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Die Behandlung des fortgeschrittenen Prostatakarzinoms befindet sich im Wandel. Neue Studiendaten und daraus resultierende neue Therapieoptionen fuhren zu immer differenzierteren Therapieentscheidungen. Trotz der sich verandernden Therapielandschaft ist und bleibt die Taxan-basierte Chemotherapie im metastasierten Stadium als lebensverlangernde Behandlung ein unverzichtbarer Therapiebestandteil fur Chemotherapie-fitte Patienten. Die aktuellen Ergebnisse der randomisierten CARD-Studie zeigen bei Patienten mit metastasiertem kastrationsresistentem Prostatakarzinom (mCRPC), die nach Behandlung mit Docetaxel und einer gegen den Androgenrezeptor gerichteten Substanz (ARTA, „androgen receptor targeted agent“) einen Progress aufweisen, dass Cabazitaxel gegenuber einer zweiten ARTA eine signifikant hohere Wirksamkeit inklusive einer signifikanten Lebensverlangerung erzielt, die mit einem besseren Effekt auf Lebensqualitatsparameter verbunden ist. Beim metastasierten kastrationsnaiven Prostatakarzinom (mCNPC) hat sich die Kombinationstherapie aus Androgendeprivationstherapie (ADT) plus Docetaxel bzw. plus einer ARTA etabliert. Daruber hinaus wurden kurzlich drei ARTA fur die Behandlung des nichtmetastasierten kastrationsrefraktaren Prostatakarzinoms (nmCRPC) zugelassen, nachdem gezeigt werden konnte, dass durch ihren Einsatz in Phase-III-Studien sowohl das metastasenfreie Uberleben als auch das Gesamtuberleben signifikant verlangert werden kann. Der potenzielle fruhe Einsatz der ARTA hat auch Auswirkungen auf die Behandlung des mCRPC. Ziel der vorliegenden Publikation ist es, vor dem Hintergrund der aktuellen Datenlage eine Orientierungshilfe fur den klinischen Alltag zu geben und Kriterien fur die individuelle Therapieentscheidung unter besonderer Berucksichtigung der Chemotherapie zu erarbeiten.

Background: Focal therapy (FT) is an option to treat localized prostate cancer (PCa) and preserve healthy prostate tissue in order to reduce known side effects from primary whole-gland treatment. The available FT modalities are manifold. Until now, national and international PCa guidelines have been cautious to propose recommendations regarding FT treatment since data from prospective controlled trials are lacking for most FT modalities. Moreover, none of the international guidelines provides a separate section on FT. In this purpose, we provide a synopsis of the consensus-based German S3 guidelines for a possible international use. Summary: The recently published update of the German S3 guidelines, an evidence- and consensus-based guideline, provides a section on FT with recommendations for diagnostic work-up, indications, modalities, and follow-up. This section consists of 12 statements and recommendations for FT in the treatment of localized PCa. Key Message: The German S3 guidelines on PCa are the first to incorporate recommendations for FT based on evidence and expert consensus including indication criteria for FT, pretreatment, and follow-up diagnostic pathways as well as an extended overview of FT techniques and the current supportive evidence.

Die Taxan-basierte Chemotherapie und die gegen den Androgenrezeptor gerichteten Substanzen („androgen receptor-targeted agent“, ARTA) haben die therapeutischen Moglichkeiten beim metastasierten Prostatakarzinom (mPC) deutlich erweitert und bieten den Patienten die Chance, langer zu uberleben. Die Therapiesequenz von ARTA und Taxanen kann Einfluss auf die Prognose haben und muss individuell entschieden werden. Ziel der vorliegenden Publikation ist es, eine Orientierungshilfe fur den klinischen Alltag zu geben und Kriterien zu erarbeiten, die bei der individuellen Therapieentscheidung berucksichtigt werden konnen. Im Fokus stehen das metastasierte hormonnaive PC, die Behandlung oligometastasierter Patienten sowie das nichtmetastasierte und das metastasierte kastrationsresistente PC.

There is an ongoing change of paradigm in the treatment of metastatic prostate cancer (mPC). Taxan-based chemotherapy demonstrated a prolonged survival of patients in several randomized phase III trials. This is true in the situation of metastatic castration-resistent prostate cancer (mCRPC) as well as in the hormone-naive stage (metastatic castration-naive PC [mCNPC]). In patients with mCNPC, treatment with docetaxel in combination with androgen deprivation therapy (ADT) prolonged the median total survival time by 15 months in comparison to ADT alone. Comparable results were obtained by the endocrine combination treatment with ADT/abiraterone. With the current data in mind it seems to be useful to discuss the value of early combination therapy with ADT/docetaxel or ADT/abiraterone as well as the impact on further treatment options in the mCRPC setting and to define criteria for treatment decisions in clinical practice.

The treatment of advanced prostate cancer is changing. New study data and the resulting new therapeutic options have led to increasingly differentiated treatment decisions. Despite the changing therapy landscape, taxane-based chemotherapy-being a life-prolonging treatment-remains an indispensable therapeutic component for chemotherapy-fit patients in the metastatic setting. The current results of the randomized study CARD show that cabazitaxel has a higher oncological effectiveness, including a significant survival benefit and no negative impact on quality of life parameters, compared to a second androgen receptor targeted agent (ARTA) in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed after treatment with docetaxel and an androgen receptor-targeted agent (ARTA). In mCNPC the combination therapies of ADT (androgen deprivation therapy) plus docetaxel or of ADT plus ARTA have been established. In addition, three ARTAs tested in recent phase III studies in a clinical setting for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) showed that their use significantly prolongs metastasis-free survival and overall survival. The potential early use of ARTAs also has implications for the treatment of mCNPC. The aim of this publication is to provide guidance for clinical routine and to develop criteria for individual therapy decisions with a special focus on the use of chemotherapy.Die Behandlung des fortgeschrittenen Prostatakarzinoms befindet sich im Wandel. Neue Studiendaten und daraus resultierende neue Therapieoptionen führen zu immer differenzierteren Therapieentscheidungen. Trotz der sich verändernden Therapielandschaft ist und bleibt die Taxan-basierte Chemotherapie im metastasierten Stadium als lebensverlängernde Behandlung ein unverzichtbarer Therapiebestandteil für Chemotherapie-fitte Patienten. Die aktuellen Ergebnisse der randomisierten CARD-Studie zeigen bei Patienten mit metastasiertem kastrationsresistentem Prostatakarzinom (mCRPC), die nach Behandlung mit Docetaxel und einer gegen den Androgenrezeptor gerichteten Substanz (ARTA, „androgen receptor targeted agent“) einen Progress aufweisen, dass Cabazitaxel gegenüber einer zweiten ARTA eine signifikant höhere Wirksamkeit inklusive einer signifikanten Lebensverlängerung erzielt, die mit einem besseren Effekt auf Lebensqualitätsparameter verbunden ist. Beim metastasierten kastrationsnaiven Prostatakarzinom (mCNPC) hat sich die Kombinationstherapie aus Androgendeprivationstherapie (ADT) plus Docetaxel bzw. plus einer ARTA etabliert. Darüber hinaus wurden kürzlich drei ARTA für die Behandlung des nichtmetastasierten kastrationsrefraktären Prostatakarzinoms (nmCRPC) zugelassen, nachdem gezeigt werden konnte, dass durch ihren Einsatz in Phase-III-Studien sowohl das metastasenfreie Überleben als auch das Gesamtüberleben signifikant verlängert werden kann. Der potenzielle frühe Einsatz der ARTA hat auch Auswirkungen auf die Behandlung des mCRPC. Ziel der vorliegenden Publikation ist es, vor dem Hintergrund der aktuellen Datenlage eine Orientierungshilfe für den klinischen Alltag zu geben und Kriterien für die individuelle Therapieentscheidung unter besonderer Berücksichtigung der Chemotherapie zu erarbeiten.

