Publications by authors named "Hendrik Van Poppel"

196 Publications

Neoadjuvant hormonal therapy before radical prostatectomy in high-risk prostate cancer.

Nat Rev Urol 2021 Sep 15. Epub 2021 Sep 15.

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

Patients with high-risk prostate cancer treated with curative intent are at an increased risk of biochemical recurrence, metastatic progression and cancer-related death compared with patients treated for low-risk or intermediate-risk disease. Thus, these patients often need multimodal therapy to achieve complete disease control. Over the past two decades, multiple studies on the use of neoadjuvant treatment have been performed using conventional androgen deprivation therapy, which comprises luteinizing hormone-releasing hormone agonists or antagonists and/or first-line anti-androgens. However, despite results from these studies demonstrating a reduction in positive surgical margins and tumour volume, no benefit has been observed in hard oncological end points, such as cancer-related death. The introduction of potent androgen receptor signalling inhibitors (ARSIs), such as abiraterone, apalutamide, enzalutamide and darolutamide, has led to a renewed interest in using neoadjuvant hormonal treatment in high-risk prostate cancer. The addition of ARSIs to androgen deprivation therapy has demonstrated substantial survival benefits in the metastatic castration-resistant, non-metastatic castration-resistant and metastatic hormone-sensitive settings. Intuitively, a similar survival effect can be expected when applying ARSIs as a neoadjuvant strategy in high-risk prostate cancer. Most studies on neoadjuvant ARSIs use a pathological end point as a surrogate for long-term oncological outcome. However, no consensus yet exists regarding the ideal definition of pathological response following neoadjuvant hormonal therapy and pathologists might encounter difficulties in determining pathological response in hormonally treated prostate specimens. The neoadjuvant setting also provides opportunities to gain insight into resistance mechanisms against neoadjuvant hormonal therapy and, consequently, to guide personalized therapy.
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http://dx.doi.org/10.1038/s41585-021-00514-9DOI Listing
September 2021

Molecular underpinnings of glandular tropism in metastatic clear cell renal cell carcinoma: therapeutic implications.

Acta Oncol 2021 Nov 27;60(11):1499-1506. Epub 2021 Aug 27.

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

Background: Glandular metastases (GM) have been associated with improved survival in metastatic clear cell renal cell carcinoma (m-ccRCC). We aimed to molecularly characterize m-ccRCC with GM.

Material And Methods: We performed a retrospective cohort study on all m-ccRCC patients with available tissue at our institution, diagnosed with metastatic disease from 2000 to 2019. We determined previously described angiogenesis- and immune-related gene expression signatures (GES) and ccrcc molecular subtypes through whole transcriptome RNA sequencing of primary tumors and metastases. We tested differences in GES and molecular subtypes across groups and studied overall (OS) and progression-free survival (PFS) using Kaplan-Meier survival analysis and Cox regression models.

Results: Primary tumors of patients who developed GM ( = 55) had higher IMmotion Angio ( < 0.001) and JAVELIN Angio ( = 0.003) GES as well as a higher proportion of angiogenic ccrcc2 molecular subtypes ( = 0.008) than primary tumors of patients with non-GM ( = 128). Metastatic lesions in glandular organs ( = 32) also had higher IMmotion Angio ( = 0.008) and JAVELIN Angio ( = 0.02) GES and were more frequently of the ccrcc2 molecular subtype ( = 0.03), compared to metastatic lesions in non-glandular organs in patients who did not develop any GM ( = 231), but not compared to metastatic lesions in non-glandular organs in patients who also developed GM ( = 18). Patients with GM had better OS (HR 0.49,  < 0.001) and PFS on first-line vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) (HR 0.64,  = 0.045) than patients with non-GM. PFS on first- or any-line immuno-oncology (IO) was not different. IMmotion Angio, JAVELIN Angio GES, and ccrcc2 molecular subtype were associated with better OS and PFS on first-line VEGFR-TKIs, but not PFS on first or any-line IO.

Conclusions: Patients with m-ccRCC who develop GM are molecularly characterized by heightened angiogenesis, translating into better prognosis and better outcomes on VEGFR-TKIs, but not IO. Based on these findings, VEGFR-TKIs should be included in the first-line treatment of m-ccRCC patients with GM.
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http://dx.doi.org/10.1080/0284186X.2021.1962971DOI Listing
November 2021

Prostate-specific Antigen Testing as Part of a Risk-Adapted Early Detection Strategy for Prostate Cancer: European Association of Urology Position and Recommendations for 2021.

