Publications by authors named "Maarten Albersen"

161 Publications

Penile cancer.

Nat Rev Dis Primers 2021 Feb 11;7(1):11. Epub 2021 Feb 11.

Laboratory of Experimental Urology, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.

Penile squamous cell carcinoma (PSCC) is a rare cancer with orphan disease designation and a prevalence of 0.1-1 per 100,000 men in high-income countries, but it constitutes up to 10% of malignancies in men in some African, Asian and South American regions. Risk factors for PSCC include the absence of childhood circumcision, phimosis, chronic inflammation, poor penile hygiene, smoking, immunosuppression and infection with human papillomavirus (HPV). Several different subtypes of HPV-related and non-HPV-related penile cancers have been described, which also have different prognostic profiles. Localized disease can be effectively managed by topical therapy, surgery or radiotherapy. As PSCC is characterized by early lymphatic spread and imaging is inadequate for the detection of micrometastatic disease, correct and upfront surgical staging of the inguinal lymph nodes is crucial in disease management. Advanced stages of disease require multimodal management. Optimal sequencing of treatments and patient selection are still being investigated. Cisplatin-based chemotherapy regimens are the mainstay of systemic therapy for advanced PSCC, but they have poor and non-durable responses and high rates of toxic effects, indicating a need for the development of more effective and less toxic therapeutic options. Localized and advanced penile cancers and their treatment have profound physical and psychosexual effects on the quality of life of patients and survivors by altering sexual and urinary function and causing lymphoedema.
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http://dx.doi.org/10.1038/s41572-021-00246-5DOI Listing
February 2021

C-reactive protein and neutrophil-lymphocyte ratio are prognostic in metastatic clear-cell renal cell carcinoma patients treated with nivolumab.

Urol Oncol 2021 Jan 20. Epub 2021 Jan 20.

Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium. Electronic address:

Objective: To evaluate the impact of markers of systemic inflammation such as C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) on outcomes of metastatic clear-cell renal cell carcinoma (m-ccRCC) patients treated with nivolumab.

Patients And Methods: We retrospectively evaluated m-ccRCC patients treated with nivolumab and collected known prognostic factors and survival data. We used Kaplan-Meier survival analysis and cox proportional hazards regression analysis to study prognostic factors for overall survival (OS) and progression-free survival (PFS) since start of nivolumab. Harrell's C-index was used to evaluate the models.

Results: We included 113 patients. Median OS and PFS after initiation of nivolumab was 15 (interquartile range 7-28) and 4 months (interquartile range 3-11), respectively. Elevated baseline CRP was associated with worse OS (HR per 25 mg/l 1.35, 95% CI 1.16-1.52, P < 0.001) and PFS (HR per 25 mg/l 1.19, 95% CI 1.08-1.35, P = 0.001), independent from the international metastatic renal cell carcinoma database consortium (IMDC) prognostic criteria, increasing the model's C-index from 0.72 to 0.77 for OS and 0.59 to 0.62 for PFS. Elevated NLR was associated with worse OS (HR 1.10, 95% CI 1.04-1.17, P = 0.002) and PFS (HR 1.06, 95% CI 1.01-1.11, P = 0.03) independent from the other IMDC prognostic criteria. The model's C-index decreased from 0.72 to 0.70 for OS and increased from 0.59 to 0.60 for PFS.

Conclusions: Elevated baseline CRP and NLR predict worse OS and PFS on nivolumab in m-ccRCC patients. Including baseline CRP in the IMDC prognostic model improves its discriminatory power to predict OS and PFS since start of nivolumab.
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http://dx.doi.org/10.1016/j.urolonc.2020.12.020DOI Listing
January 2021

Comparison of postoperative complications of ileal conduits versus orthotopic neobladders.

Transl Androl Urol 2020 Dec;9(6):2541-2554

Department of Urology, University Hospitals Leuven, Leuven, Belgium.

Background: Radical cystectomy (RC) and urinary diversion (UD), with either an ileal conduit (IC) or an orthotopic neobladder (NB), is a complex surgery, in which various complications can occur. In this study, we compared postoperative complication rates after a RC and UD performed for the treatment of muscle-invasive bladder cancer or recurring high-risk non-muscle-invasive bladder cancer in our center.

Methods: We retrospectively included 604 patients that underwent UDs from December 1996 to August 2015. Complications were classified by type and severity according to the Clavien-Dindo classification (CDC). Univariate and multivariate analyses were performed to identify predictive factors of short-term (≤30 d), intermediate-term (31-90 d), and long-term (>90 d) complications.

Results: Four hundred and forty-five (74%) and 159 (26%) patients received ICs and NBs, respectively. These groups had significantly different long-term complication rates (IC: 39.7% NB: 49%, P=0.046), but similar short-term (P=0.319) and intermediate-term complication rates (P=0.397). Short-term complications (CDC I-V) were predicted by male gender, age-adjusted Charlson comorbidity index (aCCI) ≥3, and American Society of Anesthesiologists (ASA) score ≥3. Compared to minor short-term complications (CDC I-II), major short-term complications (CDC III-V) were predicted by male gender and a previous abdominal/pelvic surgery, and long-term major complications were predicted by the type of UD (NB).

Conclusions: The increasing risk of short-term complications with increasing aCCI and ASA score can be used when counseling the patients who are planned to undergo a RC with UD. Patients that receive NBs should be informed of the increased risk of reoperations compared to an IC.
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http://dx.doi.org/10.21037/tau-20-713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807350PMC
December 2020

Surgical outcomes after collagenase Clostridium histolyticum failure in patients with Peyronie's disease in a multicenter clinical study.

Sci Rep 2021 Jan 8;11(1):166. Epub 2021 Jan 8.

Department of Surgery, Urology Section, University of Catania, Catania, Italy.

In the present study we aimed to investigate the surgical outcomes of patients with persistent penile curvature (PC) after Collagenase Clostridium histolyticum (CCH) intraplaque injections. Data from 90 patients with persistent PC after CCH in a multicentre study from 6 andrological centres were retrospectively reviewed. Three standardized surgical techniques were performed. Group 1: plaque incision grafting (PIG) with penile prosthesis implant (PPI); Group 2: PIG without PPI; Group 3: Nesbit technique. Hospital stay, operative time, postoperative complications and PC persistency/recurrence (> 20°) were evaluated. Overall satisfaction and functional outcomes were assessed through International Index of Erectile Function-Erectile Function (IIEF-EF), Peyronie's Disease Questionnaire (PDQ), Female Sexual Function Index (FSFI) administered pre and 3 months postoperatively. Of all, 25 (27.8%) patients received grafting procedure + PPI (Group 1), 18 (20.0%) patients belonged to Group 2, and 47 (52.2%) to Group 3. Bovine pericardium graft and collagen fleece have been used in in 22 (51.2%) and 21 (48.8%) patients, respectively. Median penile length after surgery was 13.0 cm (IQR 12.0-15.0). After surgery, Group 1 showed higher increase in penile length after surgery and better improvements in terms of PDQ-PS. In contrast, both IIEF-EF and FSFI scores did not differ among groups. Overall, 86 (95.6%) did not report any complication. 4 (4.4%) patients had PC recurrence; of those, 2 (8.0%), 1 (5.6%) and 1 (2.1%) cases were observed in Group 1, Group 2 and Group 3, respectively. In case of persistent PC after CCH, surgical correction by grafting with or without concomitant PPI or Nesbit technique emerged as a technically feasible, effective and safe procedure, with no significant postoperative complications.
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http://dx.doi.org/10.1038/s41598-020-80551-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794401PMC
January 2021

Management of penile cancer patients during the COVID-19 pandemic: An eUROGEN accelerated Delphi consensus study.

