Publications by authors named "Georgios Gakis"

152 Publications

Receptor Activator of NF Kappa B (RANK) Expression Indicates Favorable Prognosis in Patients with Muscle-invasive Bladder Cancer.

Eur Urol Focus 2021 May 4. Epub 2021 May 4.

Department of Urology, University Hospital, Tübingen, Germany; Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Clinical Trials Unit, Studienpraxis Urologie, Nürtingen, Germany. Electronic address:

Background: Receptor activator of NF kappa B (RANK) and its ligand have an essential role in T-cell regulation and the development of bone metastases. The role of RANK expression in muscle-invasive bladder cancer (MIBC) is unknown.

Objective: To assess the relevance of RANK expression in patients with MIBC.

Design, Setting, And Participants: Expression of RANK was assessed via immunohistochemistry of benign urothelium, MIBC tissue, and lymph node metastases from 153 patients undergoing radical cystectomy. Expression data from The Cancer Genome Atlas (TCGA) cohort were analyzed for potential associations with molecular subtypes and outcome.

Outcome Measurements And Statistical Analysis: RANK expression was correlated with clinical and pathological parameters and to individual data for the clinical course of MIBC.

Results And Limitations: Expression of RANK was significantly higher in both primary tumors (p = 0.02) and lymph node metastases (p = 0.01) compared to normal urothelium. In tumor tissue, RANK expression was significantly lower in patients with locally advanced disease and lymph node involvement compared to those with organ-confined disease (p = 0.0009) and node-negative MIBC (p = 0.0002). In univariable and multivariable analyses, high expression of RANK was associated with a longer time to recurrence (p = 0.0005 and 0.01) and better cancer-specific (p = 0.0004 and 0.007) and overall survival (p = 0.002 and 0.04). High expression of RANK was associated with better outcome for patients with luminal infiltrated tumors in the TCGA cohort.

Conclusions: RANK expression is increased in bladder cancer tissue compared to benign urothelium, with higher expression in organ-defined compared to locally advanced disease. High RANK expression indicates a favorable prognosis in MIBC. The prognostic role differs in tumors of different molecular subtypes.

Patient Summary: Expression of a protein involved in bone turnover regulation (RANK) is higher in bladder cancer tissue than in benign bladder tissue. However, high levels of RANK on tumor cells indicate favorable prognosis for patients with bladder cancer that invades the muscle layer of the bladder.
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http://dx.doi.org/10.1016/j.euf.2021.04.015DOI Listing
May 2021

Utility of pT3 substaging in lymph node-negative urothelial carcinoma of the bladder: do pathologic parameters add to prognostic sub-stratification?

World J Urol 2021 Apr 21. Epub 2021 Apr 21.

Department of Urology, University Hospital, Tübingen, Germany.

Purpose: The value of bladder cancer (BC) substaging into macroscopic (pT3b) and microscopic (pT3a) perivesical fat extension in lymph node (Ln)-negative patients is controversially discussed and limited evidence for prognostic relevance of additional histopathological factors in pT3 BC exists. We evaluated the prognostic value of pT3 substaging and established pathological and clinical parameters with focus on tumor invasive front (TIF) and tumor size.

Methods: Specimens of 52 patients treated with radical cystectomy (RC) for pT3 a/b muscle-invasive BC were reviewed and re-evaluated by a pathologist specialized in uropathology. Clinical variables and standard histopathologic characteristics were assessed including TIF and tumor size. Their value as prognosticators for overall survival (OS) and recurrence-free survival (RFS) was evaluated.

Results: Mean age of patients was 67.55 years. Tumors were staged pT3a in 28 patients (53.8%) and pT3b in 24 (46.8%). Median OS was 34.51 months. Median tumor size was 3.2 cm, median TIF was 11.0 mm. Differences in OS between pT3a and pT3b were not significant (p = 0.45). Carcinoma in situ (CIS) and lymphovascular invasion (LVI) were significantly associated with pT3b tumors. Univariate analysis could not identify pathological prognosticators like TIF or tumor size for OS and RFS (p for all > 0.05).

Conclusion: No significant differences in OS or RFS were observed comparing Ln-negative pT3 BC following radical cystectomy. Additional pathologic variables like TIF could not be identified as prognosticator. Relevance of pT3 BC substaging needs reevaluation in larger prospective cohorts.
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http://dx.doi.org/10.1007/s00345-021-03697-3DOI Listing
April 2021

Primary chondrosarcoma of the penis in a young patient: A case report and review of the literature.

IJU Case Rep 2021 Jan 8;4(1):29-31. Epub 2020 Oct 8.

Urology Department Klinikum Sindelfinge-Boeblingen Sindelfingen Germany.

Introduction: Primary chondrosarcoma of the penis is rare. We present a case of primary chondrosarcoma of the penis in a young patient.

Case Presentation: A 35-year-old man presented with a painless mass at the base of his penis for the past 6 months. Incisional biopsy of the lesion revealed a chondrosarcoma. Pelvic magnetic resonance imaging and computed tomography of the thorax, abdomen, and pelvis ruled out a primary lesion in the bones and soft tissues. The patient rejected total penectomy and decided to start chemoradiotherapy followed by local tumor resection.

Conclusion: Primary chondrosarcoma of the penis is rare. Interdisciplinary management plays an important role in planning the therapy for rare tumors. A combined chemoradiation therapy can be followed by penis-preserving surgery to improve the quality of life in young patients with proximal penile tumors.
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http://dx.doi.org/10.1002/iju5.12230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784739PMC
January 2021

Re: Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma.

Authors:
Georgios Gakis

Eur Urol 2021 May 31;79(5):702. Epub 2020 Dec 31.

Department of Urology and Pediatric Urology, University Hospital of Würzburg, Julius-Maximillians University, Würzburg, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2020.12.026DOI Listing
May 2021

A Modified Neobladder Technique: The "I-Pouch" - Illustration of Surgical Approach and Tricks.

Urology 2021 Jan 26;147:318. Epub 2020 Oct 26.

Department of Urology, Eberhard-Karls-University Tübingen, Tübingen, Germany. Electronic address:

Objective: Various techniques for orthotopic neobladder (ONB) are currently used and have shown satisfactory oncological and functional outcomes. Among the relevant oncological and functional aspects for long-term follow up is the easy accessibility of the upper urinary tract in urinary diversion for endoscopic monitoring. In addition, variety exists in the amount of ileum needed to create a urinary reservoir. Depending on the ONB technique, up to 60 cm of ileum are required, and bowel dysfunction may be a consequence especially when the ileocecal valve is used for the urinary diversion. We previously reported the technique, functional and oncologic results of the I-pouch, a modified ONB made of 40 cm of ileum, combining an antirefluxive ureter implantation technique with easy access to the uretero-intestinal anastomosis. The present video is intended to illustrate key surgical steps and pitfalls during the procedure.