Eur Urol 2021 Aug 15. Epub 2021 Aug 15.

Department of Urology, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden, Germany.

Background: Recommendations against prostate-specific antigen (PSA) testing in 2012 have increased advanced-stage diagnosis and prostate cancer-specific mortality rates.

Objective: To present the position of the European Association of Urology (EAU) in 2021 and provide recommendations for the use of PSA testing as part of a risk-adapted strategy for the early detection of prostate cancer.

Evidence Acquisition: The authors combined their review of relevant literature, including the EAU prostate cancer guidelines 2021 update, with their own knowledge to provide an expert opinion, representing the EAU's position in 2021.

Evidence Synthesis: The EAU has developed a risk-adapted early prostate cancer detection strategy for well-informed men based on PSA testing, risk calculators, and multiparametric magnetic resonance imaging, which can differentiate significant from insignificant prostate cancer. This approach largely avoids the overdiagnosis/overtreatment of men unlikely to experience disease-related symptoms during their lifetime and facilitates an early diagnosis of men with significant cancer to receive active treatment. It also reduces advanced-stage diagnosis, thereby potentially reducing prostate cancer-specific mortality and improving quality of life. Education is required among urologists, general practitioners, radiologists, policy makers, and healthy men, including endorsement by the European Commission to adapt the European Council's screening recommendations in its 2022 plan and requests to individual countries for its incorporation into national cancer plans.

Conclusions: This risk-adapted approach for the early detection of prostate cancer will reverse current unfavourable trends and ultimately save lives.

Patient Summary: The European Association of Urology has developed a patient information leaflet and algorithm for the early diagnosis of prostate cancer. It can identify men who do not need magnetic resonance imaging or a biopsy and those who would not show any symptoms versus those with more aggressive disease who require further tests/treatment. We need to raise awareness of this algorithm to ensure that all well-informed men at risk of significant prostate cancer are offered a prostate-specific antigen test. TAKE  HOME MESSAGE: A risk-adapted early prostate cancer detection strategy, incorporating prostate-specific antigen testing, multiparametric magnetic resonance imaging, risk calculators, and biomarkers, will avoid overdiagnosis/overtreatment of insignificant cancers and ensure early detection and treatment of significant cancers, thereby improving quality of life and reducing prostate cancer-related deaths.
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http://dx.doi.org/10.1016/j.eururo.2021.07.024DOI Listing
August 2021

A European Model for an Organised Risk-stratified Early Detection Programme for Prostate Cancer.

Eur Urol Oncol 2021 Aug 4. Epub 2021 Aug 4.

Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.

Context: Overdiagnosis as the argument to stop prostate cancer (PCa) screening is less valid since the introduction of new technologies such as risk calculators (RCs) and magnetic resonance imaging (MRI). These new technologies result in fewer unnecessary biopsy procedures and fewer cases of both overdiagnosis and underdetection. Therefore, we can now adequately respond to the growing and urgent need for a structured risk assessment to detect PCa early.

Objective: To provide expert discussion on the existing evidence for a previously published risk-stratified strategy regarding an organised population-based early detection programme for PCa.

Evidence Acquisition: The proposed algorithm for early detection of PCa emerged from expert consensus by the authors based on available evidence derived from a nonsystematic review of the current literature using Medline/PubMed, Cochrane Library database, ClinicalTrials.gov, ISRCTN Registry, and the European Association of Urology guidelines on PCa.

Evidence Synthesis: Although not confirmed by the highest level of evidence, current literature and guidelines point towards an algorithm for early detection of PCa that starts with risk-based prostate-specific antigen (PSA) testing, followed by multivariable risk stratification with RCs. All men who are classified to be at intermediate and high risk are then offered prostate MRI. The combined data from RCs and MRI results can be used to select men for prostate biopsy. Low-risk men return to a risk-based safety net that includes individualised PSA-interval tests and, if necessary, repeated MRI. Depending on local availability, the use of the different risk stratification tools may be adapted.

Conclusions: We present a risk-stratified algorithm for an organised population-based early detection programme for clinically significant PCa. Although the proposed strategy has not yet been analysed prospectively, it exploits and may even improve the most important available benefits of "PSA-only" screening studies, while at the same time reduces unnecessary biopsies and overdiagnosis by using new risk stratification tools.