Urol Oncol 2021 03 1;39(3):197.e9-197.e17. Epub 2021 Jan 1.

Department of Urology, University College London Hospital, London, United Kingdom; Division of Surgery and Interventional Science, University College London, United Kingdom; NIHR Biomedical Research Centre, University College London Hospital, London, United Kingdom. Electronic address:

Objectives: To develop an international consensus on managing penile cancer patients during the COVID-19 acute waves. A major concern for patients with penile cancer during the coronavirus disease 2019 (COVID-19) pandemic is how the enforced safety measures will affect their disease management. Delays in diagnosis and treatment initiation may have an impact on the extent of the primary lesion as well as the cancer-specific survival because of the development and progression of inguinal lymph node metastases.

Materials And Methods: A review of the COVID-19 literature was conducted in conjunction with analysis of current international guidelines on the management of penile cancer. Results were presented to an international panel of experts on penile cancer and infection control by a virtual accelerated Delphi process using 4 survey rounds. Consensus opinion was defined as an agreement of ≥80%, which was used to reconfigure management pathways for penile cancer.

Results: Limited evidence is available for delaying penile cancer management. The consensus rate of agreement was 100% that penile cancer pathways should be reconfigured, and measures should be developed to prevent perioperative nosocomial transmission of COVID-19. The panel also reached a consensus on several statements aimed at reconfiguring the management of penile cancer patients during the COVID-19 pandemic.

Conclusions: The international consensus panel proposed a framework for the diagnostic and invasive therapeutic procedures for penile cancer within a low-risk environment for COVID-19.
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http://dx.doi.org/10.1016/j.urolonc.2020.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831701PMC
March 2021

Development of a Novel Risk Score to Select the Optimal Candidate for Cytoreductive Nephrectomy Among Patients with Metastatic Renal Cell Carcinoma. Results from a Multi-institutional Registry (REMARCC).

Eur Urol Oncol 2020 Dec 29. Epub 2020 Dec 29.

Department of Urology, Fundacion Instituto Valenciano Oncologia, Valencia, Spain. Electronic address:

Background: Selection of patients for upfront cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) has to be improved.

Objective: To evaluate a new scoring system for the prediction of overall mortality (OM) in mRCC patients undergoing CN.

Design, Setting, And Participants: We identified a total of 519 patients with synchronous mRCC undergoing CN between 2005 and 2019 from a multi-institutional registry (Registry for Metastatic RCC [REMARCC]).

Outcome Measurements And Statistical Analysis: Cox proportional hazard regression was used to test the main predictors of OM. Restricted mean survival time was estimated as a measure of the average overall survival time up to 36 mo of follow-up. The concordance index (C-index) was used to determine the model's discrimination. Decision curve analyses were used to compare the net benefit from the REMARCC model with International mRCC Database Consortium (IMDC) or Memorial Sloan Kettering Cancer Center (MSKCC) risk scores.

Results And Limitations: The median follow-up period was 18 mo (interquartile range: 5.9-39.7). Our models showed lower mortality rates in obese patients (p = 0.007). Higher OM rates were recorded in those with bone (p = 0.010), liver (p = 0.002), and lung metastases (p < 0.001). Those with poor performance status (<80%) and those with more than three metastases had also higher OM rates (p = 0.026 and 0.040, respectively). The C-index of the REMARCC model was higher than that of the MSKCC and IMDC models (66.4% vs 60.4% vs 60.3%). After stratification, 113 (22.0%) patients were classified to have a favorable (no risk factors), 202 (39.5%) an intermediate (one or two risk factors), and 197 (38.5%) a poor (more than two risk factors) prognosis. Moreover, 72 (17.2%) and 51 (13.9%) patients classified as having an intermediate and a poor prognosis according to MSKCC and IMDC categories, respectively, would be reclassified as having a good prognosis according to the REMARCC score.

Conclusions: Our findings confirm the relevance of tumor and patient features for the risk stratification of mRCC patients and clinical decision-making regarding CN. Further prospective external validations are required for the scoring system proposed herein.

Patient Summary: Current stratification systems for selecting patients for kidney removal when metastatic disease is shown are controversial. We suggest a system that includes tumor and patient features besides the systems already in use, which are based on blood tests.
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http://dx.doi.org/10.1016/j.euo.2020.12.010DOI Listing
December 2020

Current and emerging therapies for localized high-risk prostate cancer.

Expert Rev Anticancer Ther 2021 Mar 22;21(3):267-282. Epub 2020 Dec 22.

Department of Urology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.

: Despite progress in the field of high-risk localized prostate cancer (HRPCa) treatments, high-risk patients treated with curative intent are at increased risk of biochemical recurrence, metastatic progression and cancer-related death. The optimal treatment strategy remains a topic of debate. This review provides an overview of the current and investigational therapeutic options for HRPCa.: A PubMed search was performed for papers on the current perspectives on the multimodality treatment of HRPCa. We focus on both primary local treatment as well as systemic treatment options. Finally, relevant ongoing trials focusing on systemic treatments (including [neo]adjuvant treatments) enrolling at least 50 patients were retrieved, to highlight ongoing research and treatment optimization.: Disease progression in HRPCa patients is driven by local tumor extension and subclinical metastases. Therefore, the main treatment concept is a multimodal approach targeting the primary tumor with extended surgery or RT with long-term ADT and simultaneously targeting micro-metastatic deposits. However, there is still room for optimization. Upcoming clinical trials comparing surgery versus RT as local treatment, trials with (neo)adjuvant chemotherapy or androgen receptor signaling inhibitors will likely change the treatment landscape. However, a multimodal treatment strategy will stay as the cornerstone in the treatment of HRPCa.
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http://dx.doi.org/10.1080/14737140.2021.1852932DOI Listing
March 2021

Renal and Bladder Cancer During Pregnancy: A Review of 47 Cases and Literature-based Recommendations for Management.

Urology 2020 Oct 22. Epub 2020 Oct 22.

Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium; Department of Oncology, KU Leuven, Leuven, Belgium; Department of Gynecological Oncology, Amsterdam University Medical Centres, Amsterdam, The Netherlands; Department of Gynecological Oncology, Amsterdam University Medical Centres, Amsterdam, The Netherlands and the Department of Gynecology, Antoni van Leeuwenhoek - Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address:

Objective: To provide contemporary gestational age-specific recommendations for management, a retrospective series of patients with renal or bladder cancer during pregnancy is reported.

