Why we should not routinely apply irreversible electroporation as an alternative curative treatment modality for localized prostate cancer at this stage.

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.

[Changes in the treatment of metastatic prostate cancer-new data and open questions]. / Therapie des metastasierten Prostatakarzinoms im Wandel ­ neue Daten und offene Fragen.

The availability of taxane-based chemotherapy and androgen-receptor-targeted agents (ARTAs) have significantly broadened the therapeutic options for patients with metastatic prostate cancer and may also result in longer patient survival. The therapeutic sequence of ARTAs and taxanes may influence outcome and therefore decisions should be made on an individual basis. This article provides guidance for therapeutic decision-making in daily clinical practice by working out criteria that can be used to support individual therapeutic decisions. The focus is on metastatic castration-naive prostate cancer, oligometastatic disease as well as non-metastatic and metastatic castration-resistant prostate cancer.

[Treatment situation in metastastic Castration Naive Prostate Cancer (mCRPC) and the implications on clinical routine]. / Therapiesituation beim metastasierten kastrationsnaiven Prostatakarzinom (mCNPC) und die Auswirkungen im klinischen Alltag.

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-naïve 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.

[Metastatic castration-resistant prostate cancer : Use of cabazitaxel taking into consideration current data]. / Metastasiertes kastrationsresistentes Prostatakarzinom : Neues zu Cabazitaxel unter Berücksichtigung der aktuellen Datenlage.

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.

[Advanced Prostate Cancer Consensus Conference 2017 : Discussion of the recommendations for diagnosis and treatment of metastatic prostate cancer by a German panel of experts]. / Advanced Prostate Cancer Consensus Conference 2017 : Diskussion der Empfehlungen zur Diagnostik und Therapie des metastasierten Prostatakarzinoms durch ein deutsches Expertengremium.

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.

[Metastatic prostate cancer : Update: position paper for the use of chemotherapy]. / Metastasiertes Prostatakarzinom : Update: Positionspapier zum Einsatz der Chemotherapie.

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-naïve 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-naïve 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 <12 months, tumor-associated complaints), first-line chemotherapy is indicated. After docetaxel failure, continuous treatment with cabazitaxel shows superior overall survival compared to sustained antihormonal therapy. CONCLUSION: Chemotherapy is firmly established in treating patients with mCRPC. Long-term, it will be important to identify molecular predictors. The authors suggest the early use of chemotherapy in hormone-naïve mPC, but note that the approval in this indication is currently nonexistent. After disease progression, patients should be treated analogous to mCRPC.

[Focal therapy of prostate cancer]. / Fokale Therapie des Prostatakarzinoms.

The target of focal therapy (FT) in prostate cancer (PC) is partial treatment of the prostate aiming at preserving surrounding anatomical structures. The intention is to minimize typical side effects of radical treatment options combined with local tumor control. Numerous established and new technologies are used. Results of published studies showed a good safety profile, few side effects and good preservation of functional results. Oncologic long-term data are lacking so far. Photodynamic therapy (PDT) is the only technology that has been studied in a published prospective randomized trial. The FT is challenged by the multifocality of PC; therefore, the quality of prostate biopsy, histopathological assessment as well as imaging are of paramount importance. Multiparametric magnetic resonance imaging (MRI) has gained increasing importance. The FT is experimental and should only be offered within clinical trials.

[MRI/TRUS fusion-guided prostate biopsy : Value in the context of focal therapy]. / MRT/TRUS-fusionierte Biopsiesysteme : Stellenwert bei der fokalen Therapie des Prostatakarzinoms.

BACKGROUND: Several systems for MRI/TRUS fusion-guided biopsy of the prostate are commercially available. Many studies have shown superiority of fusion systems for tumor detection and diagnostic quality compared to random biopsy. The benefit of fusion systems in focal therapy of prostate cancer (PC) is less clear. OBJECTIVES: Critical considerations of fusion systems for planning and monitoring of focal therapy of PC were investigated. MATERIALS AND METHODS: A systematic literature review of available fusion systems for the period 2013-5/2016 was performed. A checklist of technical details, suitability for special anatomic situations and suitability for focal therapy was established by the German working group for focal therapy (Arbeitskreis fokale und Mikrotherapie). RESULTS: Eight fusion systems were considered (Artemis™, BioJet, BiopSee®, iSR´obot™ Mona Lisa, Hitachi HI-RVS, UroNav and Urostation®). Differences were found for biopsy mode (transrectal, perineal, both), fusion mode (elastic or rigid), navigation (image-based, electromagnetic sensor-based or mechanical sensor-based) and space requirements. DISCUSSION: Several consensus groups recommend fusion systems for focal therapy. Useful features are "needle tracking" and compatibility between fusion system and treatment device (available for Artemis™, BiopSee® and Urostation® with Focal One®; BiopSee®, Hitachi HI-RVS with NanoKnife®; BioJet, BiopSee® with cryoablation, brachytherapy). CONCLUSIONS: There are a few studies for treatment planning. However, studies on treatment monitoring after focal therapy are missing.

