[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.

[Immunotherapy and tyrosine kinase inhibitors in first-line treatment of metastatic renal cell carcinoma-Which strategy when?] / Immuntherapie und Tyrosinkinaseinhibitoren beim metastasierten Nierenzellkarzinom in der First-line-Therapie ­ Wann welche Strategie?

Immunotherapies with checkpoint inhibitors have led to a paradigm shift in metastatic renal cell carcinoma (mRCC) as they established a new standard in first-line treatment. In addition to the established monotherapy with tyrosine kinase inhibitors, the spectrum of first-line options has now become wider. Based on data from studies and current guideline recommendations, this article discusses possible factors for individual strategies in first-line treatment of mRCC. For this decision, the leading criterion is the patient's risk score. In addition, the efficacy and tolerability of the substances, tumor burden, patient age and preferences as well as considerations about sequence treatment can support the decision. Real-world data for the new combination treatment, biomarkers for personalized medicine as well as studies on optimal sequence treatment for mRCC are needed.

[Algorithms for systemic therapy of prostate cancer, transitional cell carcinoma and renal cell carcinoma]. / Algorithmen zur Systemtherapie bei Prostata­, Urothel- und Nierenzellkarzinom.

Systemic therapy in uro-oncology is currently undergoing major changes. In the past, drug therapies only showed good treatment results in metastasized testicular tumors. New developments indicate that an improved understanding of tumor biology will lead to targeted treatment strategies for metastatic prostate, urothelial and renal cell carcinoma. In the following article, we summarize the practice-relevant innovations in systemic therapy in the guidelines on prostate cancer, transitional cell carcinoma of the bladder and renal cell carcinoma.

[Follow-up of renal cell carcinoma based on stage and initial treatment]. / Nachsorge beim Nierenzellkarzinom in Abhängigkeit des Stadiums und der erfolgten Therapie.

BACKGROUND: Renal cell carcinoma is the third most common tumor of the genitourinary system. Small tumors are increasingly treated by nephron-sparing surgery, focal therapy via cryoablation or radiofrequency ablation and also active surveillance. These treatment options are associated with increased follow-up care. OBJECTIVES: What are the current recommendations on follow-up care for different therapeutic approaches in renal cell carcinoma? MATERIALS AND METHODS: We analyzed different biological aspects regarding renal cell carcinoma, diagnostic procedures as well as recommendations of current guidelines (e.g. German S3, EAU AUA). RESULTS: Follow-up of renal cell carcinoma is not well standardized due to the limited amount of data. In general, follow-up should be intensified during the first 3 years following initial therapy as well as in patients with increased risk for tumor recurrence. For risk calculation different prognostic models based on clinical parameters have been published. CONCLUSIONS: Current recommendations on follow-up care in renal cell carcinoma are based on retrospective studies. Future strategies must include markers and be studied in a prospective manner.

[Molecular tumor board-renal cell carcinoma]. / Molekulares Tumorboard ­ Nierenzellkarzinom.

The introduction of molecular targeted agents has fundamentally changed the treatment of metastatic renal cell carcinoma. A first wave of development was based on the improved understanding of tumor biology since the discovery of the importance of the von Hippel-Lindau gene as the key driver of the disease and paved the way for antiangiogenic agents. Of relevance is the overexpression of proangiogenic and proliferation-promoting factors (VEGF, vascular endothelial growth factor; PDGF, platelet-derived growth factor) as well as an overactivation of the PI3K-Akt signaling pathway: the target structure is the "mammalian target of rapamycin" (mTOR) molecule, which is involved in the regulation of cell proliferative processes. VEGF-, PDGF-, and mTOR-signals and signaling pathways are central targets of current targeted substances. A second wave is certainly to be seen in the development of therapeutic approaches with the targeted activation and modulation of the immune system, which has brought "immunotherapy" back into the focus of interest. Central development is the application of immune-checkpoint inhibitors, with the help of which (re-)activation of the cellular defense, especially of T cells, takes place, which per se holds the potential of a cytoreductive therapy by killing the tumor cells. Even though the prognosis has improved significantly due to the rapid development of recent years, treatment remains challenging as most patients experience progress, and long-term survival is only achieved in about 20% of cases because some patients are primarily refractory or do not respond. The more intensive interlocking of molecular biology, pathology, clinical research, and interdisciplinary uro-oncology, as is the claim of molecular tumor boards, can contribute to the individual selection of a suitable therapy strategy and, thus, establish the latest findings and developments for the benefit of patients in the clinic.