Methods: Obstetric and oncological data of pregnant patients with a diagnosis of renal or bladder cancer were selected from the worldwide registry of the International Network of Cancer, Infertility and Pregnancy. In addition, the literature was reviewed for recent case reports since last reviews in 2014 for renal cancer and 2004 for bladder cancer.

Results: International Network of Cancer, Infertility and Pregnancy registered 22 cases (14 renal cancer and 8 bladder cancer), diagnosed between 1999 and 2017, and the literature reported 15 cases with renal cancer and 10 cases with bladder cancer between 2004 and 2019. Most common symptoms for renal and bladder cancer were pain (28%) and hematuria (66%), respectively. In more than half of the patients, surgical treatment was performed during pregnancy. Preterm deliveries were mostly medically induced (12 of 17, 71%) and all patients with a planned delivery before 34 weeks had advanced cancer. For renal and bladder cancer respectively, 79% and 87% of patients obtained complete remission. Advanced cancer stages had worse prognosis; 3 of 7 patients with known follow-up deceased within 15 months after diagnosis.

Conclusion: Gestational age at diagnosis determines further management of renal and bladder cancers during pregnancy. Advanced stages challenge decision-making. The maternal needs for immediate treatment, and the neonatal risks including the impact of a preterm delivery should be discussed in a multidisciplinary setting while respecting the patient's autonomy.
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http://dx.doi.org/10.1016/j.urology.2020.08.084DOI Listing
October 2020

Association Between Human Papillomavirus Infection and Outcome of Perioperative Nodal Radiotherapy for Penile Carcinoma.

Eur Urol Oncol 2020 Nov 13. Epub 2020 Nov 13.

San Raffaele Hospital and Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address:

Background: Data on the impact of human papillomavirus (HPV) infection status and outcomes for perioperative treatments for patients with lymph node-involved penile squamous-cell carcinoma (PSCC) are lacking.

Objective: To analyze the benefit from perioperative radiotherapy (RT) for PSCC according to HPV infection status.

Design, Setting, And Participants: In an international multicenter database of 1254 patients with PSCC who received inguinal lymph node dissection (ILND), 507 had suitable clinical information.

Intervention: ILND, with or without chemotherapy or RT for involved lymph nodes.

Outcome Measurements And Statistical Analysis: Kaplan-Meier and restricted mean survival time (RMST) analyses for overall survival (OS) were performed for all patients and after propensity score-matching (PSM; n = 136), for which patient age, histology, type of penile surgical procedure, pathological tumor and nodal stage, ILND laterality, pelvic LND, and perioperative treatment were taken into account when assessing differences between HPV and HPV- patients. Finally, we looked at genomic alterations in PSCC using data from the Foundation Medicine database (n = 199) to characterize HPV PSCC.

Results And Limitations: Patients with HPV PSCC (n = 86; 17%) had lower clinical N stage (p < 0.001) and inguinal lymph node metastasis density (p < 0.001). Perioperative RT was delivered in 49 patients (9.7%), with the vast majority receiving adjuvant RT (n = 40). HPV patients had similar median OS (p = 0.1) but longer RMST than HPV- patients at different time points. Nevertheless, HPV patients treated with perioperative RT exhibited longer median OS (p = 0.015) and longer RMST compared to HPV- patients. In the PSM cohorts, HPV status remained significantly associated with longer OS after RT. The HPV- PSCC group had a higher frequency of TP53 mutations compared to HPV PSCC (75% vs 15%; p < 0.001). The results are limited by the retrospective nature of the data.

Conclusions: Perioperative RT was more effective in the HPV PSCC subgroup. Reasons for the enhanced radiosensitivity may be related to the lack of TP53 mutations.

Patient Summary: We analyzed data from a large multicenter database for patients with penile cancer who had received inguinal lymph node dissection, with or without chemotherapy or radiotherapy. We found that for tumors positive for human papillomavirus (HPV), use of radiotherapy resulted in prolonged survival compared to HPV-negative tumors. On the basis of these results we are inspired to design studies on the use of radiotherapy in HPV-selected patients.
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http://dx.doi.org/10.1016/j.euo.2020.10.011DOI Listing
November 2020

Predictors of local recurrence and its impact on survival after glansectomy for penile cancer: time to challenge the dogma?

BJU Int 2020 Nov 12. Epub 2020 Nov 12.

Department of Urology, University Hospitals Leuven, Leuven, Belgium.

Objectives: To identify predictive pathological factors for local recurrence (LR) and to study the impact of LR on survival in patients treated with glansectomy for penile squamous cell carcinoma (pSCC).

Patients And Methods: We retrospectively studied patients treated with glansectomy at international, high-volume reference centres. We analysed histopathological predictors of LR, stratified patients into risk groups based on the number of risk factors present, and studied the impact of LR on survival outcomes using Kaplan-Meier survival analysis and stepwise Cox proportional hazards regression models. Subsequently, we performed sensitivity analyses excluding margin-positive cases, pT3 disease, and cN+ disease, or all of these factors.

Results: Across nine institutions, 897 patients were included, of whom 94 experienced LR. On multivariable analysis, presence of high-grade disease and pT3 stage were independent predictors of LR. LR-free survival rates significantly differed according to the number of risk factors present, with a hazard ratio (HR) of 1.90 (95% confidence interval [CI] 1.17-3.07; P = 0.01) for the intermediate-risk group (one risk factor) and 6.11 (95% CI 3.47-10.77; P < 0.001) for the high-risk group (two risk factors), using the low-risk group (no risk factors) as reference. Patients who experienced LR had significantly worse overall survival (OS; HR 2.89, 95% CI 2.02-4.14; P < 0.001) and cancer-specific survival (CSS; HR 5.64, 95% CI 3.45-9.22; P < 0.001). LR (HR 3.82, 95% CI 2.14-6.8; P < 0.001), lymphovascular invasion and cN status were significant predictors of decreased CSS. LR remained a strong predictor of both OS and CSS in all sensitivity analyses.

Conclusions: Pathological T3 stage and presence of high-grade disease were independent histopathological predictors of LR after glansectomy for primary pSCC, which allowed risk stratification into three groups with significantly different risk of developing LR. Additionally, LR is related to poor OS and CSS, indicating that LR is a manifestation of underlying aggressive disease and clearly challenging the dogma of using organ-sparing surgery whenever possible since survival is unaffected by higher LR rates.
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http://dx.doi.org/10.1111/bju.15297DOI Listing
November 2020

Penile cancer: potential target for immunotherapy?

World J Urol 2020 Nov 3. Epub 2020 Nov 3.

Department of Urology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.

Purpose: Penile cancer (PeCa) is a rare malignancy with a poor prognosis in advanced disease. There is still a limited understanding of the biological mediators that are important in the prognosis and therapy of the disease. This review aims to provide a summary of the immune micro-environment, molecular oncogenesis and the role of HPV in the disease applying to the potential of the use of immunotherapy.

