Publications by authors named "Jürgen Gschwend"

161 Publications

Ileum-Neoblase nach Hautmann.

Authors:
Jürgen Gschwend

Aktuelle Urol 2021 Apr 1;52(2):181-195. Epub 2021 Apr 1.

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http://dx.doi.org/10.1055/a-1296-2852DOI Listing
April 2021

The Diagnosis and Treatment of Patients With Bladder Carcinoma.

Dtsch Arztebl Int 2020 Apr 15;118(Forthcoming). Epub 2020 Apr 15.

Background: In Germany, bladder carcinoma accounts for 3-4 % of all malignant tumors. New study findings in the fields of endoscopy, surgery, and systemic therapy have led to multimodal treatment approaches for bladder cancer that can prolong overall survival and improve the affected patients' quality of life.

Methods: This review is based on pertinent publications retrieved by a selective search in PubMed, with special attention to the German Clinical Practice Guideline on the Early Detection, Diagnosis, Treatment, and Continuing Care of Bladder Carcinoma, along with data available on the websites of the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The bladder carcinoma guideline of the Onkopedia guidelines program was used as well.

Results: 75% of all urothelial carcinomas are diagnosed in the non-muscle-invasive stage. These carcinomas should be resected via the endoscopic transurethral approach whenever possible. Next, depending on the patient's risk profile, intravesical therapy may be needed. Patients with carcinoma in the muscle-invasive stage should be given multimodal treatment, including radical cystectomy with urinary diversion and perioperative systemic therapy; alternatively, bladder-preserving chemoradiotherapy can be offered in selected cases. For patients with metastatic bladder carcinoma, immunotherapy with checkpoint inhibitors has become well established for first- and second-line therapy alongside classic cytostatic treatment and has been shown to prolong patients' lives significantly. The administration of checkpoint inhibitors can prolong the overall survival of patients with metastases to 15-17 months.

Conclusion: The treatment of bladder carcinoma in all stages calls for interdisciplinary collaboration to ensure the provision of effective, individual multimodal treatment.
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http://dx.doi.org/10.3238/arztebl.m2021.0013DOI Listing
April 2020

Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (IMvigor010): a multicentre, open-label, randomised, phase 3 trial.

Lancet Oncol 2021 04 12;22(4):525-537. Epub 2021 Mar 12.

Barts Cancer Institute, Queen Mary University of London, St Bartholomew's Hospital, London, UK.

Background: Despite standard curative-intent treatment with neoadjuvant cisplatin-based chemotherapy, followed by radical surgery in eligible patients, muscle-invasive urothelial carcinoma has a high recurrence rate and no level 1 evidence for adjuvant therapy. We aimed to evaluate atezolizumab as adjuvant therapy in patients with high-risk muscle-invasive urothelial carcinoma.

Method: In the IMvigor010 study, a multicentre, open-label, randomised, phase 3 trial done in 192 hospitals, academic centres, and community oncology practices across 24 countries or regions, patients aged 18 years and older with histologically confirmed muscle-invasive urothelial carcinoma and an Eastern Cooperative Oncology Group performance status of 0, 1, or 2 were enrolled within 14 weeks after radical cystectomy or nephroureterectomy with lymph node dissection. Patients had ypT2-4a or ypN+ tumours following neoadjuvant chemotherapy or pT3-4a or pN+ tumours if no neoadjuvant chemotherapy was received. Patients not treated with neoadjuvant chemotherapy must have been ineligible for or declined cisplatin-based adjuvant chemotherapy. No post-surgical radiotherapy or previous adjuvant chemotherapy was allowed. Patients were randomly assigned (1:1) using a permuted block (block size of four) method and interactive voice-web response system to receive 1200 mg atezolizumab given intravenously every 3 weeks for 16 cycles or up to 1 year, whichever occurred first, or to observation. Randomisation was stratified by previous neoadjuvant chemotherapy use, number of lymph nodes resected, pathological nodal status, tumour stage, and PD-L1 expression on tumour-infiltrating immune cells. The primary endpoint was disease-free survival in the intention-to-treat population. Safety was assessed in patients who either received at least one dose of atezolizumab or had at least one post-baseline safety assessment. This trial is registered with ClinicalTrials.gov, NCT02450331, and is ongoing but not recruiting patients.

Findings: Between Oct 5, 2015, and July 30, 2018, we enrolled 809 patients, of whom 406 were assigned to the atezolizumab group and 403 were assigned to the observation group. Median follow-up was 21·9 months (IQR 13·2-29·8). Median disease-free survival was 19·4 months (95% CI 15·9-24·8) with atezolizumab and 16·6 months (11·2-24·8) with observation (stratified hazard ratio 0·89 [95% CI 0·74-1·08]; p=0·24). The most common grade 3 or 4 adverse events were urinary tract infection (31 [8%] of 390 patients in the atezolizumab group vs 20 [5%] of 397 patients in the observation group), pyelonephritis (12 [3%]) vs 14 [4%]), and anaemia (eight [2%] vs seven [2%]). Serious adverse events occurred in 122 (31%) patients who received atezolizumab and 71 (18%) who underwent observation. 63 (16%) patients who received atezolizumab had a treatment-related grade 3 or 4 adverse event. One treatment-related death, due to acute respiratory distress syndrome, occurred in the atezolizumab group.

Interpretation: To our knowledge, IMvigor010 is the largest, first-completed phase 3 adjuvant study to evaluate the role of a checkpoint inhibitor in muscle-invasive urothelial carcinoma. The trial did not meet its primary endpoint of improved disease-free survival in the atezolizumab group over observation. Atezolizumab was generally tolerable, with no new safety signals; however, higher frequencies of adverse events leading to discontinuation were reported than in metastatic urothelial carcinoma studies. These data do not support the use of adjuvant checkpoint inhibitor therapy in the setting evaluated in IMvigor010 at this time.

Funding: F Hoffmann-La Roche/Genentech.
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http://dx.doi.org/10.1016/S1470-2045(21)00004-8DOI Listing
April 2021

[Testicular and breast self-examination-a retrospective cohort study of medical students].

Urologe A 2021 Mar 2. Epub 2021 Mar 2.

Klinik und Poliklinik für Urologie, Klinikum rechts der Isar, Fakultät für Medizin, Technische Universität München, Ismaninger Str. 22, 81675, München, Deutschland.

Background: Regular self-examination can facilitate early detection of testicular cancer and malignancies of the breast and may ensure a curative treatment. In this analysis we explored the tendencies of medical students to perform self-examination and associated factors.

Methods: As part of their urology rotation, medical students of the Technical University of Munich were surveyed via questionnaires regarding their health and sexual behavior. In all, 98.8% of the students participated and data from 473 of 477 students were included in this analysis. Data were analyzed using univariate and multivariate regression analysis.

Results: In all, 64.2% (n = 177) of the male students and 72.3% (n = 296) of the female students performed regular self-examination of the testis and breast, respectively. Students who did not communicate with their partners or friends about their sex lives were less likely to preform regular self-examination (p < 0.05). Male students without sexual intercourse in the 4 weeks prior to the survey and female students who did not masturbate in the 4 weeks prior to the survey were also less likely to preform regular self-examination (p < 0.05).

