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1. PRO-P: evaluating the effect of electronic patient-reported outcome measures monitoring compared with standard care in prostate cancer patients undergoing surgery—study protocol for a randomized controlled trial

Author

Al-Monajjed, Rouvier, Albers, Peter, Droop, Johanna, Fugmann, Dominik, Noldus, Joachim, Palisaar, Rein-Jüri, Ritter, Manuel, Ellinger, Jörg, Krausewitz, Philipp, Truß, Michael, Hadaschik, Boris, Grünwald, Viktor, Schrader, Andres-Jan, Papavassilis, Philipp, Ernstmann, Nicole, Schellenberger, Barbara, Moritz, Anna, Kowalski, Christoph, Hellmich, Martin, Heiden, Pierce, Hagemeier, Anna, Horenkamp-Sonntag, Dirk, Giessing, Markus, Pauler, Luis, Dieng, Sebastian, Peters, Maria, Feick, Günter, and Karger, André

Published
2024
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10. Trophoblast cell surface antigen‐2: a promising new biomarker and potential therapeutic target in penile squamous cell carcinoma.

Author

Weiten, Richard, Storz, Enno, Kessler, Carolina, Sperber, Laurenz, Spohn, Hanna Elisa, Pfister, David, Nestler, Tim, Tolkach, Yuri, Linden, Friederike, Wirtz, Ralph, von Brandenstein, Melanie, Krausewitz, Philipp, and Heidenreich, Axel

Subjects
IMMUNOSTAINING, SQUAMOUS cell carcinoma, LYMPHATIC metastasis, GENE expression, BLOOD proteins
Abstract

Objective: To evaluate the potential utility of antibody‐drug conjugates targeting trophoblast cell surface antigen‐2 (TROP‐2) in patients with primary penile squamous cell carcinoma (PSCC), patients with recurrence (REC cohort), and patient‐matched distant metastases (MET cohort), and to assess the potential use of TROP‐2 as a predictive non‐invasive biomarker in PSCC. Methods: A cohort comprising a PRIM (n = 37), REC (n = 5) and MET subcohort (n = 7), with MET including lymph node and lung metastases, was analysed using quantitative real‐time PCR, ELISA and immunohistochemical staining with evaluation of H‐score. Results: TROP‐2 mRNA and serum protein levels were significantly increased in primary and recurrent PSCC compared to cancer‐free controls (both P < 0.001). Immunohistochemical analysis revealed that most of the PRIM cohort (n = 34/37, median H‐score 260, interquartile range [IQR] 210–300), as well as all patients in the REC (median [IQR] H‐score 200 [165–290]) and MET cohorts (median [IQR] H‐score 280 [260–300]) exhibited moderate to strong membranous TROP‐2 expression. Additionally, The H‐score (membranous TROP‐2 expression) was positively correlated with TROP‐2 mRNA (ρ = 0.69, P < 0.0001, R2 = 0.70) and protein levels (ρ = 0.86, P < 0.0001, R2 = 0.59), indicating its potential as a non‐invasive biomarker in PSCC. Conclusion: In summary, our results support further studies on TROP‐2 as a diagnostic and therapeutic target in primary, recurrent and metastatic PSCC. [ABSTRACT FROM AUTHOR]

Published
2024
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12. MP61-08 TROP-2—A PROMISING NEW THERAPEUTIC TARGET IN PENILE SQUAMOUS CELL CARCINOMA

Author

Weiten, Richard, primary, Kessler, Carolina, additional, Meisl, Christina, additional, Spohn, Hanna Elisa, additional, Storz, Enno, additional, Pfister, David, additional, Nestler, Tim, additional, Tolkach, Yuri, additional, Linden, Friederike, additional, Wirtz, Ralph, additional, von Brandenstein, Melanie, additional, Krausewitz, Philipp, additional, and Heidenreich, Axel, additional

Published
2024
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16. Exploring membranous NECTIN‐4 expression patterns and enfortumab vedotin response in prostate cancer.