[Advanced Prostate Cancer Consensus Conference (APCCC) 2015 in St. Gallen : Critical review of the recommendations on diagnosis and therapy of metastatic prostate cancer by a German expert panel]. / Advanced Prostate Cancer Consensus Conference (APCCC) 2015 in St. Gallen : Kritische Betrachtung der Empfehlungen zur Diagnostik und Therapie des metastasierten Prostatakarzinoms durch ein deutsches Expertengremium.

In March 2015, the first Advanced Prostate Cancer Consensus Conference (APCC) took place in St. Gallen. 41 experts from 17 countries reviewed important areas of controversy in advanced hormone-naive and castration-resistant prostate cancer and gave therapy recommendations. These results have been recently published in "Annals of Oncology". While most of the recommendations from St. Gallen are comprehensible, some of them need to be further discussed. Therefore, we as a German expert panel will critically debate the St. Gallen recommendations. For metastatic hormone-naive prostate cancer, continuous androgen deprivation remains the standard. There is no evidence for superiority of primary maximal androgen deprivation. Patients suitable for chemotherapy, especially in the presence of high tumour burden, should receive androgen deprivation plus taxanes upfront. In metastatic castration resistant prostate cancer, novel hormonal agents like abiraterone or enzalutamid should be the treatment of choice in the majority of patients. Taxanes should be used first-line in patients with unfavourable prognostic markers. Radium-223 is an option in symptomatic patients with bone metastases. There is first evidence that second-line hormonal treatment after first-line failure of a novel endocrine agent has a high failure rate. Cabazitaxel should be part of the treatment sequence in patients with a good performance status. Baseline staging for castration-resistant prostate cancer should include CT-abdomen/-chest and bone scan. Radiographic monitoring should be performed 2 to 3 times a year. Determination of PSA and ALP is to take place every 2 to 4 months.

[Focal therapy for small renal masses : Observation, ablation or surgery]. / Fokale Therapie von kleinen Nierentumoren : Beobachtung, Ablation oder Operation.

BACKGROUND: The rising incidence of renal cell carcinoma, its more frequent early detection (stage T1a) and the increasing prevalence of chronic renal failure with higher morbidity and shorter life expectancy underscore the need for multimodal focal nephron-sparing therapy. DISCUSSION: During the past decade, the gold standard shifted from radical to partial nephrectomy. Depending on the surgeon's experience, the patient's constitution and the tumor's location, the intervention can be performed laparoscopically with the corresponding advantages of lower invasiveness. A treatment alternative can be advantageous for selected patients with high morbidity and/or an increased risk of complications associated with anesthesia or surgery. Corresponding risk stratification necessitates previous confirmation of the small renal mass (cT1a) by histological examination of biopsy samples. Active surveillance represents a controlled delay in the initiation of treatment. RESULTS: Percutaneous radiofrequency ablation (RFA) and laparoscopic cryoablation are currently the most common treatment alternatives, although there are limitations particularly for renal tumors located centrally near the hilum. More recent ablation procedures such as high intensity focused ultrasound (HIFU), irreversible electroporation, microwave ablation, percutaneous stereotactic ablative radiotherapy and high-dose brachytherapy have high potential in some cases but are currently regarded as experimental for the treatment of renal cell carcinoma.

[Metastasized prostate cancer. Position paper on the use of chemotherapy]. / Metastasiertes Prostatakarzinom. Positionspapier zum Einsatz der Chemotherapie.

BACKGROUND: Antihormonal and cytotoxic therapy options are available for the therapy of metastasized prostate cancer (mPC). Because no comparative studies are available, especially for castration-resistant prostate cancer (mCRCP), it remains unclear which patients will profit best from which therapy. OBJECTIVES: Previous data on the sequence of the various therapy options show that correct selection of the first line therapy for mCRPC can have an influence on the prognosis of the patient. In this position paper the various therapy options are critically illustrated and the clinical and pathohistological criteria for selection of the first line therapy of mCRPC are discussed. RESULTS: Molecular markers are an important aid for future patient selection and individualized therapy for optimal use of the available forms of therapy.

[Cancer control in focus insights and future perspectives for the focal treatment of prostate cancer]. / Krebskontrolle im Fokus - Einblicke und Ausblicke rund um die fokale Therapie des Prostatakrebses.