Discussion: The rate of regular self-examination is high in medical students compared to previous studies on young adults and non-medical students. This shows that knowledge about the significance of testicular cancer and breast cancer are fundamental for promoting self-examination in teenagers and young adults. A distressed sex life might hinder young adults in preforming regular self-examination. Therefore, improved education about the significance of testicular cancer and routine urological consultations for male teenagers and young men are ways to promote testicular self-examination within this age group.
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http://dx.doi.org/10.1007/s00120-021-01479-8DOI Listing
March 2021

Patterns of care for prostate cancer radiotherapy-results from a survey among German-speaking radiation oncologists.

Strahlenther Onkol 2021 Jan 27. Epub 2021 Jan 27.

Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich (TUM), Ismaninger Straße 22, 81675, Munich, Germany.

Background: Emerging moderately hypofractionated and ultra-hypofractionated schemes for radiotherapy (RT) of prostate cancer (PC) have resulted in various treatment options. The aim of this survey was to evaluate recent patterns of care of German-speaking radiation oncologists for RT of PC.

Methods: We developed an online survey which we distributed via e‑mail to all registered members of the German Society of Radiation Oncology (DEGRO). The survey was completed by 109 participants between March 3 and April 3, 2020. For evaluation of radiation dose, we used the equivalent dose at fractionation of 2 Gy with α/β = 1.5 Gy, equivalent dose (EQD2 [1.5 Gy]).

Results: Median EQD2(1.5 Gy) for definitive RT of the prostate is 77.60 Gy (range: 64.49-84.00) with median single doses (SD) of 2.00 Gy (range: 1.80-3.00), while for postoperative RT of the prostate bed, median EQD2(1.5 Gy) is 66.00 Gy (range: 60.00-74.00) with median SD of 2.00 Gy (range: 1.80-2.00). For definitive RT, the pelvic lymph nodes (LNs) are treated in case of suspect findings in imaging (82.6%) and/or according to risk formulas/tables (78.0%). In the postoperative setting, 78.9% use imaging and 78.0% use the postoperative tumor stage for LN irradiation. In the definitive and postoperative situation, LNs are irradiated with a median EQD2(1.5 Gy) of 47.52 Gy with a range of 42.43-66.00 and 41.76-62.79, respectively.

Conclusion: German-speaking radiation oncologists' patterns of care for patients with PC are mainly in line with the published data and treatment recommendation guidelines. However, dose prescription is highly heterogenous for RT of the prostate/prostate bed, while the dose to the pelvic LNs is mainly consistent.
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http://dx.doi.org/10.1007/s00066-020-01738-1DOI Listing
January 2021

Benefit finding in long-term prostate cancer survivors.

Support Care Cancer 2021 Jan 15. Epub 2021 Jan 15.

Department of Urology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.

Purpose: Benefit finding (BF) represents possible positive changes that people may experience after cancer diagnosis and treatment and has proven to be valuable to the psychological outcome. Knowledge of such beneficial consequences of prostate cancer (PCa) is limited in long-term survivors (> 5 years). Thus, the present study investigated the occurrence of benefit finding (BF) and its determinants in a large sample of (very-) long-term PCa survivors.

Methods: BF was assessed in 4252 PCa survivors from the German database "Familial Prostate Cancer" using the German version of the Benefit Finding Scale (BFS). Associations between BF and sociodemographic, clinical, and psychosocial (e.g., depressive and anxiety symptoms and perceived severity of the disease experience) variables were analyzed using hierarchical multiple linear regression analysis.

Results: Mean age at survey was 77.4 years (SD = 6.2) after a mean follow-up of 14.8 years (SD = 3.8). Mean BFS score was 3.14 (SD = 1.0); the prevalence of moderate-to-high BF (score ≥ 3) was 59.7%. Younger age at diagnosis, lower educational level, and higher perceived severity of the disease experience were predictive of BF. Objective disease severity or family history of PCa was not uniquely associated with BF.

Conclusions: BF occurs in older, (very-) long-term PCa survivors. Our findings suggest that the self-asserted severity of the disease experience in a patient's biography is linked to BF in the survivorship course above all tangible sociodemographic and clinical factors.

Implications For Cancer Survivors: PCa survivors may express BF regardless of clinical disease severity. Treating urologists should consider inquiring BF to enrich a patient's cancer narrative.
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http://dx.doi.org/10.1007/s00520-020-05971-3DOI Listing
January 2021

[Virtual skills-training in urology : Teaching at the Technical University of Munich during the COVID-19-pandemic].

Urologe A 2021 Apr 12;60(4):484-490. Epub 2021 Jan 12.

Klinik und Poliklinik für Urologie, Universitätsklinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, München, Deutschland.

Background And Introduction: The COVID-19 pandemic presents the challenge for medical education to teach practical skills without practical training. To provide an alternative to hands-on training during the COVID-19 lockdown, we created a virtual curriculum to teach practical skills using videos combined with online exams on a virtual e‑learning platform. The goal was to convey different theoretical and practical aspects of urology.

Materials And Methods: The videos were produced by department employees using a predefined concept. The students had access to the virtual curriculum via the university's Moodle e‑learning platform. To assess the success of training, participating students had to pass an online exam about the curriculum's contents, followed by an evaluation of the course.

Results: A total of 164 participants took part in the virtual curriculum. The overall evaluation and feedback was very positive. The acceptance of the virtual alternative to hands-on teaching was high.

Discussion: The virtual curriculum offered a fast and contactless alternative to the regular hands-on teaching.
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http://dx.doi.org/10.1007/s00120-020-01431-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801874PMC
April 2021

Outcomes of palliative cystectomy in patients with locally advanced pT4 bladder cancer.

Urol Oncol 2021 Jan 8. Epub 2021 Jan 8.

Department of Urology, Technical University of Munich, Rechts der Isar Medical Center, Munich, Germany.

Background: Radical cystectomy (Cx) is the standard of care for muscle-invasive bladder cancer (BCa). In locally advanced pT4 BCa the oncologic outcome is inexplicit but Cx may be necessary for palliation.

Objectives: The aim of this retrospective study was to evaluate the outcomes of Cx performed in patients with locally advanced pT4 BCa and to identify patient subgroups with improved outcome.

Methods: Between 2008 and 2017, we identified 76 of 905 patients who underwent Cx for pT4 BCa at a single tertiary referral center. The physical patients' status was estimated according to the American Society of Anesthesiologists (ASA) classification. For the classification of postoperative complication rates, the Clavien-Dindo grading was used. Time-to-event variables with log-rank statistics were calculated with the use of the Kaplan-Meier method.

Results: Median age was 74 years (range 42-90). Preoperatively, the physical status was estimated poor in 40 (52%) patients (ASA-score of ≥3). Overall, 19 (25%) patients had pT4b BCa, 41 (54%) patients were lymph node positive (c/pN+) and 14 (18%) patients had distant metastases (c/pM+). Within 30 and 90 days after surgery, 21% and 30% of the patients, respectively, developed severe complications (Clavien-Dindo grade ≥3). Overall, 30- and 90-day mortality rates were 9% and 11%, respectively. Moreover, 86% and 75% of patients who died within 30 and 90 days after surgery, respectively, had an ASA-score ≥3. At a median postoperative follow-up of 8 months (range 0-85), 53 (70%) patients have died. During the follow-up period, 46% of the patients died due to progressive disease, 16% died of a noncancer-specific cause, and for 8% of the patients, the reason remains unknown. Median overall survival (OS) and cancer-specific survival were 13.0 and 16.0 months, respectively. In subgroup analyses ASA-score ≥3 and hemoglobin <11.7 g/dl was significantly associated with poor OS. No statistically significant differences were detected between subgroups.