Patient Summary: This paper presents a personalised strategy that enables selective early detection of prostate cancer by combining prostate-specific antigen (interval) testing' prediction models (risk calculators), and magnetic resonance imaging scans. This will likely lead to reduced prostate cancer-related morbidity and mortality, while reducing the need for prostate biopsy and limiting overdiagnosis.
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http://dx.doi.org/10.1016/j.euo.2021.06.006DOI Listing
August 2021

Molecular Subtypes and Gene Expression Signatures as Prognostic Features in Fully Resected Clear Cell Renal Cell Carcinoma: A Tailored Approach to Adjuvant Trials.

Clin Genitourin Cancer 2021 Jul 10. Epub 2021 Jul 10.

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

Background: Trials with adjuvant vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) failed to demonstrate meaningful benefit in clinically high-risk, fully resected clear cell renal cell carcinoma (ccRCC). We evaluated whether the ccrcc1-4 molecular subtypes and gene expression signatures (GES) are associated with outcomes in this setting.

Materials And Methods: We determined molecular subtypes as well as angiogenesis- and immune-related GES through RNA sequencing of 75 fresh frozen (FF) and 62 formalin-fixed, paraffin-embedded (FFPE) tumor samples. We studied disease-free (DFS) and overall survival (OS) and determined correlations among GES and Leibovich score.

Results: Angiogenesis-related GES and molecular subtypes were associated with longer DFS and OS across both cohorts, whereas immune-related GES were not. In the FF cohort, molecular subtypes (ccrcc2 & 3 vs. ccrcc1 & 4) were associated with DFS and OS, on bivariable analysis with Leibovich score (HR 0.62, 95%CI 0.39-0.98, P = .04 and HR 0.35, 95%CI 0.19-0.64, P < .001). In the FFPE cohort, molecular subtypes (ccrcc2 & 3 vs. ccrcc1&4) were also associated with DFS (HR 0.53, 95%CI 0.31-0.93, P = .03), but not OS (HR 0.59, 95%CI 0.31-1.13, P = .11) on bivariable analysis with Leibovich score. Leibovich score was significantly inversely correlated with all angiogenesis-related GES (all P < .01), but not correlated with immune-related GES.

Conclusions: Molecular subtypes and angiogenesis-related GES are prognostic for DFS and OS in fully resected, localized ccRCC. Favorable ccrcc2 & 3 molecular subtypes with high angiogenesis-related GES, which respond best to VEGFR-TKIs, are at lower risk of relapse but were probably underrepresented in the adjuvant VEGFR-TKI trials since they inversely correlate with Leibovich score. Conversely, immune-related GES are not correlated with Leibovich score and clinically high-risk tumors can display both high and low immune-related GES. Therefore, molecular characterization could guide patient selection for adjuvant treatment.
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http://dx.doi.org/10.1016/j.clgc.2021.07.005DOI Listing
July 2021

Definition and Impact on Oncologic Outcomes of Persistently Elevated Prostate-specific Antigen After Salvage Lymph Node Dissection for Node-only Recurrent Prostate Cancer After Radical Prostatectomy: Clinical Implications for Multimodal Therapy.

Eur Urol Oncol 2021 Jun 24. Epub 2021 Jun 24.

USC Institute of Urology, University of Southern California, Los Angeles, CA, USA.

Background: The optimal definition and prognostic significance of persistently elevated prostate-specific antigen (PSA) after salvage lymph node dissection (sLND) for node-only recurrent prostate cancer (PCa) remain unknown.

Objective: To assess the definition and clinical implications of persistently elevated PSA after sLND for node-only recurrent PCa after radical prostatectomy.

Design, Setting, And Participants: The study included 579 patients treated with sLND at 11 high-volume centers between 2000 and 2016.

Outcome Measurements And Statistical Analysis: We assessed the linear relationship between the first PSA after sLND and death from PCa. Different definitions of PSA persistence were included in a multivariable model predicting cancer-specific mortality (CSM) after surgery to identify the best cutoff value. We investigated the association between PSA persistence and oncologic outcomes using multivariable regression models. Moreover, the effect of early androgen deprivation therapy (ADT) after sLND was tested according to PSA persistence status and estimated risk of CSM.