Methods: The technique, surgical tips, and functional results in a as compared to a institutional control group receiving conventional Studer -Pouch-procedure are outlined.

Results: In a follow up series of 33 I-pouch and 23 S-pouch patients, there were no differences according to ONB type for 30-day major- (P = .33) and minor (P = 0.96) complication rates although 90-day major (P = 0.08) and minor (P = 0.08) complication rates tended to be associated with less complications in I-pouch patients.

Conclusion: The I-pouch can be used for neobladder substitution providing easy access to the upper urinary tract, reduced demand of ileum length along with a complication profile not distinct from Studer neobladder formation.
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http://dx.doi.org/10.1016/j.urology.2020.10.017DOI Listing
January 2021

European Association of Urology Guidelines on Primary Urethral Carcinoma-2020 Update.

Eur Urol Oncol 2020 08 27;3(4):424-432. Epub 2020 Jun 27.

Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.

Context: Primary urethral carcinoma (PUC) is a rare cancer accounting for <1% of all genitourinary malignancies.

Objective: To provide updated practical recommendations for the diagnosis and management of PUC.

Evidence Acquisition: A systematic search interrogating Ovid (Medline), EMBASE, and the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews was performed.

Evidence Synthesis: Urothelial carcinoma of the urethra is the predominant histological type of PUC (54-65%), followed by squamous cell carcinoma (16-22%) and adenocarcinoma (10-16%). Diagnosis of PUC depends on urethrocystoscopy with biopsy and urinary cytology. Pathological staging and grading are based on the tumour, node, metastasis (TNM) classification and the 2016 World Health Organization grading systems. Local tumour extent and regional lymph nodes are assessed by magnetic resonance imaging, and the presence of distant metastases is assessed by computed tomography of the thorax/abdomen and pelvis. For all patients with localised distal tumours (≤T2N0M0), partial urethrectomy or urethra-sparing surgery is a valid treatment option, provided that negative intraoperative surgical margins can be achieved. Prostatic Ta-Tis-T1 PUC can be treated with repeat transurethral resection of the prostate and bacillus Calmette-Guérin. In prostatic or proximal ≥ T2N0 disease, neoadjuvant cisplatin-based chemotherapy should be considered prior to radical surgery. All patients with locally advanced disease (≥T3N0-2M0) should be discussed within a multidisciplinary team. In men with locally advanced squamous cell carcinoma, curative radiotherapy combined with radiosensitising chemotherapy can be offered for definitive treatment and genital preservation. In patients with local urethral recurrence, salvage surgery or radiotherapy can be offered. For patients with distant metastatic disease, systemic therapy based on tumour characteristics can be evaluated.

Conclusions: These updated European Association of Urology guidelines provide up-to-date guidance for the contemporary diagnosis and management of patients with suspected PUC.

Patient Summary: Primary urethral carcinoma (PUC) is a very rare, but aggressive disease. These updated European Association of Urology guidelines provide evidence-based guidance for clinicians treating patients with PUC.
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http://dx.doi.org/10.1016/j.euo.2020.06.003DOI Listing
August 2020

Transurethral en bloc submucosal hydrodissection vs conventional resection for resection of non-muscle-invasive bladder cancer (HYBRIDBLUE): a randomised, multicentre trial.

BJU Int 2020 10 10;126(4):509-519. Epub 2020 Aug 10.

Department of Urology, University Hospital of Tübingen, Tübingen, Germany.

Objective: To determine whether transurethral en bloc submucosal hydrodissection of bladder tumours (TUEB) improves the quality of the resection compared to conventional transurethral resection of bladder tumour (TURBT) in patients with non-muscle-invasive bladder cancer (NMIBC).

Patients And Methods: A randomised, multicentre trial (HYBRIDBLUE) was conducted with a superiority design. Six German academic centres participated between September 2012 and August 2015. Based on literature analysis, a sample size for accurate histopathological assessment concerning muscle invasion was assumed to be feasible in 50% (P = 0.5) of TURBT and 80% of TUEB cases. After pre-screening of a total of 305 patients, participants were allocated to two study arms: Group I: hexaminolevulinate (HAL)-guided TUEB; Group II: conventional HAL-guided TURBT. The primary endpoint was the proportion of specimens that could be reliably evaluated pathologically concerning muscle invasiveness. Secondary endpoints included rates of histopathological completeness of the resection, muscularis propria content, recurrence, and complication rates.

Results: A total of 115 patients (TUEB 56; TURBT 59) were eligible for final analysis. Adequate histopathological assessment, which included muscularis propria content and tumour margins (R0 vs R1), was present in 48/56 (86%) TUEB patients compared to 37/59 (63%; P = 0.006) in the TURBT group. R0 was confirmed in 30/56 TUEB patients (57%) and five of 59 TURBT patients (9%; P < 0.001). No complications of Grade ≥III were observed in both arms. At 3 and 12 months, three and 19 patients recurred in the TUEB group vs seven and 11 patients in the TURBT group, respectively (P = 0.33 and P = 0.08).

Conclusions: In this randomised study, TUEB was shown to be clinically safe regarding perioperative endpoints. An adequate histopathological assessment concerning muscle invasion was significantly better assessable in the TUEB arm compared to standard TURBT. This finding indicates the clinical potential for reducing the rate of early re-resections. Yet, a larger study with recurrence-free survival as the primary endpoint is needed to assess the oncological efficacy between both techniques.
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http://dx.doi.org/10.1111/bju.15150DOI Listing
October 2020

Prognostic significance of previous tonsillectomy after radical cystectomy for bladder cancer.

Scand J Urol 2020 Aug 5;54(4):297-303. Epub 2020 Jun 5.

Department of Urology, University Hospital of Würzburg, Eberhard-Karls University, Tuebingen, Germany.

