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  • Chemotherapy
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  • 1
    Language: English
    In: Therapeutic Advances in Urology, June 2012, Vol.4(3), pp.133-138
    Description: Penile cancer is an aggressive disease and after systemic progression it is virtually incurable. While this squamous cell cancer responds to chemotherapy, successful treatment of lymphatic metastases can only be achieved with aggressive surgical treatment in combination with chemotherapy. However, because penile carcinoma is relatively rare there is a paucity of clinical data on the chemotherapy for this aggressive disease. Recent advances have included the establishment of less toxic regimens incorporating taxanes, while cisplatinum remains central to all regimens. Multi-institutional studies are urgently needed to advance the multimodal care for patients with penile cancer.
    Keywords: Penis ; Neoplasm ; Penile Cancer ; Lymph Node ; Metastasis ; Chemotherapy ; Medicine
    ISSN: 1756-2872
    E-ISSN: 1756-2880
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  • 2
    In: BJU International, January 2018, Vol.121(1), pp.101-110
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/bju.14012/abstract Byline: Malte W. Vetterlein, Philipp Gild, Luis A. Kluth, Thomas Seisen, Michael Gierth, Hans-Martin Fritsche, Maximilian Burger, Chris Protzel, Oliver W. Hakenberg, Nicolas Landenberg,Florian Roghmann, Joachim Noldus, Philipp Nuhn, Armin Pycha, Michael Rink, Felix K.-H. Chun, Matthias May, Margit Fisch,Atiqullah Aziz,, G Bartsch, C Bolenz, S Brookman-May, A Buchner, M Durschnabel, J Ellinger, M Froehner, G Georgieva, C Gilfrich, M Gorduk, MO Grimm, B Hadaschik, A Haferkamp, F Hartmann, E Herrmann, L Hertle, M Hohenfellner, G Janetschek, B Keck, N Kraischits, A Krausse, L Lusuardi, T Martini, MS Michel, R Moritz, SC Muller, V Novotny, S Pahernik, RJ Palisaar, A Ponholzer, J Roigas, M Schmid, P Schramek, C Seitz, D Sikic, CG Stief, I Syring, M Traumann, S Vallo, FM Wagenlehner, W Weidner, MP Wirth, B Wullich Keywords: blood transfusion; cystectomy; propensity score; recurrence; survival Objectives To evaluate the effect of peri-operative blood transfusion (PBT) on recurrence-free survival, overall survival, cancer-specific mortality and other-cause mortality in patients undergoing radical cystectomy (RC), using a contemporary European multicentre cohort. Patients and Methods The Prospective Multicentre Radical Cystectomy Series (PROMETRICS) includes data on 679 patients who underwent RC at 18 European tertiary care centres in 2011. The association between PBT and oncological survival outcomes was assessed using Kaplan-Meier, Cox regression and competing-risks analyses. Imbalances in clinicopathological features between patients receiving PBT vs those not receiving PBT were mitigated using conventional multivariable adjusting as well as inverse probability of treatment weighting (IPTW). Results Overall, 611 patients had complete information on PBT, and 315 (51.6%) received PBT. The two groups (PBT vs no PBT) differed significantly with respect to most clinicopathological features, including peri-operative blood loss: median (interquartile range [IQR]) 1000 (600-1500) mL vs 500 (400-800) mL (P 〈 0.001). Independent predictors of receipt of PBT in multivariable logistic regression analysis were female gender (odds ratio [OR] 5.05, 95% confidence interval [CI] 2.62-9.71; P 〈 0.001), body mass index (OR 0.91, 95% CI 0.87-0.95; P 〈 0.001), type of urinary diversion (OR 0.38, 95% CI 0.18-0.82; P = 0.013), blood loss (OR 1.32, 95% CI 1.23-1.40; P 〈 0.001), neoadjuvant chemotherapy (OR 2.62, 95% CI 1.37-5.00; P = 0.004), and a[yen]pT3 tumours (OR 1.59, 95% CI 1.02-2.48; P = 0.041). In 531 patients with complete data on survival outcomes, unweighted and unadjusted survival analyses showed worse overall survival, cancer-specific mortality and other-cause mortality rates for patients receiving PBT(P 〈 0.001, P = 0.017 and P = 0.001, respectively). After IPTW adjustment, those differences no longer held true. PBT was not associated with recurrence-free survival (hazard ratio [HR] 0.92, 95% CI 0.53-1.58; P = 0.8), overall survival (HR 1.06, 95% CI 0.55-2.05; P = 0.9), cancer-specific mortality (sub-HR 1.09, 95% CI 0.62-1.92; P = 0.8) and other-cause mortality (sub-HR 1.00, 95% CI 0.26-3.85; P 〉 0.9) in IPTW-adjusted Cox regression and competing-risks analyses. The same held true in conventional multivariable Cox and competing-risks analyses, where PBT could not be confirmed as a predictor of any given endpoint (all P values 〉0.05). Conclusion The present results did not show an adverse effect of PBT on oncological outcomes after adjusting for baseline differences in patient characteristics. Article Note: M.W.V. and P.G. contributed equally to the work. PROMETRICS 2011 Study Group members are present in Appendix 1.