Methods: Narrative, non-systematic review based on publications retrieved by PubMed and EMBASE search.

Results: The molecular mechanisms underlying penile carcinogenesis are complex, and human papillomavirus (HPV) infection is a well-characterized driver of penile cancer. Up to 50% of the penile carcinomas are HPV related. There is potential to improve prevention, treatment and follow-up strategies pertaining to the role of HPV in penile cancer. Immune response modifiers such as toll-like receptor agonists are being used in a topical fashion for penile intraepithelial neoplasia while immune checkpoint inhibitors are currently under clinical investigation for its application in penile cancer.

Conclusions: The knowledge of prognosis-relevant biological pathways in penile cancer is expanding. HPV plays an important role in the carcinogenesis. This can lead to the identification of therapeutic targets which could significantly influence the prognosis of advanced penile cancer. Clinical trials are being conducted to pave the way for immune-modifying treatment modalities.
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http://dx.doi.org/10.1007/s00345-020-03510-7DOI Listing
November 2020

Surgical Management and Outcomes of Renal Tumors Arising from Horseshoe Kidneys: Results from an International Multicenter Collaboration.

Eur Urol 2021 Jan 16;79(1):133-140. Epub 2020 Sep 16.

Department of Urology, University Hospitals Leuven, Leuven, Belgium. Electronic address:

Background: Despite being the most frequent renal fusion anomaly, tumors arising from horseshoe kidneys (HSKs) are extremely rare and management guidance is lacking.

Objective: To evaluate the perioperative, oncological, and functional outcomes of surgically treated HSK tumors.

Design, Setting, And Participants: A retrospective, multicenter cohort study of 43 HSK tumors in 40 patients was conducted, and technical description of the surgical approach has been provided.

Surgical Procedure: Surgical resection of renal tumors arising from HSKs was performed either via open surgery or via minimally invasive surgery (MIS).

Measurements: We analyzed patient and tumor characteristics as well as surgical technique, and functional and oncological outcomes.

Results And Limitations: Eight patients were treated by MIS and 32 by open surgery. One patient (2.5%) experienced an intraoperative complication and 13 patients (32.5%) experienced postoperative complications, of which three (7.5%) were Clavien-Dindo ≥3 complications. Surgical margins were positive in two tumors (4.7%). The most frequent histology was clear-cell renal cell carcinoma (46.5%). The median follow-up was 51 (interquartile range [IQR] 17-73) mo. The 5-yr overall, cancer-specific, and recurrence-free survival rates were 81.2%, 86.8%, and 83.1%, respectively. The percent decreases in estimated glomerular filtration rate at discharge and the last follow-up were 15% (IQR 4-26%) and 17% (IQR 1-31%), respectively. Limitations include the cohort's retrospective nature, heterogeneity, and small sample size.

Conclusions: Surgical management of tumors in HSKs can be approached via both open surgery and MIS, with maximal preservation of functional renal parenchyma. In this cohort, rates of complications, positive surgical margins, and renal functional decrease were acceptable, considering the anatomical complexity of these kidneys and tumors. These tumors display great variation in histological subtypes. Meticulous presurgical planning, taking advantage of advanced imaging techniques, can aid in achieving good outcomes.

Patient Summary: We evaluated the surgical management of renal tumors in horseshoe kidneys, which are very rare. Although these procedures are highly complex, outcomes are acceptable. Modern imaging techniques are often required in presurgical planning.
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http://dx.doi.org/10.1016/j.eururo.2020.09.012DOI Listing
January 2021

Too good for CARMENA: criteria associated with long systemic therapy free intervals post cytoreductive nephrectomy for metastatic clear cell renal cell carcinoma.

Scand J Urol 2020 Dec 14;54(6):493-499. Epub 2020 Sep 14.

Department of Urology, University Hospitals Leuven, Leuven, Belgium.

Purpose: The prospective CARMENA trial surprisingly suggested that patients with upfront metastatic clear-cell renal cell carcinoma (m-ccRCC) would not benefit from cytoreductive nephrectomy (CN). We aimed to identify the m-ccRCC patient subpopulation who would benefit from the continued use of CN.

Methods: We performed a retrospective cohort study on upfront m-ccRCC patients and identified three subgroups: patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) only without CN (TKI ONLY), patients undergoing CN immediately followed within 6 months by VEGFR-TKIs (CN > TKI) and patients undergoing CN followed by a considerable therapy-free interval of at least 6 months (CN > AS). Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to compare outcomes and investigate predictive factors.

Results: We included 119 patients. Overall survival was 17, 13 and 56 months for the CN > TKI, TKI only and CN > AS subgroups, respectively ( < 0.0001). Oligometastatic disease (HR = 0.33, 95% CI = 0.21-0.54,  < 0.0001), lung as only metastatic site (HR = 0.48, 95% CI = 0.31-0.76,  = 0.001) and having ≤ 2 evaluable International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria (HR = 0.56, 95% CI = 0.32-0.98,  = 0.04) were predictive for systemic therapy free survival after diagnosis.

Conclusions: The CARMENA results only apply for m-ccRCC patients in immediate need for systemic therapy, but not for patients in whom a period of AS can be expected after CN. Patients in whom systemic therapy most likely can be deferred and who are likely to benefit from CN have oligometastatic disease, only present in the lung and few (≤2) evaluable IMDC criteria.
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http://dx.doi.org/10.1080/21681805.2020.1814858DOI Listing
December 2020

MicroRNA expression profiles in molecular subtypes of clear-cell renal cell carcinoma are associated with clinical outcome and repression of specific mRNA targets.

PLoS One 2020 11;15(9):e0238809. Epub 2020 Sep 11.

Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.

Clear-cell renal cell carcinomas (ccRCC) can be divided into four transcriptomic subtypes, two of which have a favorable and two an unfavorable prognosis. To assess mechanisms driving these subtypes, we investigated their miRNA expression patterns. miRNAs are master regulators of mRNAs, that are widely deregulated in cancer. Unsupervised clustering in our dataset (n = 128) and The Cancer Genome Atlas (TCGA) validation set identified two distinct miRNA clusters that overlapped with the transcriptomic subtypes, underscoring the validity of these subtypes on a multi-omics level and suggesting a driving role for miRNAs. Discriminatory miRNAs for the favorable subtypes repressed epithelial-to-mesenchymal transition, based on gene set enrichment analysis and target-mRNA expression levels. Strikingly, throughout the entire dataset, miRNAs associated with favorable subtypes were also associated with longer overall survival after diagnosis, and miRNAs associated with unfavorable subtypes with shorter overall survival (Pearson r = -0.54, p<0.0001). These findings indicate a general shift in miRNA expression between more and less aggressive tumors. This adds to current literature, which usually suggests only a small subset of miRNAs as markers of aggressive disease. In conclusion, this study reveals distinct mRNA expression patterns underlying transcriptomic ccRCC-subtypes, whereby miRNAs associated with favorable subtypes counteract epithelial-to-mesenchymal transition. There is a general shift in miRNA expression in ccRCC, between more and less aggressive tumors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238809PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485767PMC
November 2020

Pushing the limits of metastasis-directed treatment in metastatic renal cell carcinoma in the era of targeted therapy.