To examine whether previous tonsillectomy (TE) impacts on survival after radical cystectomy (RC) for bladder cancer (BC). A total of 320 patients were staged cM0 and underwent RC for BC between 2002 and 2013. We retrospectively investigated whether patients had undergone TE prior to RC. Chi-square/Fisher-Exact test was carried out to compare clinicopathological features between the TE- and non-TE-group. Kaplan-Meier analysis with log-rank test was used to estimate recurrence-free survival (RFS) and multivariable Cox-regression analysis of risk factors of recurrence. The median follow-up was 31 months (interquartile range: 9-54). A history of TE was present in 18 of the 320 patients (5.6%). All TEs were performed for benign conditions. TE prior to RC was associated with a history of appendectomy ( = 0.045), lower age at RC ( = 0.029), tumor unifocality ( < 0.001), advanced histopathological tumor stage ( = 0.015), non-pure urothelial carcinoma ( = 0.025), lymphovascular invasion ( = 0.035) and receipt of palliative chemotherapy ( = 0.004). The 3-year RFS was 39.2% for patients with previous TE and 62.4% for those without ( = 0.008). In multivariable analysis, adjusted for all significant parameters of univariable analysis, lymph-node tumor involvement ( = 0.017), positive surgical margins ( = 0.047), tumor grade ( = 0.032), advanced tumor stage (≥pT3a;  = 0.049) and a history of TE ( = 0.021) remained independent prognosticators of recurrence. In this series, previous TE was an independent predictor of recurrence after RC for BC. Further studies are needed to assess whether TE induces immunological alterations that might exert adverse effects on cancer progression of patients with invasive BC.
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http://dx.doi.org/10.1080/21681805.2020.1773530DOI Listing
August 2020

European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2020 Guidelines.

Eur Urol 2021 01 29;79(1):82-104. Epub 2020 Apr 29.

Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Context: This overview presents the updated European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC).

Objective: To provide practical evidence-based recommendations and consensus statements on the clinical management of MMIBC with a focus on diagnosis and treatment.

Evidence Acquisition: A broad and comprehensive scoping exercise covering all areas of the MMIBC guideline has been performed annually since its 2017 publication (based on the 2016 guideline). Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. A level of evidence and a grade of recommendation were assigned. Additionally, the results of a collaborative multistakeholder consensus project on advanced bladder cancer (BC) have been incorporated in the 2020 guidelines, addressing those areas where it is unlikely that prospective comparative studies will be conducted.

Evidence Synthesis: Variant histologies are increasingly reported in invasive BC and are relevant for treatment and prognosis. Staging is preferably done with (enhanced) computerised tomography scanning. Treatment decisions are still largely based on clinical factors. Radical cystectomy (RC) with lymph node dissection remains the recommended treatment in highest-risk non-muscle-invasive and muscle-invasive nonmetastatic BC, preceded by cisplatin-based neoadjuvant chemotherapy (NAC) for invasive tumours in "fit" patients. Selected men and women benefit from sexuality sparing RC, although this is not recommended as standard therapy. Open and robotic RC show comparable outcomes, provided the procedure is performed in experienced centres. For open RC 10, the minimum selected case load is 10 procedures per year. If bladder preservation is considered, chemoradiation is an alternative in well-selected patients without carcinoma in situ and after maximal resection. Adjuvant chemotherapy should be considered if no NAC was given. Perioperative immunotherapy can be offered in clinical trial setting. For fit metastatic patients, cisplatin-based chemotherapy remains the first choice. In cisplatin-ineligible patients, immunotherapy in Programmed Death Ligand 1 (PD-L1)-positive patients or carboplatin in PD-L1-negative patients is recommended. For second-line treatment in metastatic disease, pembrolizumab is recommended. Postchemotherapy surgery may prolong survival in responders. Quality of life should be monitored in all phases of treatment and follow-up. The extended version of the guidelines is available at the EAU website: https://uroweb.org/guideline/bladder-cancer-muscle-invasive-and-metastatic/.

Conclusions: This summary of the 2020 EAU MMIBC guideline provides updated information on the diagnosis and treatment of MMIBC for incorporation into clinical practice.

Patient Summary: The European Association of Urology Muscle-invasive and Metastatic Bladder Cancer (MMIBC) Panel has released an updated version of their guideline, which contains information on histology, staging, prognostic factors, and treatment of MMIBC. The recommendations are based on the current literature (until the end of 2019), with emphasis on high-level data from randomised clinical trials and meta-analyses and on the findings of an international consensus meeting. Surgical removal of the bladder and bladder preservation are discussed, as well as the use of chemotherapy and immunotherapy in localised and metastatic disease.
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http://dx.doi.org/10.1016/j.eururo.2020.03.055DOI Listing
January 2021

Management of bladder cancer in older patients: Position paper of a SIOG Task Force.

J Geriatr Oncol 2020 09 10;11(7):1043-1053. Epub 2020 Feb 10.

Department of Urology and Paediatric Urology, University Hospital of Würzburg, Germany.

Median age at bladder cancer (BC) diagnosis is older than for other major tumours. Age should not determine treatment, and patients should be fully involved in decisions. Patients should be screened with Mini-Cog™ for cognitive impairment and the G8 to ascertain need for comprehensive geriatric assessment. In non-muscle invasive disease, older adult patients should have standard therapy. Age does not contraindicate intravesical therapy. Independent of age and fitness, patients with muscle-invasive BC should have at least cross-sectional imaging. Data suggest extensive undertreatment in older adult patients, leading to poor outcomes. Standard treatment for a fit patient differs between countries. Radical cystectomy and trimodality therapy are first-line options. Radical cystectomy patients should be referred to an experienced centre and prehabilitation is mandatory. Older adult patients should be considered for neoadjuvant and adjuvant therapy, according to guidelines. In urinary diversion, avoiding bowel surgery for reconstruction of the lower urinary tract significantly reduces complications. If a patient is unfit for or refuses standard treatment, RT alone, or TURBT in selected cases should be considered. In metastatic BC, older adult patients should receive standard systemic therapy, depending on fitness for cisplatin and prognosis. Efficacy and tolerability of immunotherapy (IO) appears similar to younger patients. Second line IO is standard in platinum pre-treated patients, with benefit and tolerability in the older adult similar to younger patients. The toxicity profile seems to favour IO in the older adult but more data are needed. Patients progressing on IO may respond to further systemic treatment. In metastatic disease, palliative care should begin early.
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http://dx.doi.org/10.1016/j.jgo.2020.02.001DOI Listing
September 2020

Management of Muscle-invasive Bladder Cancer in the 2020s: Challenges and Perspectives.

Authors:
Georgios Gakis

Eur Urol Focus 2020 07 25;6(4):632-638. Epub 2020 Jan 25.

