Systemic therapy in metastatic renal cell carcinoma (mRCC): an evidence-based recommendation of the German interdisciplinary RCC guidelines group.

PURPOSE: The treatment landscape in metastatic renal cell carcinoma (mRCC) has evolved dramatically in recent years. Within the German guideline committee for RCC we evaluated current medical treatments and gave recommendations. METHODS: A systematic review of published evidence for medical treatment of mRCC was performed (July 2016-August 2019) to cover the duration from last guideline update in 2016. Evidence was graded according to SIGN ( http://www.sign.ac.uk/pdf/sign50.pdf ). Recommendations were made on the basis of a nominal group work with consensus approach and included patient advocates and shareholder of the German RCC treatment landscape. Each recommendation was graded according to its strength as strong recommendation (A) or recommendation (B). Expert statements were given, where appropriate. RESULTS: Strong first-line recommendations (IA) exist for axitinib + pembrolizumab (all risk categories) and ipilimumab + nivolumab (intermediate or poor risk only). Axitinib + avelumab is a recommended first-line treatment across patients with any risk category (IB). In patients who are not candidates for immune check point inhibitor (ICI) combinations, targeted agents should be offered as an alternative treatment. Subsequent treatment after ICI-based combinations remain ill-defined and no standard of care can be formulated. CONCLUSION: ICI-based combinations are the first-line standard of care and should be considered accordingly. There is an unmet medical need for pivotal studies that define novel standards in patients with failure of ICI-based combinations.

[Intraoperative frozen section diagnosis of the genitourinary tract]. / Intraoperative Schnellschnittdiagnostik des Urogenitaltrakts.

Up to now intraoperative frozen section, diagnosis has been of limited utility in urologic oncology. In the future, it may become more important due to a significant increase in the number of nerve-sparing operations performed for prostate cancer. Accuracy and benefit of intraoperative frozen sections depend both on a good communication between surgeons and pathologists as well as on a strict assessment of the need for surgery in the individual patient. In order to optimize cost-efficiency and to reduce the associated risks the indications for intraoperative frozen sections must be rigorously appraised. This report outlines clinically relevant indications for intraoperative frozen section diagnosis in tumors of the urinary tract, kidneys, prostate, testis and penis according to the most recent guidelines. The diagnostic scope and problems of this method are also discussed.

[Palliative care guidelines in uro-oncology]. / Leitliniengerechte palliativmedizinische Therapie in der Uroonkologie.

Palliative care is an integral part in the treatment of patients in uro-oncology. The German S3 guideline palliative care for patients with incurable cancer is an essential working basis for physicians and healthcare workers. In addition to basic recommendations in palliative care, the guideline provides evidence-based advice in a symptom-oriented approach. Basic knowledge in palliative care is recommended for every urologist who is treating uro-oncologic patients.

The role of annexins I, II and IV in tumor development, progression and metastasis of human penile squamous cell carcinomas.

PURPOSE: The outcome of patients with penile squamous cell carcinomas (PSCC) largely depends on occurrence of metastasis. Therefore, prognostic markers indicating the risk for tumor cell spreading would be useful. Since Annexins are potential prognostic markers in a variety of tumors, we immunohistochemically examined the expression of Annexins I, II and IV (ANX AI, ANX AII and ANX AIV) in PSCC. METHODS: Samples originated from 29 patients subjected to surgical resection of invasive PSCC. Immunohistochemistry was done on paraffin-embedded sections using monoclonal antibodies against ANX AI, ANX AII and ANX AIV. Expression of ANXs was compared with clinical data. RESULTS: ANX AI expression was found in conventional PSCC and was absent in basaloid and sarcomatoid subtypes. High ANX AI score was significantly associated with higher T stages (P = 0.006). Strong expression in the invasion front of carcinomas was significantly associated with the occurrence of lymph node metastasis (P = 0.001). ANX AIV expression was weak in conventional PSCC, while it was strong in basaloid and sarcomatoid subtypes. Strong expression of Annnexin IV in the invasion front also showed a significant association with metastasis (P = 0.019). CONCLUSION: Expression of ANXs was different in histologic subtypes of penile carcinomas. Strong expression of ANX AI and ANX AIV in the invasion front seems to indicate a higher risk of lymph node metastasis.

[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.