Urol Oncol 2020 Dec 6;38(12):937.e1-937.e9. Epub 2020 Sep 6.

University Hospitals Leuven, Department of Urology, Leuven, Belgium.

Objective: To assess the role of metastasis directed therapy and in particular surgical metastasectomy (MxT) in metastatic renal cell carcinoma (mRCC) in the era of targeted therapy.

Method: The files of all patients who underwent MxT for treatment of mRCC in University Hospitals Leuven between 1989 and 2015 were reviewed.

Results: One hundred and thirty eight patients met the inclusion criteria. Mean age at MxT was 59.3 (IQR: 57.5-61.0) years. Median follow-up was 50.1 (42.3-63.8) months. Due to adequate patient selection, 91.9% of MxT achieved no evidence of disease status, which resulted in long median overall survival of 87.8 (63.8-113.4) months and median cancer specific survival of 92.8 (69.5-123.4) months. On multivariate analysis, primary tumor stage >pT2 (hazard ratio [HR] 2.79 [1.47-5.28] P= 0.002), unreached no evidence of disease status (HR 8.62 [3.19-23.32] P< 0.001), presence of nonpulmonary metastasis (HR 2.29 [1.02-5.10] P= 0.0449) and sarcomatoid dedifferentiation in the primary tumor (HR 4.52 [1.15-17.69] P= 0.03) significantly impacted overall survival. Survival did not differ for MxT performed before and after the advent of vascular endothelial growth factor receptor-tyrosine kinase inhibitors.

Discussion: Our study confirms the validity of MxT in mRCC in the tyrosine kinase inhibitors era. MxT should be considered in mRCC whenever the patient is fit enough to undergo surgery and complete removal of metastasis is considered possible, independent of number, location, and chronology of appearance of metastasis. Patients with pulmonary metastasis only, seem to be the best candidates for surgical MxT.
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http://dx.doi.org/10.1016/j.urolonc.2020.08.017DOI Listing
December 2020

Oncological Outcomes of Metastasis-Directed Therapy in Oligorecurrent Prostate Cancer Patients Following Radical Prostatectomy.

Cancers (Basel) 2020 Aug 13;12(8). Epub 2020 Aug 13.

Department of Urology, University Hospitals Leuven, Leuven 3000, Belgium.

Several retrospective and a few prospective studies have shown that metastasis-directed therapy (MDT) could delay clinical progression and postpone the initiation of systemic treatment in oligorecurrent prostate cancer (PCa) patients. However, these endpoints are strongly influenced by variables such as concomitant use of androgen deprivation therapy (ADT) and follow-up imaging protocols. The aim of this manuscript was to assess palliative ADT- and metastatic castration-resistant prostate cancer (mCRPC)-free survival as long-term oncological outcomes in oligorecurrent PCa treated by MDT. We retrospectively identified consecutive post-prostatectomy oligorecurrent PCa patients treated by MDT (salvage lymphadenectomy, radiotherapy, or metastasectomy) at our tertiary referral center. Patients were eligible for inclusion if they developed recurrence following radical prostatectomy, had ≤5 metastatic lesions on imaging and had a serum testosterone >50 ng/dL or a testosterone suppression therapy-free interval of >2 years prior to the first MDT as an assumption of recovered serum testosterone (if no testosterone measurement available). Patients with castration-resistant or synchronous oligometastatic PCa at the time of first MDT were excluded. Repeated MDTs were allowed, as well as a period of concomitant ADT. Kaplan-Meier analyses were performed to assess palliative ADT-free and mCRPC-free survival. We identified 191 eligible patients who underwent MDT. Median follow-up from first MDT until last follow-up or death was 45 months (IQR 27-70; mean 51 months). Estimated median palliative-ADT free survival was 66 months (95% CI 58-164) and estimated median mCRPC-free survival was not reached (mean 117 months, 95% CI 103-132). In total, 314 MDTs were performed and 25 patients (13%) received ≥3 MDTs. This study demonstrated that (repeated) MDT is feasible and holds promise in terms of palliative ADT-free and mCRPC-free survival for patients with oligorecurrent PCa. However, these findings should be confirmed in prospective randomized controlled trials.
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http://dx.doi.org/10.3390/cancers12082271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464259PMC
August 2020

Utility of Minimally Invasive Technology for Inguinal Lymph Node Dissection in Penile Cancer.

J Clin Med 2020 Aug 3;9(8). Epub 2020 Aug 3.

Department of Urology, Emory University School of Medicine, Atlanta, GA 30322, USA.

Our aim is to review the benefits as well as techniques, surgical outcomes, and complications of minimally invasive inguinal lymph node dissection (ILND) for penile cancer. The PubMed, Wiley Online Library, and Science Direct databases were reviewed in March 2020 for relevant studies limited to those published in English and within 2000-2020. Thirty-one articles describing minimally invasive ILND were identified for review. ILND has an important role in both staging and treatment of penile cancer. Minimally invasive technologies have been utilized to perform ILND in penile cancer patients with non-palpable inguinal lymph nodes and intermediate to high-risk primary tumors or patients with unilateral palpable non-fixed inguinal lymph nodes measuring less than 4 cm, including videoscopic endoscopic inguinal lymphadenectomy (VEIL) and robotic videoscopic endoscopic inguinal lymphadenectomy (RVEIL). Current data suggest that VEIL and RVEIL are feasible and safe with minimal intra-operative complications. Perhaps the strongest appeal for the use of minimally-invasive approaches is their faster post-operative recovery and less post-operative complications. As a result, patients can tolerate this procedure better and surgeons can offer surgery to patients who otherwise would not be a candidate or personally willing to undergo surgery. When compared to open technique, VEIL and RVEIL have similar dissected nodal count, a surrogate metric for oncological adequacy, and a none-inferior inguinal recurrence rate. Larger randomized studies are encouraged to investigate long-term outcome and survival rates using these minimally-invasive techniques for ILND.
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http://dx.doi.org/10.3390/jcm9082501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465352PMC
August 2020

Metastasectomy of oligometastatic urothelial cancer: a single-center experience.

Transl Androl Urol 2020 Jun;9(3):1296-1305

Department of Urology, University Hospitals Leuven, Leuven, Belgium.

Background: Survival in patients with urothelial cancer (UC) recurrence after initial treatment with curative intent is limited and treatment options are sparse. Metastasectomy could be considered a treatment option in selected cases. Identifying prognostic factors for survival can be used to counsel patients and aid multidisciplinary teams in making treatment decisions.