Results And Limitations: We found an inverse relationship between the first PSA after sLND and the probability of cancer-specific survival. PSA persistence defined as first postoperative PSA ≥0.3 ng/ml provided the best discrimination accuracy (C index 0.757). According to this cutoff, 331 patients (57%) experienced PSA persistence. The median follow-up for survivors was 48 mo (interquartile range 27-74). After adjusting for confounders, men with persistently elevated PSA had higher risk of clinical recurrence (hazard ratio [HR] 1.61), overall mortality (HR 2.20), and CSM (HR 2.59; all p < 0.001) after sLND. Early ADT administration after sLND improved survival only for patients with PSA persistence after surgery (HR 0.49; p = 0.024). Similarly, when PSA persistence status was included in multivariable models accounting for pathologic features, early ADT use after sLND was beneficial only for patients with a predicted risk of CSM at 5 yr of >10%.

Conclusions: PSA persistence after sLND independently predicts adverse prognosis, with the best discrimination accuracy for CSM provided by a definition of PSA ≥ 0.3 ng/ml. We showed that when stratifying patients by final pathology results and PSA persistence status, early ADT use after sLND was beneficial only for patients with PSA persistence or with a calculated 5-yr risk of CSM of >10%, which could be useful as we await results from ongoing prospective trials.

Patient Summary: We found that for patients with prostate cancer who had lymph nodes removed after their cancer recurred, persistently elevated prostate-specific antigen (PSA) levels predict poorer prognosis. We showed that a PSA level of ≥0.3 ng/ml provides the best accuracy in identifying patients with worse prognosis. This may help to improve risk stratification after lymph node removal and allow physicians to optimize treatment strategies after surgery.
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http://dx.doi.org/10.1016/j.euo.2021.06.003DOI Listing
June 2021

Radium-223 in patients with prostate specific antigen (PSA) progression and without clinical metastases following maximal local therapy: A pilot study.

Urol Oncol 2021 Jun 4. Epub 2021 Jun 4.

Department of Urology, University Hospitals Leuven, Leuven, Belgium; Department of development and regenaration, Leuven, Belgium.

Background: Despite the curative intent of radical prostatectomy (RP) (+/- radiotherapy (RT)), 30% of the clinically localized prostate cancer (CaP) patients will develop rising PSA (prostate specific antigen). In absence of clinical recurrence, there is a lack of effective treatment strategies in order to control the disease at its earliest (micro)metastatic stage. The aim of this study was to assess safety, tolerability, and biochemical response of off-label Radium-223 (Xofigo) treatment in CaP patients with PSA relapse following maximal local therapy.

Methods: We conducted a prospective, single arm, single center open-label, pilot study with Radium-223 in CaP patients with rising PSA (>0.2 ng/ml) following RP + adjuvant/salvage RT. Negative staging with Ga-PSMA-11 PET/CT and whole-body MRI was mandatory at time of inclusion. Patients were eligible if they exhibited adverse clinico-pathological features predictive of significant recurrence. Safety, tolerability, biochemical progression (defined as PSA increase >50% from PSA nadir) and clinical recurrence were assessed.

Results: In total, 23 patients were screened of whom 8 patients were included is the study. Radium-223 treatment was safe with no serious treatment related adverse events. One patient developed grade 3 lymphopenia. All patients rapidly developed PSA progression (median PSA progression-free survival: 5.5 months). Eventually all patients experienced clinical recurrence (median clinical recurrence-free survival 11.0 months) of whom only 2 patients developed skeletal recurrence.

Conclusions: Radium-223 in patients with PSA relapse following maximal local treatment without clinical metastases is safe. However, the clinical benefit of Ra-223 in this setting is doubtful as significant oncological benefit is lacking.
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http://dx.doi.org/10.1016/j.urolonc.2021.04.034DOI Listing
June 2021

Neoadjuvant treatment with androgen receptor signaling inhibitors prior to radical prostatectomy: a systematic review.

World J Urol 2021 Sep 12;39(9):3177-3185. Epub 2021 Feb 12.

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

Context: There is an urgent need to develop novel treatment strategies in patients with unfavorable intermediate- and high-risk localized prostate cancer (PCa) to optimize the outcome of these patients. Androgen receptor signaling inhibitors (ARSI) have demonstrated a survival benefit in metastatic hormonesensitive and castration-resistant PCa. A similar benefit might be expected in the localized setting.

