the treatment of RCC.

Systemische und operative Therapie des metastasierten Nierenzellkarzinoms

Several targeted therapies have become available for first-line (sunitinib, bevacizumab, pazopanib, temsirolimus) and second-line (sorafenib, pazopanib, everolimus) use in recent years. The superior outcomes achieved with these targeted agents have led to replacement of the formerly administered cytokines. New developments have raised the question of whether patients benefit from sequential therapies with tyrosine kinase inhibitors and/or whether combination regimes can improve clinical outcomes. This review gives an overview of the current therapeutic options for first- and second-line treatment in metastatic RCC as well as sequential and combination therapies. Adjuvant and neoadjuvant treatment options are being discussed. Furthermore, this review addresses surgical alternatives in the treatment of RCC.

[Transurethral en bloc resection of non-muscle invasive bladder cancer. What is the state of the art?].

ZusammenfassungDas Harnblasenkarzinom entwickelt sich aufgrund verschiedener Faktoren zu einer zunehmenden sozioökonomischen Herausforderung. Einerseits kann die im Alter nachgewiesene gesteigerte Inzidenz auf eine längere Wirkung potentiell kanzerogener Noxen mit weitreichenden Auswirkungen auf eine alternde Gesellschaft zurückgeführt werden, andererseits stellt gerade eine alternde Population vor dem Hintergrund zunehmender Komorbiditäten eine Herausforderung unter Beeinflussung der chirurgischen Indikationsstellung an die behandelnde Ärzteschaft dar.Das Standardverfahren zur histologischen Sicherung und Behandlung nicht muskelinvasiver Urothelkarzinome ist die transurethrale Resektion (TURB). Mit dem Holmiumlaser (Ho:YAG), Thuliumlaser (Tm:YAG) sowie mit dem HybridKnife® stehen modifizierte Alternativverfahren insbesondere für En-bloc-Resektionen zur Verfügung. Als Vorteile dieser modifizierten Verfahren sind eine verbesserte Schnittpräzision sowie eine sofortige Hämostase beschrieben worden. Ziele sind eine Reduktion peri- und postoperativer Risiken, eine bessere pathohistologische Aufarbeitung des entnommenen Gewebes sowie ein verlängertes rezidivfreies Überleben.Diese Übersichtsarbeit gibt eine Zusammenfassung hinsichtlich der aktuellen Datenlage zu En-bloc-Resektionen von Harnblasentumoren, der dabei zur Verfügung stehenden technischen Möglichkeiten sowie der peri- und postoperativen Komplikationsraten. Ferner werden die Vorteile eines pathohistologischen Aufarbeitens en bloc resezierten Gewebes diskutiert. Vor dem Hintergrund fehlender randomisierter, prospektiver, TURB vergleichender Studien ist eine onkologische Bewertung der Studienergebnisse zum aktuellen Stand nicht möglich.AbstractBladder cancer of the urothelium is the second most common malignancy among urological tumors. In view of a worldwide aging population and the fact that increased incidence rates are associated with higher age, new socioeconomic challenges will appear. Even nowadays the treatment of bladder cancer bears the highest lifetime treatment costs per patient among all forms of cancer. In conjunction with higher comorbidity rates among older patients urologists are facing new challenges in the treatment and care of patients with bladder cancer. The standard treatment for non-muscle invasive bladder cancer (NMIBC) is monopolar transurethral resection using resection loops (TURB). Based on experience in the surgical treatment of benign prostatic hyperplasia, different concepts of en bloc resection of bladder tumors using alternative energy resources (e.g. holmium laser, thulium laser and the water-jet HybridKnife®) have been developed. Goals of new treatment modalities are reduction of perioperative and postoperative comorbidities, better pathological work-up of the specimens and increased recurrence-free survival. Postulated advantages using laser devices are a more precise cutting line as well as better hemostasis. The evidential value of this review is limited due to the lack of randomized, prospective studies. However, there is a tendency towards a limitation of perioperative and postoperative morbidities as well as higher chance of well-preserved tissues for better pathohistological evaluation using en bloc resection methods. More studies with long-term follow-up periods and better randomization are needed to clarify whether en bloc strategies provide better long-term oncological survival.Bladder cancer of the urothelium is the second most common malignancy among urological tumors. In view of a worldwide aging population and the fact that increased incidence rates are associated with higher age, new socioeconomic challenges will appear. Even nowadays the treatment of bladder cancer bears the highest lifetime treatment costs per patient among all forms of cancer. In conjunction with higher comorbidity rates among older patients urologists are facing new challenges in the treatment and care of patients with bladder cancer. The standard treatment for non-muscle invasive bladder cancer (NMIBC) is monopolar transurethral resection using resection loops (TURB). Based on experience in the surgical treatment of benign prostatic hyperplasia, different concepts of en bloc resection of bladder tumors using alternative energy resources (e.g. holmium laser, thulium laser and the water-jet HybridKnife) have been developed. Goals of new treatment modalities are reduction of perioperative and postoperative comorbidities, better pathological work-up of the specimens and increased recurrence-free survival. Postulated advantages using laser devices are a more precise cutting line as well as better hemostasis. The evidential value of this review is limited due to the lack of randomized, prospective studies. However, there is a tendency towards a limitation of perioperative and postoperative morbidities as well as higher chance of well-preserved tissues for better pathohistological evaluation using en bloc resection methods. More studies with long-term follow-up periods and better randomization are needed to clarify whether en bloc strategies provide better long-term oncological survival.