Department of Urology and Pediatric Urology, Julius Maximillians University, Würzburg, Germany. Electronic address:

Despite an increased use of neoadjuvant and adjuvant chemotherapy, the long-term survival rates after radical cystectomy or trimodal therapy (TMT) for muscle-invasive bladder cancer (MIBC) remain basically unchanged for decades. Detection and effective treatment of micrometastatic disease are still a clinical dilemma. Assessment of circulating tumor DNA in combination with improved imaging modalities may improve the prediction of micrometastatic disease. Different genetic subtypes of MIBC show varying degrees of chemosensitivity. Further progress needs to be made in order to develop a common molecular classifier that can be used easily for daily clinical decision making. With the advent on immuno-oncology, bladder-sparing protocols are on the rise as an alternative to surgery. The extent of transurethral bladder tumor resection has a marked impact on the response rates to TMT and neoadjuvant chemotherapy. This review focuses on strategies regarding how to integrate surgery, radiotherapy, and molecular-based systemic treatment for improved oncological outcomes of patients with MIBC. PATIENT SUMMARY: Effective treatment of micrometastatic disease is the key to improved oncological outcomes in muscle-invasive bladder cancer and requires a multidisciplinary approach.
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http://dx.doi.org/10.1016/j.euf.2020.01.007DOI Listing
July 2020

The Importance of Hospital and Surgeon Volume as Major Determinants of Morbidity and Mortality After Radical Cystectomy for Bladder Cancer: A Systematic Review and Recommendations by the European Association of Urology Muscle-invasive and Metastatic Bladder Cancer Guideline Panel.

Eur Urol Oncol 2020 04 19;3(2):131-144. Epub 2019 Dec 19.

Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.

Context: In bladder cancer patients treated with radical cystectomy (RC), controversy exists regarding the impact of the annual hospital volume (HV) and/or surgeon volume (SV) on oncological outcomes and quality of care.

Objective: A systematic review was performed to evaluate the impact of HV and SV on clinical outcomes. Primary outcomes included in-hospital, 30-d, and 90-d mortality. Secondary outcomes included complications, long-term survival, positive surgical margin rate, lymphadenectomy performance, length of hospital stay, neobladder performance, and blood loss/transfusion rate.

Evidence Acquisition: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched. Comparative studies published after the year of 2000 including patients who underwent RC for bladder cancer were eligible for inclusion. Partial cystectomy was an exclusion criterion. Risk of bias (RoB) assessment was performed according to the ROBINS-1 tool.

Evidence Synthesis: After screening of 1190 abstracts, 39 studies recruiting 549 542 patients were included. All studies were retrospective observation cohort studies (level of evidence 3). Twenty-two studies reported on HV only, six studies on SV only, and 12 on both. Higher HV, specifically an HV of >10, was associated with improved primary and secondary outcomes in most studies. In addition, there is some evidence that an HV of >20 improves outcomes. For SV, limited and conflicting data are reported. Most studies had moderate to high RoB. The results were synthesized narratively.

Conclusions: Acknowledging the lower level of evidence, HV is likely associated with in-hospital, 30- and 90-d mortality, as well as the secondary outcomes assessed. Based on this study, the European Association of Urology Muscle-invasive and Metastatic Bladder Cancer Guideline Panel recommends hospitals to perform at least 10, and preferably >20, RCs annually or refer the patient to a center that reaches this number. For SV, limited and conflicting data are available. The available evidence suggests HV rather than SV to be the main driver of perioperative outcomes.

Patient Summary: Current literature suggests that the number of bladder removal operations per hospital per year is associated with postoperative survival as well as the quality of care provided.
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http://dx.doi.org/10.1016/j.euo.2019.11.005DOI Listing
April 2020

Radical Cystectomy in Female Patients - Improving Outcomes.

Curr Urol Rep 2019 Nov 28;20(12):83. Epub 2019 Nov 28.

Department of Urology and Pediatric Urology, University Hospital of Würzburg, Julius Maximillians University, Oberdürrbacher Strasse 6, 97080, Würzburg, Germany.

Purpose Of Review: To review the methods of improving surgical, oncological, and functional outcomes in women with bladder cancer treated with radical cystectomy.

Recent Findings: Οrthotopic urinary diversion (ONB) is a safe option for well-selected women as it combines high rates of daytime and nighttime continence with exceptional oncologic outcomes. It is considered safe even for patients with limited lymph node disease and trigone involvement, as long as a preoperative biopsy of the bladder neck or an intraoperative frozen section analysis of distal urethral margin rules out malignant disease. Nerve-sparing techniques have shown promising results. For well-selected patients with early invasive disease, sparing of internal genitalia has proven to be oncologically safe. Yet, generally accepted and evidence-based oncological and functional follow-up schemes for women after radical cystectomy are still lacking. Properly designed prospective studies are needed with adequate number of participants in order to safely conclude about a broader use of pelvic organ-sparing cystectomy.
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http://dx.doi.org/10.1007/s11934-019-0951-zDOI Listing
November 2019

EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer-An International Collaborative Multistakeholder Effort: Under the Auspices of the EAU-ESMO Guidelines Committees.

Eur Urol 2020 02 19;77(2):223-250. Epub 2019 Nov 19.

Department of Biomedical Sciences, Humanitas University, Milan, Italy; Humanitas Research Hospital, Milan, Italy.

Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.

Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.

Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.

Setting: Online Delphi survey and consensus conference.

Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.

Outcome Measurements And Statistical Analysis: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).

Results And Limitations: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.

Conclusions: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.

Patient Summary: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.
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http://dx.doi.org/10.1016/j.eururo.2019.09.035DOI Listing
February 2020

Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): overall survival and updated results of a randomised, double-blind, phase 3 trial.

Lancet Oncol 2020 01 18;21(1):105-120. Epub 2019 Nov 18.

Institut Català d'Oncologia L'Hospitalet, Institut d'Investigacio Biomedica de Bellvitge, University of Barcelona, Barcelona, Spain.

Background: Ramucirumab-an IgG1 vascular endothelial growth factor receptor 2 antagonist-plus docetaxel was previously reported to improve progression-free survival in platinum-refractory, advanced urothelial carcinoma. Here, we report the secondary endpoint of overall survival results for the RANGE trial.

Methods: We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 investigative sites (hospitals, clinics, and academic centres) in 23 countries. Previous treatment with one immune checkpoint inhibitor was permitted. Patients were randomly assigned (1:1) using an interactive web response system to receive intravenous ramucirumab 10 mg/kg or placebo 10 mg/kg volume equivalent followed by intravenous docetaxel 75 mg/m (60 mg/m in Korea, Taiwan, and Japan) on day 1 of a 21-day cycle. Treatment continued until disease progression, unacceptable toxicity, or other discontinuation criteria were met. Randomisation was stratified by geographical region, Eastern Cooperative Oncology Group performance status at baseline, and visceral metastasis. Progression-free survival (the primary endpoint) and overall survival (a key secondary endpoint) were assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT02426125; patient enrolment is complete and the last patient on treatment is being followed up for safety issues.