Objective: To perform a systematic review about the role of neoadjuvant ARSI in unfavorable intermediate and high-risk localized PCa.

Evidence Acquisition: We performed a systematic review of the following databases: MEDLINE (PubMed), EMBASE, Cochrane Library and Web of Science. Publications of ASCO were consulted to identify meeting abstract with early results of ongoing trials. This systematic review was performed and reported in accordance with the PRISMA guidelines.

Evidence Synthesis: Pathological complete response (pCR) following neoadjuvant ARSI treatment was observed in 4%-13% of the patients. Minimal residual disease response ranged from 36% to 73.9% when defined as residual cancer burden < 0.25 cm at final pathology and from 8% to 20% when defined as the diameter of the remaining tumor < 5 mm. Despite intense neoadjuvant ARSI treatment, residual pT3 disease was observed in 48%-76% of the patients. In contrast, positive surgical margins (PSM) were present in only 5%-22%. Only one trial reported BCR following neoadjuvant ARSI therapy (44% BCR at a median follow-up of 4 years).

Conclusion: Despite intense neoadjuvant ARSI therapy, pCR is rarely attained and high proportions of pT3 disease are still observed at final pathology. In contrast, promising results are obtained in terms of PSMs. Long-term survival outcomes are eagerly awaited.
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http://dx.doi.org/10.1007/s00345-021-03611-xDOI Listing
September 2021

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

Urol Oncol 2021 04 21;39(4):239.e17-239.e25. Epub 2021 Jan 21.

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
April 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

Early Detection of Prostate Cancer in 2020 and Beyond: Facts and Recommendations for the European Union and the European Commission.

Eur Urol 2021 03 29;79(3):327-329. Epub 2020 Dec 29.

Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.

The burden of prostate cancer is increasing. Therefore, we need to implement a contemporary, organized, risk-stratified program for early detection to reduce both the harm from the disease and potential overdiagnosis and overtreatment, while avoiding underdiagnosis to considerably improve the harm-to-benefit ratio.
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http://dx.doi.org/10.1016/j.eururo.2020.12.010DOI Listing
March 2021

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

Uro-oncology in the era of social distancing: the principles of patient-centered online consultations during the COVID-19 pandemic.

Cent European J Urol 2020 28;73(3):260-264. Epub 2020 Jul 28.

Department of Urology, University Hospital K.U. Leuven, Leuven, Belgium.

Introduction: The COVID-19 pandemic poses significant challenges to healthcare facilities and as per social distancing measures, many consultations are now being carried out via means of telemedicine. As some urologists may not be skilled with remote consultations, there is a need for recommendations on patient-centered online medical counseling.

Material And Methods: We have identified eight areas of excellence and defined the principles based on our experience.

Results: A professional setting should be provided, in which the privacy of the patient can be ensured. Accompanying persons should be encouraged into the consultation. Proper introduction could serve not only to verify the personality of the patient, but also to provide them with a sense of confidentiality. The interview should be held in a way to overcome the limitations of non-physical encounters, and pande-mic-specific issues should be taken into consideration. When arranging plans, the physician should judge accordingly in regards to what type of management is inevitable or safe, as well as available at this point; strict follow-up should be arranged. As home isolation may lead to unfavorable changes in lifestyle, this issue should be addressed too. The patient should be guided on how to self-educate. Concluding the visit should be aimed at proper evaluation of the patient's comprehension of the consultation.

Conclusions: It is vital to pursue consistency in providing care to patients. While online counseling may seem challenging, if one adheres to the principles of patient-centered practice, telemedicine may become a valuable tool in maintaining the best-quality care amid the ongoing pandemic.
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http://dx.doi.org/10.5173/ceju.2020.0171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587487PMC
July 2020

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

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

Propelling Health Care into the Twenties.

Biomed Hub 2020 May-Aug;5(2):15-67. Epub 2020 May 27.

Stockholm School of Economics (SSE), Stockholm, Sweden.