[Interdisciplinary recommendations for the treatment of metastatic renal cell carcinoma]. / Interdisziplinäre Empfehlungen zur Behandlung des metastasierten Nierenzellkarzinoms.

Patients with metastatic renal cell carcinoma have a life-limiting prognosis. Therefore, the aim of therapy is normally palliative care. Nevertheless, substantial achievements have been made in the past years. Cytokines as long-term standard therapy have been replaced by new targeted therapies. Sunitinib, the combination of bevacizumab+interferon-alfa, pazopanib and temsirolimus are now approved for first-line therapy. Sunitinib and pazopanib can also be administered as second-line options - for pazopanib the use is restricted to the event of cytokine failure. Everolimus (after TKI therapy) und sorafenib (after cytokines) are other compounds now available for second-line therapy. In addition, axitinib was approved for second-line therapy after failure of sunitinib or cytokines. For questions regarding the optimal sequence, first study results are now available from the phase III trial.The purpose of an interdisciplinary expert meeting held in 2014 was to debate about which criteria should influence the therapy decision. The members discussed several aspects of treating patients with the disease. Results from the 2012 conference provided the basis for the 2014 meeting 1. As in previous years, the experts intended to provide common recommendations for clinical practice. The results of the 2012 conference are presented as short theses and a current therapy algorithm.

[Active surveillance for renal cell carcinoma]. / Aktive Überwachung beim Nierenzellkarzinom.

The incidence of renal cell carcinoma (RCC) and especially that of small RCCs is increasing. However, not all tumours are malignant and not all malignant tumours are RCCs. Although partial nephrectomy is the therapeutic standard of care, an increasing number of patients is being treated with cryoablation, radiofrequency ablation, or active surveillance. The latter options require a pretherapeutic tumour biopsy. Approximately 85% of all biopsies can distinguish benign from malignant tumours. In the case of a RCC, histological subtype and grading are correctly diagnosed in 85% and 65%, respectively. However, tumour growth and metastasis in patients undergoing active surveillance cannot be predicted. A later tumour growth is the main trigger to change to active therapy. In this paper the results of tumour biopsy and active surveillance of patients with a renal mass are presented.

[Endourological imaging with narrow band imaging]. / Endourologische Bildgebung mittels "narrow band imaging".

Narrow band imaging (NBI) is an optical diagnostic procedure which utilizes the narrowing of the wavelength of visible light in the range between 415 and 550 nm. The NBI is mostly used for the diagnostics of inflammation or tumors of the gastrointestinal tract. The first investigations for diagnostics of bladder cancer using NBI date from 2008. Currently data on resection, follow-up and recurrence behavior of bladder cancer are available. In all publications NBI was tested against white light. A randomized study comparing NBI with photodynamic diagnostics has not yet been carried out. In this article current study results on the application of NBI for bladder cancer will be presented.

Laparoscopic versus open bilateral nephrectomy in transplant recipients with medication-resistant hypertension: final results of a multicenter study with 15 years of follow-up.

BACKGROUND: The objective of this study was to evaluate the outcomes of laparoscopic bilateral nephrectomy (LBN) compared with open bilateral nephrectomy (OBN) in transplant recipients with medication-resistant hypertension. MATERIAL AND METHODS: Between 1994 and 2009, 66 renal transplant recipients underwent LBN due to poorly controlled hypertension. We compared them with 44 previous patients who underwent OBN. RESULTS: The mean operative times for LBN and OBN were 195.4 ± 60.1 minutes and 145.7 ± 30.2 minutes, respectively (P = .013). The mean hospital stays were 4.2 ± 2.1 in the LBN versus 10.3 ± 3.9 days in the OBN groups; the mean complication rates were 9.1% versus 18.2%, respectively. At follow-up, the blood pressure (mean value 130/90 mm Hg) in 45 patients (68.2%) among the LBN group was well controlled without the need for antihypertensive medications. In 19 patients (28.8%) significantly fewer antihypertensive drugs (1 or 2) were needed compared with the preoperative status. The remaining 2 patients (3%), both of whom had returned to hemodialysis due to chronic transplant rejection, remained on a combination of 3 or more antihypertensive drugs. Among the open surgery group, 23 subjects (52.3%) showed significantly decreased arterial blood pressure without needing medical therapy; 18 patients (40.9%) required 1 or 2 drugs and the remaining 3 (6.8%) were on a combination of 3 or more antihypertensives. The last cohort had returned to hemodialysis due to chronic transplant rejection. CONCLUSIONS: LBN showed a higher efficacy than open surgery to treat medication-resistant hypertension after renal transplantation, reducing the postoperative trauma and the morbidity rate in high-risk transplant recipients.

