[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.

[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.

[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.

[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.

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.

[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.

[National second opinion network for testicular cancer patients - transferring guidelines into practice!]. / Nationales Zweitmeinungsnetzwerk Hodentumoren - ein System zum Evidenztransfer!

The second opinion network for testicular cancer is an internet-based platform addressed to physicians treating testicular cancer patients. They are offered a second opinion before determining further therapy after orchiectomy and completion of staging procedures. The platform has been used in more than 3,000 cases of testicular cancer to date. The rate of discrepancies between first and second opinions is higher than 30%. This suggests a deficit in the implementation of published therapy guidelines. According to our present interim analysis, the second opinion platform helps in avoiding overtreatment of testicular cancer. The high acceptance of the project and the encouraging results of this interim analysis open the door for expansion of the second opinion model to other diseases, e. g., penile carcinoma.

[Diagnostics and treatment of seminomatous germ cell tumors]. / Diagnostik und Therapie seminomatöser Hodentumoren.

Currently, seminomas account for about 60% of newly diagnosed testicular cancers in Germany, with an increasing trend. In lower tumor stages the main focus is on the avoidance of over therapy. This is of special interest in stage I where radiotherapy, carboplatin monotherapy and surveillance are available therapies as well as in stage IIA/B. Due to high late toxicity, radiotherapy of the retroperitoneal space is obsolete for young patients with clinical stage I and, in its present form, discussed controversially for patients with clinical stage IIA/B. The cause for this paradigm shift is the high percentage of secondary malignancies resulting after radiotherapy of the retroperitoneal space. Furthermore, 10-25% of the patients receiving radiotherapy alone for clinical stage IIA/B seminoma suffer from a relapse of the disease due to tumor recurrence in extraregional lymph nodes. Therefore, an ongoing study is investigating if a combined treatment with neoadjuvant carboplatin and radiotherapy with a limited target volume can reduce toxicity without jeopardizing the cure rate. Patients with residual tumors >3 cm should undergo 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) computed tomography scanning after a minimum interval of 6 weeks after chemotherapy. In the case of a positive FDG-PET-CT result, the further therapeutic strategy should be the subject of interdisciplinary discussions.

[Congenital adrenal hyperplasia in girls/young women]. / Das adrenogenitale Syndrom beim Mädchen/junger Frau.

BACKGROUND: With a mean global incidence of 1:14500, congenital adrenal hyperplasia (CAH) is the most common disorder of sexual differentiation (DSD). In case of female karyotype, the prenatal surplus of androgens causes virilization of the external genitalia. This includes clitoral hypertrophy and an increasing higher confluence of the urethra and normal developed proximal vagina, creating the urogenital sinus. Internal genitalia are female. METHOD: Until recently feminizing surgery was performed within the first 18 months of life, at least concerning clitoroplasty. Though the cosmetic result of this kind of surgery is quite good, functional shortcomings like clitoral hyposensibility were often reported. RESULTS: The latest discussion about treatment of intersex patients resulted in recommendations to prevent early surgery and observe the development of the child, until the child can decide for itself, if and in what direction it wants to undergo surgery. Though CAH patients are seen as a special group within intersex disorders, these recommendations should also be considered for them. The appropriateness of this change in treatment strategy is supported by publications concerning the long-term follow-up of patients, who finally chose a gender that was different from what physicians and parents had expected.

[Pharmacological therapy of urogenital cancer: rational routine diagnostic imaging]. / Medikamentöse Tumortherapie urogenitaler Malignome: Rationale bildgebende Diagnostik.

BACKGROUND: Imaging studies are an integral and important diagnostic modality to stage, monitor, and follow-up patients with metastatic urogenital cancer. The currently available guidelines on diagnosis and treatment of urogenital cancer do not provide the clinician with evidence-based recommendations for daily routine. It is the aim of the current manuscript to develop scientifically valid recommendations with regard to the most appropriate imaging technique and the most useful time interval in metastatic urogenital cancer patients undergoing systemic therapy. RESULTS: Therapeutic response of soft tissue metastases is evaluated with the use of the RECIST criteria. In skeletal metastases, bone scans with validated algorithms must be performed to assess response. In patients with testicular germ cell tumors, computed tomography (CT) of the chest, the retroperitoneum, and the abdomen represents the standard imaging technique of choice usually performed prior to and at the end of systemic chemotherapy. Only in seminomas with residual tumors > 3 cm in diameter should FDG-PET/CT be performed about 6 weeks after chemotherapy. Metastatic renal cell carcinomas treated with molecular targeted therapies are routinely evaluated by CT scans at 3 month intervals. In specific cases, FDG-PET/CT is able to predict responses as early as 8 weeks after initiation of treatment. In patients with metastatic urothelial carcinomas, imaging studies should be performed after every second cycle of cytotoxic therapy. In patients with metastatic prostate cancer, the modality and the frequency of imaging studies depends on the type of the treatment. In men undergoing androgen deprivation therapy, no routine imaging studies are recommended except for patients with new onset symptoms or significant PSA progression prior to change of treatment. In men with metastatic castration-resistant PCA who are treated with cytotoxic regimes, routine imaging studies in the presence of decreasing or stable PSA serum concentrations are not indicated. In men treated with lyase inhibitor or inhibitors of the androgen receptor signaling cascade, imaging studies should be performed at 3 month intervals due to the low correlation of PSA serum concentrations with clinical response. CONCLUSIONS: Imaging studies to assess therapeutic response to systemic treatment in metastatic cancers of the urogenital tract must be chosen depending on the treatment regime, primary organ, and potential consequences of the findings. Routine imaging studies without specific clinical or therapeutic relevance are not justified.

[Diagnosis and treatment of nonseminomatous germ cell tumors]. / Diagnostik und Therapie nichtseminomatöser Hodentumoren.

Testicular cancer currently shows excellent rates of curing and even in advanced stages of disease about 70% can be achieved. This was possible due to continuously carrying out studies. To reduce long-term toxicity the focus is now put on reduction of treatment. In nonseminomatous germ cell cancer this is discussed especially for stage I disease where different therapeutic strategies can be offered. Concerning advanced disease the aim is a further improvement of treatment results. Polychemotherapy and surgical procedures are equally important in this scenario. Concerning residual tumor resection it should always be considered that the procedure can be extended by adjuvant surgery, e.g. cava resection. Therefore, those resections should only be performed at centers where all possibly needed surgical disciplines are available.

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.