Conclusion: Cx performed in patients with locally advanced pT4 BCa is associated with an increased mortality rate within 90 days postoperatively. Our study revealed that the ASA-score is a relevant and easily available tool to rate the patient´s condition and estimate postoperative outcome.
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http://dx.doi.org/10.1016/j.urolonc.2020.11.042DOI Listing
January 2021

Activity and Adverse Events of Actinium-225-PSMA-617 in Advanced Metastatic Castration-resistant Prostate Cancer After Failure of Lutetium-177-PSMA.

Eur Urol 2021 Mar 5;79(3):343-350. Epub 2020 Dec 5.

Department of Nuclear Medicine, School of Medicine, Technical University of Munich, Munich, Germany; German Cancer Consortium (DKTK), partnersite Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Background: Beta-emitting Lu-177-labeled prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a new option for metastatic castration-resistant prostate cancer (mCRPC), but its antitumor effect can decrease over time.

Objective: To report the safety and activity of alpha-emitting Ac-225-PSMA-617 RLT in mCRPC that has progressed after Lu-177-PSMA.

Design, Setting, And Participants: Twenty-six patients were treated under a compassionate use protocol. The eligibility criteria included previous treatment with abiraterone or enzalutamide, previous taxane-based chemotherapy, progression after Lu-177-PSMA, and positive PSMA-ligand uptake. The median number of previous mCRPC regimens was 6. Ac-225-PSMA-617 was given every 8 wk until progression/intolerable side effects.

Outcome Measurements And Statistical Analysis: Prostate-specific antigen (PSA) decline, PSA progression-free survival (PSA-PFS), clinical progression-free survival (cPFS), overall survival (OS), and toxicity were measured.

Results And Limitations: Sixty-one cycles of Ac-225-PSMA-617 (median number of cycles 2; median activity 9 MBq) were administered. A PSA decline of ≥50% was achieved in 17/26 patients. The median PSA-PFS, cPFS, and OS periods were 3.5 (95% confidence interval [CI] 1.8-11.2), 4.1 (95% CI 3-14.8), and 7.7 (95% CI 4.5-12.1) mo, respectively. Liver metastases were associated with shorter PSA-PFS (median 1.9 vs 4.0 mo; p = 0.02), cPFS (median 1.8 vs 5.2 mo; p = 0.001), and OS (median 4.3 vs 10.4 mo; p = 0.01). Hematological grade 3/4 toxicities were anemia (35%), leucopenia (27%), and thrombocytopenia (19%). All patients experienced grade 1/2 xerostomia. Two and six patients stopped due to hematological toxicity and xerostomia, respectively. A limitation is the retrospective design.

Conclusions: Ac-225-PSMA-617 showed measurable antitumor effect after Lu-177-PSMA failure in late-stage mCRPC. Grade 3/4 hematological side effects were observed in up to one-third of patients, and xerostomia led to treatment halt in a relevant number of patients.

Patient Summary: Ac-225-labeled prostate-specific membrane antigen (PSMA)-617 therapy showed substantial antitumor effect in late metastatic castration-resistant prostate cancer after Lu-177-PSMA failure. However, dry mouth is a common side effect that caused about a quarter of patients to stop therapy.
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http://dx.doi.org/10.1016/j.eururo.2020.11.013DOI Listing
March 2021

No detrimental effect of a positive family history on postoperative upgrading and upstaging in men with low risk and favourable intermediate-risk prostate cancer: implications for active surveillance.

World J Urol 2020 Oct 13. Epub 2020 Oct 13.

Department of Urology, School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, Ismaninger Strasse 22, 81675, Munich, Germany.

Purpose: To assess whether a first-degree family history or a fatal family history of prostate cancer (PCa) are associated with postoperative upgrading and upstaging among men with low risk and favourable intermediate-risk (FIR) PCa and to provide guidance on clinical decision making for active surveillance (AS) in this patient population.

Methods: Participants in the German Familial Prostate Cancer database diagnosed from 1994 to 2019 with (1) low risk (clinical T1c-T2a, biopsy Gleason Grade Group (GGG) 1, PSA < 10 ng/ml), (2) Gleason 6 FIR (clinical T1c-T2a, GGG 1, PSA 10-20 ng/ml), and (3) Gleason 3 + 4 FIR (clinical T1c-T2a, GGG 2, PSA < 10 ng/ml) PCa who were subsequently treated with radical prostatectomy (RP) were analysed for upgrading, defined as postoperative GGG 3 tumour or upstaging, defined as pT3-pT4 or pN1 disease at RP. Logistic regression analysis was used to assess whether PCa family history was associated with postoperative upgrading or upstaging.

Results: Among 4091 men who underwent RP, mean age at surgery was 64.4 (SD 6.7) years, 24.7% reported a family history, and 3.4% a fatal family history. Neither family history nor fatal family history were associated with upgrading or upstaging at low risk, Gleason 6 FIR, and Gleason 3 + 4 FIR PCa patients.

Conclusion: Results from the current study indicated no detrimental effect of family history on postoperative upgrading or upstaging. Therefore, a positive family history or fatal family history of PCa in FIR PCa patients should not be a reason to refrain from AS in men otherwise suitable.
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http://dx.doi.org/10.1007/s00345-020-03485-5DOI Listing
October 2020

[Interdisciplinary recommendations for the treatment of advanced metastatic renal cell carcinoma].

Aktuelle Urol 2020 Dec 7;51(6):572-581. Epub 2020 Oct 7.

Medizinische Hochschule Hannover, Urology, Hannover.

Due to novel therapies, the prognosis of patients with metastatic renal cell carcinoma (mRCC) has improved. A median overall survival of more than two years is a realistic goal. Immunotherapy combinations with checkpoint inhibitors or checkpoint inhibitors and the tyrosine kinase inhibitor axitinib are new first-line options.Sunitinib, pazopanib, tivozanib and the combination of bevacizumab + interferon alpha are approved for first-line therapy regardless of the progression risk score. The use of both the combination of nivolumab + ipilimumab and cabozantinib is restricted to intermediate and high-risk patients. In this subgroup, the immunotherapy combination was more effective in terms of overall survival compared with sunitinib. Temsirolimus is only approved for high-risk patients.Sunitinib and pazopanib can also be applied as second-line options - for pazopanib the use is restricted to the event of cytokine failure. Nivolumab and cabozantinib demonstrated superior overall survival compared with everolimus. Furthermore, the combination of lenvatinib + everolimus and axitinib are approved treatment options in the second-line and further settings. Everolimus has been replaced in the second-line setting by these new options.The question regarding the optimal sequence is still unanswered.The purpose of an interdisciplinary expert meeting was to debate which criteria should influence treatment. The members discussed several aspects of treating patients with advanced or metastatic RCC. As in previous years, the experts intended to provide recommendations for clinical practice. The results are presented in this publication.
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http://dx.doi.org/10.1055/a-1252-1780DOI Listing
December 2020

KLK3 and TMPRSS2 for molecular lymph-node staging in prostate cancer patients undergoing radical prostatectomy.

Prostate Cancer Prostatic Dis 2020 Sep 25. Epub 2020 Sep 25.

Department of Urology, Rechts der Isar Medical Center, Technical University of Munich, Munich, Germany.

