Clinical characteristics, treatment patterns and relapse in patients with clinical stage IS testicular cancer.

PURPOSE: Clinical stage I (CSI) testicular germ cell tumors (TGCT) represents disease confined to the testis without metastasis and CSIS is defined as persistently elevated tumor markers (TM) after orchiectomy, indicating subclinical metastatic disease. This study aims at assessing clinical characteristics and oncological outcome in CSIS. METHODS: Data from five tertiary referring centers in Germany were screened. We defined correct classification of CSIS according to EAU guidelines. TM levels, treatment and relapse-free survival were assessed and differences between predefined groups (chemotherapy, correct/incorrect CSIS) were analyzed with Fisher's exact and Chi-square test. RESULTS: Out of 2616 TGCT patients, 43 (1.6%) were CSIS. Thereof, 27 were correctly classified (cCSIS, 1.03%) and 16 incorrectly classified (iCSIS). TMs that defined cCSIS were in 12 (44.4%), 10 (37%), 3 (11.1%) and 2 (7.4%) patients AFP, ß-HCG, AFP plus ß-HCG and LDH, respectively. In the cCSIS group, six patients were seminoma and 21 non-seminoma. Treatment consisted of active surveillance, carboplatin-mono AUC7 and BEP (bleomycin, etoposide and cisplatin). No difference between cCSIS and iCSIS with respect to applied chemotherapy was found (p = 0.830). 5-year relapse-free survival was 88.9% and three patients (11%) in the cCSIS group relapsed. All underwent salvage treatment (3xBEP) with no documented death. CONCLUSION: Around 1% of all TGCT were classified as cCSIS patients. Identification of cCSIS is of critical importance to avoid disease progression and relapses by adequate treatment. We report a high heterogeneity of treatment patterns, associated with excellent long-term survival irrespective of the initial treatment approach.

[German national second-opinion network for testicular cancer and penile carcinoma : Two sources for evidence-based information]. / Nationale Zweitmeinungsnetzwerke Hodentumoren und Peniskarzinom : Zwei "Evidenz-Pipelines".

BACKGROUND: The second-opinion network for testicular cancer is an internet-based platform addressing physicians treating testicular cancer patients. They are offered a second-opinion before determining further therapy after orchiectomy and completion of staging. THEME: The high rate of discrepancies between the first and second opinion in more than 30 % supports the assumption of a deficit in the implementation of treatment guidelines. In 2015, approximately 22 % of the newly diagnosed cases with testicular cancer in Germany were covered by this system. According to the present interim analysis, the second-opinion platform helps to avoid overtreatment of testicular cancer patients. The high acceptance of the project and the encouraging results of this interim analysis gave rise to considerations to apply the second-opinion model to penile carcinoma. Data from the UK and the Netherlands show that the second-opinion network for penile cancer could help to improve treatment standards and results in Germany. Current data and the intended further development of the system are discussed.

[Recent Therapy of Organ-confined Testis Cancer]. / Aktuelle Therapie organbegrenzter Hodentumoren.

BACKGROUND: In Germany, testicular cancer accounts for about 1-2% of all malignant tumours. Although, therefore, this is a rare tumour, it assumes an exceptional position among malignant tumours in several respects. In male patients aged 20-35 years it is the most common tumour, which directly affects the family and life planning of young men, a matter of prime importance at this age. Another aspect of testicular cancer is its excellent prognosis since the introduction of platinum-based chemotherapy into the armamentarium of testicular cancer therapy. Therefore, therapeutic innovations increasingly focus on reducing the radicality of treatment, even more so since this therapy, in addition to acute toxicity, can cause severe long-term consequences up to and including secondary malignancies. OBJECTIVES: This article gives an overview of the present therapeutic standard of stage I testicular cancer treatment. MATERIAL AND METHODS: Selective PubMed research Results and Discussion: Besides potential implications for organ-sparing surgery, the article elucidates the benefits of a risk-adapted therapeutic approach and indications for a surveillance strategy for patients with localised testicular cancer.

[Secondary prevention in patients with superficial urothelial carcinoma]. / Sekundäre Prävention bei Patienten mit oberflächlichem Urothelkarzinom.

