[Differences in sexual development-S2k guideline update]. / Varianten der Geschlechtsentwicklung ­ Aktualisierung der S2k-Leitlinie.

BACKGROUND: Human beings with a difference in sexual development (DSD) often underwent gender reassignment surgery during early childhood. However, the medical decision was often not congruent with the gender identity that affected persons developed later on. OBJECTIVES: To represent the interests of affected persons, an interdisciplinary guideline in cooperation with support groups was written. MATERIALS AND METHODS: The revision of the first version of the guideline, published in 2016, was edited by 18 professional societies and working groups as well as 3 support groups. A literature search was performed for each of the 12 chapters. Recommendations and statements created by the working groups were voted on during four consensus conferences. RESULTS: The guideline highlights the right of self-determination of affected persons. In this context, new legal requirements are reported. Other than necessary primary diagnostics, medical procedures should be postponed. Most important is the psychological support of parents and patients. Tumor risk of the gonads and protection of fertility are analyzed and discussed in detail. CONCLUSION: The content of the guideline represents a paradigm shift in dealing with human beings with a difference of sexual development. Projects as DSD Care and Empower-DSD help to promote the practical implementation of the guideline's recommendations.

[Update of the German S3 guideline on renal cell carcinoma]. / Aktualisierte S3-Leitlinie Nierenzellkarzinom.

BACKGROUND: Renal cell carcinoma is the third most common tumor among urological tumors. In Germany more than 14,000 people are affected every year. The sex ratio is 2/3 men and 1/3 women. OBJECTIVES: The S3 guideline is intended to provide all disciplines dealing with renal cell carcinoma with the current status of diagnostics, therapy and follow-up care of the patients with this tumor. MATERIALS AND METHODS: The first version of the German guideline on renal cell carcinoma was published in 2015. The development was carried out at S3 level, which means that a structured, evidence-based literature search was carried out, recommendations and statements were developed in topic-related working groups and were approved by an interdisciplinary group of officials elected by the different medical societies. The chapters were gradually revised in 2017, 2020 and 2021 to reflect new aspects. This article provides information about the most important innovations of the most recent update from 2023. RESULTS: In the epidemiology subsection, the substance trichlorethene has been added as a risk factor for the development of renal cell carcinoma. While there were no new data on neoadjuvant therapy, the checkpoint inhibitor pembrolizumab was the first substance to demonstrate improved disease-specific and overall survival in the adjuvant situation. The combination nivolumab plus cabozantinib and lenvatinib plus pembrolizumab were included in the chapter on systemic therapy for metastatic clear cell renal cell carcinoma. New are the chapters on non-clear cell renal cell carcinoma and hereditary tumors. CONCLUSIONS: The S3 guideline provides a structured, evidence-based overview of all aspects of renal cell carcinoma.

Maintaining success, reducing treatment burden, focusing on survivorship: highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer.

In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, ∼50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.

Gender reassignment surgery--a 13 year review of surgical outcomes.

PURPOSE: The aim of this study is to thoroughly report on surgical outcomes from 332 patients who underwent male to female gender reassignment surgery (GRS). MATERIAL AND METHODS: Records from 332 patients who underwent GRS from 1995 to 2008 were reviewed. All patients were submitted to penile inversion vaginoplasty with glans-derived sensate clitoroplasty. Mean age was 36.7 years (range 19-68 years). Surgical complications were stratified in 5 main groups: genital region, urinary tract, gastrointestinal events, wound healing disorders and unspecific events. RESULTS: Progressive obstructive voiding disorder due to meatal stenosis was the main complication observed in 40% of the patients, feasibly corrected during the second setting. Stricture recurrence was found in 15%. Stricture of vaginal introitus was observed in 15% of the cases followed by 12% and 8% of vaginal stenosis and lost of vaginal depth, respectively. Rectal injury was seen in 3% and minor wound healing disorders in 33% of the subjects. CONCLUSION: Regarding male to female GRS, a review of the current literature demonstrated scarce description of complications and their treatment options. These findings motivated a review of our surgical outcomes. Results showed a great number of adverse events, although functionality preserved. Comparision of our outcomes with recent publications additionally showed that treatment options provide satisfying results. Moreover, outcomes reaffirm penile inversion vaginoplasty in combination with glans-derived sensate clitoroplasty as a safe technique. Nevertheless, discussing and improving surgical techniques in order to reduce complications and their influence on patient's quality of life is still strongly necessary and theme of our future reports.