[Human placental alkaline phosphatase (hPLAP) is the most frequently elevated serum marker in testicular cancer]. / Die humane plazentare alkalische Phosphatase (hPLAP) ist der am häufigsten erhöhte Serummarker beim Hodentumor.

BACKGROUND: Testicular cancer is the most frequent cancer in patients between 20 and 40 years of age. Cure rates are very high due to standardised operative treatment as well as additional chemotherapy and radiotherapy according to -histological subtype and tumour stage. Histological subtypes are seminoma, non-seminoma and mixed tumours (partly seminoma and partly non-seminoma). The aim of this study was to determine the value of different tumour markers in the primary diagnosis of testicular cancer. MATERIAL AND METHODS: In a retrospective study we investigated 152 consecutive patients with testicular cancer as well as 75 patients with benign scrotal conditions. In all patients the tumour markers human alkaline phosphatase (hPLAP), alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG) and the enzyme lactate dehydrogenase (LDH) were measured. Statistical analyses included descriptive analysis, boxplots, fourfold table, receiver operating characteristic (ROC), calculation of confidence intervals and analysis of variance (ANOVA). RESULTS: 145 patients with a mean age of 34.3 years were eligible. There were 72 seminomas, 33 non-seminomas and 40 mixed tumours with 69% of patients being in Lugano stage I, 19% in stage II and 11% in stage III. hPLAP, AFP and hCG were statistically significantly higher in patients with testicular cancer compared to patients with benign scrotal conditions (p < 0.005). hPLAP showed the best sensitivity/specificity (51.1%/84.0%) followed by AFP (35.7%/97.1%), hCG (32.6%/98.6%) and LDH (31.4%/97.8%). ROC analysis demonstrated no difference between hPLAP, AFP and hCG in the specificity range of 80-100%. However, a combination of hPLAP, AFP and hCG provided statistically significantly better results than single markers (p < 0.001). CONCLUSION: hPLAP is the most often elevated marker in the serum of patients with testicular cancer and potentially demonstrates a significant benefit for therapy monitoring. In our opinion there is a need to debate the consideration of hPLAP in the usual guide-lines of the cancer societies. The unspecific elevation in smokers must be considered. In this regard, reference values of hPLAP depending on smoking habits could be a solution, but valid data are not yet available.

[How accurate is the correlation between clinical and pathological TNM stages in renal tumours?]. / Wie gut ist die Korrelation zwischen klinischen und pathologischen TNM-Stadien bei Nierentumoren?

PURPOSE: In clinical practice the tumour size measured in the histopathological examination of the operative specimen is used both to determine tumour stage. We have investigated the agreement between tumour size determined by preoperative computed tomography (CT) and pathological tumour size. MATERIAL AND METHODS: Between 2000 and 2007 a total of 444 consecutive patients was diagnosed with a renal tumour and treated operatively at our clinic. A total of 276 patients was eligible and thus included in the study. RESULTS: There were 62% men and 38% women with a median age of 65 years. There were 255 renal cell carcinomas, 7 oncocytomas, 3 angiomyolipomas, and 11 tumours of other histology. Mean tumour size was 65 mm in preoperative radiographic estimates and thereby a mean of 3 mm smaller than the mean pathological tumour size (62 mm, p = 0.0000066). In the radiographic estimate only 67% of the tumours were in the range of a 1 cm size difference of the postoperatively determined tumour size and in only 53% of the cases did the clinical and pathological TNM stages match. In 28/276 cases (10%) the clinical tumour stage was ≥ T2 but the histopathological examination showed a pTNM stage < T2. CONCLUSIONS: Different tomographs as well as observers are probably the main causes for the present results. Standardisation should be established to provide an accurate basis for a differentiated discussion about therapeutic options. This is especially true for low tumour stages where tumour size is the only criterion for staging.

[Metastatic renal cell cancer in Germany in 2010. Impact of different target therapies]. / Sequenztherapie beim metastasierten Nierenzellkarzinom in Deutschland 2010. Bedeutung der verschiedenen Target-Substanzen.