Author

Weiten, Richard, Bernhardt, Marit, Niemann, Max, Kristiansen, Glen, Grünwald, Viktor, Ritter, Manuel, Hölzel, Michael, Eckstein, Markus, Alajati, Abdullah, Klümper, Niklas, and Krausewitz, Philipp

Subjects
PROSTATE cancer patients, IMMUNOSTAINING, TRANSITIONAL cell carcinoma, CYTOTOXINS, PROSTATE cancer
Abstract

Antibody‐drug conjugates (ADCs) represent a novel type of targeted cancer therapy combining the specificity of monoclonal antibodies with the cytotoxicity of conventional chemotherapy. Recently, ADCs have demonstrated practice‐changing efficacy across diverse solid cancers. The anti‐NECTIN‐4 ADC enfortumab vedotin (EV) has just been approved for patients with urothelial cancer and is currently under investigation for patients with castration‐resistant prostate cancer (CRPC e.g. Phase II ENCORE trial). Our objective was to evaluate the efficacy of EV in established prostate cancer (PCa) cell lines and to examine the membranous NECTIN‐4 expression in primary tumours (PRIM) and distant metastases (MET). NECTIN‐4 was heterogeneously expressed in the panel of PCa cell lines. EV led to growth inhibition in NECTIN‐4 expressing PCa cells (22Rv1 and LNCaP), whereas the NECTIN‐4‐negative PC‐3 cells were significantly less responsive to EV, emphasizing the dependence of EV response on its target expression. Immunohistochemical staining revealed moderate membranous NECTIN‐4 expression only in a small subgroup of CRPC patients with lung and peritoneal MET [n = 3/22 with H‐score ≥100, median H‐score 140 (IQR 130–150)], while 100% of PRIM (n = 48/48) and 86.4% of common MET sites (n = 19/22), including lymph node, bone and liver MET, were NECTIN‐4 negative. In summary, EV may be effective in NECTIN‐4‐positive PCa. However, our findings demonstrate that the tumoural NECTIN‐4 expression is predominantly low in metastatic PCa, which suggests that EV may only be effective in a biomarker‐stratified subgroup. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Preclinical evidence for the use of anti‐Trop‐2 antibody‐drug conjugate Sacituzumab govitecan in cerebral metastasized castration‐resistant prostate cancer.

Author

Weiten, Richard, Niemann, Max, Below, Eduard, Friker, Lea L., Ralser, Damian J., Toma, Marieta, Kristiansen, Glen, Hahn, Oliver, Zechel, Sabrina, Grünwald, Viktor, Bald, Tobias, Siewert, Johannes, Pietsch, Torsten, Ritter, Manuel, Hölzel, Michael, Eckstein, Markus, Alajati, Abdullah, Krausewitz, Philipp, and Klümper, Niklas

Subjects
CASTRATION-resistant prostate cancer, ANTIBODY-drug conjugates, PROSTATE cancer, IMMUNOSTAINING, PROTEIN expression, SURVIVAL rate
Abstract

Purpose: Improved survival rates have been observed in castration‐resistant prostate cancer (CRPC) due to advancements in treatment options. However, individuals with brain metastases still have limited therapeutic options and an unfavorable prognosis. Therefore, there is an urgent need to explore new therapeutic avenues, such as antibody‐drug conjugates (ADCs), which have demonstrated significant clinical activity against active brain metastases in solid tumors. Our objective was to determine the expression levels of the ADC targets Trop‐2 and NECTIN‐4 in cerebral metastasized CRPC (mCRPC). Methods: Immunohistochemical staining of Trop‐2 and NECTIN‐4 with evaluation of H‐score was performed in CRPC brain metastases (n = 31). Additionally, we examined Trop‐2 protein expression in prostate cancer cell lines and studied their responsiveness to the anti‐Trop‐2 ADC Sacituzumab govitecan (SG) in vitro. Results: Our analysis revealed that most patients exhibited moderate to strong Trop‐2 expression [n = 27/31 with H‐score ≥100, median H‐score 220 (IQR 180–280)], while NECTIN‐4 was absent in all cerebral metastases. Mechanistically, we demonstrated that the efficacy of SG depends on Trop‐2 expression levels in vitro. Overexpression of Trop‐2 in Trop‐2‐negative PC‐3 cells led to sensitization to SG, whereas CRISPR‐Cas9‐mediated knockdown of Trop‐2 in Trop‐2‐expressing DU‐145 cells conferred resistance to SG. Conclusion: The substantial expression of Trop‐2 in cerebral metastases, along with our preclinical in vitro results, supports the efficacy of SG in treating cerebral mCRPC. Thus, our results extend the understanding of the potential of ADCs in prostate cancer treatment and provide an additional treatment strategy for the challenging subset of patients with cerebral metastases. [ABSTRACT FROM AUTHOR]