Background: Lymph-node (LN) metastasis in prostate cancer (PC) is a main risk factor for tumor recurrence after radical prostatectomy (RP). Molecular analysis facilitates detection of small-volume LN metastases with higher sensitivity than histopathology. We aimed to prospectively evaluate six candidate gene markers for detection of pelvic LN metastases and to determine their ability to predict biochemical recurrence-free survival (bRFS) in patients treated with RP.

Methods: The expression of kallikrein 2, 3, and 4 (KLK2, KLK3, and KLK4), prostate-specific membrane antigen (PSMA), transmembrane serine protease 2 (TMPRSS2) and transient receptor potential cation channel subfamily M member 8 (TRPM8) was assessed using qPCR. We analyzed LNs from 111 patients (intermediate PC, n = 32 (29%); high-risk PC, n = 79 (71%)) who underwent RP and extended pelvic lymph-node dissection without neoadjuvant treatment.

Results: Overall, 2411 LNs were examined by molecular and histopathologic examination. Histopathology detected 69 LN metastases in 28 (25%) patients. KLK2 and KLK3 diagnostically performed best and classified all pN1-patients correctly as molecular node-positive (molN1/pN1). The concordance on LN level was best for KLK3 (96%). KLK2, KLK3, KLK4, PSMA, TMPRSS2, and TRPM8 reclassified 27 (24%), 32 (29%), 29 (26%), 8 (7%), 13 (12%), and 23 (21%) pN0-patients, respectively, as node-positive (pN0/molN1). On multivariable cox regression analysis molecular LN status (molN1 vs. molN0) using KLK3 (HR 4.0, p = 0.04) and TMPRSS2 (HR 5.1, p = 0.02) were independent predictors of bRFS. Median bRFS was shorter in patients with only molecular positive LNs (molN1/pN0) for KLK3 (24 months, p = 0.001) and for TMPRSS2 (12 months, p < 0.001) compared to patients with negative nodes (molN0/pN0) (median bRFS not reached).

Conclusions: For diagnostic purposes, KLK3 showed highest concordance with histopathology for detection of LN metastases in PC patients undergoing RP. For prognostic purposes, KLK3 and TMPRSS2 expression were superior to histopathologic LN status and other transcripts tested for molecular LN status. We suggest a combined KLK3/TMPRSS2 panel as a valuable diagnostic and prognostic tool for molecular LN analysis.
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http://dx.doi.org/10.1038/s41391-020-00283-3DOI Listing
September 2020

Functional Outcome and Complications following Ileal Neobladder Reconstruction in Male Patients without Tumor Recurrence. More than 35 Years of Experience from a Single Center.

J Urol 2021 Jan 28;205(1):174-182. Epub 2020 Aug 28.

Department of Urology, Klinikum Heidenheim, Heidenheim, Germany.

Purpose: There is a lack of data on true long-term functional outcome of orthotopic bladder substitution. The primary study objective was to report our 35-year clinical experience.

Materials And Methods: Since October 1985, 259 male patients from a large single center radical cystectomy series with complete followup of more than 60 months (median 121, range 60-267) without recurrence, irradiation or undiversion that might have affected the functional outcome, were included.

Results: Median age at radical cystectomy and at survey was 63 (range 23-81) and 75 (range 43-92) years, respectively. Overall 87% of patients voided spontaneously and residual-free. This rate decreased with increasing age at the time of surgery (less than 50 years old 94%, 70 years old or older 82%). Overall day/nighttime continence rates were 90%/82%. These rates decreased with increasing age at the time of surgery from 100%/88% to 87%/80%. The overall pad-free rate was 71%/47%. Bicarbonate use decreased from 51% (5 years) to 19% (25 years). Patients with a followup of more than 20 years had the lowest rate of residual urine and clean intermittent catheterization (0.0%) as well as use of more than 1 pad at daytime/nighttime (6.3%/12.5%) and mucus obstruction (0.0%). Serum creatinine showed only the age related increase. The surgical complication rate was 27% and correlated inversely with functional results (chi-squared 11.227, p <0.005), even when the younger age at the time of surgery (younger than 60 years) was related to higher rates of surgical complications (chi-squared 6.80, p <0.05).

Conclusions: The ileal neobladder represents an excellent long-term option for urinary diversion with an acceptable complication rate.
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http://dx.doi.org/10.1097/JU.0000000000001345DOI Listing
January 2021

[68Ga-PSMA-11 PET/mpMRI for local detection of primary prostate cancer in men with a negative prior biopsy].

Aktuelle Urol 2021 Apr 27;52(2):143-148. Epub 2020 Aug 27.

Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München.

Introduction And Objective:  Multiparametric MRI (mpMRI) represents the current gold standard for the detection of primary prostate cancer (PC) after a negative biopsy. PSMA PET imaging has been introduced in the diagnostic work-up of PC with high accuracy, but is currently mainly utilised in the setting of biochemical recurrence. This study aimed to determine the efficacy of combined Ga-PSMA-11 PET/mpMRI imaging to detect PC in patients with previously negative prostate biopsies.

Methods:  A total of 57 patients who had undergone at least one prior negative prostate biopsy were included in this retrospective analysis. All patients underwent Ga-PSMA-11 PET/mpMRI imaging of the prostate. mpMRI was evaluated according to the PIRADS classification system and Ga-PSMA-11 PET was rated on a 5-point Likert scale (1: PC highly unlikely; 2: PC unlikely; 3: presence of PC is equivocal; 4: PC likely; 5: PC highly likely). All patients received a systematic random biopsy as well as a targeted transrectal biopsy of lesions suspicious on imaging. Imaging and histological biopsy outcomes were compared on a per-patient basis.

Results:  In the histological analysis, 35/57 (61.4 %) patients harboured PC lesions. In patients with biopsy-proven PC, 21/35 (60.0 %) had a PI-RADS 4 or 5 lesion on mpMRI and 28 /35 (80.0 %) had a PET rating of 4 or 5. Combined Ga-PSMA-11 PET/mpMRI missed only one patient with a Gleason score (GS) 7a tumour (rating of 1 or 2 in both PET and mpMRI). Limitations include the retrospective analysis as well as possible false negative biopsy results even in a fusion biopsy setting.

Conclusion:  In this initial analysis, the combined Ga-PSMA-11 PET/mpMRI proved to be a valuable imaging tool to guide prostate biopsies for the detection of PC in patients with a negative prior biopsy. In this approach, Ga-PSMA-11 PET and mpMRI show partially complementary findings that enhance the detection of PC lesions.
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http://dx.doi.org/10.1055/a-1198-2305DOI Listing
April 2021

Clinical Practice Guidelines for Bladder Cancer: A Systematic Review and Meta-Analysis Using the AGREE II Instrument.

Urol Int 2021 21;105(1-2):31-40. Epub 2020 Aug 21.

Department of Urology, Rechts der Isar Medical Center, Technical University of Munich, Munich, Germany.

Context: Numerous health care organizations have established guidelines on diagnosis and treatment of bladder cancer. However, the lack of a standardized guideline development approach results in considerable differences of the guidelines' methodological quality.

Objective: To assess the methodological quality of all relevant clinical practice guidelines (CPGs) for urinary bladder cancer and provide a reference for clinicians in choosing guidelines of high methodological quality.