Methods: We collected a retrospective case series of patients undergoing metastasectomy for oligometastatic UC between 1999 and 2018 at University Hospitals Leuven. Oligometastatic UC was defined as recurrence of UC in a single organ with ≤3 metastases. Survival outcomes of interest were: overall survival (OS), cancer-specific survival (CSS), and secondary recurrence-free survival (RFS2). Complications were reported using the Clavien-Dindo classification (CDC). Survival analysis are descriptive and were performed using Kaplan-Meier plots to visualize survival data and log-rank was used to compare survival between groups.

Results: From 1999 to 2018, a total of 22 patients underwent metastasectomy of oligometastatic UC. Metastasectomy sites were: pulmonary (59.1%), loco-regional (13.6%), hepatic (9.1%), adrenal (4.5%), testicular (4.5%), nodal above aortic bifurcation (4.5%), and renal transplant (4.5%). The 5-year OS, CSS and RFS2 after metastasectomy were 51.4%, 57.0%, and 49.9%, respectively. Patients with primary upper tract urothelial cancer (UTUC) involvement and patients treated with hepatic metastasectomy had a significantly worse OS, CSS, and RFS2. Patients with a lesion size >8 mm and patients with >1 pulmonary lesion had a significantly worse CSS. Two CDC grade 3B occurred during follow-up and were both non-procedure related.

Conclusions: Metastasectomy of oligometastatic UC is feasible and can achieve durable cancer control in a highly selected subgroup of patients. Our results suggest that patients with hepatic metastases or primary UTUC involvement could be considered poor candidates for metastasectomy, while patients with a small (<8 mm) or solitary pulmonary lesion might benefit most. These findings should be validated in multi-institutional collaborations or prospective clinical studies.
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http://dx.doi.org/10.21037/tau-19-624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354317PMC
June 2020

European Society for Sexual Medicine Consensus Statement on the Use of the Cavernous Nerve Injury Rodent Model to Study Postradical Prostatectomy Erectile Dysfunction.

Sex Med 2020 Sep 13;8(3):327-337. Epub 2020 Jul 13.

Department of Urology, University College London Hospitals NHS Trust, London, UK; Division of Surgery and Interventional Science, UCL, London, UK; Unit of Urology, Division of Experimental Oncology, Urological Research Institute (URI), IRCCS Ospedale San Raffaele, Milan, Italy; Departement of Urology, Vita-Salute San Raffaele University, Milan, Italy. Electronic address:

Introduction: Rodent animal models are currently the most used in vivo model in translational studies looking into the pathophysiology of erectile dysfunction after nerve-sparing radical prostatectomy.

Aim: This European Society for Sexual Medicine (ESSM) statement aims to guide scientists toward utilization of the rodent model in an appropriate, timely, and proficient fashion.

Methods: MEDLINE and EMBASE databases were searched for basic science studies, using a rodent animal model, looking into the consequence of pelvic nerve injury on erectile function.

Main Outcome Measures: The authors present a consensus on how to best perform experiments with this rodent model, the details of the technique, and highlight possible pitfalls.

Results: Owing to the specific issue-basic science-Oxford 2011 Levels of Evidence criteria cannot be applied. However, ESSM statements on this topic will be provided in which we summarize the ESSM position on various aspects of the model such as the use of the Animal Research Reporting In Vivo Experiments guideline and the of common range parameter for nerve stimulation. We also highlighted the translational limits of the model.

Conclusion: The following statements were formulated as a suggestive guidance for scientists using the cavernous nerve injury model. With this, we hope to standardize and further improve the quality of research in this field. It must be noted that this model has its limitations. Weyne E, Ilg MM, Cakir OO, et al. European Society for Sexual Medicine Consensus Statement on the Use of the Cavernous Nerve Injury Rodent Model to Study Postradical Prostatectomy Erectile Dysfunction. Sex Med 2020;8:327-337.
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http://dx.doi.org/10.1016/j.esxm.2020.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471127PMC
September 2020

A risk calculator predicting recurrence in lymph node metastatic penile cancer.

BJU Int 2020 11 7;126(5):577-585. Epub 2020 Aug 7.

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.

Objectives: To develop and externally validate a risk calculator for prediction of any cancer recurrence in patients with penile squamous cell carcinoma (pSCC) and inguinal lymph node metastases (ILNM), as to date no validated prognostic tool is available for patients with pSCC and ILNM.

Patients And Methods: The development cohort included 234 patients from seven referral centres. The external validation cohort included 273 patients from two additional referral centres. Cox regression identified predictors of any recurrence, which were used to develop a risk calculator. The risk-calculator grouped the development and the validation cohorts according to the individual risk of any recurrence at 24 months (24m-R). Adjuvant treatment effects were tested on overall survival (OS) according to the derived tertiles, within the development and validation cohorts.

Results: Positive surgical margins, pN , and ILNM ratio were associated with higher recurrence rate. The 2-year OS rates were lower for patients with high (>37%) and intermediate (19-37%) compared to low (<19%) 24m-R risk of recurrence, for both the development (43% and 58% vs 83%, P < 0.001) and validation cohort (44% and 50% vs 85%, P < 0.001). Results were confirmed in the subgroup of patients who did not receive adjuvant treatment (P < 0.001), but not in patients who did receive adjuvant treatments in both the development and validation cohorts (P > 0.1).

Conclusion: Adjuvant treatment planning is crucial in patients with pSCC with ILNM, where only weak evidence is available. The current tool proved to successfully stratify patients according to their individual risk, potentially allowing better tailoring of adjuvant treatments.
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http://dx.doi.org/10.1111/bju.15177DOI Listing
November 2020

The Cancer of the Bladder Risk Assessment (COBRA) score for estimating cancer-specific survival after radical cystectomy: external validation in a large bi-institutional cohort.

BJU Int 2020 12 12;126(6):704-714. Epub 2020 Aug 12.

Department of Urology, University Hospitals Leuven, Leuven, Belgium.

Objective: To perform an external validation of the Cancer of the Bladder Risk Assessment (COBRA) score for estimating cancer-specific survival (CSS) after radical cystectomy (RC) in a large bi-institutional cohort of patients.

Patients And Methods: Patients treated with RC and lymph node dissection (LND) between May 1996 and July 2017 were retrieved from the RC databases of Leuven and Turin. Collected variables were age at RC, tumour stage, lymph node (LN) density, neoadjuvant chemotherapy, the extent of LND, and nodal stage. The primary outcome was CSS visualised using Kaplan-Meier plots. Cox proportional hazard models were used to assess the impact of variables on CSS. We performed a pairwise comparison between the COBRA score levels using a log-rank test corrected by Bonferroni, and developed a simplified COBRA score with three risk categories. To compare models, we assessed concordance indices (C-indices), receiver operating characteristic curves with area under the curve (AUC), calibration plots, and decision curve analysis (DCA). Finally, we compared both COBRA and simplified COBRA models with the established American Joint Committee on Cancer (AJCC) model.