Transurethrale En-bloc-Resektion nicht muskelinvasiver HarnblasenkarzinomeTransurethral en bloc resection of non-muscle invasive bladder cancer

ZusammenfassungDas Harnblasenkarzinom entwickelt sich aufgrund verschiedener Faktoren zu einer zunehmenden sozioökonomischen Herausforderung. Einerseits kann die im Alter nachgewiesene gesteigerte Inzidenz auf eine längere Wirkung potentiell kanzerogener Noxen mit weitreichenden Auswirkungen auf eine alternde Gesellschaft zurückgeführt werden, andererseits stellt gerade eine alternde Population vor dem Hintergrund zunehmender Komorbiditäten eine Herausforderung unter Beeinflussung der chirurgischen Indikationsstellung an die behandelnde Ärzteschaft dar.Das Standardverfahren zur histologischen Sicherung und Behandlung nicht muskelinvasiver Urothelkarzinome ist die transurethrale Resektion (TURB). Mit dem Holmiumlaser (Ho:YAG), Thuliumlaser (Tm:YAG) sowie mit dem HybridKnife® stehen modifizierte Alternativverfahren insbesondere für En-bloc-Resektionen zur Verfügung. Als Vorteile dieser modifizierten Verfahren sind eine verbesserte Schnittpräzision sowie eine sofortige Hämostase beschrieben worden. Ziele sind eine Reduktion peri- und postoperativer Risiken, eine bessere pathohistologische Aufarbeitung des entnommenen Gewebes sowie ein verlängertes rezidivfreies Überleben.Diese Übersichtsarbeit gibt eine Zusammenfassung hinsichtlich der aktuellen Datenlage zu En-bloc-Resektionen von Harnblasentumoren, der dabei zur Verfügung stehenden technischen Möglichkeiten sowie der peri- und postoperativen Komplikationsraten. Ferner werden die Vorteile eines pathohistologischen Aufarbeitens en bloc resezierten Gewebes diskutiert. Vor dem Hintergrund fehlender randomisierter, prospektiver, TURB vergleichender Studien ist eine onkologische Bewertung der Studienergebnisse zum aktuellen Stand nicht möglich.AbstractBladder cancer of the urothelium is the second most common malignancy among urological tumors. In view of a worldwide aging population and the fact that increased incidence rates are associated with higher age, new socioeconomic challenges will appear. Even nowadays the treatment of bladder cancer bears the highest lifetime treatment costs per patient among all forms of cancer. In conjunction with higher comorbidity rates among older patients urologists are facing new challenges in the treatment and care of patients with bladder cancer. The standard treatment for non-muscle invasive bladder cancer (NMIBC) is monopolar transurethral resection using resection loops (TURB). Based on experience in the surgical treatment of benign prostatic hyperplasia, different concepts of en bloc resection of bladder tumors using alternative energy resources (e.g. holmium laser, thulium laser and the water-jet HybridKnife®) have been developed. Goals of new treatment modalities are reduction of perioperative and postoperative comorbidities, better pathological work-up of the specimens and increased recurrence-free survival. Postulated advantages using laser devices are a more precise cutting line as well as better hemostasis. The evidential value of this review is limited due to the lack of randomized, prospective studies. However, there is a tendency towards a limitation of perioperative and postoperative morbidities as well as higher chance of well-preserved tissues for better pathohistological evaluation using en bloc resection methods. More studies with long-term follow-up periods and better randomization are needed to clarify whether en bloc strategies provide better long-term oncological survival.Bladder cancer of the urothelium is the second most common malignancy among urological tumors. In view of a worldwide aging population and the fact that increased incidence rates are associated with higher age, new socioeconomic challenges will appear. Even nowadays the treatment of bladder cancer bears the highest lifetime treatment costs per patient among all forms of cancer. In conjunction with higher comorbidity rates among older patients urologists are facing new challenges in the treatment and care of patients with bladder cancer. The standard treatment for non-muscle invasive bladder cancer (NMIBC) is monopolar transurethral resection using resection loops (TURB). Based on experience in the surgical treatment of benign prostatic hyperplasia, different concepts of en bloc resection of bladder tumors using alternative energy resources (e.g. holmium laser, thulium laser and the water-jet HybridKnife) have been developed. Goals of new treatment modalities are reduction of perioperative and postoperative comorbidities, better pathological work-up of the specimens and increased recurrence-free survival. Postulated advantages using laser devices are a more precise cutting line as well as better hemostasis. The evidential value of this review is limited due to the lack of randomized, prospective studies. However, there is a tendency towards a limitation of perioperative and postoperative morbidities as well as higher chance of well-preserved tissues for better pathohistological evaluation using en bloc resection methods. More studies with long-term follow-up periods and better randomization are needed to clarify whether en bloc strategies provide better long-term oncological survival.