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Objectives: Cisplatin-based chemotherapy represents the gold standard in the treatment of advanced bladder cancer (BC) both in the neoadjuvant and adjuvant setting. Since novel immunooncologic agents are available for cisplatin-resistant or ineligible patients, biological markers for the prediction of cisplatin resistance become more important in treatment decisions. Therefore, we aimed to assess the therapy predictive value of 8 promising tissue biomarkers with regard to cisplatin therapy., Methods: Emmprin, survivin, HMGA2, MTA1, RhoGDI, PEG10, TGM2, and TLN1 expressions were analyzed in paraffin-embedded bladder cancer tissue samples of 106 patients who underwent adjuvant or salvage cisplatin-based chemotherapy by using immunohistochemistry. Results were correlated with the clinicopathological and follow-up data by performing both univariable and multivariable survival analyses., Results: Higher HMGA2 nuclear staining intensity and positive survivin nuclear staining were associated with worse overall survival (OS) (P = 0.045 and P = 0.002, respectively). In accordance, survivin nuclear staining also significantly correlated with shorter progression free survival (PFS, P = 0.024), while HMGA2 nuclear positivity tended to correlate with shorter PFS (P = 0.069) after at least 2 cycles of chemotherapy. In the multivariable analyses only survivin remained as an independent predictor of both OS and PFS (P = 0.008 and P = 0.025). None of the other markers proved to be significant predictors of adjuvant or salvage cisplatin-based chemotherapy., Conclusions: Our results demonstrate that survivin represents a promising marker for the prediction of cisplatin resistance in BC. In addition the therapy predictive role of HMGA2 should be further investigated. Immunohistochemical analysis of BC samples provides a feasible way for the prediction of cisplatin-resistance and may therefore provide a valuable tool for optimizing treatment decisions in advanced BC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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 T‑lymphocyte-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.

Background: In 2014, 15 500 persons in Germany were given the diagnosis of renal cell carcinoma. This disease is the third most common cancer of the urogenital system. The mean age at diagnosis is 68 years in men and 71 in men., Methods: Pertinent publications up to 2014 were retrieved by a systematic literature search and reviewed in a moderated, formalized consensus process. Key questions were generated and answered by the adaptation of existing international guidelines, on the basis of an independent literature review, and by expert consensus. Representatives of 30 medical specialty societies, patient self-help groups, and other organizations participated in the process., Results: The search for guidelines yielded 80 hits, 23 of which were judged by DELBI to be potentially relevant; 7 were chosen for adaptation. Smoking, obesity, and hypertension increase the risk of renal cell carcinoma. Its 5-year survival rate is 75% for men and 77% for women. Renal cell carcinoma accounts for 2.6% of all deaths from cancer in men and 2.1% in women. Nephrectomy and partial nephrectomy are the standard treatments. Locally confined tumors in clinical stage T1 should be treated with kidney-preserving surgery. Minimally invasive surgery is often possible as long as the surgeon has the requisite experience. For patients with metastases, overall and progression-free survival can be prolonged with VEGF and mTOR inhibitors. The resection or irradiation of metastases can be a useful palliative treatment for patients with brain metastases or osseous metastases that are painful or increase the risk of fracture., Conclusion: Minimally invasive surgery and new systemic drugs have expanded the therapeutic options for patients with renal cell carcinoma. The search for new predictive and prognostic markers is now in progress.

Purpose: Cisplatin-based chemotherapy is standard first-line treatment for metastatic urothelial carcinoma. However, cisplatin is frequently avoided in elderly patients due to concerns regarding toxicities. We analyzed the efficacy, and tolerability, of cisplatin-based chemotherapy in elderly patients., Methods: Individual patient data were pooled from 8 phase II and III trials evaluating cisplatin-based first-line chemotherapy in patients with metastatic urothelial carcinoma. Adverse events, treatment delivery, response proportions, and survival outcomes were compared between patients aged<70 vs. ≥ 70 years., Results: Of the 543 patients included, 162 patients (30%) were ≥ 70 years old. The majority (93%) of elderly patients were aged 70 to 79 years. There was no significant difference in the proportions of patients experiencing Grade 3 to 4 renal failure, febrile neutropenia, or treatment-related death between younger and older patient cohorts. The median survival of the patients ≥ 70 years was 12.1 months compared to 12.8 months for patients<70 years (P = 0.91). There was no significant difference in survival between age groups when controlling for baseline performance status or the presence of visceral metastases or both., Conclusions: Fit septuagenarians, with adequate renal function, tolerate cisplatin-based chemotherapy similarly to their younger counterparts and achieve comparable clinical outcomes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

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.