    Keywords: Blood Transfusion ; Cystectomy ; Propensity Score ; Recurrence ; Survival
    ISSN: 1464-4096
    E-ISSN: 1464-410X
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  • 3
    Language: English
    In: European Urology, January 2015, Vol.67(1), pp.142-150
    Description: Penile cancer has high mortality once metastatic spread has occurred. Local treatment can be mutilating and devastating for the patient. Progress has been made in organ-preserving local treatment, lymph node management, and multimodal treatment of lymphatic metastases, requiring an update of the European Association of Urology guidelines. To provide an evidence-based update of treatment recommendations based on the literature published since 2008. A PubMed search covering the period from August 2008 to November 2013 was performed, and 352 full-text papers were reviewed. Levels of evidence were assessed and recommendations graded. Because there is a lack of controlled trials or large series, the levels of evidence and grades of recommendation are low compared with those for more common diseases. Penile squamous cell carcinoma occurs in distinct histologic variants, some of which are related to human papilloma virus infection; others are not. Primary local treatment should be organ preserving, if possible. There are no outcome differences between local treatment modes in superficial and T1 disease. Management of inguinal lymph nodes is crucial for prognosis. In impalpable nodes, invasive staging should be done depending on the risk factors of the primary tumour. Lymph node metastases should be treated by surgery and adjuvant chemotherapy in N2/N3 disease. Organ preservation has become the standard approach to low-stage penile cancer, whereas in lymphatic disease, it is recognised that multimodal treatment with radical inguinal node surgery and adjuvant chemotherapy improves outcome. Approximately 80% of penile cancer patients of all stages can be cured. With increasing experience in the management of penile cancer, it is recognized that organ-preserving treatment allows for better quality of life and sexual function and should be offered to all patients whenever feasible. Referral to centres with experience is recommended. Penile preservation should be offered as the primary treatment modality to men with localised penile cancer. Conservative surgery may improve quality of life; however, the risk of local recurrence is higher than after radical surgery (eg, partial penectomy). The management of regional lymph nodes is decisive for long-term patient survival.
    Keywords: Penile Cancer ; Squamous Cell Carcinoma ; Lymph Node ; Invasive Disease ; Metastasis ; Surgery ; Laser ; Chemotherapy ; Reconstruction ; Follow-Up ; Quality of Life ; Guidelines ; European Association of Urology ; Medicine
    ISSN: 0302-2838
    E-ISSN: 1873-7560
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  • 4
    Language: English
    In: Expert Opinion on Emerging Drugs, 01 December 2009, Vol.14(4), pp.607-618
    Description: Bladder cancer is a very common and aggressive tumor entity. Unfortunately, common chemotherapy is not able to cure advanced bladder cancer. Therefore, several attempts have been made to improve the response to chemotherapy. Because changes in apoptotic pathways are frequent events in the development...