[Testicular and penile cancer-survival and quality of life : New guideline and network for second opinions]. / Hodentumor und Peniskarzinom ­ Überleben mit Lebensqualität : Neue Leitlinien und Zweitmeinungsnetzwerk.

Testicular cancer occupies a special position in several respects. Although it belongs to the group of rare tumors, which is why extensive experience in treating this tumor can not be guaranteed, interdisciplinary experts collaboration and the consequent implementation of clinical studies have resulted in standardized treatment recommendations. Because testicular cancer is one of the most curable cancers, long-term toxicity and treatment sequelae are of special importance. In the early stages, toxicity could be reduced by minimizing therapy to the extent possible, but without decreasing treatment success. Nevertheless, treatment is still controversially discussed, especially concerning treatment of stage I disease. Finally particular focus should be paid to non-germinal tumors which are even more rare, but partly also more dangerous. Therefore known facts should be made available for the broad medical community. In penile cancer, which is also a very rare tumor entity, organ-sparing surgery and consequent invasive lymph node staging are mandatory.

[Guidelines-a European project]. / Leitlinien ­ ein europäisches Projekt.

Clinical guidelines represent the latest standard of medical knowledge concerning diagnostics, treatment and follow up of diseases and should support doctors and patients to choose the best treatment. Depending on the prevalence of a disease there exist less or more published data. Therefore, several levels of guidelines are possible. In case of few data the expertise of the attending physicians is of greater importance (S1, S2-guidelines). In case of a huge amount of literature, especially phase III studies or metaanalyses, a S3-guideline can be written. The article describes the process of developing a guideline in Germany under the guidance of the Association of the Scientific Medical Societies in Germany (AWMF) in comparison to the process by the European Association of Urology (EAU). The aim for the future is to join resources. Another aspect of the article is to inform about different procedures how to control the implementation of the guidelines.

[A multi-disciplinary approach to the treatment of germ cell tumors]. / Multimodale Therapiekonzepte von Keimzelltumoren.

The management of patients with germ cell tumors must be based upon complete staging and should be risk-adapted. Seminoma stage I can be managed by either active surveillance, adjuvant carboplatin therapy, or radiotherapy. Seminoma stage IIA should receive radiotherapy, stage IIB can be managed with either radiotherapy or chemotherapy. Seminoma stage IIC and III are treated with three (to four) cycles of PEB (cisplatin, etoposide, bleomycin). Nonseminoma stage I should be managed by either active surveillance or adjuvant chemotherapy with one (to two) cycles of PEB, based upon the risk factor vascular invasion. Treatment of advanced nonseminoma consists of either 3 or 4 cycles of PEB and must be guided by the IGCCCG prognostic subgroup. Prognosis is particularly poor in patients with either primary mediastinal nonseminoma, and/or metastases to liver, brain or bone, or inadequate tumor marker decline. In these cases, intensification of therapy with high dose chemotherapy can be justified. Complex cases with poor prognosis and all patients with relapsed disease should exclusively be treated by experts in a tertiary care setting to achieve highest possible cure rates in these young patients.

[Reforms in the treatment of people with variants of sexual differentiation]. / Reformen in der Behandlung von Menschen mit Varianten der Geschlechtsdifferenzierung.

Individuals born with a variant of gender development still have a special status in our dyadic-oriented society that even nowadays impairs their life in many ways. Thus, physicians and parents regulated the life's journey of these children until less than 30 years ago by conducting a gender assignment after birth and its implementation by surgical interventions. This approach was ensued in the hope that the child would develop the relevant gender identity, an assumption that did not hold true in many cases. Only during the last 20 years, especially due to the public relations activities of associations of affected individuals, a process of rethinking has taken place that strives to focus on the child's right to self-determination. Reforms of the Personal Statute Act have already been accomplished. Apart from the entry "female" and "male" for newborn children, the categories "open" and "diverse" also now exist. This should exonerate the parents and enable affected persons to later register a distinct term. A draft Act about the interdiction of gender-modifying interventions in the case of a child unable to consent already exists, but is controversially discussed, particularly among CAH associations that do not class themselves as variants of gender differentiation and still advocate early surgical operations. Furthermore, there is also an absolute necessity for structural reforms on the care level to ensure a competent counselling, support and/or treatment for individuals born with a variant of gender differentiation.