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.

Background: Although urothelial cancer is more common in men, women with urothelial cancer have inferior survival outcomes. The potential existence of gender-related disparities in patients with metastatic urothelial cancer has not been extensively explored., Patients and Methods: Individual patient data were pooled from 8 phase II and phase III trials evaluating first-line cisplatin-based combination chemotherapy in patients with metastatic urothelial carcinoma. Adverse events, treatment delivery, response proportions, and survival outcomes were compared between male and female patients., Results: Of the 543 patients included in the analysis, 100 patients (18%) were women. There was no significant difference in the number of cycles of chemotherapy administered or in the proportions of patients experiencing severe toxicities when comparing male and female patients. There was no difference in the survival distributions between male and female patients (P = .08); the median survival of male patients was 11.7 months (95% confidence interval [CI], 10.5-13.2) compared with 16.2 months for female patients (95% CI, 12.8-20.4). There was no significant difference in survival between men and women when controlling for baseline performance status and/or the presence of visceral metastases., Conclusion: Female patients with metastatic urothelial cancer tolerate cisplatin-based chemotherapy similarly to male patients and achieve comparable clinical outcomes. Although gender-associated survival disparities in patients with metastatic urothelial cancer cannot be completely ruled out, if such disparities exist, they are unlikely related to tolerability or efficacy of chemotherapy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Context: Some controversy still exists regarding the management of testis cancer following chemotherapy for disseminated disease., Objective: To review the available literature concerning the management of postchemotherapy testis cancer., Evidence Acquisition: A Medline search was conducted to identify original and review articles, as well as guidelines addressing the management of testis cancer following first-line chemotherapy. Keywords included germ cell tumor, testis cancer, retroperitoneal lymph node dissection, and chemotherapy. The most relevant articles were critically reviewed with the consensus of all the collaborative authors, who have expertise in the management of germ cell tumors (GCTs)., Evidence Synthesis: Approximately one-third of patients who undergo chemotherapy for metastatic GCTs have residual retroperitoneal disease. All patients with residual masses ≥1cm after chemotherapy for nonseminomatous GCTs should undergo postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) because of the risk of mature teratoma in 40-45% of cases and of viable GCT in 10-15% of cases. Patients who obtain a complete serologic remission and radiographic residual <1 cm after chemotherapy have a 6-9% risk of relapse. Patients with a completely resected teratoma in only the PC-RPLND specimen have a >90% chance of cure, while patients with viable GCTs should be considered for additional therapy, depending on the percentage of viable tumor. In patients with disseminated seminoma, postchemotherapy masses <3cm may be safely observed, while patients with masses >3 cm should be evaluated with positron emission tomography (PET)/computed tomography 2 mo after completion of chemotherapy, with very selective administration of PC-RPLND. Late relapse occurring >2 yr after chemotherapy is rare, and surgery remains the mainstay of therapy in cases of resectable masses independent of tumor markers. There is still controversy on whether high-dose chemotherapy confers a survival benefit compared with conventional-dose chemotherapy in the salvage setting. Surgery should always be considered for resectable masses following salvage therapies or in chemoresistant disease to maximize chance of cure., Conclusions: Patients with advanced GCTs can achieve long-term disease-free survival when chemotherapy is combined with expert and judicious resection of residual disease. PC-RPLND is recommended for residual masses >1cm identified on postchemotherapy imaging in nonseminomatous GCT and possibly for PET-positive residual disease ≥3cm in treated seminomas., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Unlike conventional systemic chemotherapies, the aim of targeted therapeutic approaches is not to address general mechanisms involved in cellular replication. In contrast, they aim at such regulatory pathways that have been identified to be involved in the progression of human malignant disease. Whereas the application of targeted therapeutic modalities is well established for the treatment of metastatic renal cell cancer, only very few data on their clinical efficacy during the treatment of other urological tumours such as prostate and bladder cancer are currently available. The aim of this paper is to reflect on the current status regarding the relevance of targeted therapeutic approaches during the treatment of urological cancers of different origin.