Results: A total of 812 patients were included. All COBRA score variables had a significant impact on CSS in a Cox proportional hazard model. However, pairwise comparison of the COBRA subscores could not differentiate significantly between all COBRA score levels. Based on these findings, we developed a simplified COBRA score by introducing three categories within the following COBRA score ranges: low- (0-1) vs intermediate- (2-4) vs high-risk (5-7). A pairwise comparison could discriminate significantly between all COBRA risk categories. When finally comparing COBRA and simplified COBRA models with the AJCC model, AJCC performed better than both. C-indices, AUCs, calibration plots and DCA for AJCC were all better compared with the original and simplified COBRA models.

Conclusion: We performed an external validation of the COBRA score in a large bi-institutional cohort. We observed that several risk groups had overlapping CSS, demonstrating suboptimal performance of the COBRA score. Therefore, we constructed a simplified model with three COBRA score risk categories. This model resulted in demarcated risk groups with non-overlapping CSS and good predictive accuracy. However, both COBRA score models were outperformed by the AJCC staging system. Therefore, we conclude that the AJCC staging system should remain the current standard for stratifying patients after RC for CSS.
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http://dx.doi.org/10.1111/bju.15163DOI Listing
December 2020

Quality of Information in YouTube Videos on Erectile Dysfunction.

Sex Med 2020 Sep 24;8(3):408-413. Epub 2020 Jun 24.

Department of Urology, Herlev and Gentofte Hospital, Herlev, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

Introduction: Many patients seek information online including on social media.

Aim: To assess the quality of information regarding erectile dysfunction (ED) in YouTube videos.

Methods: We searched "erectile dysfunction" on YouTube in October 2019 and evaluated the first 100 videos in English sorted by relevance.

Main Outcome Measure: We recorded the user engagement, video producer, intended audience, and content. Videos containing medical information were evaluated using the Patient Education Materials Assessment Tool (PEMAT) and the DISCERN quality criteria for consumer health information. The PEMAT evaluates the understandability and actionability of materials as a percentage. The DISCERN assesses the quality of information by a scale from 1 (serious or extensive shortcomings) to 5 (minimal shortcomings).

Results: The median number of total views was 22,450 (range 591-20,255,133) and the median number of views/month was 654 (range 9-723,398). 42 percent of the videos were posted by professional medical institutions, and 21% were posted by individual medical professionals. Most videos were aimed at the general public or patients suffering from ED. The median PEMAT understandability and actionability scores were both 100% (range 50-100% and 33-100%, respectively). The median DISCERN score was 2 (range 1-5) with 80.4% receiving a score of ≤3. Overall, 28% of the videos contained direct misinformation. DISCERN scores were higher in videos produced by medical institutions (P = .0104), not selling specific products (P = .007) and not promoting alternative medicine (P = .0002). The number of subscribers was an independent predictor of views/month (P < .0001).

Conclusion: Patients may be exposed to videos of poor quality when searching for information about ED on YouTube. The medical community needs to adapt a strategy to improve the quality of online medical information. Fode M, Nolsøe AB, Jacobsen FM, et al. Quality of Information in YouTube Videos on Erectile Dysfunction. J Sex Med 2020;8:408-413.
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http://dx.doi.org/10.1016/j.esxm.2020.05.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471071PMC
September 2020

Metastasis-directed therapy for oligometastatic urological tumours: still no second-hand news.

Ecancermedicalscience 2020 7;14:1036. Epub 2020 May 7.

Department of Radiation Oncology, Leuven University Hospital, Leuven, Belgium.

For patients presenting with limited metastatic disease burden, known as the oligometastatic state of disease, a more aggressive treatment approach targeting the new or progressive metastatic lesions might improve patient outcome, with no or only limited toxicity to be expected from the treatment. This review provides an overview of the existing evidence and on-going trials on oligometastatic disease and metastasis-directed therapy in the field of renal, bladder and prostate cancer.
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http://dx.doi.org/10.3332/ecancer.2020.1036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289610PMC
May 2020

Cutting-edge Management of Muscle-invasive Bladder Cancer in 2020 and a Glimpse into the Future.

Eur Urol Oncol 2020 12 15;3(6):789-801. Epub 2020 Jun 15.

Sorbonne University, GRC 5 Predictive ONCO-URO, AP-HP, Urology, Pitié-Salpêtrière Hospital, Paris, France. Electronic address:

This case-based discussion describes the clinical course of a 63-yr-old patient who presented with gross hematuria and was diagnosed with a muscle-invasive bladder cancer at transurethral resection. Computed tomography revealed a locally advanced tumor, and the patient underwent neoadjuvant chemotherapy followed by open radical cystectomy with standard pelvic lymph node dissection. In a step-by-step fashion, we elaborate on diagnostic and therapeutic treatment options from two different vantage points: (1) guideline-adherent treatment with the state-of-the-art standard of care, and (2) a glimpse into the future discussing the evidence of potential additional or alternative approaches based on recent scientific advances. PATIENT SUMMARY: In this case-based discussion, we follow the clinical course of a patient with advanced bladder cancer and elaborate how the state-of-the-art treatment looks like in 2020, based on the best available evidence. This is compared with potential future treatment strategies, which may change and alternate our understanding of optimal bladder cancer care.
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http://dx.doi.org/10.1016/j.euo.2020.06.001DOI Listing
December 2020

Establishment, Characterization, and Imaging of a First Platinum-resistant Penile Cancer Patient-derived Xenograft in Nude Mice: A eUROGEN Project.

Eur Urol 2020 08 11;78(2):294-296. Epub 2020 Jun 11.

Laboratory of Experimental Urology, Department of Development and Regeneration, KU Leuven, Department of Urology, University Hospitals Leuven, Leuven, Belgium. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2020.05.033DOI Listing
August 2020

Impact of concomitant acid suppressive therapy on pazopanib efficacy and dose reductions in patients with metastatic renal cell carcinoma.

Eur J Clin Pharmacol 2020 Sep 30;76(9):1273-1280. Epub 2020 May 30.

Pharmacy Department, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.

Purpose: The aim of this study was to investigate the impact of acid suppressive therapy on clinical efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma (mRCC).

Methods: A single-center retrospective study was carried out. Charts of mRCC patients who received pazopanib as first-line treatment were reviewed and concomitant use of proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) was studied. Two groups of patients were identified, namely patients receiving PPI/H2RA and patients without acid suppressive therapy. Both groups were compared with regard to progression free survival (PFS), overall survival (OS), tumor response, and time to dose reduction of pazopanib.

Results: Ninety-one patients were included. Median PFS was 8 months in the PPI/H2RA group vs. 7 months in the no PPI/H2RA group (hazard ratio (HR) 0.76 (95% confidence interval (CI) 0.42-1.35)), p = 0.35. Median OS was 27 months in the PPI/H2RA group vs. 23 months in the no PPI/H2RA group (HR 0.87 (95% CI 0.46-1.66)), p = 0.68. Mean tumor response was 17% (95% CI 8-25%) in the PPI/H2RA group vs. 11% (95% CI 0-21%) in the no PPI/H2RA group, p = 0.52. Median time to first dose reduction was 9 months in both subgroups (HR 1.25 (95% CI 0.65-2.39)), p = 0.51. Median time to second dose (< 600 mg) reduction was 17 months in the PPI/H2RA group vs. 7 months in the no PPI/H2RA group (HR 0.26 (95% CI 0.07-0.89)), p = 0.03.