[Conventional grading vs. molecular grading : Decision aids for clinical routine]. / Konventionelles vs. molekulares Grading : Entscheidungshilfen für den klinischen Alltag.

Conventional histopathological grading of a cancer is of utmost importance for the management and prognosis of the patient. Histopathological grading is predominantly a function of the differentiation and proliferation of tumor cells, the amount of necrosis present and the pattern of invasion. In addition, the molecular set-up of a given cancer which can be determined to some degree by immunohistochemistry or by methods analyzing genetic and epigenetic alterations can be used in some instances to improve the information gained by conventional histopathologic grading. Indeed, this latter option implies the promise of individualized tumor therapy. While this promise is on the horizon, the clinical implications for penile cancer are not yet transferable to individualized penile cancer treatment.

[Diagnosis and treatment of lower urinary tract trauma]. / Verletzungen des unteren Harntrakts und des Urogenitalsystems.

Injuries of the lower urinary tract occur in patients with multiple injuries and trauma to the lower abdominal and pelvic region. Injuries of the male urethra including complete ruptures occur in 10% of pelvic fractures in males, while they are a rarity in females. Ruptures of the urinary bladder are either intra- or extraperitoneal. Ureteral injuries are relatively rare in blunt injuries and usually become manifest with infectious symptoms with a delay of days. Intraperitoneal ruptures of the urinary bladder always require urgent surgical repair while extraperitoneal ruptures can mostly be managed conservatively with catheter drainage of the bladder. In male patients with pelvic fractures any attempt of urethral catheterization which can otherwise make an urethral injury worse should be withheld until adequate urological examinations have led to the diagnosis or exclusion of urethral injury. The definitive surgical repair of a disruption of the male urethra should be undertaken with an interval of weeks to months. Long term sequelae of male urethral injury can be impotence and chronic stricture disease.

[Penile cancer : Diagnosis and treatment]. / Peniskarzinom : Diagnose und Therapie.

The incidence of penile cancer in central Europe and North America is low, and patients often present at a late stage of the disease. The diagnosis can very often be made by visual examination of the primary tumor. Its morphology, size, and location as well as the inguinal lymph nodes are of clinical interest. The removal of (micro)metastatic lymph nodes is decisive for the prognosis. These cannot be diagnosed clinically or by imaging with sufficient reliability, which makes invasive lymph node staging necessary. Penile cancer can only be cured by surgery in patients with localized cancer and early stage regional lymph node metastasis. The primary tumor, including metastatic lymph nodes, must be completely excised as early as possible. If indicated, organ preservation must be performed with strict adherence of safety margins. Optimal lymph node management is crucial for long-term survival.

Chemotherapy in patients with penile carcinoma.

The prognosis of patients with advanced penile carcinoma is poor. There are only few studies, mostly with a low number of patients, which show a low response rate with severe toxicity. While adjuvant and palliative chemotherapy for penile cancer is universally characterized by low efficacy, neoadjuvant approaches for patients with fixed lymph node metastases have shown some response. Overall, recent experiences with new chemotherapeutic approaches (i.e. taxane-based combinations) have shown some encouraging results. Therefore, these combinations should be investigated in larger and multi-center studies.

[Molecular tumor board penile cancer-a challenge]. / Molekulares Tumorboard Peniskarzinom ­ eine Herausforderung.

Due to its low incidence there is only very limited data concerning molecular markers in penile cancer. Recent studies show potential prognostic markers for lymph node metastasis, survival and response to chemotherapy or targeted therapy. Nevertheless the number of patients in the studies is very limited. Therefor clear recommendations for clinical decisions remain very weak. Patients with metastatic disease should be treated in clinical trials with translational biomarker research to improve the molecular tumor board in the future.

Down-regulation of the metastasis suppressor protein KAI1/CD82 correlates with occurrence of metastasis, prognosis and presence of HPV DNA in human penile squamous cell carcinoma.