[Results of the randomised phase III study of the German Testicular Cancer Study Group. Retroperitoneal lymphadenectomy versus one cycle BEP as adjuvant therapy for non-seminomatous testicular tumours in clinical stage I]. / Ergebnisse der randomisierten Phase-III-Studie der "German Testicular Cancer Study Group". Retroperitoneale Lymphadenektomie vs. 1 Zyklus PEB als adjuvante Therapie beim nichtseminomatösen Hodentumor im klinischen Stadium I.

OBJECTIVE: As 30% of non-seminomas in clinical stage I will progress during active surveillance, alternative adjuvant strategies of 2 cycles of bleomycin, etoposid, cisplatin (BEP) or nerve sparing retroperitoneal lymphadenectomy (RPLND) can be offered. The risk of relapse is reduced to 2% and 10%, respectively. Without prognostic markers and with lowered toxicity it is postulated that only one cycle of BEP could significantly reduce the recurrence rate in comparison to RPLND. MATERIALS AND METHODS: Between 1996 and 2005, 382 patients were randomly assigned to receive either RPLND (n=191) or 1 cycle of BEP (n=191). In accordance with the protocol, 174 patients were treated with 1 cycle of BEP and 173 underwent RPLND. The primary study end-point was a reduction of recurrence from 10% after RPLND to a maximum of 3% after 1 cycle of BEP. RESULTS: After a mean follow-up of 4.7 years, there were 2 and 13 recurrences in the according-to-protocol population with chemotherapy and surgery, respectively. The difference between chemotherapy (1.15%) and surgery (7.5%) was statistically significant (p=0.0033). The tumor-specific survival was 100%. CONCLUSION: This largest randomized trial investigating treatment strategies in clinical stage I non-seminomas (AUO AH 01/94) showed the superiority of one cycle BEP over RPLND. The data obtained represent the basis for a reduced chemotherapy.

Variations of sex development: The first German interdisciplinary consensus paper.

INTRODUCTION: The term variations of sex development subsumes a large number of congenital conditions including chromosomal mosaics and variations of chromosomal, gonadal, and phenotypic sex. A situation of this nature may cause severe distress to both, parents and affected persons. One of the reasons for this is the binary form of gender classification in the society. In the past, because of a fear of possible stigmatization and an inability to cope with complex situations, it has been medical policy and practice for newborns to undergo early, mostly 'feminizing' elective surgery with the aim of achieving an outer genital appearance that is unambiguously male or female. Protests by advocacy groups for the most part as well as the results of outcome studies have shown that the development of affected persons may be very different to what has been expected and often does not result in the intended clear female or male gender identity as had been intended. It, therefore, seemed a matter of urgency to implement this new awareness as well as the ethical and personal human rights perspectives in the recommendations for the medical and psychosocial management of diverse sex development (DSD) in the future. STUDY DESIGN: In 2012, an interdisciplinary group of German academics engaged in the field of DSD decided to work on a consensus paper for this topic. It involved the participation of all faculties and non-scientific groups dealing with DSD, in particular advocacy and service-user groups. In a structured consensus, process recommendations were developed based on scientific literature as well as personal experiences of clinicians and affected individuals. RESULTS: Finally, 37 recommendations were agreed on. The strength of consensus is reflected in the degree of agreement as expressed in percentages. CONCLUSION: The introduction of the consensus paper reflects on the emerging paradigm shift and the necessity for a more open view of gender within society. The paper is intended to aid the performance of appropriate diagnostics in DSD-affected newborns and especially to help parents and affected persons cope with the biological and social consequences of DSD. With regard to medical or surgical therapy, it gives information about the most recent treatment trends.

[Advanced bladder cancer : From chemo- to immunotherapy]. / Fortgeschrittenes Urothelkarzinom : Von der Chemotherapie zur Immuntherapie.