Faced with the dilemma of choosing between the extremes of standard whole gland therapy and active surveillance, those affected by prostate cancer have recently been on the lookout for less invasive alternatives. Particularly the question of whether it would be possible in low risk cancer to treat only the tumour itself while sparing the organ has long been considered. This article discusses the pros and cons of focal treatment and elucidates the latest innovative technologies. High overtreatment rates in low-risk patients submitted to standard therapy and considerable technological advances in diagnosis (particularly multiparametric MRI) and therapy are regarded by the authors as key arguments for abandoning complete tumour eradication with its side effects in favour of sufficient local cancer control by focal treatment with better preserved quality of life in suitable cases.

[Irreversible electroporation. Current value for focal treatment of prostate cancer]. / Irreversible Elektroporation. Aktueller Stellenwert in der fokalen Therapie des Prostatakarzinoms.

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.

The prognostic value of p53 for long-term and recurrence-free survival following radical prostatectomy.

In the present study, 76 specimens (T1-T4) from 76 randomly selected patients undergoing radical prostatectomy at Hannover University as well as in the Josef Hospital Regensburg (13 patients) between 1980 and 1992 for whom tissue sections for immunohistochemical investigation were available, were investigated for different biological and clinical characteristics as predictors for long-term and recurrence-free survival: age, depth of tumour infiltration, histological grade, lymph node status, as well as overexpression of the p53 protein (monoclonal antibody DO-1). After a median follow-up of 50 months, 6 of 18 patients (33%) with more than 20% of tumour cells stained positively for p53 died from tumour progression compared with 9 of 58 patients (16%) with less than 20% of tumour cells positive for p53. During univariate analysis, p53 overexpression (P = 0.011), histological grading (P = 0.009) and tumour stage (P = 0.024) were significant prognostic factors for survival, among which only p53 overexpression (P = 0.026) remained an independent significant predictor in multivariate analysis. Additionally, 18 of 66 patients (27%) with less than 40% positivity for p53 suffered tumour recurrence in contrast to 6 of 10 patients (60%) with more than 40% tumour cells exhibiting a positive staining reaction. In multivariate analysis, p53 overexpression was identified as the only prognostic parameter for recurrence-free survival (P = 0.005). Prospective studies are needed to confirm the independent prognostic potential of p53 overexpression in patients with localised prostate cancer. The availability of more refined prognostic factors should assist decision making regarding the value of radical prostatectomy versus a surveillance strategy for prognostically defined subgroups of patients.

Cavernous and systemic testosterone levels in different phases of human penile erection.

OBJECTIVES: To examine changes in testosterone levels in the cavernous and peripheral blood during different phases of erection because, although the determination of systemic testosterone levels has been well established in the diagnostic workup of erectile dysfunction, the exact role of testosterone in adult male sexual function remains unclear. METHODS: Blood samples were drawn simultaneously from the corpus cavernosum and the cubital vein of 54 healthy and normally potent volunteers during four different stages of the cavernous erectile tissue (flaccidity, tumescence, rigidity, and detumescence). Penile erections were induced by audiovisual and tactile stimulation, and testosterone levels were determined by radioimmunoassay. RESULTS: The mean testosterone level in the corpus cavernosum plasma during the flaccid state was 2.9 +/- 1.2 ng/mL. During tumescence and rigidity, the testosterone levels in the cavernous blood significantly increased, to 4.3 +/- 1.3 ng/mL and 4. 4 +/- 1.4 ng/mL, respectively. During detumescence, the cavernous testosterone levels dropped to 3.5 +/- 1.4 ng/mL. The changes in the testosterone levels in the peripheral plasma were less pronounced. A significant increase was also found in the peripheral testosterone levels from flaccidity (4.1 +/- 1.1 ng/mL) to tumescence (4.4 +/- 1. 4 ng/mL). No further increase in testosterone occurred during the phase of rigidity. From rigidity to detumescence, the peripheral testosterone levels dropped to 4.1 +/- 1.2 ng/mL. CONCLUSIONS: Penile erection was found to be accompanied by a significant increase in cavernous and systemic testosterone plasma levels. The estimated difference between the systemic and cavernous testosterone levels during penile flaccidity, when blood flow through the cavernous body is minimized, might be a diagnostic tool to evaluate the amount of bioavailable testosterone and the activity of testosterone receptors in the corpus cavernosum smooth musculature.

Analysis of the cyclin-dependent kinase inhibitor p27Kip1 in muscle invasive bladder cancer.