In penile squamous cell carcinoma (PSCC), the outcome largely depends on early detection and resection of inguinal lymph node metastases. We investigated the role of metastasis suppressor protein kang ai 1 (KAI1)/cluster of differentiation 82 (CD82), which is known to be of prognostic significance for a wide variety of cancers. Moreover, we analysed the tumours for human papillomavirus (HPV) DNA and loss of heterozygosity at the 11p11.2 locus. Tissue samples of 30 primary PSCCs were investigated immunohistochemically using an anti-KAI1/CD82 polyclonal antibody. The expression was assessed according to the degree of KAI1/CD82-positive tumour cells as positive, decreased or negative. The presence of HPV6/11, HPV16 and HPV18 DNA was analysed by polymerase chain reaction. All patients with decreased or negative expression of KAI1/CD82 in primary lesions had lymph node metastases (p = 0.0002). Patients with positive KAI1/CD82 expression showed a significant better prognosis for survival compared to the other groups (p = 0.0042). Presence of HPV DNA was associated with decreased or negative KAI1/CD82 expression. Lacking or decreased expression of metastasis suppressor gene KAI1/CD82 appears to be a prognostic parameter for the occurrence of lymph node metastases in PSCC. Our study suggests an association of decreased KAI1/CD82 expression with tumour progression, development of metastases and disease-specific death.

[Treatment of advanced penile cancer. Do we need new methods for chemotherapy?]. / Zur Therapie des fortgeschrittenen Peniskarzinoms. Brauchen wir neue Wege in der Chemotherapie?

Penile cancer is a squamous epithelial neoplasia with a very high mortality in advanced stages. Only few series with small patient numbers have addressed the systemic treatment of advanced penile carcinoma. Established regimens are characterized by high toxicity and poor efficacy. Due to the relative paucity of data, recommendations and guidelines on the treatment of metastatic penile carcinoma are vague. New approaches and large-scale studies that will allow better definition of adequate and more effective treatment options are needed. Encouraging results with newer chemotherapeutic agents are at present mainly anecdotal but are still encouraging.

[Local treatment of penile cancer]. / Lokale Therapie beim Peniskarzinom.

In recent decades, the local treatment of penile cancer has focused primary on the removal of the primary tumor. Due to the significant psycho-oncological effects of treating the primary tumor, the guidelines on penile cancer now contain a clear recommendation for preserving the target organ and prior to each surgical procedure histological examination should be performed to confirm the penile cancer. For more advanced tumors, reconstructive plastic surgery should also be considered. The treatment of the primary tumor should be based on the stage and the local extent and size of the tumor. The aim of this article is to highlight current standards in the local treatment of penile cancer.

[Lymph-node-positive penile cancer : Management and systemic therapy]. / Lymphknotenpositives Peniskarzinom : Management und systemische Therapie.

Cancer-specific survival in men with penile cancer depends foremost on regional lymphatic metastasis and its extent. Patients with limited inguinal lymph node metastases have a 5-year survival of up to 80%. However, those with pelvic lymph node metastases and/or systemic disease have a 5-year survival prognosis of only 0-33%. In any case, in patients with regional lymph node metastases multimodal treatment with complete lymphadenectomy and adjuvant chemotherapy is indicated.

[Penile cancer: diagnosis and staging]. / Peniskarzinom: Diagnose und Staging.

Penile cancer is often an obvious visual diagnosis but histologic verification should be obtained prior to treatment. The clinical examination should determine the tumor stage and whether it has infiltrated the cavernous bodies and/or the urethra and it should adequately assess the inguinal lymph nodes. Preoperative imaging of the lesion is only indicated in equivocal cases. Curative treatment requires the complete removal of the primary tumor and all metastatic lymph nodes. Lymph node management is the key prognostic factor in the treatment of penile cancer. No imagining technique such as the ultrasound, CT, MRI or PET/CT is able to adequately detect micrometastatic lymph nodes. Therefore, invasive (inguinal) lymph node diagnosis is indicated for all tumour stages from pT1G2. Over 90% of penile cancer cases can be cured with early diagnosis and adequate treatment if routine self-examination and physical examinations are regularly performed.

[Surgical treatment of metastatic penile cancer - what is the scientific rationale?] / Operative Therapie von Metastasen beim Peniskarzinom ­ gibt es eine wissenschaftliche Grundlage?

The treatment of metastases of penile cancer is confined to lymphatic metastases. Limited lymph node metastasis in penile cancer can be cured by radical lymph node surgery if complete removal of all lymph nodes of the region is achieved. Adjuvant chemotherapy is recommended. This approach applies to the regional lymph nodes of the inguinal and pelvic regions. Applying this concept to retroperitoneal lymph node metastases may also be reasonable in selected cases. The individual prognosis depends on the extent of lymphatic spread.