In November 2016, the results of a phase III clinical trial with the protein cell death (PD)-1 inhibitor pembrolizumab for second-line treatment of metastatic urothelial carcinoma were published and showed an overall survival benefit in comparison with conventional chemotherapy with vinflunine, docetaxel, or paclitaxel. In a similar trial the PD-L1 antibody atezolizumab showed no significant benefit in comparison to chemotherapy in the subgroup of PD-L1-positive patients and, thus, missed its primary endpoint. For other PD-1/PD-L1 directed substances, large phase I/II trials reported data concerning response rates and overall survival. This substance class will most likely become the new treatment standard in second-line treatment of metastatic urothelial cancer. Currently, PD-1/PD-L1 inhibitors are also being tested within randomized phase III trials for first-line treatment using different approaches either as a monotherapy or a combination with conventional chemotherapy or cytotoxic T­lymphocyte-associated protein (CTLA)-4 inhibitors. Whereas data from single-arm phase II clinical trials have already been published, preliminary phase III data are expected in 2018.

[Inductive systemic therapy of urological tumors with curative intent]. / Induktive Systemtherapie mit kurativer Zielsetzung urologischer Tumoren.

Up to now systemic therapy with curative intent is possible in only a few tumors. Concerning advanced malignant tumors in urology only testicular cancer can be cured. In metastatic urothelial cancer of the bladder this might be possible in single cases. In advanced renal cell carcinoma a recent group of new substances, so-called target-specific substances, have gained attention. In several phase III studies with sunitinib, sorafenib, and temsirolimus at least progression-free survival could be clearly prolonged. The amazing results in testicular cancer were possible by consistent performance of clinical trials. The success in treatment also is an example for interdisciplinarity. Especially in advanced stages treatment consists of two components, chemotherapy, correctly performed concerning dose and interval, followed by complete residual tumor resection.

[Testicular perfusion injury. Cytokines and cell adhesion molecules in humans]. / Testikuläre Ischämie. Verlauf von Zytokinen und Zelladhäsionsmolekülen beim Menschen.

BACKGROUND: Ischemia and reperfusion (I/R) lead to cellular damage. A disturbance of testicular perfusion occurs during the therapy of cryptorchidism and in cases of testicular torsion. This results in the activation of mediator cells with an increasing synthesis of mediators of infection like TNF-alpha and the expression of cell adhesion molecules like ICAM (intercellular adhesion molecule) and VCAM (vascular cell adhesion molecule) at the cellular surface. METHODS: The expression of the cytokines IL-10 and TNF-alpha and the adhesion molecules ICAM and VCAM after defined testicular I/R injury in nine male transsexuals was evaluated with rt-PCR. Furthermore we examined lactate and the diameter of the testicular tubulus under ischemic conditions. RESULTS: During ischemia ICAM, IL-10, and VCAM do not show significant changes on the side of testicular ischemia and the contralateral side; the same was seen for the tubulus diameter. TNF-alpha and the testicular lactate values showed a significant change of the expression pattern. DISCUSSION: The statistical changes of TNF-alpha and testicular lactate are the expression of leukocyte migration, infectious reaction, and immune response. To what extent the TNF-alpha expression represents a severe immunological reaction remains undefined. This human study shows primary results for the immunological understanding of and cellular response to testicular ischemia.

[The management of cutaneous metastases]. / Management kutaner Metastasen.

Cutaneous metastases are rare and usually signify a poor prognosis. The manifestation of cutaneous metastases is variable; crucial to their diagnosis is their inclusion in the differential diagnosis. The therapy occurs mostly with palliative intention. The quality of life of the patient should take first priority. A combination chemotherapy is usually carried out because of systemic progress. For local tumor control and wound care, metastasis surgery and radiotherapy are used.

[Off-label use: update and relevance for urology]. / Off-Label-Use: Update und Bezug zur Urologie.