Background: Intravesical instillation of bacillus Calmette-Guerin (BCG) is an accepted strategy to prevent recurrence of non–muscle-invasive bladder cancer (NMIBC) but associated with significant toxicity. Objective: NIMBUS assessed whether a reduced number of standard-dose BCG instillations are noninferior to the standard number and dose in patients with high-grade NMIBC. Design, setting, and participants: A total of 345 patients from 51 sites were randomised between December 2013 and July 2019. We report results after a data review and safety analysis by the Independent Data Monitoring Committee based on the cut-off date of July 1, 2019. Intervention: The standard BCG schedule was 6 wk of induction followed by 3 wk of maintenance at 3, 6, and 12 mo (15 instillations). The reduced frequency BCG schedule was induction at wks 1, 2, and 6 followed by 2 wk (wks 1 and 3) of maintenance at 3, 6, and 12 mo (nine instillations). Outcome measurements and statistical analysis: The primary endpoint was time to first recurrence. Secondary endpoints included progression to ≥ T2 and toxicity. Results and limitations: In total, 170 patients were randomised to reduced frequency and 175 to standard BCG. Prognostic factors at initial resection were as follows: Ta/T1: 46/54%; primary/recurrent: 92/8%; single/multiple: 57/43%; and concomitant carcinoma in situ: 27%. After 12 mo of median follow-up, the intention-to-treat analysis showed a safety-relevant difference in recurrences between treatment arms: 46/170 (reduced frequency) versus 21/175 patients (standard). Additional safety analyses showed a hazard ratio of 0.40 with the upper part of the one-sided 97.5% confidence interval of 0.68, meeting a predefined stopping criterion for inferiority. Conclusions: The reduced frequency schedule was inferior to the standard schedule regarding the time to first recurrence. Further recruitment of patients was stopped immediately to avoid harm in the reduced frequency BCG arm. Patient summary: After surgical removal of the tumour, patients with high-grade non–muscle-invasive bladder cancer are treated with bacillus Calmette-Guerin to prevent recurrence and progression. This is associated with significant side effects. We report the results of a clinical trial showing a reduction in the number of instillations (from 15 to nine in total) being inferior to the standard protocol. From today's perspective, complete tumour resection and a standard number of instillations remain the standard of care. In high-grade non–muscle-invasive bladder cancer, a reduced frequency of bacillus Calmette-Guerin (BCG) instillations during induction and maintenance is inferior to the standard BCG schedule regarding time to first recurrence. Repeated transurethral resection followed by the standard BCG regimen, as recommended by the European Association of Urology guideline, remains the state of the art. (Less)

63 Background: Metastatic castration-resistant prostate cancer (mCRPC) is a lethal disease with significant morbidity. Poly adenosine diphosphate-ribose polymerase inhibitors (PARPi) are targeted therapeutics approved to treat mCRPC patients with genetic mutations in homologous recombination repair (HRR). However, to benefit from PARPi as a single agent, patients usually need to undergo biomarker testing to determine their mutation status. As an initial step to understand patient preferences for mCRPC treatments, this study investigated the treatment features important to mCRPC patients and their preferences for and perceptions of biomarker testing. Methods: This preliminary qualitative study included 25 men in the US, UK, Germany, Spain, and Japan with self-reported mCRPC diagnosed at least 6 months previously. Participants completed a 60-minute one-on-one interview about mCRPC treatments and disease impact. Results: Participants had a mean age of 62 years and were diagnosed with prostate cancer an average of 68 months prior. About half (52%) had metastasized > 1 year prior and more than half (56%) reported no HRR genetic mutation . The most frequently reported symptoms were pain (60%), urinary problems (56%), and fatigue (32%). Participants stated that pain impacted their sleep, daily activities, and social lives. 60% reported they shared treatment decision-making with their physician, some (24%) shared it with partners or caregivers, and others (32%) left treatment decisions up to their physician due to their lack of knowledge. Quality of life (QoL) was the most important treatment benefit reported (56%), followed by progression-free survival (PFS) (52%), overall survival (OS) (48%), and reduced pain (44%). Some participants reported their desire for prolonged survival needed to be balanced with adequate QoL. Few participants reported reduced fatigue (24%) or urinary problems (12%) as desired treatment benefits. 64% had previously undergone biomarker testing to determine mutation status. 56% of tested participants reported that their physician discussed the purpose and benefits of testing. Based on conversations with their physicians, both tested and untested participants felt that biomarker testing would inform them about heritable risk of mutation and help find new targeted treatments. Untested participants with a negative view of biomarker testing (22%) reported concerns about the need for further invasive biopsies. Conclusions: QoL followed by PFS, OS, and reduced pain were the most important benefits of treatment to participants. More than half of participants had a positive view of biomarker testing, especially if testing could lead to targeted therapies and inform about heritable risk. These results will inform the design of an international discrete choice study of biomarker testing among men with mCRPC.

In March 2017 the 'Advanced Prostate Cancer Consensus Conference' (APCCC) took place in St. Gallen (Switzerland). The APCCC-panelists are internationally well known experts. With the actual data in mind they discussed treatment options for patients with advanced prostate cancer in order to update the international APCCC-recommendations from the previous meeting in 2015. Recently these consensus recommendations have been published in "European Urology".A group of German experts discussed this year APCCC-votes during the meeting and the recommendations that were concluded from the votes from the German perspective. Reasons for an additional German discussion are country-specific variations that may have influenced the APCCC-votes und recommendations. Due to the concept of the APCCC-meeting the wording of the questions could not always be as necessary.One focus of this year consensus discussion was the treatment of metastatic castration-naive prostate cancer (mCNPC). There are new data which may also influence the therapeutic situation of patients with metastatic castration-resistant prostate cancer (mCRPC). Further points of discussion were the impact of new imaging procedures in the clinical setting as well as the treatment of oligometastatic prostate cancer.