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.

Background: The aim was to investigate the use of single agent carboplatin in patients with seminoma stage IIA/B., Patients and Methods: In a prospective phase II trial, single agent carboplatin at a dose of AUC 7 mg.min/ml every 4 weeks for three cycles in stage IIA (n=51) or four cycles in stage IIB (n=57) was given to 108 patients with previously untreated seminoma stage IIA/B. Patients with residual masses of >or=3 cm were scheduled to receive secondary surgery., Results: A complete response (CR) was achieved by 88/108 (81%) patients, 17/108 (16%) achieved a partial response (PR), two of 108 (2%) showed no change, and one patient progressed. In all patients with PR the residual disease was

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.

Testicular cancer is one of the few tumors which are curable even at an advanced stage. This has been achieved both by the use of platinum based chemotherapy and by the interdisciplinary approach by urologists, internal oncologists and radio-oncologists. In 1988, the Interdisciplinary Testicular Cancer Study Group was founded. The aim of this group is to initiate clinical trials to improve the results in the treatment of this tumor. Furthermore, the group has published evidenced-based national and international guidelines for testicular cancer. This article gives an overview on the work of the group including current studies.

The indication for chemotherapy is quite different in urological malignancies. In case of testicular tumors the availability of chemotherapy is one of the milestones in their successful treatment. Patients with low-volume metastases will be cured in nearly 100% and even far advanced disease can be cured in more than 50%. Contrarily in renal cell carcinoma chemotherapy is without any significance, response rates are <8%. Comparable is the situation in penile cancer. Though in hormone-refractory prostate cancer chemotherapy also can not prevent further disease progression, it shows good palliative effects., (Copyright 2003 S. Karger GmbH, Freiburg)

Objective: Though para-aortal and ipsilateral iliacal radiation is the established adjuvant treatment for clinical stage I seminoma, promising results have been reported on adjuvant single-agent carboplatin therapy., Patients and Methods: We treated 43 patients with clinical stage I seminoma according to this option. They received 2 courses of single-agent carboplatin (400 mg/m2) at an intervall of 3 weeks. Therapy could be performed on an outpatient basis within 2 h., Results: Therapy was well tolerated. Apart from minor gastrointestinal disorders and mild myelosuppression, no adverse reactions were observed. The median follow-up is 28 months. Up to now no recurrences have been noted., Conclusions: If the recurrence rate remains as low as after adjuvant radiotherapy, which should be proved in a phase III study, single-agent carboplatin therapy will be an alternative adjuvant approach for clinical stage I seminoma.

So far, no curative treatment is available for hormone-refractory prostate carcinoma. Therapy is thus focused on alleviating symptomatic tumor progression with the aim of improving quality of life. Therefore, anthracyclin-derived mitoxantrone was administered to 25 patients with hormone-refractory prostate carcinoma and symptomatic progressive disease. After a median treatment of 13 weeks, a median of 4 cycles and a follow-up of 14 months, 48% of the patients (12/25) reported improvement in tumor-related pain; in 60% (15/25) there was improvement of the self-assessment symptom score and 32% of the patients (8/25) gained weight. Additionally, partial tumor response with regression of lymph-node metastases occurred in 3/25 patients (12%). In 10/25 patients the serum level of prostate-specific antigen (PSA) decreased as well as the alkaline phosphatase (AP) in 7/25 patients. Side effects subsequent to chemotherapy were leucopenia WHO grade III in 25% of the patients and thrombocytopenia WHO grade III in 3/25 and grade V (treatment-related death) in 1/25 patients. Non-hematological toxicity occurred in 2 patients (cardiotoxicity n = 1, nephrotoxicity n = 1, WHO grade II each).

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. [ABSTRACT FROM AUTHOR]