Evidence Acquisition: A systematic literature search was conducted in Medline via PubMed, 4 CPG databases, and 7 databases of interdisciplinary organizations. CPGs for non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) with the topics screening, pathology, diagnosis, treatment, and aftercare published in English language between 2012 and 2018 were included. The CPG quality was analyzed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument.

Evidence Synthesis: A total of 16 CPGs were included for the quality appraisal. Because of predefined criteria, 5 CPGs were "strongly recommended" (American Urological Association NMIBC, European Association of Urology [EAU] NMIBC, EAU MIBC, National Institute for Health and Care Excellence, and National Comprehensive Cancer Network), 4 CPGs were "weakly recommended" and 7 CPGs were "not recommended."

Conclusions: The methodological quality of bladder cancer guidelines is diverse. Considering the rapid development of new therapies (e.g., immune checkpoint inhibitors), "living guidelines" of high methodological quality, such as the EAU NMIBC or MIBC guideline, will become more relevant in the future guideline's landscape.
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http://dx.doi.org/10.1159/000509431DOI Listing
August 2020

Clinical Practice Guidelines for Bladder Cancer: A Systematic Review and Meta-Analysis Using the AGREE II Instrument.

Urol Int 2021 21;105(1-2):31-40. Epub 2020 Aug 21.

Department of Urology, Rechts der Isar Medical Center, Technical University of Munich, Munich, Germany.

Context: Numerous health care organizations have established guidelines on diagnosis and treatment of bladder cancer. However, the lack of a standardized guideline development approach results in considerable differences of the guidelines' methodological quality.

Objective: To assess the methodological quality of all relevant clinical practice guidelines (CPGs) for urinary bladder cancer and provide a reference for clinicians in choosing guidelines of high methodological quality.

Evidence Acquisition: A systematic literature search was conducted in Medline via PubMed, 4 CPG databases, and 7 databases of interdisciplinary organizations. CPGs for non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) with the topics screening, pathology, diagnosis, treatment, and aftercare published in English language between 2012 and 2018 were included. The CPG quality was analyzed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument.

Evidence Synthesis: A total of 16 CPGs were included for the quality appraisal. Because of predefined criteria, 5 CPGs were "strongly recommended" (American Urological Association NMIBC, European Association of Urology [EAU] NMIBC, EAU MIBC, National Institute for Health and Care Excellence, and National Comprehensive Cancer Network), 4 CPGs were "weakly recommended" and 7 CPGs were "not recommended."

Conclusions: The methodological quality of bladder cancer guidelines is diverse. Considering the rapid development of new therapies (e.g., immune checkpoint inhibitors), "living guidelines" of high methodological quality, such as the EAU NMIBC or MIBC guideline, will become more relevant in the future guideline's landscape.
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http://dx.doi.org/10.1159/000509431DOI Listing
August 2020

Single-institutional outcome-analysis of low-dose stereotactic body radiation therapy (SBRT) of adrenal gland metastases.

BMC Cancer 2020 Jun 8;20(1):536. Epub 2020 Jun 8.

Department of Radiation Oncology, Technical University of Munich (TUM), Ismaninger Straße 22, Munich, Germany.

Background: Adrenal gland metastases are a common diagnostic finding in various tumor diseases. Due to the increased use of imaging methods, they are diagnosed more frequently, especially in asymptomatic patients. SBRT has emerged as a new, alternative treatment option in the field of radiation oncology. In the past, it was often used for treating inoperable lung, liver, prostate, and brain tumors. Meanwhile, it is also an established keystone in the treatment of oligometastatic diseases. This retrospective study aims to evaluate the effect of low-dose SBRT in patients with adrenal metastases.

Methods: We analyzed a group of 31 patients with 34 adrenal gland lesions treated with low-dose SBRT between July 2006 and July 2019. Treatment-planning was performed through contrast-enhanced CT, followed by image-guided stereotactic radiotherapy using cone-beam CT. The applied cumulative median dose was 35 Gy; the median single dose was 7 Gy. We focused on local control (LC), progression-free survival (PFS), overall survival (OS), as well as acute and late toxicity.

Results: Seven adrenal gland metastases (20.6%) experienced local failure, 80.6% of the patients faced a distant progression. Fourteen patients were still alive. Median follow-up for all patients was 9.8 months and for patients alive 14.4 months. No treatment-related side-effects >grade 2 occurred. Of all, 48.4% suffered from acute gastrointestinal disorders; 32.3% reported acute fatigue, throbbing pain in the renal area, and mild adrenal insufficiency. Altogether, 19.4% of the patients faced late-toxicities, which were as follows: Grade 1: 12.9% gastrointestinal disorders, 3.2% fatigue, Grade 2: 9.7% fatigue, 6.5% headache, 3.2% loss of weight. The 1-year OS and probability of LF were 64 and 25.9%, respectively.

Conclusion: Low-dose SBRT has proven as an effective and safe method with promising outcomes for treating adrenal metastases. There appeared no high-grade toxicities >grade 2, and 79.4% of treated metastases were progression-free. Thus, SBRT should be considered as a therapy option for adrenal metastases as an individual therapeutic concept in the interdisciplinary discussion as an alternative to surgical or systemic treatment.
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http://dx.doi.org/10.1186/s12885-020-07030-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282163PMC
June 2020

A CT-based radiomics model to detect prostate cancer lymph node metastases in PSMA radioguided surgery patients.

Eur J Nucl Med Mol Imaging 2020 12 28;47(13):2968-2977. Epub 2020 May 28.

Department of Radiation Oncology, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich (TUM), Ismaninger Straße 22, 81675, Munich, Germany.

Purpose: In recurrent prostate carcinoma, determination of the site of recurrence is crucial to guide personalized therapy. In contrast to prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) imaging, computed tomography (CT) has only limited capacity to detect lymph node metastases (LNM). We sought to develop a CT-based radiomic model to predict LNM status using a PSMA radioguided surgery (RGS) cohort with histological confirmation of all suspected lymph nodes (LNs).

Methods: Eighty patients that received RGS for resection of PSMA PET/CT-positive LNMs were analyzed. Forty-seven patients (87 LNs) that received inhouse imaging were used as training cohort. Thirty-three patients (62 LNs) that received external imaging were used as testing cohort. As gold standard, histological confirmation was available for all LNs. After preprocessing, 156 radiomic features analyzing texture, shape, intensity, and local binary patterns (LBP) were extracted. The least absolute shrinkage and selection operator (radiomic models) and logistic regression (conventional parameters) were used for modeling.

Results: Texture and shape features were largely correlated to LN volume. A combined radiomic model achieved the best predictive performance with a testing-AUC of 0.95. LBP features showed the highest contribution to model performance. This model significantly outperformed all conventional CT parameters including LN short diameter (AUC 0.84), LN volume (AUC 0.80), and an expert rating (AUC 0.67). In lymph node-specific decision curve analysis, there was a clinical net benefit above LN short diameter.

Conclusion: The best radiomic model outperformed conventional measures for detection of LNM demonstrating an incremental value of radiomic features.
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http://dx.doi.org/10.1007/s00259-020-04864-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680305PMC
December 2020

PSMA-PET/CT-based Lymph Node Atlas for Prostate Cancer Patients Recurring After Primary Treatment: Clinical Implications for Salvage Radiation Therapy.

Eur Urol Oncol 2021 Feb 22;4(1):73-83. Epub 2020 May 22.