Background At the 2016 ASCO annual meeting, new data from two randomized phase III studies concerning taxane-based chemotherapy as a treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC) were presented. Objectives The focus is on the clinical impact of these data. Materials and methods A group of German experts in the field of urogenital-oncologic expertise discussed the clinical impact with respect to the current data. Results The study results support the current clinical data. They confirm the efficacy and safety of cabazitaxel beyond first-line therapy with docetaxel for patients with mCRPC. Conclusions Cabazitaxel is an important treatment option after docetaxel progression. With respect to the performance status of a patient, it is adequate to reduce the dosage to 20 mg/m2 cabazitaxel.

Ziel der fokalen Therapie (FT) des Prostatakarzinoms (PC) ist eine Teilbehandlung der Prostata unter Schonung der angrenzenden Strukturen. Dadurch sollen typische Nebenwirkungen radikaler Therapieoptionen bei gleichzeitiger Tumorkontrolle minimiert werden. Zahlreiche etablierte und neue Technologien kommen dazu zum Einsatz. Ergebnisse zahlreicher Fallserien belegen ein geringes Nebenwirkungsspektrum bei guten funktionellen Ergebnissen. Onkologische Langzeitergebnisse liegen bislang nicht vor.

BACKGROUND Taxen-based chemotherapy has been established as an effective treatment option in castration-resistant metastatic prostate cancer (mCRPC). Randomized phase III studies, however, have shown that even in the hormone-naive metastatic state, the early use of chemotherapy in addition to the classical androgen deprivation therapy (ADT) approach leads to a significant increase in median overall survival. OBJECTIVE This position paper aims to provide current data and orientation in the evidence-based treatment of mPC patients in daily clinical practice. MATERIALS AND METHODS A German group of clinical experts analyzed the current data and developed criteria for the treatment of mPC patients in daily clinical practice. RESULTS In the current treatment of hormone-naive mPC, a beneficial effect of chemotherapy in addition to ADT has become evident. Provided patients are in an appropriate condition, those with a high metastatic load should receive chemotherapy in addition to ADT. Especially in high-risk mCRPC patients (PSA >114 ng/ml, visceral metastasis, ADT response

Es existieren zahlreiche Systeme zur MRT/TRUS-fusionierten Biopsie der Prostata. Insgesamt liegt ausreichend Literatur zur Fusionsbiopsie vor, die einen Vorteil bei der Tumordetektion und der Diagnosequalitat gegenuber der Randombiopsie belegt. Der Nutzen der Systeme im Rahmen der fokalen Therapie des Prostatakarzinoms (PC) ist unklar. Ziel war die kritische Prufung der vorhandenen Fusionssysteme fur die Planung und Verlaufskontrolle einer fokalen Therapie des PC. Es erfolgte eine systematische Literaturrecherche zu den erhaltlichen Fusionssystemen fur den Zeitraum 2013–5/2016. Durch den Arbeitskreis „Fokale und Mikrotherapie“ wurde ein Kriterienkatalog zu technischen Details, der Eignung in speziellen Situationen und der Eignung im Rahmen der fokalen Therapie des PC erstellt. Acht Fusionssysteme wurden betrachtet (Artemis™, BioJet, BiopSee®, iSR’obot™ Mona Lisa, Hitachi HI-RVS, UroNav und Urostation®). Unterschiede zwischen den Systemen bestehen u. a. in der Art der Biopsie (transrektal, perineal, beides moglich), im Fusionsmodus (starr bzw. elastisch), in der Navigationsart (bildbasiert, elektromagnetisch bzw. mechanisch) sowie im Platzbedarf. Fusionssysteme werden im Rahmen der fokalen Therapie des PC von verschiedenen Konsensusgruppen empfohlen. Wunschenswerte Eigenschaften sind neben dem „needle tracking“ die Ubertragbarkeit des Biopsiedatensatzes in ein Behandlungsgerat (Artemis™, BiopSee® und Urostation®: jeweils mit Focal One®, BiopSee®, Hitachi HI-RVS: jeweils mit Nanoknife®, BioJet und BiopSee®: Kryoablation, Brachytherapie). Studien zur Planung einer fokalen Therapie liegen nur fur vereinzelte Systeme vor und fehlen fur die Verlaufskontrolle nach fokaler Therapie.

Die fokale Therapie des Prostatakarzinoms gehort zu den aktuellen Innovationen in der Urologie. Ihr Ansatz: Tumorgewebe eliminieren ohne umgebende Strukturen zu schadigen. Jedoch sollten Patienten unter dieser Therapie derzeit noch in Studienprotokolle eingebunden sein.

Irreversible electroporation (IRE), a new tissue ablation procedure available since 2007, could meet the requirements for ideal focal therapy of prostate cancer with its postulated features, especially the absence of a thermal ablation effect. Thus far, there is not enough evidence of its effectiveness or adverse effects to justify its use as a definitive treatment option for localized prostate cancer. Moreover, neither optimal nor individual treatment parameters nor uniform endpoints have been defined thus far. No advantages over established treatment procedures have as yet been demonstrated. Nevertheless, IRE is now being increasingly applied for primary prostate cancer therapy outside clinical trials, not least through active advertising in the lay press. This review reflects the previous relevant literature on IRE of the prostate or prostate cancer and shows why we should not adopt IRE as a routine treatment modality at this stage.