Published
2024
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25. Deep Learning Super-Resolution Reconstruction for Fast and Motion-Robust T2-weighted Prostate MRI

Author

Bischoff, Leon M., primary, Peeters, Johannes M., additional, Weinhold, Leonie, additional, Krausewitz, Philipp, additional, Ellinger, Jörg, additional, Katemann, Christoph, additional, Isaak, Alexander, additional, Weber, Oliver M., additional, Kuetting, Daniel, additional, Attenberger, Ulrike, additional, Pieper, Claus C., additional, Sprinkart, Alois M., additional, and Luetkens, Julian A., additional

Published
2023
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27. Identification of F-Box/SPRY Domain-Containing Protein 1 (FBXO45) as a Prognostic Biomarker for TMPRSS2–ERG-Positive Primary Prostate Cancers

Author

von Danwitz, Marthe, primary, Klümper, Niklas, additional, Bernhardt, Marit, additional, Cox, Alexander, additional, Krausewitz, Philipp, additional, Alajati, Abdullah, additional, Kristiansen, Glen, additional, Ritter, Manuel, additional, Ellinger, Jörg, additional, and Stein, Johannes, additional

Published
2023
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30. DEPROMP Trial: The additive value of PSMA-PET/CT-guided biopsy for prostate cancer management in biopsy naïve men – study protocol for a randomized controlled trial

Author

Krausewitz, Philipp, primary, Bundschuh, Ralph Alexander, additional, Gaertner, Florian C., additional, Essler, Markus, additional, Attenberger, Ulrike, additional, Luetkens, Julian, additional, Kristiansen, Glen, additional, Muders, Michael, additional, Ohlmann, Carsten-Henning, additional, Hauser, Stefan, additional, Ellinger, Jörg, additional, and Ritter, Manuel, additional

Published
2022
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35. Lessons learned after one year of COVID-19 from a urologist and radiotherapist view: A German survey on prostate cancer diagnosis and treatment

Author

Harke, Nina N., primary, Wagner, Christian, additional, Hermann, Robert M., additional, Hadaschik, Boris A., additional, Radtke, Jan Philipp, additional, Altay-Langguth, Alev, additional, Aufderklamm, Stefan, additional, Bach, Christian, additional, Becker-Schiebe, Martina, additional, Blana, Andreas, additional, Bruns, Frank, additional, Buse, Stephan, additional, Combs, Stephanie E., additional, Engels, Christina L., additional, Ezzibdeh, Emad, additional, Fiedler, Marcel, additional, Fischer, Laura-Anna, additional, Farzat, Mahmoud, additional, Frismann, Alexander, additional, Heck, Matthias M., additional, Henkenberens, Christoph, additional, Roesch, Marie C., additional, Käding, Christoph, additional, Klautke, Gunther, additional, Krausewitz, Philipp, additional, Kuczyk, Markus A., additional, Leitsmann, Conrad, additional, Lettmaier, Sebastian, additional, Mahjoub, Samy, additional, Manseck, Andreas, additional, Medenwald, Daniel, additional, Meyer, Andreas, additional, Micke, Oliver, additional, Moritz, Rudolf, additional, Ott, Marcel, additional, Peters, Inga, additional, Pokupic, Sasa, additional, Porres, Daniel, additional, Preisser, Felix, additional, Reichel, Kathrin, additional, Schneider, Andreas, additional, Schwentner, Christian, additional, Scobioala, Sergiu, additional, Truss, Michael, additional, Wegener, Daniel, additional, Wezel, Felix, additional, Willborn, Kay, additional, Witt, Jörn H., additional, Wittig, Andrea, additional, Wittlinger, Michael, additional, Wolff, Hendrik A., additional, Zimmermanns, Volker, additional, and Christiansen, Hans, additional