Department of Radiation Oncology, Technical University Munich (TUM), Munich, Germany; Department of Radiation Sciences (DRS), Institute of Radiation Medicine (IRM), Helmholtz Zentrum München, Munich, Germany; Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partner Site Munich, Munich, Germany.

Background: Many patients experience recurrence of prostate cancer after radical prostatectomy.

Objective: The aim of this study was to visually analyze typical patterns of lymph node (LN) involvement for prostate cancer (PC) patients with biochemical recurrence after radical prostatectomy and lymphadenectomy by creating a color-coded heat map using gallium-68 prostate-specific membrane antigen positron emission tomography (Ga-PSMA-PET) imaging. Further, we evaluated which LNs were covered by the Radiation Therapy Oncology Group (RTOG) clinical target volume (CTV) contouring guidelines.

Design, Setting, And Participants: A total of 1653 Ga-PSMA-PET/computed tomography (CT) datasets were screened retrospectively. After meeting the eligibility criteria, 233 patients with 799 LN metastases were included in our study.

Outcome Measurements And Statistical Analysis: We created a comprehensive three-dimensional color-coded LN atlas. Further, the coverage of LN metastases by RTOG CTV was assessed and stratification for risk factors was performed.

Results And Limitations: In the overall, mainly high risk, collective, complete coverage by the standard RTOG CTV was accomplished in 31.0% of all LN metastases. The vast majority of uncovered LNs are situated in the para-aortal, pararectal, paravesical, preacetabular, presacral, and inguinal regions. Concerning examined stratification factors, prostate-specific antigen (PSA) levels at the time of PET/CT imaging had the highest predictive value for extrapelvic metastatic LN spread. Every increase of 1 ng/mL in PSA raises the risk of metastases outside the CTV by a factor of 1.43.

Conclusions: We developed the first LN atlas for patients with recurrent PC using a heat map technique, in order to illustrate hot spots of LN recurrence. The vast majority of detected LNs are not covered by a standard CTV as recommended by the RTOG. Application of the standard RTOG CTV for pelvic irradiation in the salvage setting for high-risk PC patients seems to be inappropriate.

Patient Summary: We visualized typical lymph node recurrence sites for patients after prostate cancer surgery.
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http://dx.doi.org/10.1016/j.euo.2020.04.004DOI Listing
February 2021

[Vorwort].

Oncol Res Treat 2020 19;43 Suppl 2. Epub 2020 May 19.

Urologische Klinik und Poliklinik der Technischen Universität München, Universitätsklinikum rechts der Isar, München, Deutschland.

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http://dx.doi.org/10.1159/000507053DOI Listing
January 2021

Final results of the PräVAC trial: prevention of wound complications following inguinal lymph node dissection in patients with penile cancer using epidermal vacuum-assisted wound closure.

World J Urol 2021 Feb 5;39(2):613-620. Epub 2020 May 5.

Department of Urology, Rechts der Isar Medical Center, Technical University of Munich, Ismaningerstr. 22, 81375, Munich, Germany.

Purpose: Inguinal lymphadenectomy in penile cancer is associated with a high rate of wound complications. The aim of this trial was to prospectively analyze the effect of an epidermal vacuum wound dressing on lymphorrhea, complications and reintervention in patients with inguinal lymphadenectomy for penile cancer.

Patients And Methods: Prospective, multicenter, randomized, investigator-initiated study in two German university hospitals (2013-2017). Thirty-one patients with penile cancer and indication for bilateral inguinal lymph node dissection were included and randomized to conventional wound care on one side (CONV) versus epidermal vacuum wound dressing (VAC) on the other side.

Results: A smaller cumulative drainage fluid volume until day 14 (CDF) compared to contralateral side was observed in 15 patients (CONV) vs. 16 patients (VAC), with a median CDF 230 ml (CONV) vs. 415 ml (VAC) and a median maximum daily fluid volume (MDFV) of 80 ml (CONV) vs. 110 ml (VAC). Median time of indwelling drainage: 7 days (CONV) vs. 8 days (VAC). All grade surgery-related complications were seen in 74% patients (CONV) vs. 74% patients (VAC); grade 3 complications in 3 patients (CONV) vs. 6 patients (VAC). Prolonged hospital stay occurred in 32% patients (CONV) vs. 48% patients (VAC); median hospital stay was 11.5 days. Reintervention due to complications occurred in 45% patients (CONV) vs. 42% patients (VAC).

Conclusions: In this prospective, randomized trial we could not observe a significant difference between epidermal vacuum treatment and conventional wound care.
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http://dx.doi.org/10.1007/s00345-020-03221-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910363PMC
February 2021

[Stereotactic body radiotherapy (SBRT) for the treatment of bone metastases in oligometastasised prostate cancer].

Aktuelle Urol 2020 06 8;51(3):265-270. Epub 2020 Apr 8.

Klinikum rechts der Isar der Technischen Universität München, Klinik für RadioOnkologie und Strahlentherapie, München.

Background: Local radiation therapy of metastases in prostate cancer patients has become increasingly important in recent years. In order to improve the evaluation of the outcome, we have studied oligometastatic prostate cancer patients who were treated with stereotactic radiation therapy.

Patients And Methods: 24 patients with a total of 30 bone metastases were included in the study. We examined the response to SBRT (biochemical and imaging), as well as progression-free survival and time to start of antihormonal therapy (aHT).

Results: The mean follow-up interval after completion of SBRT was 32.7 months (1.4 - 84 months). The SBRT was well tolerated, without acute or late adverse effects. In 16 patients, the PSA value decreased from a mean of 4.58 ng/mL (0.05 - 50.25 ng/mL) before SBRT to 1.19 ng/mL (0.01 - 8.85 ng/mL) after completion of SBRT. The mean biochemical progression-free survival of these patients was 17.6 months (0.7 - 85.0 months). Six patients received aHT, either before or during SBRT. In ten patients, the aHT was initiated after a mean interval of 20.6 months (1.8 - 85.0 months) after completion of the SBRT. Another six patients were not given any aHT during the whole period of observation. In 18 of 30 metastases, there was a decrease in PSMA expression within the area of SBRT in the PSMA-PET - in accordance with a partial functional response. In five patients, PSMA hyperexpression was unchanged; in 7 patients there was no PSMA imaging for follow up. In 17 patients, distant metastasis progression was diagnosed by imaging after a mean of 16.2 months (1.6 - 40.6 months). Three patients had a local recurrence in the prostatic fossa.

Conclusion: SBRT of bone metastases in oligometastatic prostate carcinoma patients is an effective and well tolerated therapy and can help to achieve high local control in the area of the metastases as well as delay the start or the escalation of systemic therapy. Nevertheless, the high rate of progression of distant metastases shows how important correct patient selection is and that combination with aHT may be necessary.
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http://dx.doi.org/10.1055/a-1140-5646DOI Listing
June 2020

The role of fatal family history and mode of inheritance in prostate cancer for long-term outcomes following radical prostatectomy.

World J Urol 2020 Dec 11;38(12):3091-3099. Epub 2020 Mar 11.

Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Department of Urology, Munich, Germany.

Purpose: To determine whether fatal family history (FFH) or mode of inheritance in prostate cancer (PCa) has an impact on long-term outcomes following radical prostatectomy (RP).