Im Marz 2015 fand erstmalig die Advanced Prostate Cancer Consensus Conference (APCCC) in St. Gallen statt. Kontroversen rund um das fortgeschrittene Prostatakarzinom wurden von 41 Experten aus 17 Landern diskutiert mit dem Ziel, Konsensusempfehlungen auszusprechen. Die Ergebnisse wurden aktuell in der Fachzeitschrift „Annals of Oncology“ publiziert. Obwohl ein Grosteil der in St. Gallen ausgesprochenen Empfehlungen nachvollziehbar ist, sind einige Stellungnahmen kritisch zu betrachten. Als deutsches Expertengremium nehmen wir hierzu Stellung. Im hormonnaiven metastasierten Stadium sollte die kontinuierliche Androgendeprivation (ADT) als Standard gesehen werden. Fur eine Uberlegenheit der primar maximalen Androgenblockade gibt es keine Evidenz. Nach aktueller Datenlage sollte Patienten mit gutem Allgemeinzustand, insbesondere bei hoher Tumorlast, eine Kombinationstherapie aus ADT plus Taxanen angeboten werden. Im metastasierten kastrationsresistenten Stadium ist als Erstlinientherapie eine Hormonmanipulation mit neuartigen endokrinen Medikamenten Therapie der Wahl in der Mehrheit der Patienten. Taxane haben eine primare Indikation bei ungunstigen Prognoseparametern. Radium-223 ist eine Option bei ossarer Metastasierung. Von einer nochmaligen Hormonmanipulation nach Versagen von Abirateron oder Enzalutamid in der Erstlinie sollte wenn moglich Abstand genommen werden. Bei Patienten mit gutem Allgemeinzustand sollte Cabazitaxel einen festen Stellenwert in der Sequenztherapie haben. Fur das initiale Staging im kastrationsresistenten Stadium ist ein CT-Abdomen/-Thorax plus Knochenszintigramm empfehlenswert. Eine erneute Bildgebung empfiehlt sich bei Tumorprogress, ansonsten alle 4–6 Monate. Bezuglich der Biomarker sollte eine Bestimmung von Serum-PSA und AP alle 2–4 Monate erfolgen.

Background Irreversible electroporation (IRE), a new tissue ablation procedure available since 2007, could meet the requirements for ideal focal therapy (FT) with its postulated features, especially the absence of a thermal ablative effect. Thus far, there is no adequate tumor-entity-specific proof of its effectiveness, and its clinical application has hitherto been confined to very small patient cohorts. This also holds true for prostate cancer (PCA). Nevertheless, it is now being increasingly applied outside clinical trials-to a certain extent due to active advertising in the lay press. Aim of the study In this study, current discrepancies between the clinical application and study situation and the approval and market implementation of the procedure are described. The media portrayal of IRE is discussed from different perspectives, particularly with reference to the FT of PCA. This is followed by a final clinical assessment of IRE using the NanoKnife® system. Discussion Strict requirements govern new drug approvals. According to the German Drug Act (AMG), evidence of additional benefit over existing therapy must be provided through comparative clinical trials. For medicotechnical treatment procedures, on the other hand, such trial-based proof is not required according to the Medical Devices Act (MPG). The use of IRE even outside clinical trials has been actively promoted since the NanoKnife® system was put on the market. This has led to an increase in the number of uncontrolled IRE treatments of PCA in the last 2 years. The patients have to cover the high treatment costs themselves in these cases. If articles in the lay press advertise the procedure with promising but unverified contents, false hopes are raised in those concerned. This is disastrous if it delays the use of truly effective treatment options. Conclusion IRE basically still has high potential for the treatment of malignancies; however, whether it can really be used for FT remains unclear due to the lack of data. This also holds true for the treatment of PCA. Only carefully conducted scientific research studies can clarify the unresolved issues regarding IRE of PCA. The urgently needed development of universally valid treatment standards for IRE is unnecessarily hampered by the flow commercially driven patients.

Hintergrund Fur die Therapie des metastasierten Prostatakarzinoms (mPC) stehen sowohl antihormonelle als auch zytotoxische Therapieoptionen zur Verfugung. Da v. a. beim metastasierten kastrationsresistenten Prostatakarzinom (mCRPC) bisher keine vergleichenden Studien zur Verfugung stehen bleibt unklar, welcher Patient von welcher Therapie am besten profitiert.

Im Spannungsfeld zwischen Ganzdrusenstandardtherapien auf der einen und aktiver Uberwachung auf der anderen Seite suchen Betroffene bei Prostatakrebs seit einigen Jahren nach wenig invasiven Alternativen. Insbesondere wird schon lange die Moglichkeit hinterfragt, ob nicht bei begrenzten Risikosituationen nur eine Behandlung des Tumors selbst unter Schonung des Restorgans moglich ware. Der vorliegende Artikel stellt Argumente fur und gegen eine fokale Behandlung gegenuber und erlautert technische Innovationen der letzten Jahre. Ein relativ hoher Anteil von durch eine Standardtherapie uberbehandelten Patienten in der Niedrigrisiko-Situation auf der einen Seite und eine wesentlich verbesserte Technik in Diagnostik (v. a. mpMRT) und Therapie sind wesentliche Argumente, die nach Ansicht der Autoren zu einer Verschiebung vom Konzept der vollstandigen Eradikation des Tumors unter Inkaufnahme von Nebenwirkungen hin zur ausreichend effektiven lokalen Tumorkontrolle durch eine fokale Behandlung mit besserem Erhalt der Lebensqualitat in geeigneten Fallen fuhren wird.

Transrectal ultrasound-guided prostate biopsy is considered the gold standard in the primary investigation of a suspicious prostate-related finding. The procedure can be carried out with ten probes or more on the lateral side of the prostate, after administering antibiotic prophylaxis and applying local anesthesia. The indication for a biopsy depends on the results of the digitorectal examination, on the serum prostate-specific antigen level, on the individual patient's wish and on his comorbidities. Whether multiparametric imaging should be used before or during the course of a primary or repeated biopsy in order to identify suspicious prostate lesions is the subject of current investigations. Extended biopsy protocols require further clinical investigations before they can become the new standard in the diagnostic work-up. This review delivers an update on the indication for, and technique of, prostate biopsies.

In der Behandlung des lokalisierten Niedrigrisikoprostatakarzinoms besteht ein Dilemma zwischen einer moglichen Ubertherapie mit einem der Standardverfahren und einer potenziell ungenugenden Tumorkontrolle bei aktiver Uberwachung. Die fokale Therapie (FT) bietet sich als Alternative an, da mit ihr zugleich der Organerhalt und die Beseitigung des Tumorfokus angestrebt werden. Im vorliegenden Beitrag wird der aktuelle Status der FT in der Behandlung lokalisierter Niedrigrisikoprostatakarzinome in Deutschland beschrieben. Des Weiteren werden Kriterien vorgeschlagen, anhand derer Patienten fur diese Therapie ausgewahlt werden sollen. Die Wirksamkeit der FT wird in Deutschland derzeit in zwei prospektiven Multicenterstudien uberpruft: TOOKAD und HEMI. Das lokalisierte Niedrigrisikoprostatakarzinom bleibt eine diagnostische Herausforderung. Neben der transrektalen Biopsie werden die multiparametrische Magnetresonanztomographie sowie eine histopathologische Zweitmeinung als obligate Schritte angesehen. Die onkologischen Ergebnisse von TOOKAD und HEMI werden fur alle FT-Formen zur Behandlung des Prostatakarzinoms in Deutschland wegweisend sein. Die Akzeptanz unter den Patienten ist bereits bemerkenswert hoch.