Findings: Between July 20, 2015, and April 4, 2017, 530 patients were randomly allocated to ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267) and comprised the intention-to-treat population. At database lock (March 21, 2018) for the final overall survival analysis, median follow-up was 7·4 months (IQR 3·5-13·9). In our sensitivity analysis of investigator-assessed progression-free survival at the overall survival database lock, median progression-free survival remained significantly improved with ramucirumab compared with placebo (4·1 months [95% CI 3·3-4·8] vs 2·8 months [2·6-2·9]; HR 0·696 [95% CI 0·573-0·845]; p=0·0002). Median overall survival was 9·4 months (95% CI 7·9-11·4) in the ramucirumab group versus 7·9 months (7·0-9·3) in the placebo group (stratified HR 0·887 [95% CI 0·724-1·086]; p=0·25). Grade 3 or worse treatment-related treatment-emergent adverse events in 5% or more of patients and with an incidence more than 2% higher with ramucirumab than with placebo were febrile neutropenia (24 [9%] of 258 patients in the ramucirumab group vs 16 [6%] of 265 patients in the placebo group) and neutropenia (17 [7%] of 258 vs six [2%] of 265). Serious adverse events were similar between groups (112 [43%] of 258 patients in the ramucirumab group vs 107 [40%] of 265 patients in the placebo group). Adverse events related to study treatment and leading to death occurred in eight (3%) patients in the ramucirumab group versus five (2%) patients in the placebo group.

Interpretation: Additional follow-up supports that ramucirumab plus docetaxel significantly improves progression-free survival, without a significant improvement in overall survival, for patients with platinum-refractory advanced urothelial carcinoma. Clinically meaningful benefit might be restricted in an unselected population.

Funding: Eli Lilly and Company.
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http://dx.doi.org/10.1016/S1470-2045(19)30668-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946880PMC
January 2020

Prognostic impact of tumor-associated immune cell infiltrates at radical cystectomy for bladder cancer.

Urol Oncol 2020 01 16;38(1):4.e7-4.e15. Epub 2019 Sep 16.

Department of Urology and Pediatric Urology, University Hospital of Wuerzburg, Julius-Maximilians University, Wuerzburg, Germany; Department of Urology, University Hospital of Tuebingen, Eberhard-Karls University, Tuebingen, Germany. Electronic address:

Objectives: To assess whether the presence and location of tumor-associated immune cell infiltrates (TAIC) on histological slides obtained from cystectomy specimens impacts on oncological outcomes of patients with bladder cancer (BC).

Material And Methods: A total of 320 consecutive patients staged with cM0 bladder cancer underwent radical cystectomy (RC) between 2004 and 2013. The presence of TAIC (either located peritumorally [PIC] and/or intratumorally [IIC]) on histological slides was retrospectively assessed and correlated with outcomes. Kaplan-Meier analyses were used to estimate the impact of TAIC on recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS). Multivariable Cox-regression analysis was carried out to evaluate risk factors of recurrence. The median follow-up was 37 months (IQR: 10-55).

Results: Of the 320 patients, 42 (13.1%) exhibited IIC, 141 (44.1%) PIC and 137 (42.8%) no TAIC in the cystectomy specimens. Absence of TAIC was associated with higher ECOG performance status (P = 0.042), histologically advanced tumor stage (≥pT3a; P < 0.001), lymph node tumor involvement (pN+; P = 0.022), positive soft tissue surgical margins (P = 0.006), lymphovascular invasion (P < 0.001), and elevated serum C-reactive protein levels (P < 0.001). The rate of never smokers was significantly higher in the IIC-group (64.3%) compared to the PIC-group (39.7%, P = 0.007) and those without TAIC (35.8%, P = 0.001). The 3-year RFS/CSS/OS was 73.9%/88.5%/76.7% for patients with IIC, 69.4%/85.2%/70.1% for PIC and 47.6%/68.5%/56.1% for patients without TAIC (P < 0.001/<0.001/0.001 for TAIC vs. no TAIC). In multivariable analysis, adjusted for all significant parameters of univariable analysis, histologically advanced tumor stage (P = 0.003), node-positive disease (P = 0.002), and the absence of TAIC (P = 0.035) were independent prognosticators for recurrence.

Conclusions: In this analysis, the presence and location of TAIC in cystectomy specimens was a strong prognosticator for RFS after RC. This finding suggests that the capability of immune cells to migrate into the tumor at the time of RC is prognostically important in invasive bladder cancer.
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http://dx.doi.org/10.1016/j.urolonc.2019.08.013DOI Listing
January 2020

Editorial Comment.

Authors:
Georgios Gakis

J Urol 2019 10 6;202(4):768-769. Epub 2019 Sep 6.

Department of Urology and Pediatric Urology, Julius Maximillians University, Würzburg, Germany.

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http://dx.doi.org/10.1097/01.JU.0000576696.71791.47DOI Listing
October 2019

Performance of the Bladder EpiCheck™ Methylation Test for Patients Under Surveillance for Non-muscle-invasive Bladder Cancer: Results of a Multicenter, Prospective, Blinded Clinical Trial.

Eur Urol Oncol 2018 09 17;1(4):307-313. Epub 2018 Jul 17.

Department of Urology, Meir Medical Center, Kfar Saba, Israel.

Background: The highly frequent strategy of surveillance for non-muscle-invasive bladder cancer (NMIBC) involves cystoscopy and cytology. Urine assays currently available have not shown performance sufficient to replace the current gold standard for follow-up, which would require a very high negative predictive value (NPV), especially for high-grade tumors. Bladder EpiCheck (BE) is a novel urine assay that uses 15 proprietary DNA methylation biomarkers to assess the presence of bladder cancer.

Objective: To assess the performance of BE for NMIBC recurrence.

Design, Setting, And Participants: This was a blinded, single-arm, prospective multicenter study. The inclusion criteria were age ≥22 yr, urothelial carcinoma (UC) being monitored cystoscopically at 3-mo intervals, all UC resected within 12 mo, able to produce 10ml of urine, and able to consent.

Outcome Measurements And Statistical Analysis: The BE test characteristics were calculated and compared to cytology and cystoscopy results confirmed by pathology.

Results And Limitations: Out of 440 patients recruited, 353 were eligible for the performance analysis. Overall sensitivity, specificity, NPV, and positive predictive value were 68.2%, 88.0%, 95.1%, and 44.8%, respectively. Excluding low-grade (LG) Ta recurrences, the sensitivity was 91.7% and NPV was 99.3%. The area under receiver operating characteristic (ROC) curves with and without LG Ta lesions was 0.82 and 0.94, respectively.

Conclusions: In follow-up of NMIBC patients, the BE test showed an overall high NPV of 95.1%, and 99.3% when excluding LG Ta recurrences. With high specificity of 88.0%, the test could be incorporated in NMIBC follow-up since high-grade recurrences would be instantly detected with high confidence. Thus, the current burden of repeat cystoscopies and cytology tests could be reduced.