Methods: 1076 PCa patients after RP with at least one deceased first-degree relative with PCa were included and stratified by FFH (four subgroups: fraternal, paternal, multiple, and none) and by mode of inheritance (two subgroups: male to male, non-male to male). We compared clinicopathological characteristics between subgroups with Fisher's exact or Chi-square tests. Biochemical recurrence-free survival (BRFS) and cancer-specific survival (CSS) were analyzed using the method of Kaplan and Meier. Simple and multiple Cox regression with backward elimination were performed to select prognostic factors for BRFS and CSS.

Results: Median age at surgery was 63.3 (range 35.9-79.4) years. The overall Kaplan-Meier estimated BRFS rate at 10 and 15 years was 65.6% and 57.0%, respectively. The overall Kaplan-Meier estimated CSS rate at 10 and 15 years was 98.1% and 95.7%, respectively. Neither FFH nor mode of inheritance were factors associated with worse BRFS. However, in multiple Cox regression, paternal FFH was an important prognostic factor for a better CSS (HR 0.19, CI 0.05-0.71, p = 0.014) compared to non-FFH.

Conclusion: FFH and mode of inheritance do not seem to be prognostic factors of worse long-term outcomes following RP. Rather, a paternal FFH was associated with a better CSS; however, the reasons remain unclear. Nevertheless, patients after RP and FFH could be reassured that their own PCa diagnosis is not associated with a worse long-term outcome.
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http://dx.doi.org/10.1007/s00345-020-03147-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716855PMC
December 2020

Molecular lymph node staging for bladder cancer patients undergoing radical cystectomy with pelvic lymph node dissection.

Urol Oncol 2020 07 4;38(7):639.e11-639.e19. Epub 2020 Mar 4.

Technical University of Munich, School of Medicine, Rechts der Isar Medical Center, Department of Urology, Munich, Germany.

Objective: Presence of lymph node (LN) metastasis in bladder cancer (BCa) is a main risk factor for tumor recurrence after radical cystectomy (RC). Molecular analysis facilitates detection of small-volume LN metastases with higher sensitivity than standard histopathology. The aim of the present study was to establish molecular LN analysis in BCa patients undergoing RC with lymph node dissection (LND) and to determine its ability to predict tumor recurrence.

Patients And Methods: Five transcripts with overexpression in BCa (FXYD3, KRT17, KRT20, SPINK1, UPKII) were evaluated for molecular LN analysis. We included 76 BCa patients from the prospective, randomized surgical phase-III trial (LEA AUO AB 25/02, NCT01215071) investigating extended vs. limited LND at RC. The primary endpoint was recurrence-free survival (RFS). As control, 136 LNs from 45 patients without BCa were analyzed to determine a threshold for pathologic gene expression.

Results: About 1,319 LNs were investigated with molecular and histopathologic examination. Histopathology detected 39 LN metastases in 17 (22%) patients. Of the tested genes FXYD3 performed best and classified all pN+-patients correctly as node-positive (pN+/molN+). In addition, FXYD3 reclassified 43 histopathologic negative LNs and 7 (9%) pN0-patients as molecular node-positive (pN0/molN+). Molecular and histopathologic LN status (pN0/molN0 vs. pN0/molN+ vs. pN+/molN+) was significantly associated with locally advanced disease (P = 0.006) and poor RFS (P < 0.001). Median RFS was not reached in LN-negative patients (pN0/molN0), 45 months (95%CI 8-83) in exclusively molecular positive patients (pN0/molN+) and 9 months (95%CI 5-13) in patients with histopathologic and molecular positive LNs (pN+/molN+).

Conclusions: Molecular LN analysis with FXYD3 identified additional LN metastases in histopathologic negative LNs and identified patients with elevated risk of tumor recurrence after RC. Thus, molecular LN analysis improves LN staging and might serve as a tool to guide adjuvant treatment.
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http://dx.doi.org/10.1016/j.urolonc.2020.01.018DOI Listing
July 2020

Radiation therapy before radical cystectomy combined with immunotherapy in locally advanced bladder cancer - study protocol of a prospective, single arm, multicenter phase II trial (RACE IT).

BMC Cancer 2020 Jan 3;20(1). Epub 2020 Jan 3.

Department of Urology, School of Medicine, Rechts der Isar Medical Center, Technical University of Munich, Ismaninger Straße 22, 81675, Munich, Germany.

Background: Patients with locally advanced bladder cancer (cT3/4 cN0/N+ cM0) have a poor prognosis despite radical surgical therapy and perioperative chemotherapy. Preliminary data suggest that the combination of radiation and immunotherapy does not lead to excess toxicity and may have synergistic (abscopal) anti-tumor effects. We hypothesize that the combined preoperative application of the PD-1 checkpoint-inhibitor Nivolumab with concomitant radiation therapy of the bladder and pelvic region followed by radical cystectomy with standardized lymphadenectomy is safe and feasible and might improve outcome for patients with locally advanced bladder cancer.

Methods: Study design: "RACE IT" (AUO AB 65/18) is an investigator initiated, prospective, multicenter, open, single arm phase II trial sponsored by Technical University Munich. Study drug and funding are provided by the company Bristol-Myers Squibb. Study treatment: Patients will receive Nivolumab 240 mg i.v. every 2 weeks for 4 cycles preoperatively with concomitant radiation therapy of bladder and pelvic region (max. 50.4 Gy). Radical cystectomy with standardized bilateral pelvic lymphadenectomy will be performed between week 11-15. Primary endpoint: Rate of patients with completed treatment consisting of radio-immunotherapy and radical cystectomy at the end of week 15. Secondary endpoints: Acute and late toxicity, therapy response and survival (1 year follow up). Main inclusion criteria: Patients with histologically confirmed, locally advanced bladder cancer (cT3/4, cN0/N+), who are ineligible for neoadjuvant, cisplatin-based chemotherapy or who refuse neoadjuvant chemotherapy. Main exclusion criteria: Patients with metastatic disease (lymph node metastasis outside pelvis or distant metastasis) or previous chemo-, immune- or radiation therapy. Planned sample size: 33 patients, interim analysis after 11 patients.

Discussion: This trial aims to evaluate the safety and feasibility of the combined approach of preoperative PD-1 checkpoint-inhibitor therapy with concomitant radiation of bladder and pelvic region followed by radical cystectomy. The secondary objectives of therapy response and survival are thought to provide preliminary data for further clinical evaluation after successful completion of this trial. Recruitment has started in February 2019.

Trial Registration: Protocol Code RACE IT: AB 65/18; EudraCT: 2018-001823-38; Clinicaltrials.gov: NCT03529890; Date of registration: 27 June 2018.
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http://dx.doi.org/10.1186/s12885-019-6503-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942254PMC
January 2020

Impact of a Changing Population Structure and Clustering of Cancer in Prostate Cancer Patients Depending on a First-Degree Family History.

Urol Int 2020 20;104(3-4):222-229. Epub 2019 Dec 20.

Department of Urology, Faculty of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany,

Introduction: In the last century, there have been major changes within the population structure in Germany. The aim of this study was to determine the impact of a changing population structure on identification of familial prostate cancer (PCa), and to investigate how many and which types of other cancers have occurred in patients and their first-degree relatives.

Materials And Methods: A total of 19,540 patients were evaluated in a prospectively collected PCa family database and divided into four birth cohorts: 1925-1934 (cohort A), 1935-1944 (cohort B), 1945-1954 (cohort C), and 1955-1964 (cohort D). Other primary cancers and cancers of first-degree relatives were evaluated.