[Renal decapsulation for the treatment of anuria : A "forgotten" treatment from the early 20th century]. / Die Dekapsulierung der Niere als Therapie der Anurie : Ein "vergessenes" Therapieverfahren aus dem frühen 20. Jahrhundert.

In the early 20th century, Harrison first performed renal decapsulation in anuric children with scarlet fever and observed improvement in renal function postoperatively. The pathophysiological explanation was seen in intraparenchymal renal pressure due to edema which was improved by surgical decapsulation. The technique of decapsulation was simple excision after incision and blunt dissection of the renal parenchyma. Renal decapsulation then became a procedure commonly used for many indications in inflammatory renal conditions; indications were renal angioneurosis, hydronephrosis, toxic, bacterial and chronic nephritis, renal abscess and even eclampsia. With the beginning of the antibiotic era, renal decapsulation became obsolete and has disappeared from the urological spectrum completely.

[Psychosocial stress in patients with prostate cancer : Experiences by using psychooncological screening questionnaires]. / Psychosoziale Belastungen bei Patienten mit Prostatakarzinom : Erfahrungen im Einsatz mit psychoonkologischen Screeningfragebögen.

BACKGROUND: Prostate cancer is the most common malignancy in men and accounts for most surgical procedures in uro-oncology. Stressful sequelae of radical prostatectomy are incontinence and erectile dysfunction. Hormone ablation and radiation therapy are also known stressors. Mental stress has a low prevalence compared to other tumor entities. It is highly probable that there is an underexpression of verbally reported emotional experiences. Therefore, a low-threshold access to psycho-oncological services and accurate identification of patients with mental comorbidities is important. The aim of this study was to identify the distress level with clarification of the stress in patients with prostate cancer. MATERIALS AND METHODS: Prospective evaluation of prostate cancer patients (n = 81, mean age 69 years) with regard to stress level, stress factors and the need for care using the Distress Thermometer, a standardized ultrashort stress-screening questionnaire. RESULTS: The mean stress level was 4.4 points. In total, 56% of patients indicated a stress level ≥5, i. e. a clinically relevant psychological burden was indicated. Main stressors were sexual problems (35%), reduced mobility (30%), pain (27.5%), tingling paresthesia (26%) and worries (26%). CONCLUSION: The psychological burden of prostate cancer patients is not as high as in other solid organ malignancies. However, some patients have a significantly increased psychosocial stress level. Identifying this subgroup and clarifying the correlation with specific stress and risk factors are important tasks of clinical care.

Is there evidence for a close connection between side of intravesical tumor location and ipsilateral lymphatic spread in lymph node-positive bladder cancer patients at radical cystectomy? Results of the PROMETRICS 2011 database.

PURPOSE: To evaluate the possible association between bladder tumor location and the laterality of positive lymph nodes (LN) in a prospectively collected multi-institutional radical cystectomy (RC) series. METHODS: The study population included 148 node-positive bladder cancer (BC) patients undergoing RC and pelvic lymph node dissection in 2011 without neoadjuvant chemotherapy and without distant metastasis. Tumor location was classified as right, left or bilateral and compared to the laterality of positive pelvic LN. A logistic regression model was used to identify predictors of ipsilaterality of lymphatic spread. Using multivariate Cox regression analyses (median follow-up: 25 months), the effect of the laterality of positive LN on cancer-specific mortality (CSM) was estimated. RESULTS: Overall, median 18.5 LN [interquartile range (IQR), 11-27] were removed and 3 LN (IQR 1-5) were positive. There was concordance of tumor location and laterality of positive LN in 82% [95% confidence interval (CI), 76-89]. Patients with unilateral tumors (n = 78) harbored exclusively ipsilateral positive LN in 67% (95% CI 56-77). No criteria were found to predict ipsilateral positive LN in patients with unilateral tumors. CSM after 3 years in patients with ipsilateral, contralateral, and bilateral LN metastasis was 41, 67, and 100%, respectively (p = 0.042). However, no significant effect of the laterality of positive pelvic LN on CSM could be confirmed in multivariate analyses. CONCLUSIONS: Our prospective cohort showed a concordance of tumor location and laterality of LN metastasis in BC at RC without any predictive criteria and without any influence on CSM. It is debatable, whether these findings may contribute to a more individualized patient management.