Patient Summary: The Bladder EpiCheck urine test has a clinically relevant and high negative predictive value. Its use in clinical routine could reduce the number of follow-up cystoscopies, and thus associated patient and financial burdens.
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http://dx.doi.org/10.1016/j.euo.2018.06.011DOI Listing
September 2018

The prognostic impact of hexaminolevulinate-based bladder tumor resection in patients with primary non-muscle invasive bladder cancer treated with radical cystectomy.

World J Urol 2020 Feb 27;38(2):397-406. Epub 2019 Apr 27.

Department of Urology, University Hospital of Tübingen, Eberhard-Karls University, Tübingen, Germany.

Purpose: To investigate whether hexaminolevulinate-based (HAL) bladder tumor resection (TURBT) impacts on outcomes of patients with primary non-muscle-invasive bladder cancer (NMIBC) who were eventually treated with radical cystectomy (RC).

Methods: A total of 131 consecutive patients exhibiting NMIBC at primary diagnosis were retrospectively investigated whether they had undergone any HAL-guided TURBT prior to RC. Uni- and multivariable analyses were used to evaluate the impact of HAL-TURBT on cancer-specific (CSS) and overall survival (OS). The median follow-up was 38 months (IQR 13-56).

Results: Of the 131 patients, 69 (52.7%) were managed with HAL- and 62 (47.3%) with white light (WL)-TURBT only prior to RC. HAL-TURBT was associated with a higher number of TURBTs prior to RC (p = 0.002) and administration of intravesical chemotherapy (p = 0.043). A trend towards a higher rate of tumor-associated immune cell infiltrates in RC specimens (p = 0.07) and a lower utilization rate of post-operative systemic chemotherapy (p = 0.10) was noted for patients who were treated with HAL-TURBT. The 5-year CSS/OS was 90.9%/74.5% for the HAL-group and 73.8%/55.8% for the WL-group (p = 0.042/0.038). In multivariable analysis, lymph node tumor involvement (p = 0.007), positive surgical margins (p = 0.001) and performance of WL-TURBT only (p = 0.040) were independent predictors for cancer-specific death.

Conclusions: The present data suggest that the resection of NMIBC under HAL exerts a beneficial impact on outcomes of patients who will need to undergo RC during their course of disease. This finding may be due to improved risk stratification as the resection under HAL may allow more patients to be treated timely and adequately.
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http://dx.doi.org/10.1007/s00345-019-02780-0DOI Listing
February 2020

Re: Extended Versus Limited Lymph Node Dissection in Bladder Cancer Patients Undergoing Radical Cystectomy: Survival Results from a Prospective, Randomized Trial.

Authors:
Georgios Gakis

Eur Urol 2019 07 13;76(1):126. Epub 2019 Mar 13.

Department of Urology, University Hospital of Würzburg, Julius-Maximillians University, Würzburg, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2019.02.034DOI Listing
July 2019

The Role of Magnetic Resonance Imaging in the Diagnosis of Penile Fracture in Real-Life Emergency Settings: Comparative Analysis with Intraoperative Findings.

J Urol 2019 09 8;202(3):552-557. Epub 2019 Aug 8.

Department of Urology and Pediatric Urology, Julius-Maximilians-University of Würzburg, Würzburg, Germany.

Purpose: We evaluated the role of magnetic resonance imaging of the penis in the diagnosis of penile fracture and/or concomitant urethral lesions in real-life emergency settings compared with intraoperative findings.

Materials And Methods: A total of 43 patients presented with suspicion of penile fracture between January 2006 and December 2016. Magnetic resonance imaging was performed in 28 patients prior to surgical treatment in the emergency setting. Surgery was done in all patients via a subcoronal, circumferential degloving approach. We calculated sensitivity, specificity, and positive and negative predictive values as well as likelihood ratios of the positive and negative results of the agreement between magnetic resonance imaging and intraoperative findings.

Results: Intraoperatively penile fracture was confirmed in 19 of 28 patients (67.9%) and a concomitant urethral lesion was observed in 5 of 28 (17.9%). Magnetic resonance imaging findings were highly associated with intraoperative findings of tunical rupture, including 100% sensitivity (95% CI 98.5-100), 77.8% specificity (95% CI 50.6-100), 90.5% positive predictive value (95% CI 78-100), 100% negative predictive value (95% CI 97.6-100) and a positive result likelihood ratio of 4.5. Magnetic resonance imaging had lower accuracy for urethral lesions with 60% sensitivity (95% CI 17.1-100), 78.3% specificity (95% CI 61.5-95.1), 37.5% positive predictive value (95% CI 4-71), 90% negative predictive value (95% CI 76.9-100) and a positive result likelihood ratio of 2.76.

Conclusions: Magnetic resonance imaging may be applicable in the emergency setting if the goal is to treat all men who warrant intervention. It has high sensitivity and negative predictive value for tunical rupture and concomitant urethral lesions. Therefore, it could help avoid unnecessary surgery by excluding the diagnosis. However, solitary magnetic resonance imaging is not sufficient for diagnosis and it should not replace clinical assessment or delay surgical exploration.
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http://dx.doi.org/10.1097/JU.0000000000000211DOI Listing
September 2019

Editorial Comment.

Authors:
Georgios Gakis

J Urol 2019 01;201(1):54-55

Department of Urology and Pediatric Urology, University Hospital of Würzburg, Julius-Maximillians University, Würzburg, Germany.

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http://dx.doi.org/10.1097/01.ju.0000550123.08098.adDOI Listing
January 2019

Optical improvements in the diagnosis of bladder cancer: implications for clinical practice.

Ther Adv Urol 2017 Nov 4;9(11):251-260. Epub 2017 Sep 4.

Department of Urology, University Hospital Tübingen, Hoppe-Seyler-Str. 3, Tübingen, 72076, Germany.

Background: For over 100 years white-light cystoscopy has remained the gold-standard technique for the detection of bladder cancer (BCa). Some limitations in the detection of flat lesions (CIS), the differentiation between inflammation and malignancy, the inaccurate determination of the tumor margin status as well as the tumor depth, have led to a variety of technological improvements. The aim of this review is to evaluate the impact of these improvements in the diagnosis of BCa and their effectiveness in clinical practice.

Methods: A systematic literature search was conducted according to the PRISMA statement to identify studies reporting on imaging modalities in the diagnosis of NMIBC between 2000 and 2017. A two-stage selection process was utilized to determine eligible studies. A total of 74 studies were considered for final analysis.