    Keywords: Apoptosis ; Bladder Cancer ; Chemotherapy ; Pro-Apoptotic ; Sensitization ; Economics
    ISSN: 1472-8214
    E-ISSN: 1744-7623
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  • 5
    Language: English
    In: European Urology Focus, July 2018, Vol.4(4), pp.599-607
    Description: For penile cancer (PC) there are no known molecular predictors of lymphatic spread and/or chemoresistance. To identify functional biomarkers that can predict malignant progression and treatment responsiveness. We used four patient-derived PC cell lines and measured invasion and capillary tube formation, chemoresponsiveness, and mRNA and protein expression. Data were further validated in E2F1 transcription factor knockdown and overexpression experiments. We quantified E2F1 transcript levels in a set of nonmetastatic tumours (NM), metastasised primary tumours (PT), and lymph node metastases (M) from 24 patients. E2F1 immunohistochemistry was performed in another set of 13 PC biopsies. Relationships between different parameters were analysed using Student tests. Transcript levels in patient samples were compared using Mann-Whitney tests. Significance was set at 〈 0.05. In cell lines established from lymph node metastases, E2F1 was more abundantly expressed, pRB was inactivated, and CDK2, CDK4, and cyclins D and E were elevated in comparison to cells from primary PC. Overexpression of E2F1 enhanced migratory capacity and lymphatic endothelial tubule formation, while depletion reduced invasiveness and increased chemosensitivity. VEGFR-3 and VEGF-C and mesenchymal markers were upregulated by high E2F1. E2F1 was clearly upregulated in infiltrative and metastatic primary tumours and metastases (NM vs PT, 〈 0.05; NM vs M, 〈 0.0005). E2F1 Quick scores increased from grade I to grade III tumours. A limitation of the study is the small number of patients. E2F1 is a driver of invasion and lymphatic dissemination and promotes chemoresistance. E2F1-related biomarkers might assist in stratifying PC patients for different treatment regimens. The availability of penile cancer cell lines allows molecular research on the mechanisms underlying metastasis and chemotherapy. A critical pathway involved in both features has been identified and may lead to better patient stratification for treatment selection. Functional analyses in cell lines from patients with primary and metastatic penile cancer revealed that E2F1 drives invasiveness, lymphogenic metastasis, and chemoresistance. This allowed identification of prognostic biomarkers that could open up entirely new possibilities in cancer diagnosis and therapy.
    Keywords: Penile Squamous Cell Carcinoma ; E2f1 ; Cancer Invasion ; Chemotherapy ; Lymphangiogenesis ; Experimental Therapeutics ; Medicine
    ISSN: 2405-4569
    E-ISSN: 2405-4569
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  • 6
    Language: English
    In: Clinical Genitourinary Cancer, October 2017, Vol.15(5), pp.548-555.e3
    Description: Patients with locally advanced penile squamous-cell carcinoma have a poor prognosis. No difference in survival was noted when using chemotherapy before or after surgery. Uncertainties persist regarding the optimal management of these patients, and new treatments are urgently required, particularly for patients at highest risk, with bilateral and/or pelvic lymph node involvement. The prognosis of patients with locally advanced penile squamous-cell carcinoma is primarily related to the extent of lymph node metastases. Surgery alone yields suboptimal results, and there is a paucity of data on these patients' outcomes. This retrospective study evaluated patients who received neoadjuvant or adjuvant chemotherapy from 1990 onward at 12 centers. Cox models were used to investigate prognostic factors for relapse-free survival and overall survival (OS). Among the 201 included patients, 39 (19.4%) had disease of T3-4 and N0 clinical stage; the remaining patients had clinical lymph node involvement (cN+). Ninety-four patients received neoadjuvant chemotherapy (group 1), 78 received adjuvant chemotherapy (group 2), and 21 received both (group 3). Eight patients for whom the timing of perioperative chemotherapy administration was unavailable were included in the Cox analyses. Forty-three patients (21.4%) received chemoradiation. Multivariate analysis for OS (n = 172) revealed bilateral disease (  = .035) as a negative prognostic factor, while pelvic cN+ tended to be nonsignificantly associated with decreased OS (  = .076). One-year relapse-free survival was 35.6%, 60.6%, and 45.1% in the 3 groups, respectively. One-year OS was 61.3%, 82.2%, and 75%, respectively. No significant differences were seen on univariable analyses for OS between the groups (  = .45). Platinum type of chemotherapy and chemoradiation were not significantly associated with any outcome analyzed. Benchmark survival estimates for patients receiving perioperative chemotherapy for locally advanced penile squamous-cell carcinoma have been provided, with no substantial differences observed between neoadjuvant and adjuvant administration. This analysis may result in improved patient information, although prospective studies are warranted.
    Keywords: Penile Cancer ; Preoperative Chemotherapy ; Regional Lymph Nodes ; Squamous Cell Carcinoma ; Survival ; Medicine
    ISSN: 1558-7673
    E-ISSN: 1938-0682
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