BACKGROUND: Since 2006 in Germany six different target drugs for therapy in metastatic renal cell cancer (mRCC) have been used. Comparative studies for the application with the same indication are absent, and the order of potential sequential therapy is up to now unclear. The aim of the study was to collect data on therapy decisions in Germany regarding mRCC in the age of "targeted therapy". At the same time the study addressed the central question of sequencing of the different therapy options. In addition, the data of this study were to be compared to a study already published in 2008. PATIENTS AND METHODS: In 2010, four groups of doctors specialized in the therapy of patients with mRCC were asked for their behaviour in the first-, second- and third-line or sequential therapy. Those questioned included urologists in private practice (n=40), oncologists in private practice (n=40), hospital urologists (n=35) and hospital oncologists (n=35). Further the reasons for a therapy decision should be stated or weighted. RESULTS: Altogether 92% of all patients with mRCC were treated. Urologists in private practice treat only 30% of their patients themselves. The earlier used immune therapies (IFN, IL-2) no longer play a role. Sunitinib is used most often in first-line therapy by urologists in private practice (50.4%) and oncologists in private practice (47.1%). In second- and third-line therapy everolimus is used by urologists in private practice (27.1%, 26.3%) and sorafenib (28.6%) or everolimus (26.4%) by oncologists in private practice. Hospital oncologists use primarily sunitinib (56.1%), in second-line sorafenib (45.5%) and in third-line above all everolimus (19.4%). Hospital urologists use sunitinib most often for first-line therapy (57.6%) and sorafenib for second-line treatment (37.3%), while in third-line therapy temsirolimus (49.6%) and also everolimus (30.4%) were used. CONCLUSIONS: The therapy of mRCC is determined very strongly by the substances sunitinib and sorafenib. The mTOR inhibitors have recently been increasingly included in the second- and third-line therapy. With the introduction of the new targeted therapies, the treatment of these special patients is performed less by urologists and increasingly more by oncologists. This trend is strengthened in comparison to the DGFIT study from 2008.

[Ureteropelvic junction obstruction with renal hypertension]. / Renaler Hypertonus bei Ureterabgangsenge.

Renal hypertension can occur with unilateral ureteropelvic junction obstruction and consecutive hydronephrosis. It is rarely the main symptom, normally in adults flank pain is in the foreground. We report a case of renal hypertension with ureteropelvic junction obstruction successfully corrected by laparoscopic pyeloplasty and discuss the pathophysiology.

Whose transplant function fails after ureteral revision following kidney transplantation?

BACKGROUND: Kidney transplantation is associated with ureteral complications in about 5% of cases. While many reasons for ureteral complications are known, it is currently unknown whether transplant outcomes are affected by operative revision of the transplanted ureter. In a retrospective analysis, we compared patients with versus without loss of transplant function after operative revision for a ureteral complication. PATIENTS AND METHODS: Between 1997 and 2005, a total of 43 ureteral complications occurred in 636 patients (6.8%) after kidney transplantation. Thirty-one of 43 patients underwent open operative revision of the transplant ureter. One patient died from suicide. The remaining 30 patients were analyzed for clinical parameters and transplant outcome. RESULTS: At median 5-year follow-up, 18/30 patients (60%) had functioning transplants and 12/30 (40%) had returned to dialysis. Various parameters such as number of mismatches, ischemia times, number of previous transplantations, and interval from transplantation to occurrence of ureteral complication as well as posttransplant and postrevision serum creatinine values showed no influence on transplant outcomes. CONCLUSIONS: In our retrospective analysis, transplant outcome was not affected by specific parameters associated with operative revision of the transplant ureter.

[Stromal tumour of uncertain malignant potential of the prostate (STUMP) - a case report]. / Stromatumor der Prostata von ungewissem malignem Potenzial (STUMP) - Ein Fallbericht.

A prostatic stromal tumour of uncertain malignant potential (STUMP) is a non-epithelial, mesenchymal spindle-cell tumour that can be classified as a specialised stromal tumour of the prostate. Although in most cases STUMP is not of an aggressive nature, occasional cases have been documented with an extension into adjacent tissues or recurrence after resection. A minority of cases develop a sarcomatous dedifferentiation.We report the case of a 53-year-old male with symptoms of febrile prostatitis. After consolidation we performed TUR-P due to urinary retention. Finally, we made the pathological diagnosis of prostatic STUMP. The patient is being seen -frequently in our clinic to take prostate biopsies to exclude a progression into a stromal sarcoma (active surveillance). After 13 months the STUMP is still detectable, but with no signs of sarcoma.