The use of pharmaceuticals beyond the approved indication and conditions (off-label use) is of increasing public interest in times of necessary financial constraints in public health together with the high requirements for drug safety to protect the patient. Remarkably, more than half of the therapies in oncology are performed as off-label use. The discussion on off-label use is controversial and based on different points of interests. Evaluation of therapeutic agents by the pharmaceutical industry is predominantly driven by marketing and business requirements. As a consequence, treatment of rare diseases is often only possible by off-label use, creating more or less an off-label need. Reimbursement by health-care insurance is based on the approval of a pharmaceutical substance for a particular situation, because only the rigorous licensing process assures that the verified efficacy is higher than the, often severe, adverse side effects. It is a well known fact that the sometimes adverse events, which occur on administration of substances in an off-label fashion, are not included in the information on the regular use of a given drug. Finally, physicians request a controlled off-label use, which only allows experienced colleagues and (sub)-specialized oncologists to use pharmaceuticals in an off-label fashion. Up to date no legal documents exist that provide regulations for such an off-label usage.

[Chemotherapy of testicular cancer]. / Chemotherapie des Hodentumors.

Platinum-based polychemotherapy has increased the cure rate in testicular cancer dramatically: at first, chemotherapy was mainly used in advanced disease. Recently it has also become common in low-stage disease, though other therapeutic options are equivalent. Risk factors might help to find the right decision. The success of treatment in patients with metastatic disease results from the combination of chemotherapy and secondary surgery. High-dose chemotherapy for patients with poor prognosis or recurrent disease is being evaluated in clinical trials. Concerning the success in these stages prognostic factors are of special importance. Patients with advanced-stage nonseminoma need residual tumor resection after chemotherapy if no complete remission could be achieved. The therapist should be aware of the indication for and schedule of chemotherapy, its side effects, and supportive care.

["Second opinion centers". Approach for improving the quality of treatment for testicular tumors]. / "Zweitmeinungszentren". Ansatz zur Verbesserung der Versorgungsqualität bei Hodentumoren.

According to estimations of the German Cancer Research Center in Heidelberg, the management of germ cell tumors in Germany is characterized by a marked difference between the actual mortality and the mortality to be expected with adequate implementation of the therapy standard. Our aim is to reduce the mortality rate by introducing a treatment procedure supported by a second opinion center.

[Geriatric urology -- tumour diseases]. / Geriatrische Urologie -- Tumorerkrankungen.

Due to demographic developments malignancies of urogenital origin will gain increasing importance. The urologist will face a growing group of patients with co-morbidities and functional disabilities as these neoplasms increase with age. Optimisation of peri-interventional management successfully reduces the risks of surgery. Integration of taxane-based cytostatic regimes achieves a prolongation of survival in hormone-refractory metastatic prostatic cancer. The introduction of gemcitabine in the management of malignancies of the bladder seems to have reduced toxicity while maintaining anti-tumour activity in comparison to MVAC. The role of haematopoetic growth factors remains to be defined in urologic malignancies - increasing dose intensity for better activity or reduction of toxicity. Individualisation of treatment requires early cooperation of the urologist, the oncologist and the geriatrician for an optimal outcome.

[Effects of modified inclusion criteria and negative reporting about PSA screening on the number of potentially recruitable patients for the PREFERE study]. / Auswirkungen geänderter Einschlusskriterien und negativer Berichterstattung zum PSA-Screening auf die Zahl potentiell für die PREFERE-Studie rekrutierbarer Patienten.

BACKGROUND: The PREFERE study is currently below expectations. The objective of this study was to investigate the effect of the modification of the inclusion criteria in 2015 on the number of recruitable patients with localized prostate cancer. Furthermore we analyzed whether fewer cases of low-risk prostate cancer were detected in 2014 than in 2010. PATIENTS AND METHODS: Prostate biopsies of 2136 patients (9 hospitals) of the years 2010 and 2014 were retrospectively reviewed, regarding the eligibility for participation in the PREFERE study. RESULTS: According to PREFERE criteria version 3.2, 16.8 % (in 2010) and 16.7 % (in 2014) of the patients fulfilled the inclusion criteria for the study, whereas 41.9 % (in 2010) and 30.1 % (in 2014) of the patients met the criteria in version 5.0. CONCLUSIONS: Our results indicate that the modified inclusion criteria result in an increase in the number of recruitable patients for the PREFERE study. Furthermore, there were 11.8 % fewer cases of potentially recruitable patients in 2014 than in 2010 by use of version 5.0. This is a possible indication for an altered use of prostate biopsy.