Die Behandlung des metastasierten Prostatakarzinoms (mPC) erlebt derzeit einen Paradigmenwechsel. Verschiedene randomisierte Phase-III-Studien konnten zeigen, dass die Chemotherapie mit Taxanen das Uberleben der Patienten mit mPC signifikant verlangert. Das gilt sowohl fur die metastasierte Erkrankung in der Kastrationsresistenz (metastasiertes kastrationsresistentes Prostatakarzinom [mCRPC]), als auch im hormonnaiven Stadium der Erkrankung (metastasiertes kastrationsnaives Prostatakarzinom [mCNPC]). Beim mCNPC verlangerte Docetaxel in Kombination mit der Androgendeprivationstherapie (ADT) die mediane Gesamtuberlebenszeit der Patienten gegenuber der alleinigen ADT um 15 Monate. Vergleichbare Ergebnisse erreichte die endokrine Kombinationstherapie mit ADT/Abirateron. Vor dem Hintergrund der aktuellen Datenlage erscheint es sinnvoll, den Stellenwert der fruhen Kombinationstherapie mit ADT/Docetaxel bzw. ADT/Abirateron sowie deren Auswirkungen auf die Folgetherapien beim mCRPC zu diskutieren und Hinweise fur den klinischen Alltag zu formulieren.

What's known on the subject? and What does the study add? The development of side effects characteristic for the different treatment methods with impact on the patients' quality of life plays a growing role for individual patients with early stage prostate cancer. Using permanent brachytherapy a high dose to the prostate can be applied with a steep dose gradient to the normal tissue. However, small partial volumes of normal tissue may be exposed to high doses inducing special side effects including lower urinary tract symptoms and/or erectile dysfunction. In the literature there are only few publications so far regarding segmental dosimetry and its influence on side effects and the results are conflicting. We could not identify any dosimetric parameter in segmental dosimetry that may have an influence at certain time intervals on the development of side effects such as lower urinary tract symptoms or erectile dysfunction. However, we could state clearly that the preoperative situation is the most important factor for postoperative outcome. Objective To report on the side effects of patients with low to low–intermediate risk prostate cancer treated with permanent interstitial brachytherapy with special emphasis on segmental dosimetry. Patients and Methods A series of 186 consecutive patients treated for early stage prostate cancer receiving definitive I-125 brachytherapy (permanent seed implantation) between November 2001 and April 2005 at our institution were examined for the development of side effects. Morbidity was assessed prospectively using the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF-5) in a mean follow-up interval of 30 months. The scores were correlated with segmental dosimetry performed 6 weeks after the implantation. Results The mean postoperative dose to 90% of the prostate volume (D90) was 180.2 Gy, the mean preoperative IPSS 7.2 and the mean IIEF-5 14.35, with all scores showing a maximum deterioration after 6 weeks with normalization after 24 months. After correlating the segmental dosimetry and the scores at different time intervals, only the baseline scores remained statistically significant in multivariate regression analysis at all time intervals (P < 0.00). Conclusions We could not demonstrate a correlation of segmental dosimetry with induction of side effects. There is no relationship between dose exposure of partial volumes and the development of radiation-induced toxicities. The preoperative situation regarding lower urinary tract symptoms and erectile function are the most important factors for postoperative outcome.

INTRODUCTION Patients with low-risk prostate cancer (PCa) face the difficult decision between a potential overtreatment by one of the standard therapies and active surveillance (AS) with the potential insecurity regarding cancer control. A focal therapy (FT) implies a treatment of the tumor within the prostate only. METHODS This review evaluates the current literature and expert opinion of different therapies suited for FT as well as concepts for prostate imaging, biopsy and histopathological evaluation. RESULTS Currently there is a lack of multicenter, randomized, prospective data on the effectiveness of FT. Nonetheless, the published data indicate a sufficient tumor control with a favorable side effect profile. There are still flaws in the diagnostics with regard to tumor detection and histological evaluation. Multicenter studies are currently recruiting worldwide which will provide new data with a higher level of evidence. CONCLUSION At present, the effectiveness of FT should not be compared directly to standard radical therapies and FT should only be performed within studies. In cases of cancer progression after FT a salvage treatment should still be possible.

What's known on the subject? and What does the study add? Whole gland brachytherapy has been used to successfully treat prostate cancer but the protocol for focal therapy has not previously been established. The consensus findings provide guidance on patient selection for focal brachytherapy as well as recommendations for conducting therapy and patient follow-up. Low dose rate prostate brachytherapy is an effective treatment for localized prostate cancer. Recently, it has been considered for use in a focused manner whereby treatment is targeted only to areas of prostate cancer. The objective of focal brachytherapy is to provide effective cancer control for low-risk disease but with reduced genitourinary and rectal side-effects in a cost-effective way. We report on the outputs of a consensus meeting of international experts in brachytherapy and focal therapy convened to consider the feasibility and potential development of focal brachytherapy. A number of factors were considered for focal brachytherapy including optimal patient selection, disease characterization and localization, treatment protocols and outcome measures. The consensus meeting also addressed the design of a clinical trial that would assess the oncological outcomes and side-effect profiles resulting from focal brachytherapy.

Elective nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) has gained general acceptance as an alternative to radical nephrectomy. To achieve haemostasis without risk of local ischaemia and necrosis of kidney parenchyma after standard haemostatic suturing, we investigated TachoSil's efficacy and safety as atraumatic haemostatic treatment after kidney tumour resection.A total of 185 patients scheduled for NSS for small, superficial kidney tumours were included in an open, randomised, prospective, multicentre, parallel-group trial. Primary objectives were to test haemostatic efficacy and safety of TachoSil versus standard suturing. Efficacy was tested by comparing intraoperative time to haemostasis (primary end point). Secondary objectives included proportion of subjects with haemostasis after 10 min of trial treatment, occurrence of haematoma on day 2 after surgery, volume and haemoglobin concentration of postoperative drainage fluid, and surgeon's rating of usefulness of trial treatments. Safety was evaluated by occurrence of adverse events.In the intent-to-treat population, time to haemostasis was significantly shorter with TachoSil versus standard suturing (mean: 5.3 vs. 9.5 min [p0.0001]). Haemostasis was obtained within 10 min in 92% of patients in the TachoSil group and in 67% in the standard treatment group (p0.0001). Differences in other secondary end points were not statistically significant. Both treatments were well tolerated. Surgeons rated TachoSil higher in terms of convenience to prepare and apply, and impression of efficacy.TachoSil was superior to standard suturing in obtaining intraoperative control of haemorrhage and was as well tolerated as standard haemostatic treatment during NSS.