Published
2022
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36. Single-course bleomycin, etoposide, and cisplatin (1xBEP) as adjuvant treatment in testicular nonseminoma clinical stage 1: outcome, safety, and risk factors for relapse in a population-based study

Author

Dieckmann, Klaus-Peter, Pokrivcak, Tomas, Geczi, Lajos, Niehaus, David, Dralle-Filiz, Inken, Matthies, Cord, Dienes, Tamas, Zschaebitz, Stefanie, Paffenholz, Pia, Gschliesser, Tanja, Pichler, Renate, Mego, Michal, Bader, Pia, Zengerling, Friedemann, Heinzelbecker, Julia, Krausewitz, Philipp, Krege, Susanne, Aurilio, Gaetano, Aksoy, Cem, Hentrich, Marcus, Seidel, Christoph, Toerzsoek, Peter, Nestler, Tim, Majewski, Matthaeus, Hiester, Andreas, Buchler, Tomas, Vallet, Sonia, Studentova, Hana, Schoenburg, Sandra, Niedersuess-Beke, Dora, Ring, Julia, Trenti, Emanuela, Heidenreich, Axel, Wuelfing, Christian, Isbarn, Hendrik, Pichlmeier, Uwe, Pichler, Martin, Dieckmann, Klaus-Peter, Pokrivcak, Tomas, Geczi, Lajos, Niehaus, David, Dralle-Filiz, Inken, Matthies, Cord, Dienes, Tamas, Zschaebitz, Stefanie, Paffenholz, Pia, Gschliesser, Tanja, Pichler, Renate, Mego, Michal, Bader, Pia, Zengerling, Friedemann, Heinzelbecker, Julia, Krausewitz, Philipp, Krege, Susanne, Aurilio, Gaetano, Aksoy, Cem, Hentrich, Marcus, Seidel, Christoph, Toerzsoek, Peter, Nestler, Tim, Majewski, Matthaeus, Hiester, Andreas, Buchler, Tomas, Vallet, Sonia, Studentova, Hana, Schoenburg, Sandra, Niedersuess-Beke, Dora, Ring, Julia, Trenti, Emanuela, Heidenreich, Axel, Wuelfing, Christian, Isbarn, Hendrik, Pichlmeier, Uwe, and Pichler, Martin

Abstract

Introduction: Clinical stage 1 (CS1) nonseminomatous (NS) germ cell tumors involve a 30% probability of relapse upon surveillance. Adjuvant chemotherapy with one course of bleomycin, etoposide, and cisplatin (1xBEP) can reduce this risk to <5%. However, 1xBEP results are based solely on five controlled trials from high-volume centers. We analyzed the outcome in a real-life population. Patients and Methods: In a multicentric international study, 423 NS CS1 patients receiving 1xBEP were retrospectively evaluated. Median follow-up was 37 (range, 6-89) months. Primary end points were relapse-free and overall survival evaluated after 5 years. We also looked at associations of relapse with clinico-pathological factors using stratified Kaplan-Meier methods and Cox regression models. Treatment modality and outcome of recurrences were analyzed descriptively. Results: The 5-year relapse-free survival rate was 96.2%. Thirteen patients (3.1%; 95% confidence interval, 1.65-5.04%) relapsed after a median time of 13 months, of which 10 were salvaged (77%). Relapses were mostly confined to retroperitoneal nodes. Three patients succumbed, two to disease progression and one to toxicity of chemotherapy. Pathological stage >pT2 was significantly associated with relapse rate. Conclusion: The relapse rate of 3.1% found in this population of NS CS1 patients treated with 1xBEP at the routine care level was not inferior to the median rate of 2.3% reported from a meta-analysis of controlled trials. Also, the cure rate of relapses of 77% is consistent with the previously reported rate of 80%. This study clearly shows that the 1xBEP regimen represents a safe treatment for NS CS1 patients.