It has been suggested that a deregulated cell cycle control contributes to the development of human malignancies due to the loss of critical antiproliferative mechanisms. The cell cycle is controlled at two checkpoints, one at the G1-S and another at the G2-M transition. Several genes including the structurally related p21WAF/CIP1 gene, the downstream mediator of the p53 tumor suppressor gene, and the p27Kip1 gene have been identified as inducers of cell cycle arrest at the G1 checkpoint when substantial DNA damage has occurred to avoid further replication of the altered genome. Recently, a heat stable 27 kDa protein, the transcript of the p27Kip1 gene, has been identified and was suggested to substantially participate in cell cycle control at the G1 checkpoint. Previous investigations have correlated decreased expression of the p27Kip1 protein with an increased biological aggressiveness of breast and small cell lung cancer. However, the molecular-genetic analysis of a variety of human malignancies including prostate cancer failed to identify any alteration at the p27Kip1 gene locus, therefore suggesting a loss of p27Kip1 protein expression to result from post-transcriptional/post-translational events or from so far unknown regulatory mechanisms. So far, bladder cancer specimens have neither been investigated for p27Kip1 alterations on the DNA level, nor has the result of molecular genetic analysis been correlated with an immunohistochemically detected expression of the gene product, the p27Kip1 protein. The present study is the first to describe p27Kip1 gene alterations on the DNA level in 3 of 42 muscle invasive bladder cancer specimens. In contrast, loss of p27Kip1 protein expression was observed in 14 of 42 (33%) tumors. According to the previously reported observation in a variety of human malignancies, in bladder cancer loss of p27Kip1 protein expression seems to result from post-transcriptional or post-translational events.

Predictive value of altered p27Kip1 and p21WAF/Cip1 protein expression for the clinical prognosis of patients with localized prostate cancer.

The p21WAF/Cip and the p27Kip1 genes have been identified as inductors of cell cycle arrest at the G1-checkpoint. Alterations of both genes have been suggested to be involved in the development of a variety of human malignancies due to a loss of critical antiproliferative mechanisms. To evaluate the prognostic importance of these alterations for patients with clinically localized prostate cancer, in 86 specimens (T1-T4) from 86 patients undergoing radical prostatectomy at the Department of Urology at Hannover University Medical School, were investigated. The immunohistochemical expression of the p27Kip1 and p21WAF/Cip protein was correlated to recurrence-free and long-term survival, age, depth of tumour infiltration, histological grade and lymph node status in these patients. After a median follow-up of 71 months (1-198 months), 14 of 20 (70%) patients (Group 1) with loss of p27Kip1 protein expression or a relative amount of < 10% of positively stained tumour cells developed recurrent disease in contrast to 18 of 66 (27%) patients (Group 2) with retained p27Kip1 protein expression (> or = 10% of positively stained tumour cells). The median recurrence-free survival times were 39 (4-134) months and 67 (4-198) months for patients in Groups 1 and 2 (p < 0.01), respectively. In multivariate analysis, loss of p27Kip1 protein expression was identified as the only independent prognostic parameter for recurrence-free survival. Univariate analysis (log-rank test) identified histological grading (p < 0.01) and reactivity for p27Kip1 (p = 0.046) (> or = 10% positivity) as prognostic factors for disease-specific long-term survival. However, during multivariate analysis none of the biological variables investigated retained independent prognostic importance regarding overall survival. Neither a low or a high expression of p21Waf/Cip could be correlated with the clinical prognosis of the patients following radical prostatectomy. This study confirms the independent prognostic value of decreased p27Kip1 protein expression in patients with localized prostate cancer, while a prognostic importance of p21Waf/Cip in addition to established patients' and tumour characteristics like tumour stage and histological grading appears rather unlikely.

The MXI1 tumor suppressor gene is not mutated in primary prostate cancer.

For prostate cancer, allelic deletions from the long arm of chromosome 10 (#10q23-25), the locus of the putative tumor suppressor gene MXI1 (#10q24-25), have been identified as a frequently occurring genetic event. During the development of several human malignancies, the c-myc proto-oncogene has been identified to enhance cellular transformation, mitogenesis and cell proliferation. The MXI1 gene, belonging to the helix-loop-helix (bHLH) gene family, was demonstrated to display tumor suppressor function by antagonizing c-myc induced transcriptional activities. Due to the detection of point mutations in the retained alleles of four primary adenocarcinomas of the prostate, MXI1 gene alterations have been suggested to be involved in the development and/or the progression of prostate cancer. To evaluate the role of MXI1 gene alterations for the development of adenocarcinoma of the prostate, 42 primary prostate cancers of different stage (T1-4) and histological grade (G1-3) were investigated for alterations within exons 4 and 5 of the MXI1 gene (spanning 6 exons in total), encoding for the functional HLH-Zip domain, by RNA-SSCP analysis and direct PCR-DNA-sequencing following the microscopically guided tumor cell dissection from 5 microm fresh-frozen buffer-soaked tissue sections. Even by application of this highly elaborated technical approach, MXI1 gene alterations could not be deleted in any of the tumor specimens investigated. Therefore, a substantial involvement of MXI1 gene alterations in the development of prostate cancer appears unlikely. The newly identified putative tumor suppressor gene PTEN, located at #10q23, might be responsible for the frequently observed allelic deletions from #10q23-25 in prostate cancer.