BACKGROUND The prospective diagnostic efficiency of quantitative glutathione S transferase (GSTP1) promoter hypermethylation analysis in biopsy washing samples has not been determined so far. METHODS Biopsies were obtained prospectively from 86 patients suspicious for prostate cancer (CaP). After isolation of DNA from biopsy washings and bisulfite conversion methylated and unmethylated GSTP1 sequences were specifically quantitated by real-time fluorescence PCR. Relative degrees of methylation were compared to results of histopathological examination. RESULTS Increased relative methylation was found for the CaP group (mean 28.1%) compared to biopsies without histological evidence for malignancy (5.2%; P

Objectives As the number of patients with prostate cancer treated with permanent radioactive implants is increasing world wide, long-term data on tumor control and treatment morbidity become available. Materials Biochemical and clinical tumor control appears to be as effective as after radical prostatectomy or external beam radiation therapy in early prostate cancer. Results The risk of posttreatment urinary incontinence and bowel dysfunction is low and erectile function can be preserved in the majority of patients. However, prostate brachytherapy requires a careful selection of patients as pretreatment factors predict for long-term outcome. The need for combined modality approaches in intermediate and high risk patients remains controversely discussed. The continuous refinement of intraoperative planning techniques and the elucidation of the etiology of urinary, sexual and bowel dysfunction should result in further improvements in biochemical outcomes and decreased morbidity. Conclusions Improved and standardized postimplantation evaluation will make outcome data more reliable and comparable.

Die Positronenemissionstomographie (PET) unter Einsatz der (18F)2-Fluoro-D-2-desoxyglukose (FDG) hat sich bei zahlreichen nichturologischen Tumoren als eine Untersuchungsform mit hoher Sensitivitat und Spezifitat in der Primardiagnostik, zum Rezidivnachweis und zur Therapiekontrolle gezeigt. Aufgabe dieses Reviews war eine Untersuchung der Bedeutung der PET als bildgebendes Verfahren bei malignen Tumoren des Urogenitaltrakts.

In approximately 4%-10% of patients presenting with renal cell cancer, the transluminal propagation of a tumour thrombus into the vena cava inferior or the right atrium comes to diagnosis. Recent investigations have indicated that the presence of neoplastic extension into the venous system does not reveal independent prognostic value regarding the clinical course of the disease. Although the complete surgical removal of vena cava thrombosis in patients without simultaneously occurring regional lymph node or distant metastases has become a well established treatment modality, several questions concerning this surgical strategy still remain the subject of ongoing discussions. In the present investigation that included 92 patients with renal cell cancer and intracaval neoplastic extension, it was clearly demonstrated that using cardiopulmonary bypass, deep hypothermia and circulatory arrest - preferably, during the removal of intracaval thrombosis extending into the right atrium - does not result in a substantially increased treatment-related intra- or postoperative mortality. However, in contrast to a previously reported observation, this treatment option did not reveal any substantial impact on the long-term survival of the patients following surgical therapy. Accordingly, the cranial extension of intracaval thrombosis was not identified as a biological variable of any prognostic importance for renal cell cancer patients.

Die optimale Versorgung des politraumatisierten Patienten verlangt ein koordiniertes interdisziplinares Vorgehen, wobei zwischen der Erstversorgung am Unfallort, der meist in der Klinik durchgefuhrten Akutversorgung und der spater auch durch den niedergelassenen Kollegen gewahrleisteten Spatversorgung von evtl. Folgezustanden des Traumas differenziert werden muss. Der nachfolgende Beitrag beschaftigt sich sich mit der Diagnostik und der Therapie der Verletzungen von Harnblase und Urethra, da diese Verletzungen des ableitenden Harntrakts bei politraumatisierten Patienten neben dem Nierentrauma die hochste Inzidenz aufweisen.

Since it is difficult to predict the probability of persistent teratoma or of a viable tumor in patients with normalized tumor markers and a normal CT scan following chemotherapy for advanced stage testis cancer, recommendations regarding adjunctive surgery have ranged from observation to surgical exploration for all patients. Suggested variables for patients in whom surgery can be omitted safely, include normal post-chemotherapy CT scans, residual abdominal masses of less than 1.5 cm, a 90% or greater decrease in the volume of the retroperitoneal mass with chemotherapy and no teratomatous elements in the orchiectomy specimen. In contrast, during several investigations, the application of the above mentioned criteria resulted in a false-negative prediction of approximately 20%. However, recognizing the morbidity of the operative procedure itself in addition to the fact that only 2-4% of patients will develop recurrent tumor confined to the retroperitoneal space that can then be managed surgically or by administration of further chemotherapy, secondary surgery should be avoided if a sufficient follow-up after chemotherapy is guaranteed. The extent of adjunctive surgery in patients revealing a residual tumor mass after first-line chemotherapy remains a subject of ongoing discussions. It has been indicated that extensive retroperitoneal surgery after chemotherapy is associated with significant clinical morbidity. A limitation of post-chemotherapy surgery to a resection of the residual mass with or without an additional modified template dissection appears to result in an acceptable frequency of retroperitoneal recurrences and a decreased complication rate.

The observation of extremely variable clinical courses for patients with renal cell carcinomas of an identical pathological stage as well as a comparable histological differentiation resp. growth pattern strongly indicates the existence of tumors harboring different biological aggressiveness. Currently available histopathological classification systems do not predict the biological behaviour of renal cell cancer as sufficiently as the establishment of a therapeutical strategy adjusted to the individual patient would require. The need for a more refined characterization of the biological potential of the indidual tumor results from the introduction of modified operative strategies as organ-preserving surgery, for example, as well as from the recently suggested application of an adjuvant systemic therapy adapted to the individual risk for tumor recurrence resp. the development of progressive disease. Therefore, the clinically orientated basic scientist and the basic scientifically orientated clinician intensively try to determine prognostically important biological variables which would allow to better predict the biological aggressiveness of a single tumor in addition to “classical” prognostic parameters (T-stage, histological grading, growth patterns). In this context, several biological parameters including the identification of alterations on the DNA-, RNA- and protein level have been discussed as possible biological prognostic markers for renal cell cancer. The present review tries to reflect currently available biological characteristics of RCC which might gain clinical importance with regard to an individualized therapy in the near future.

In approximately 4-10 % of patients presenting with renal cell cancer the transluminal propagation of a tumor thrombus into the vena cava inferior or the right atrium comes to diagnosis. Recent investigations have indicated that the presence of neoplastic extension into the venous system does not reveal independent prognostic value regarding the clinical course of the disease. Although the complete surgical removal of vena cava thrombosis in patients without simultaneously occurring regional lymph node or distant metastases has become a well established treatment modality, several questions concerning this surgical strategy still remain the subject of ongoing discussions. In the present investigation that included 92 patients with renal cell cancer and intracaval neoplastic extension it was clearly demonstrated that the use of cardiopulmonary bypass, deep hypothermia and circulatory arrest preferably during the removal of intracaval thrombosis extending into the right atrium does not result in a substantially increased treatment-related intra- or postoperative mortality. However, in contrast to a previously reported observation this treatment option did not reveal any substantial impact on the long-term survival of the patients following surgical therapy. Accordingly, the cranial extension of intracaval thrombosis was not identified as a biological variable of any prognostic importance for renal cell cancer patients.