Results: The percentage of PCa patients with ≥2 sons declined (A: 28.9% to D: 21.6%). The percentage of patients whose fathers lived for ≥65 years increased (B: 64.2% to D: 73.0%). Malignancies of the skin, the urinary tract, and the lymphoid/hematopoietic tissue were more common in patients with a positive first-degree PCa family history and their first-degree relatives. Additionally, first-degree relatives reported more often neoplasms of respiratory/intrathoracic organs and the female breast.

Conclusions: A small family size, an early deceased father, and a high number of sporadic cases complicate the identification of familial PCa patients. Thus, a detailed family history should also include unaffected first-degree relatives to avoid any misclassification. Findings of other primary cancers in patients and their relatives warrant further investigation.
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http://dx.doi.org/10.1159/000504789DOI Listing
January 2021

Adjuvant versus early salvage radiotherapy: outcome of patients with prostate cancer treated with postoperative radiotherapy after radical prostatectomy.

Radiat Oncol 2019 Nov 11;14(1):198. Epub 2019 Nov 11.

Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich (TUM), Munich, Germany.

Background: Adjuvant (ART) and salvage radiotherapy (SRT) are two common concepts to enhance biochemical relapse free survival (BCRFS) in patients with prostate cancer (PC). We analyzed differences in outcome between ART and SRT in patients with steep decline of PSA-levels after surgery to compare outcome.

Methods: We evaluated 253 patients treated with postoperative RT with a median age of 66 years (range 42-85 years) treated between 2004 and 2014. Patients with additive radiotherapy due to PSA persistence and patients in the SRT group, who did not achieve a postoperative PSA level <0.1 ng/mL were excluded. Hence, data of 179 patients was evaluated. We used propensity score matching to build homogenous groups. A Cox regression model was used to determine differences between treatment options. Median follow-up was 32.5 months (range 1.4-128.0 months).

Results: Early SRT at PSA levels <0.3 ng/mL was associated with significant longer BCRFS than late SRT (HR: 0.32, 95%-CI: 0.14-0.75, p = 0.009). Multiple Cox regression showed pre-RT PSA level, tumor stage, and Gleason score as predictive factors for biochemical relapse. In the overall group, patients treated with either ART or early SRT showed no significant difference in BCRFS (HR: 0.17, 95%-CI: 0.02-1.44, p = 0.1). In patients with locally advanced PC (pT3/4) BCRFS was similar in both groups as well (HR: 0.21, 95%-CI:0.02-1.79, p = 0.15).

Conclusion: For patients with PSA-triggered follow-up, close observation is essential and early initiation of local treatment at low PSA levels (<0.3 ng/mL) is beneficial. Our data suggest, that SRT administered at early PSA rise might be equieffective to postoperative ART in patients with locally advanced PC. However, the individual treatment decision must be based on any adverse risk factors and the patients' postoperative clinical condition.

Study Registration: The present work is approved by the Ethics Commission of the Technical University of Munich (TUM) and is registered with the project number 320/14.
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http://dx.doi.org/10.1186/s13014-019-1391-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849377PMC
November 2019

Impact of Resection Technique on Perioperative Outcomes and Surgical Margins after Partial Nephrectomy for Localized Renal Masses: A Prospective Multicenter Study.

J Urol 2020 03 14;203(3):496-504. Epub 2019 Oct 14.

Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.

Purpose: The impact of resection technique on partial nephrectomy outcomes is controversial. The aim of this study was to evaluate the pattern of resection techniques during partial nephrectomy and the impact on perioperative outcomes, acute kidney injury, positive surgical margins and the achievement of the Trifecta (negative surgical margins, no perioperative Clavien-Dindo grade 2 or greater surgical complications and no postoperative acute kidney injury).

Materials And Methods: We prospectively collected data on consecutive patients with cT1-2N0M0 renal masses treated with partial nephrectomy at a total of 16 referral centers from September 2014 to March 2015. After partial nephrectomy the resection technique was classified by the surgeon as enucleation, enucleoresection or resection according to the SIB (Surface-Intermediate-Base) margin scores 0 to 2, 3 or 4 and 5, respectively. Multivariable logistic regression analysis was done to evaluate the potential impact of the resection technique on postoperative surgical complications, positive surgical margins, acute kidney injury and Trifecta achievement.

Results: Overall 507 patients were included in analysis. The resection technique was classified as enucleation in 266 patients (52%), enucleoresection in 150 (30%) and resection in 91 (18%). The resection technique (enucleoresection vs enucleation and resection) was the only significant predictor of positive surgical margins. Tumor complexity, surgical approach (open and laparoscopic vs robotic) and resection technique (enucleoresection vs enucleation) were significant predictors of Clavien-Dindo grade 2 or greater surgical complications. The surgical approach (open and laparoscopic vs robotic), the resection technique (enucleoresection vs enucleation) and warm ischemia time were significantly associated with postoperative acute kidney injury and Trifecta achievement.

Conclusions: Resection techniques significantly impact surgical complications, early functional outcomes and positive surgical margins after partial nephrectomy of localized renal masses.
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http://dx.doi.org/10.1097/JU.0000000000000591DOI Listing
March 2020

[What causes prostate cancer: patient-perceived causes].

Aktuelle Urol 2021 Apr 8;52(2):136-142. Epub 2019 Oct 8.

Klinikum rechts der Isar, Technische Universität München, Klinik und Poliklinik für Urologie, München.

Background:  Psychosocial distress caused by prostate cancer (PCa) can persist in patients for years after treatment. A possible factor in this context is the subjectively perceived cause of the disease, which can have a significant influence on the experience of distress, therapy adherence and preventive behaviour. The aim of this study was to record subjective reasons for PCa in long-term survivors and to investigate associated factors.

Material And Methods:  PCa survivors from the national research project "Familial Prostate Cancer" were included in the study. As part of the annual postal follow-up questionnaire, PCa survivors were asked about subjectively perceived causes of their PCa. Responses were assigned to 18 possible categories. In addition, the association between the subjectively perceived causes of PCa and secondary tumours, a positive family history of tumour diseases and sociodemographic factors was investigated.

Results:  Of the 9 047 PCa survivors surveyed, 4 054 (44.8 %) provided information on the subjectively perceived causes of their PCa and were included in this analysis. The mean time since diagnosis was 10.1 years with a mean age of 63.1 years at diagnosis. The most frequent responses were "don't know" (31.8 %), genetics (30.1 %) and stress (18.5 %). Age, the most important risk factor for PCa, was rarely mentioned (2.5 %). In addition to these responses, unusual non-evidence-based reasons were also reported. Men with a positive family history of PCa cited genetics as the cause of their disease about 4 times more frequently than sporadic cases. This proportion increased with the number of affected family members. PCa survivors aged ≤ 65 years at diagnosis indicated stress as the cause of their PCa approximately 2 times more often than men who were older than 65 years at PCa diagnosis.

Conclusion:  Most men surveyed reported non-evidence-based causes of their PCa. Preventive programs should address the evidence-based causes more distinctly and with a high visibility. Due to the significance of lay illness beliefs for the experience of distress and the adherence to treatment, the patient's subjective cause of disease should be surveyed and considered by the urologist in charge.
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http://dx.doi.org/10.1055/a-1005-6273DOI Listing
April 2021