Prognostic value of p27Kip1 and p21WAF/Cip protein expression in muscle invasive bladder cancer.

Two genes, namely p27Kip1 and p21WAF/Cip1 that reveal distinct structural homology, have been identified as inductors 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 was demonstrated that the p21WAF/Cip1 gene is induced by pathways dependent and independent from a functionally intact p53 tumour suppressor protein. It has been suggested that decreased expression both of the p21WAF/Cip1 and p27Kip1 protein may contribute to the development of human malignancies due to loss of critical antiproliferative mechanisms. So far, the role of altered p21WAF/Cip1 and mainly of a decreased p27Kip1 protein expression in patients with muscle invasive bladder cancer has not been investigated. In the present study, 50 tumour specimens from 50 patients undergoing radical cystectomy (T2-T4) were investigated for different biological and clinical characteristics as possible prognostic factors: age, depth of tumour infiltration (T-stage), histological grading (G), lymph node status as well as immunohistochemical staining for the p21WAF/Cip1 and p27Kip1 proteins. The median recurrence-free survival for patients with and without retained p21WAF/Cip1 protein expression was 54 months (3-86 months) and 13 months (1-40 months), respectively (p=0.07). During univariate analysis, loss of p21WAF/Cip1 protein expression (p=0.02), T-stage (p=0.02) and histological grading (p=0.03) were significant prognostic factors for survival, among which a negative reaction for the p21WAF/Cip1 protein (p=0.02) as well as T-stage (p=0.005) remained independent significant predictors during multivariate analysis. Loss of p27Kip1 protein expression was not correlated with the recurrence-free or the overall survival of the patients. Prospective studies are needed to confirm the independent prognostic potential of cell-cycle associated proteins such as p21WAF/Cip1 in patients with muscle invasive bladder cancer. The availability of more refined prognostic factors should assist decision making regarding the value of more aggressive treatment options, such as adjuvant or neoadjuvant chemotherapy, for defined subgroups of patients.

[Positron emission tomography (PET) for diagnosis and monitoring of treatment for urological tumors]. / Positronenemissionstomographie (PET) zur Diagnostik und zum Therapiemonitoring bei urologischen Tumoren.

Positron emission tomography (PET) using ((18)F)2-fluoro-D-2-desoxyglucose (FDG) has been shown to be a highly sensitive and specific imaging modality in the diagnosis of primary and recurrent tumors and in the control of therapies in numerous non-urologic cancers. It was the aim of this review to validate the significance of PET as a diagnostic tool in malignant tumors of the urogenital tract. A systematic review of the current literature concerning the role of PET for malignant tumors of the kidney, testicles, prostate, and bladder was carried out. The role of FDG PET for renal cell cancer can be seen in the detection of recurrences after definitive local therapy and metastases. The higher sensitivity of PET in comparison to other therapeutic modalities (CT, ultrasound, MRI) in recurrent and metastatic renal cell cancer suggests a supplemental role of this diagnostic procedure to complement other imaging modalities.The clinical value of PET is established for the identification of vital tumor tissue after chemotherapy of seminomatous germ cell tumors. This diagnostic method has little significance for primary tumor staging and diagnosis of non-seminomatous germ cell tumor because of the high probability of false-negative results in adult teratomas. FDG PET is not sensitive enough in the diagnosis of primary or recurrent tumors in prostate or bladder cancer. Also PET did not prove to be superior to conventional bone scintigram in the detection of mostly osteoblastic metastases in prostate cancer. The recent use of alternative tracers, which are partly not eliminated by urinary secretion (acetate, choline) has increased the sensitivity and specificity of PET also in this tumor entity so that further clinical investigations are needed to validate these technical modifications in their significance for this imaging modality. PET appears to be sufficiently evaluated only for the diagnostic follow-up of patients with seminomatous germ cell tumors after chemotherapy to regard it is the diagnostic tool of first choice. For all other tumors of the urogenital tract this proof is still awaited.