Die medikamentose Therapie der erektilen Dysfunktion umfast die systemische (orale, transkutane, intramuskulare) sowie die lokale (intrakavernose, intraurethrale) Applikation von Pharmaka. Die bisher einzigen in Deutschland zugelassenen oralen Substanzen sind das seit vielen Jahren bekannte Yohimbin, ein zentral wirksamer Alpharezeptorenblocker sowie das 1998 eingefuhrte Sildenafil, ein Phosphodiesterase-Isoenzym V Inhibitor mit uberwiegend peripherem Wirkmechanismus. Weitere in der Entwicklung befindliche, orale Substanzen sind Trazodon und Apomorphin (zentraler Angriffspunkt) sowie Phentolamin (peripherer Ansatzpunkt). Fur eine eher kleine Gruppe von Patienten mit Testosterondefizit besteht die Moglichkeit einer transkutanen oder intramuskularen Substitutionstherapie. Zur lokalen Applikation stehen sowohl die intrakavernose (Schwellkorperautoinjektionstherapie-SKAT) als auch die die intraurethrale (MUSE) Anwendungsweise zur Verfugung. Zur Zeit befinden sich mehrere erfolgversprechende Substanzen mit unterschiedlichstem Wirkansatz und verschiedenen Darreichungsformen in der Entwicklung. Ziel dieser intensiven grundlagenwissenschaftlichen und klinischen Forschung ist eine patientenadaptierte, „masgeschneiderte“ Therapie fur den individuellen Patienten. Die pharmakologische Therapie der erektilen Dysfunktion wird auch kunftig durch apparative (Vakuumpumpen, „Funktionelle Elektromyostimulation des Corpus cavernosum“-FEMCC) und operative (Gefaschirurgie, Prothetik) Behandlungsstrategien erganzt werden.

For clinically localized prostate cancer, recent studies strongly indicate that the determination of p53 inactivation allows the identification of a highly aggressive subgroup of prostatic tumors associated with decreased recurrence-free and long-term survival following radical prostatectomy. However, several questions regarding the determination of p53 alterations in prostate cancer, such as the poor correlation between immunohistochemistry and molecular genetic analysis, remain to be clarified. On the DNA level, p53 gene alterations have been identified in only up to 64% of tumors exhibiting immunohistochemically detected overexpression of the p53 oncoprotein. This discrepancy can be explained either by the genetic microheterogeneity of prostate cancer or by stabilization of the wild-type protein due to posttranslational events. In the present study we tried to determine the concordance between an immunohistochemically detected p53 overexpression and the result of molecular genetic analysis. Therefore, tumor tissue obtained by microdissection from 40 prostate cancer specimens was subjected to DNA-sequence analysis. Microdissection was based either only on histopathologic criteria or on the result of the immunohistochemical staining reaction. In 8 of 14 (57%) tumors a positive immunohistochemical reaction could be confirmed by DNA sequencing, which revealed a missense point mutation at the p53 gene locus, mainly in the form of G → A transversion in exon 5 of the p53 gene. Following the micropreparation of tumor cells exhibiting p53 oncoprotein overexpression, missense point mutation could be detected in an additional 4 cases. Following a microscopically guided tumor cell dissection according to the result of immunohistochemistry, DNA sequencing confirmed an immunohistochemically detected p53 overexpression in 86% of cases investigated. This result indicates that a microdissectional tumor cell preparation is recommended for molecular genetic analysis of histologically heterogeneous tissue specimens such as prostate cancer and should be performed according to and in addition to the result of immunohistochemistry when an immunohistochemical approach is available.

The p27Kip1 gene has been identified as inductor of cell cycle arrest at the G1 checkpoint to prevent entry of somatic cells into the S phase of the cell cycle when substantial DNA damage has occurred. It has been suggested that decreased expression of the p27Kip1 protein may contribute to the development of human malignancies due to loss of critical antiproliferative mechanisms. In the present study, 95 specimens (T1–T4) from 95 randomly selected patients undergoing radical prostatectomy at the Urological Department of Hannover University (82 patients) as well as in the Josef Hospital Regensburg (13 patients) between 1981 and 1992 for whom tissue blocks for immunohistochemical investigation were available, were investigated for different biological and clinical characteristics as possible predictors for recurrence-free and long-term survival: age, depth of tumour infiltration, histological grade, lymph node status, as well as decreased expression of the p27Kip1 protein. After a median follow-up up of 56 months (24–151 months), seven of 21 (33%) patients (Group 1) with loss of p27Kip1 protein expression or a relative amount of

The independent prognostic value of neoplastic extension of renal cell cancer (RCC) into the vena cava inferior has been the subject of several investigations reported to date. However, the use of vena cava thrombosis as an independent prognosticator of a patient's long-term survival is still debated. We have therefore correlated the clinical course of 53 patients with RCC and vena cava thrombosis with a control group consisting of 47 patients with renal cell tumors without vena cava thrombosis (follow-up: 1–154 months). The median long-term survival of patients with and without vena cava thrombosis was 32 and 35 months, respectively. Neither the propagation of the tumor into the vena cava (P = 0.391) nor the cranial extension of the thrombosis (P = 0.158) – even in case of propagation into the right atrium – could be identified as parameters of any prognostic value during univariate or multivariate statistical analysis.

During the past two years several reports have substantially contributed to the surgical stratification of patients with late-stage renal cell cancer and simultaneously occurring intracaval neoplastic extension, and our knowledge about the clinical prognosis of the patients after nephrectomy with complete removal of the tumour thrombosis has been extended. Recognizing the importance of a tolerable perioperative and postoperative morbidity and mortality, it is now well documented in the literature that a multidisciplinary approach involving the combined use of deep hypothermia, cardiac arrest and cardiopulmonary bypass has dramatically improved the feasibility of surgical treatment of the venous extension above the hepatic veins. Furthermore, the diagnostic approach for patients with intracaval thrombosis, aiming at the reliable delineation of the cranial margin of venous extension, has been rationalized without compromising important diagnostic information required for the surgical stratification. This review assesses the current opinion of the surgical stratification of patients with renal cell cancer and intracaval neoplastic extension, the most reliable and least invasive diagnostic approach for the preoperative staging and, finally, the independent prognostic value of neoplastic venous extension for the clinical course of the disease.