BACKGROUND: Urothelial cancer is the 4th most common cancer in men and the 7th most common malignancy in women in Germany. 95 % of all tumors of the urinary bladder are urothelial carcinomas. At the time of diagnosis approximately 80 % of these carcinomas are not invasive. The affection is often multicentric. Approximately 10-15 % of the tumors develop into muscle-invasive growth. In this prospective study, we analyzed measures patients independently took to reduce their risk of bladder cancer recurrence. MATERIALS AND METHODS: During the period January 2012 to December 2013, we surveyed a total of 97 patients with superficial transitional cell carcinoma (pTa). The question was how far the diagnosis of urothelial cancer has changed their lives, eating and drinking habits or whether follow-up consultations had been carried out regularly. Furthermore, we recorded whether they accepted psychological care or had autonomously adopted prophylactic measures, as well as changed their smoking habits, if they had smoked. RESULTS: Of the 97 patients questioned, there were 79 men and 18 women (56 smokers and 41 nonsmokers). The median age was 71 years (range 36-96 years). For 22 patients (22.7 %), the diagnosis resulted in no changes. In 33 patients the changes were small (44 %), moderate in 20 (26.7 %), in 14 (18.6 %) strong and very strong in 8 (10.7 %). A total of 25 patients (25.8 %) changed their eating habits. In all, 49 patients changed their drinking habits; 48 patients claimed to drink more (> 2.0 L/day). One patient reduced his drinking amount. Regarding smoking, 40 patients (71.4 %) had stopped and 7 (12.5 %) reduced consumption, while 6 patients (10.7 %) had not changed their smoking habits. Overall, 44 patients (45.4 %) changed their physical activity: 11 (25 %) exercised more, 8 (18.1 %) less. Only 3 patients (3.1 %) used psycho-oncological care and 39 (40.2 %) patients used supportive/complementary medicine measures of favorablly influence their disease (mistletoe therapy, vitamin supplements). In addition, 22 patients (22.7 %) sought advice from their physician. However, 45.4 % of all patients did not believe in the success of their measures taken. CONCLUSION: Of all patients diagnosed with urothelial carcinoma, 77.3 % reported a change in their living habits and they were willing to take specific steps, such as giving up smoking, being more physically active, changing drinking and eating habits in order to positively influence their disease. However, almost half of the patients (45.4 %) did not believe in a resounding success of their measures taken.

[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.

[Organ-sparing therapy for testicular cancer]. / Organerhaltende Hodentumortherapie.

BACKGROUND: The therapy of malignant testicular neoplasms has always been characterized by a high degree of radicality. Thanks to a number of medical achievements the cure rate of testicular cancer has notably increased through the last decades. In the meanwhile the main focus is on reducing therapy load, scrutinizing radical orchiectomy as the only adequate therapy for the primary tumour. OBJECTIVES: This article discusses the question, if and under which conditions an organ-sparing approach can be used appropriately in clinical practice. MATERIALS AND METHODS: A selective literature search was performed in PubMed. RESULTS: A set of data suggest that endocrine and exocrine function of the testis can be preserved using an organ-sparing approach and many patients could benefit regarding their quality of life, e.g., preserving the ability to father a child at least temporarily and avoiding the need for hormone substitution. Different from kidney tumors, precancerous lesions (testicular intraepithelia neoplasia, TIN) can almost inevitably be found in the surrounding tissue of testicular tumors. This has to be considered when making a decision in favor of an organ-sparing approach, because radiation therapy on the affected testis has to be performed after tumor resection. Despite the absence of prospective data, organ-sparing surgical tumor resection can be recommended in carefully selected patients. CONCLUSION: After careful selection of patients, particularly young men can profit from an organ-sparing therapy regimen. Therefore, organ preservation should always be considered in the surgical treatment of testicular masses.

[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.

[National second-opinion network for testicular cancer patients. Results of a user survey]. / Nationales Zweitmeinungsnetzwerk testikuläre Keimzelltumoren. Ergebnisse einer Nutzerbefragung.

BACKGROUND: The national second opinion project of the German Testicular Cancer Study Group (GTCSG) has served to improve the quality of care provided to testicular cancer patients since 2006. AIM: A recent online survey was carried out to characterize the users of the second opinion offer and clarify their motivation for participating in the project. Furthermore, the aim was to identify weaknesses of the project which could be improved. A total of 440 users of the second opinion project were contacted of whom 192 participated in the survey. RESULTS: In summary, the data collected showed a high degree of satisfaction among the participants who appreciated the second opinions received. Some issues with a need for improvement, predominantly in the structural organisational area, were disclosed. These served as a basis for a recently completed revision of the project immanent internet-based communication platform with a new data mask facilitating the introduction of patients with relapsed tumors. Interestingly, a high proportion of survey participants expressed the desire for establishment of a similar second opinion project for patients with penile cancer (77.1% of the participants).