Conclusion: In this limited patient series, no evidence of a negative impact of PPI/H2RA on clinical outcome and time to first dose reduction was observed. These results suggest that PPI/H2RA might be considered, when there is a clinical need, in patients treated with pazopanib for mRCC. However, a prospective study is warranted to confirm these results.
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http://dx.doi.org/10.1007/s00228-020-02902-3DOI Listing
September 2020

Metastasis-directed therapy in castration-refractory prostate cancer (MEDCARE): a non-randomized phase 2 trial.

BMC Cancer 2020 May 24;20(1):457. Epub 2020 May 24.

Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium.

Background: Patients diagnosed with metastatic castration-refractory prostate cancer (mCRPC) rely on a limited number of therapeutic agents resulting in a median survival of 2-3 years. A subgroup of those patients with mCRPC presents with oligoprogressive disease, with a limited number of progressive lesions while other metastases are still controlled by ongoing systemic treatment.

Methods: In this single arm prospective phase II trial, we aim to include 18 patients with oligoprogressive mCRPC (1-3 metastases and/or local recurrence) who will be treated with metastasis-directed therapy to all visible progressive lesions. Progression is based on conventional imaging, as the use of PSMA PET-CT is considered investigational. However all patients will undergo PSMA PET-CT and the images will be blinded until progression. Primary endpoint is the postponement of the start of next-line systemic treatment (NEST) and the additional clinical value of PSMA PET-CT. Recruitment of patients for this trial started in January 2020 and will be completed approximately by December 2020.

Discussion: In this phase 2 trial on oligoprogressive mCRPC, we will investigate the benefit of progression-directed therapy while continuing ongoing systemic treatment. We hypothesize that progression-directed therapy (PDT) with surgery or stereotactic body radiation therapy for these oligoprogressive lesions will postpone the start of next-line systemic treatment and therefore serve as a new or add-on therapy in the spectrum of treatments available for mCRPC. The results of this trial will serve as guidance for a later randomized phase 3 trial. All participants are given an information sheet and are required to give written informed consent. Results will be published in a peer-reviewed journal.

Trial Registration: This study is registered at ClinicalTrials.gov: NCT04222634 (December 18th 2019).
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http://dx.doi.org/10.1186/s12885-020-06853-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245754PMC
May 2020

Bone metastasis is associated with poor prognosis in metastatic papillary renal cell carcinoma patients treated with first agent angiogenesis inhibitors.

Urol Oncol 2020 08 17;38(8):686.e1-686.e9. Epub 2020 May 17.

Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. Electronic address:

Objective: Papillary renal cell carcinoma (papRCC) is a rare (10%-15%) subtype of renal cancer. Few prognostic biomarkers have been described in metastatic papRCC (m-papRCC) patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). We aimed to study the prognostic impact of bone metastases (BM) on response rate, progression-free and overall survival (PFS and OS) in patients with m-papRCC treated with first agent VEGFR-TKIs.

Patients And Methods: A multicentric, retrospective analysis of patient records was conducted. BM were detected by computed tomography and/or bone scintigraphy. The International Metastatic RCC Database Consortium (IMDC) score was calculated at start of first agent VEGFR-TKI treatment.

Results: Forty-nine patients were included. Best objective response was partial response in 20%, stable disease in 60% and early progressive disease in 20% of patients. Median PFS (mPFS) was 6.0 months and median OS (mOS) 14.0 months after start of first agent VEGFR-TKI. The IMDC score correlated with mOS: 77.5 months in good, 17.0 months in intermediate and 8.0 months in poor risk patients (P = 0.002). Patients with BM had a poorer outcome compared to patients without BM: mPFS was 4.0 vs. 7.0 months (P = 0.006) and mOS 7.5 vs. 19.0 months (P = 0.002). On bivariate analysis, the presence of BM was independently associated with PFS (P = 0.02) and OS (P = 0.049), independent of the IMDC risk groups.

Conclusion: In m-papRCC patients treated with first agent VEGFR-TKIs, the presence of BM is an unfavorable prognostic factor, associated with shorter PFS and OS.
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http://dx.doi.org/10.1016/j.urolonc.2020.04.031DOI Listing
August 2020

Site-specific relapse patterns of patients with biochemical recurrence following radical prostatectomy assessed by Ga-PSMA-11 PET/CT or C-Choline PET/CT: impact of postoperative treatments.

World J Urol 2021 Feb 16;39(2):399-406. Epub 2020 May 16.

Department of Urology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.

Background: Salvage radiotherapy (RT) (± androgen deprivation therapy (ADT)) is often used as a treatment in patients with biochemical recurrence (BCR) following radical prostatectomy (RP). Unfortunately, even after RT ± ADT, a significant number of patients will develop 'second' BCR. The aim of this study was to investigate the impact of postoperative treatments (adjuvant/salvage radiotherapy (RT) ± androgen deprivation therapy) on the recurrence pattern in patients with BCR following RP assessed by 11C-Choline PET/CT or 68 Ga-PSMA PET/CT.

Methods: Patients who developed BCR following RP and who had at least one positive lesion on PET/CT were retrospectively assessed. Positive spots were mapped as local, lymph node (LN), skeletal or visceral recurrence. A distinction was made between locoregional (prostate bed and pelvic LN) and extrapelvic recurrence (skeletal, visceral and/or extrapelvic LN). Patients were categorized according to postoperative treatment received in three subgroups (RT, ADT and RT + ADT) and compared with the reference group (RP only). The impact of the radiation field was also investigated.

Results: We identified 200 patients assessed by Ga-PSMA-11 (80%) or C-Choline PET/CT (20%). Patients who received postoperative RT + ADT had less LN recurrence distal to the common iliac bifurcation (26.7% vs 66.6%; p = 0.0004), but more recurrence to retroperitoneal LN than the reference group (38% vs. 14.4%, p = 0.02). Moreover, the RT + ADT subgroup had more extrapelvic recurrence compared to the reference group (66.2% vs 40.8%, p = 0.02). Patients who received RT to the prostate bed had more recurrence distal to the common iliac bifurcation compared to those who received RT to the prostate bed + pelvic LN (51.6% vs 26.1%, p = 0.0069).

Conclusion: Post-prostatectomy treatments (ADT and/or RT) and the postoperative radiation field (prostate bed vs. prostate bed + pelvis) have a significant impact on the recurrence pattern. This knowledge can help clinicians to counsel their patients on their chances of being eligible for (locoregional) metastasis-directed therapies.
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http://dx.doi.org/10.1007/s00345-020-03220-0DOI Listing
February 2021