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The development of side effects characteristic for the different treatment methods with impact on the patients' quality of life plays a growing role for individual patients with early stage prostate cancer. Using permanent brachytherapy a high dose to the prostate can be applied with a steep dose gradient to the normal tissue. However, small partial volumes of normal tissue may be exposed to high doses inducing special side effects including lower urinary tract symptoms and/or erectile dysfunction. In the literature there are only few publications so far regarding segmental dosimetry and its influence on side effects and the results are conflicting. We could not identify any dosimetric parameter in segmental dosimetry that may have an influence at certain time intervals on the development of side effects such as lower urinary tract symptoms or erectile dysfunction. However, we could state clearly that the preoperative situation is the most important factor for postoperative outcome.To report on the side effects of patients with low to low-intermediate risk prostate cancer treated with permanent interstitial brachytherapy with special emphasis on segmental dosimetry.A series of 186 consecutive patients treated for early stage prostate cancer receiving definitive I-125 brachytherapy (permanent seed implantation) between November 2001 and April 2005 at our institution were examined for the development of side effects. Morbidity was assessed prospectively using the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF-5) in a mean follow-up interval of 30 months. The scores were correlated with segmental dosimetry performed 6 weeks after the implantation.The mean postoperative dose to 90% of the prostate volume (D90) was 180.2 Gy, the mean preoperative IPSS 7.2 and the mean IIEF-5 14.35, with all scores showing a maximum deterioration after 6 weeks with normalization after 24 months. After correlating the segmental dosimetry and the scores at different time intervals, only the baseline scores remained statistically significant in multivariate regression analysis at all time intervals (P0.00).We could not demonstrate a correlation of segmental dosimetry with induction of side effects. There is no relationship between dose exposure of partial volumes and the development of radiation-induced toxicities. The preoperative situation regarding lower urinary tract symptoms and erectile function are the most important factors for postoperative outcome.

Recent improvements in radioactive seed implantation techniques have established prostate brachytherapy as a highly effective treatment modality for localized prostate cancer, with long-term local and biochemical control similar to outcomes observed after radical prostatectomy and external beam radiation therapy.

What's known on the subject? and What does the study add? Very few comparative studies to date evaluate the results of treatment options for prostate cancer using the most sensitive measurement tools. PSA has been identified as the most sensitive tool for measuring treatment effectiveness. To date, comprehensive unbiased reviews of all the current literature are limited for prostate cancer. This is the first large scale comprehensive review of the literature comparing risk stratified patients by treatment option and with long-term follow-up. The results of the studies are weighted, respecting the impact of larger studies on overall results. The study identified a lack of uniformity in reporting results amongst institutions and centres. A large number of studies have been conducted on the primary therapy of prostate cancer but very few randomized controlled trials have been conducted. The comparison of outcomes from individual studies involving surgery (radical prostatectomy or robotic radical prostatectomy), external beam radiation (EBRT) (conformal, intensity modulated radiotherapy, protons), brachytherapy, cryotherapy or high intensity focused ultrasound remains problematic due to the non-uniformity of reporting results and the use of varied disease outcome endpoints. Technical advances in these treatments have also made long-term comparisons difficult. The Prostate Cancer Results Study Group was formed to evaluate the comparative effectiveness of prostate cancer treatments. This international group conducted a comprehensive literature review to identify all studies involving treatment of localized prostate cancer published during 2000-2010. Over 18,000 papers were identified and a further selection was made based on the following key criteria: minimum/median follow-up of 5 years; stratification into low-, intermediate- and high-risk groups; clinical and pathological staging; accepted standard definitions for prostate-specific antigen failure; minimum patient number of 100 in each risk group (50 for high-risk group). A statistical analysis (standard deviational ellipse) of the study outcomes suggested that, in terms of biochemical-free progression, brachytherapy provides superior outcome in patients with low-risk disease. For intermediate-risk disease, the combination of EBRT and brachytherapy appears equivalent to brachytherapy alone. For high-risk patients, combination therapies involving EBRT and brachytherapy plus or minus androgen deprivation therapy appear superior to more localized treatments such as seed implant alone, surgery alone or EBRT. It is anticipated that the study will assist physicians and patients in selecting treatment for men with newly diagnosed prostate cancer.

What's known on the subject? and What does the study add? Whole gland brachytherapy has been used to successfully treat prostate cancer but the protocol for focal therapy has not previously been established. The consensus findings provide guidance on patient selection for focal brachytherapy as well as recommendations for conducting therapy and patient follow-up. Low dose rate prostate brachytherapy is an effective treatment for localized prostate cancer. Recently, it has been considered for use in a focused manner whereby treatment is targeted only to areas of prostate cancer. The objective of focal brachytherapy is to provide effective cancer control for low-risk disease but with reduced genitourinary and rectal side-effects in a cost-effective way. We report on the outputs of a consensus meeting of international experts in brachytherapy and focal therapy convened to consider the feasibility and potential development of focal brachytherapy. A number of factors were considered for focal brachytherapy including optimal patient selection, disease characterization and localization, treatment protocols and outcome measures. The consensus meeting also addressed the design of a clinical trial that would assess the oncological outcomes and side-effect profiles resulting from focal brachytherapy.

Objectives The tumour suppressor gene p16INK4a is a cyclin-dependent kinase inhibitor, for which inactivation attributable to promoter hypermethylation or homozygous deletion has been described in malignancies. Little is known about p16INK4a protein levels in renal cell carcinoma (RCC) and its association with clinicopathologic parameters or disease progression. Methods The expression of the p16INK4a gene was analysed with the use of immunohistochemistry and tissue microarrays (TMA). Tissue cores were obtained from the primary tumour itself, the tumoural invasion front, and histologically benign peritumoural tissue of 397 nephrectomies. For statistical analysis, sections were classified into four groups according to the relative amount of positively stained cells: negative (0%), low (1–10%), intermediate (11–50%), and high positivity (>50%). Follow-up data were analyzed for 198 patients (follow-up period: 2–240 mo; median: 138 mo). Results Absent or low expression of p16INK4a was observed in 82% of tumour samples. No statistically significant association was found between protein levels detected in tumour, invasion front, or normal renal tissues and any of the clinicopathologic variables. Survival analysis by Kaplan-Meier revealed a significant association between high expression (>50%) of p16INK4a in tumours and better disease-specific survival ( p =0.03, log-rank test). Cox regression analysis showed that p16INK4a expression is an independent covariate in disease-specific survival ( p Conclusions The absence of p16INK4a expression in most tumour cells indicates that p16INK4a could be involved in the tumourigenesis of RCC. Immunohistochemically detected positivity for p16INK4a is a positive prognosticator for specific survival in both uni- and multivariate analyses.