Published
2022

37. Single-course bleomycin, etoposide, and cisplatin (1xBEP) as adjuvant treatment in testicular nonseminoma clinical stage 1: outcome, safety, and risk factors for relapse in a population-based study

Author

Dieckmann, Klaus-Peter, primary, Pokrivcak, Tomas, additional, Geczi, Lajos, additional, Niehaus, David, additional, Dralle-Filiz, Inken, additional, Matthies, Cord, additional, Dienes, Tamas, additional, Zschäbitz, Stefanie, additional, Paffenholz, Pia, additional, Gschliesser, Tanja, additional, Pichler, Renate, additional, Mego, Michal, additional, Bader, Pia, additional, Zengerling, Friedemann, additional, Heinzelbecker, Julia, additional, Krausewitz, Philipp, additional, Krege, Susanne, additional, Aurilio, Gaetano, additional, Aksoy, Cem, additional, Hentrich, Marcus, additional, Seidel, Christoph, additional, Törzsök, Péter, additional, Nestler, Tim, additional, Majewski, Matthaeus, additional, Hiester, Andreas, additional, Buchler, Tomas, additional, Vallet, Sonia, additional, Studentova, Hana, additional, Schönburg, Sandra, additional, Niedersüß-Beke, Dora, additional, Ring, Julia, additional, Trenti, Emanuela, additional, Heidenreich, Axel, additional, Wülfing, Christian, additional, Isbarn, Hendrik, additional, Pichlmeier, Uwe, additional, and Pichler, Martin, additional

Published
2022
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38. Omitting routine cystography after RARP: Analysis of complications and readmission rates in suprapubic and transurethral drained patients.

Author

Krausewitz, Philipp, Farzat, Mahmoud, Ellinger, Jörg, and Ritter, Manuel

Subjects
*PATIENT readmissions, *URINARY catheterization, *URINARY catheters, *RADICAL prostatectomy, *SURGICAL complications, *TRANSURETHRAL prostatectomy
Abstract

Objectives: Robot‐assisted radical prostatectomy (RARP) has become the therapy of choice for local treatment of prostate cancer. Postoperatively, urologists perform cystography before removing urinary catheters due to concerns about the integrity of the vesicourethral anastomosis. This study aims to evaluate the safety of waiving cystography before early catheter removal after RARP. Methods: A total of 514 patients from two tertiary referral centers who underwent RARP were retrospectively included. Patients received postoperative urinary drainage by transurethral (TUC) or suprapubic catheter (SPC). During the first year, both centers performed routine cystography before removing TUC or SPC on postoperative day 5. In the following year, management changed and catheters were removed without cystography unless indicated by the surgeon. Demographic and perioperative data were analyzed. Postoperative complications and readmission rates were compared between standard cystography (StCG), no cystography (NCG), and selective cystography (SCG). Results: Groups were comparable regarding demographic and oncological parameters. Analysis showed no significant difference regarding major complications and readmission rates between standard and no cystography (p = 0.155 and 0.998 respectively). Omitting routine cystography did not lead to inferior postoperative courses regardless of both urinary drainage used and tumor stage. Subgroup analysis showed an increase of major complications in SCG patients when compared with NCG (p = 0.003) while readmissions remained comparable (p = 0.554). Conclusion: Waiving routine cystography before early catheter removal after RARP appears to be safe and feasible regardless of urinary drainage. However, the selective cystogram at the surgeon's request still plays a role in monitoring patients with an elevated risk profile. [ABSTRACT FROM AUTHOR]

Published
2023
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