Results: Optical imaging technologies have emerged as an adjunct to white-light cystoscopy and can be classified according to their scope as macroscopic, microscopic and molecular. Macroscopic techniques including photodynamic diagnosis (PDD), narrow-band imaging (NBI) and the Storz Professional Image Enhancement System (IMAGE1 S, formerly known as SPIES) are similar to white-light cystoscopy, but are superior in the detection of bladder tumors by means of contrast enhancement. Especially the detection rate of very mute lesions in the bladder mucosa (CIS) could be significantly increased by the use of these methods. Microscopic imaging techniques like confocal laser endomicroscopy and optical coherence tomography permit a real-time high-resolution assessment of the bladder mucosa at a cellular and sub-cellular level with spatial resolutions similar to histology, enabling the surgeon to perform an 'optical biopsy'. Molecular techniques are based on the combination of optical imaging technologies with fluorescence labeling of cancer-specific molecular agents like antibodies. This labeling is intended to favor an optical distinction between benign and malignant tissue.

Conclusions: Optical improvements of the standard white-light cystoscopy have proven their benefit in the detection of BCa and have found their way into clinical practice. Especially the combination of macroscopic and microscopic techniques may improve diagnostic accuracy. Nevertheless, HAL-PDD guided cystoscopy is the only approach approved for routine use in the diagnosis of BCa by most urological associations in the EU and USA to date.
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http://dx.doi.org/10.1177/1756287217720401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896854PMC
November 2017

Urethral recurrence after radical cystectomy for urothelial carcinoma: A systematic review and meta-analysis.

Urol Oncol 2018 02 28;36(2):54-59. Epub 2017 Nov 28.

Department of Urology, University Hospital Würzburg, Würzburg, Germany.

Purpose: Currently, identified factors for urethral recurrence (UR) are based on individual reporting which has displayed controversy. In addition, risk of UR is one of the limiting factors to offer neobladder diversion during radical cystectomy (RC). We aim to systematically evaluate the incidence and risk factors of UR post-RC and its effect on survival.

Materials And Methods: A systematic online search was conducted according to PRISMA statement for publications reporting on UR after RC. From initial 802 results, 14 articles including 6169 patients were included finally after exclusion of ineligible studies.

Results: The incidence rate of UR was 4.4% (1.3%-13.7%). It was significantly lower with neobladder diversion (odds ratio = 0.44, 95% CI: 0.24-0.79, P = 0.006). Muscle invasion (hazard ratio = 1.18, 95% CI: 0.86-1.62, P = 0.31), carcinoma in situ (hazard ratio 0.97, 95% CI: 0.64-1.47, P = 0.88), prostatic stromal involvement (hazard ratio = 2.26, 95% CI: 0.01-627.75, P = 0.78), and prostatic urethral involvement (hazard ratio = 2.04, 95% CI: 0.20-20.80, P = 0.55) have no significant effect on UR. Men displayed tendency toward higher incidence of UR (odds ratio = 2.21, 95% CI: 0.96-5.06, P = 0.06). Absence of recurrence displayed tendency toward better disease specific survival, yet not significant (hazard ratio = 0.84, 95% CI: 0.66-1.08, P = 0.17). These results are limited by the retrospective nature of the included studies.

Conclusion: Muscle invasion, carcinoma in situ and prostatic stromal or urethral involvement at time of RC have no significant effect on UR. Orthotopic neobladder is associated with a significant lower risk of UR after RC.
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http://dx.doi.org/10.1016/j.urolonc.2017.11.007DOI Listing
February 2018

Perioperative morbidity, bowel function and oncologic outcome after radical cystectomy and ileal orthotopic neobladder reconstruction: Studer-pouch versus I-pouch.

Eur J Surg Oncol 2018 Jan 20;44(1):178-184. Epub 2017 Oct 20.

Department of Urology, Eberhard Karls University Tübingen, 72076, Tübingen, Germany. Electronic address:

Objective: To investigate whether the length of ileum used for ileal orthotopic neobladder (ONB) reconstruction (60 cm vs. 40 cm) after radical cystectomy (RC) for bladder cancer (BC) impacts on bowel function, postoperative complications or survival outcome.

Material And Methods: In this retrospective study, we included 56 patients who received an ONB (Studer (S)-Pouch: 23 patients; I-Pouch: 33 patients) after RC for BC between 2003 and 2011. Preoperative comorbidities were assessed by the Charlson Comorbidity Index (CCI) and surgical complications as graded by the Clavien-Dindo classification. Changes of perioperative bowel habits were retrospectively evaluated by the validated Gastrointestinal Quality of Life Index (GIQLI). Kaplan-Meier analyses calculated survival outcomes between both ONB types.

Results: Preoperative CCI was comparable between S- and I-pouch patients. No significant differences were observed for 30-day major- (p = 0.33) and minor (p = 0.96) complication rates between both neobladder types. S-Pouch patients reported higher preoperative stool frequencies (S-pouch: mean 2.7; I-pouch: mean 3.4; p = 0.049) and tended to suffer from urgency (S: mean 2.9; I: mean 3.4; p = 0.059). No significant differences in postoperative bowel disorders were found between both neobladder types (S-Pouch: 15.9, IQR; I-Pouch: 16.6 IQR; p = 0.84). Furthermore, we observed no overall-, cancer specific- or recurrence free survival advantage for either of both ONB variants (p = 0.81; 0.65 and 0.78), respectively.

Conclusion: Comorbidities, perioperative complication rates and bowel habits were similar between both ONB substitutes and did not influence survival outcomes. These stratified data suggest that the length of ileum used for ONB reconstruction (60- vs. 40 cm) does not impact per se on postoperative bowel function.
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http://dx.doi.org/10.1016/j.ejso.2017.10.208DOI Listing
January 2018

A systematic review and meta-analysis on the oncological long-term outcomes after trimodality therapy and radical cystectomy with or without neoadjuvant chemotherapy for muscle-invasive bladder cancer.

Urol Oncol 2018 02 6;36(2):43-53. Epub 2017 Nov 6.

Department of Urology, University Hospital Würzburg, Würzburg, Germany.

Objective: This study aimed to comprehensively analyze the oncological long-term outcomes of trimodal therapy (TMT) and radical cystectomy (RC) for the treatment of muscle-invasive bladder cancer (BC) with or without neoadjuvant chemotherapy (NAC).

Patients And Methods: A systematic search was conducted according to the PRISMA guidelines for studies reporting on outcomes after TMT and RC. A total of 57 studies including 30,293 patients were included. The 10-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) rates for TMT and RC were assessed.