[Clinical stage I seminoma. Is surveillance a new therapy standard?]. / Seminom klinisches Stadium I. Neuer Therapiestandard Surveillance?

BACKGROUND: The therapy of stage I seminoma is under constant change. While surveillance, adjuvant radiotherapy and adjuvant chemotherapy were seen as equal therapeutic alternatives up to a few years ago, recently published studies make it necessary to adopt a more differentiated approach. DISCUSSION: In this review, recent data on the long-term effects of adjuvant radiotherapy and chemotherapy, the question of risk stratification as well as the advantages and limitations of a surveillance strategy are discussed.

[The use of Surgisis® optimizes and simplifies partial nephrectomy for large renal tumors]. / Anwendung von Surgisis® zur Optimierung und Vereinfachung der Nierenteilresektion bei größeren renalen Neoplasmen.

BACKGROUND: With lower rates of postoperative renal failure, diabetes and cardiovascular disease, partial nephrectomy achieves longer overall survival and equally long tumor-specific survival. It is thus the current gold standard treatment for renal tumors and now also for those ≥ 4 cm in size. The main complications of nephron-sparing surgery, particularly for large and centrally located tumors, are postoperative parenchymal bleeding and urinary fistulas after opening the urinary collecting system (UCS). MATERIAL AND METHODS: Between August 2003 and April 2012, 76 partial nephrectomies for tumors ≥ 4 cm in size were performed using porcine small intestinal submucosa (SIS, Surgisis®) to close the capsular, renal and in some cases, UCS defects. RESULTS: The median tumor size was 5.0 cm (range 4.0-13.0 cm) and the intervention was performed with warm ischemia in 25 cases (32.8 %), with cold perfusion in 16 cases (21.2 %) and without ischemia in 35 cases (46.0 %). A total of 4 patients (5.5 %) developed postoperative urinary fistulas and 4 (5.5 %) required revision surgery because of significant postoperative bleeding. There were no local infections or allergic reactions to the foreign material. CONCLUSIONS: Surgisis® enables a quick and technically uncomplicated closure of the renal defect after partial nephrectomy for tumors. It has the potential to further minimize postoperative bleeding and urinary fistulas and to facilitate the intervention to the extent that nephron-sparing surgery will gain broader acceptance even in patients with tumors ≥4 cm in size.

Anti-tumour activity of two novel compounds in cisplatin-resistant testicular germ cell cancer.

BACKGROUND: Resistance to cisplatin-based chemotherapy is associated with poor prognosis in testicular germ cell cancer, emphasising the need for new therapeutic approaches. In this respect, the therapeutic concept of anti-angiogenesis is of particular interest. In a previous study, we presented two novel anti-angiogenic compounds, HP-2 and HP-14, blocking the tyrosine kinase activity of angiogenic growth factor receptors, such as vascular endothelial growth factor receptor-2 (VEGFR-2), and related signalling pathways in testicular cancer. In this study, we investigated the efficacy of these new compounds in platinum-resistant testicular germ cell tumours (TGCTs), in vitro and in vivo. METHODS AND RESULTS: Drug-induced changes in cell proliferation of the cisplatin-sensitive TGCT cell line 2102EP and its cisplatin-resistant counterpart 2102EP-R, both expressing the VEGFR-2, were evaluated by crystal violet staining. Both compounds inhibited the growth of cisplatin-resistant TGCT cells in a dose-dependent manner. In combination experiments with cisplatin, HP-14 revealed additive growth-inhibitory effects in TGCT cells, irrespective of the level of cisplatin resistance. Anti-angiogenic effects of HP compounds were confirmed by tube formation assays with freshly isolated human umbilical vein endothelial cells. Using TGCT cells inoculated onto the chorioallantoic membrane of fertilised chicken eggs (chicken chorioallantoic membrane assay), the anti-angiogenic and anti-proliferative potency of the novel compounds was also demonstrated in vivo. Gene expression profiling revealed changes in the expression pattern of genes related to DNA damage detection and repair, as well as in chaperone function after treatment with both cisplatin and HP-14, alone or in combination. This suggests that HP-14 can revert the lost effectiveness of cisplatin in the resistant cells by altering the expression of critical genes. CONCLUSION: The novel compound HP-14 effectively inhibits the growth of cisplatin-resistant TGCT cells and suppresses tumour angiogenesis. Thus, HP-14 may be an interesting new agent that should be further explored for TGCT treatment, especially in TGCTs that are resistant to cisplatin.