Results: The mean 10-year OS was 30.9% for TMT and 35.1% for RC (P = 0.32). The mean 10-year DSS was 50.9% for TMT and 57.8% for RC (P = 0.26). NAC was administered before therapy to 453 (13.3%) of 3,402 patients treated with TMT and 812 (3.0%) of 27,867 patients treated with RC (P<0.001). Complete response (CR) was achieved in 1,545 (75.3%) of 2,051 evaluable patients treated with TMT. A 5-year OS, DSS, and RFS after CR were 66.9%, 78.3%, and 52.5%, respectively. Downstaging after transurethral bladder tumor resection or NAC to stage ≤pT1 at RC was reported in 2,416 (29.1%) of 8,311 patients. NAC significantly increased the rate of pT0 from 20.2% to 34.3% (P = 0.007) in cT2 and from 3.8% to 23.9% (P<0.001) in cT3-4. A 5-year OS, DSS, and RFS in downstaged patients (≤pT1) at RC were 75.7%, 88.3%, and 75.8%, respectively.

Conclusion: In this analysis, the survival outcomes of patients after TMT and RC for MIBC were comparable. Patients who experienced downstaging after NAC and RC exhibited improved survival compared to patients treated with RC only. Best survival outcomes after TMT are associated with CR to this approach.
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http://dx.doi.org/10.1016/j.urolonc.2017.10.002DOI Listing
February 2018

The prognostic effect of salvage surgery and radiotherapy in patients with recurrent primary urethral carcinoma.

Urol Oncol 2018 01 18;36(1):10.e7-10.e14. Epub 2017 Oct 18.

Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Background: To evaluate the impact of salvage therapy (ST) on overall survival (OS) in recurrent primary urethral cancer (PUC).

Patients: A series of 139 patients (96 men, 43 women; median age = 66, interquartile range: 57-77) were diagnosed with PUC at 10 referral centers between 1993 and 2012. The modality of ST of recurrence (salvage surgery vs. radiotherapy) was recorded. Kaplan-Meier analysis with log-rank was used to estimate the impact of ST on OS (median follow-up = 21, interquartile range: 5-48).

Results: The 3-year OS for patients free of any recurrence (I), with solitary or concomitant urethral recurrence (II), and nonurethral recurrence (III) was 86.5%, 74.5%, and 48.2%, respectively (P = 0.002 for I vs. III and II vs. III; P = 0.55 for I vs. II). In the 80 patients with recurrences, the modality of primary treatment of recurrence was salvage surgery in 30 (37.5%), salvage radiotherapy (RT) in 8 (10.0%), and salvage surgery plus RT in 5 (6.3%) whereas 37 patients did not receive ST for recurrence (46.3%). In patients with recurrences, those who underwent salvage surgery or RT-based ST had similar 3-year OS (84.9%, 71.6%) compared to patients without recurrence (86.7%, P = 0.65), and exhibited superior 3-year OS compared to patients who did not undergo ST (38.0%, P<0.001 compared to surgery, P = 0.045 to RT-based ST, P = 0.29 for surgery vs. RT-based ST).

Conclusions: In this study, patients who underwent ST for recurrent PUC demonstrated improved OS compared to those who did not receive ST and exhibited similar survival to those who never developed recurrence after primary treatment.
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http://dx.doi.org/10.1016/j.urolonc.2017.09.012DOI Listing
January 2018

The effect of AB0 and Rhesus blood grouping systems on oncological outcome in patients undergoing radical nephroureterectomy for upper tract urothelial carcinoma.

Urol Oncol 2017 12 8;35(12):671.e17-671.e23. Epub 2017 Sep 8.

Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Objectives: To investigate the effect of AB0 and Rhesus factor expression blood group systems on outcomes of upper tract urothelial carcinoma patients treated with radical nephroureterectomy.

Patients And Methods: We analyzed data from 271 patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy at 3 German academic institutions. Cox and logistic regression models assessed the association of AB0 blood group antigen and Rhesus factor expression with tumor biologic features and outcomes, respectively.

Results: In total, 119 patients (43.9%) had blood group antigen A0, 42 patients (15.4%) antigen B0, 15 patients (5.5%) antigen AB, and 95 patients (35.0%) the antigen 00. A total of 231 patients (85.2%) were Rhesus factor positive. The AB0 blood group antigen expression was associated with a higher tumor grade (P = 0.049) and sessile tumor architecture (P = 0.019). Both, AB0 blood group system and Rhesus factor expression, were associated with worse performance status (P = 0.024, and P = 0.003, respectively). In contrast, Rhesus factor expression status was not associated with any clinicopathologic characteristics. Neither the AB0 blood group antigens nor the Rhesus factor was associated with survival.

Conclusion: AB0 blood group antigens and Rhesus factor expression are not associated with survival. The association of the AB0 blood group antigens with adverse pathological features warrants further validation.
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http://dx.doi.org/10.1016/j.urolonc.2017.08.007DOI Listing
December 2017

The Role of Radical Prostatectomy and Radiotherapy in Treatment of Locally Advanced Prostate Cancer: A Systematic Review and Meta-Analysis.

Urol Int 2017 4;99(3):249-256. Epub 2017 Jul 4.

Department of Urology, Universiti Putra Malaysia (UPM), Serdang, Malaysia.

Background: The role of radical prostatectomy (RP) is still controversial for locally advanced prostate cancer (PC). Radiotherapy (RT) and hormonal therapy (HT) are usually used as a primary treatment.

Material And Methods: A systematic online search was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Eligible publications reporting the overall survival (OS) and/or disease-specific survival (DSS) were included. A total of 14 studies, including 17,869 patients, were considered for analysis. The impact of therapeutic modalities on survival was assessed, with a risk of bias assessment according to the Newcastle Ottawa Scale.

Results: For RP, RT, and HT, the mean 10-year OS was 70.7% (95% CI 61.3-80.2), 65.8% (95% CI 48.1-83.3), and 22.6% (95% CI 4.9-40.3; p = 0.001), respectively. The corresponding 10-year DSS was 84.1% (95% CI 75.1-93.2), 89.4% (95% CI 70.1-108.6), and 50.4% (95% CI 31.2-69.6; p = 0.0127), respectively. Among all treatment combinations, RP displayed significant improvement in OS when included in the treatment (Z = 4.01; p < 0.001). Adjuvant RT significantly improved DSS (Z = 2.7; p = 0.007). Combination of RT and HT favored better OS in comparison to monotherapy with RT or HT (Z = 3.61; p < 0.001).

Conclusion: Improved outcomes in advanced PC were detected for RP plus adjuvant RT vs. RP alone and RT plus adjuvant HT vs. RT alone with comparable survival results between both regimens. RP with adjuvant RT may present the modality of choice when HT is contraindicated.
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http://dx.doi.org/10.1159/000478789DOI Listing
June 2018