The scope and potential of personalised health care are underappreciated and underrealised, often because of resistance to change. The consequence is that many inadequacies of health care in Europe persist unnecessarily, and many opportunities for improvement are neglected. This article identifies the principal challenges, outlines possible approaches to resolving them, and highlights the benefits that could result from greater adoption of personalised health care. It locates the discussion in the context of European policy, focusing particularly on the most recent and authoritative reviews of health care in the EU Member States, and on the newly acquired spirit of readiness and pragmatism among European officials to embrace change and innovative technologies in a new decade. It highlights the attention now being given by policymakers to incentives, innovation, and investment as levers to improve European citizens' prospects in a rapidly evolving world, and how these distinct and disruptive themes contribute to a renaissance in thinking about delivering optimal health care in Europe. It explores the chances offered to patients by specific initiatives in health domains such as cancer and antimicrobial resistance, and by innovative science, novel therapies, earlier diagnosis tools, and deeper understanding of health promotion and prevention. And it reflects on how health care providers could benefit from a shift towards better primary care and towards deploying health data more effectively, including the use of artificial intelligence, coupled with a move to a smoother organisational/regulatory structure and realigned professional responsibilities. The conclusion is that preparing Europe's health care systems for the inevitable strains of the coming years is both possible and necessary. A more courageous approach to embracing personalised health care could guarantee the sustainability of Europe's health care systems before rising demands and exponential costs overwhelm them - an exercise in future-proofing, in ensuring that they are equipped to withstand whatever lies ahead. A focus on the potential and implementation of personalised care would permit more efficient use of resources and deliver better quality health-preserving care.
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http://dx.doi.org/10.1159/000508300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392387PMC
May 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

Considerations for the use of gonadotropin-releasing hormone agonists and antagonists in patients with prostate cancer.

Int J Urol 2020 10 13;27(10):830-837. Epub 2020 Jul 13.

Department of Urology, Lund University, Malmø, Sweden.

Prostate cancer is the second most common cause of cancer-related deaths in men, representing a major source of morbidity and mortality. Androgen deprivation therapy is the primary treatment for patients with advanced prostate cancer at disease presentation, which can be achieved either with surgical or chemical castration. The development of gonadotropin-releasing hormone agonists revolutionized the treatment of advanced prostate cancer, replacing the need for surgical castration. Agonists downregulate gonadotropin-releasing hormone agonist receptors in the pituitary gland, and thus decrease the release of luteinizing hormone and testosterone. Although agonists are a common therapeutic option to date, their use is associated with testosterone surges, metabolic dysfunction and an increase in the risk of cardiovascular disease; they might contribute to tumor flares and potentially an increase in non-cancer mortality. More recently, gonadotropin-releasing hormone antagonists have entered the prostate cancer treatment landscape. Unlike agonists, antagonists directly inhibit the androgen receptor in the pituitary gland, and thus do not cause initial testosterone surges. In this article, we provide a concise review of the mechanism of actions, safety and efficacy of the approved agonists and antagonists for prostate cancer treatment.
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http://dx.doi.org/10.1111/iju.14303DOI Listing
October 2020

Telemedicine and Smart Working: Recommendations of the European Association of Urology.

Eur Urol 2020 12 10;78(6):812-819. Epub 2020 Jul 10.

Department of Urology, La Paz University Hospital, Madrid, Spain; Young Academic Urologist-Urotechnology Working Party (ESUT-YAU), European Association of Urology, Arnhem, The Netherlands. Electronic address:

Context: Telemedicine provides remote clinical support using technological tools. It may facilitate health care delivery while reducing unnecessary visits to the clinic. The coronavirus disease 2019 (COVID-19) outbreak has caused an abrupt change in our daily urological practice, converting many of us to be reliant on telehealth.

Objective: To provide practical recommendations for effective use of technological tools in telemedicine.

Evidence Acquisition: A Medline-based and gray literature search was conducted through April 2020. We selected the most relevant articles related to "telemedicine" and "smart working" that could provide important information.

Evidence Synthesis: Telemedicine refers to the use of electronic information and telecommunications tools to provide remote clinical health care support. Smart working is a model of work that uses new or existing technologies to improve performance. Telemedicine is becoming a useful invaluable tool during and even beyond the COVID-19 pandemic. It is time for us to formalize the place of telemedicine in routine urological practice, and it is our responsibility to adapt and learn about all the tools and possible strategies for their optimal implementation during the pandemic to ensure that the quality of care received by patients and the outcomes of patients and their families are of the highest standard.

Conclusions: Telemedicine facilitates specialized urological clinical support at a distance, solves problems of limitations in mobility, reduces unnecessary visits to clinics, and is useful for reducing the risk of viral transmission in the current COVID-19 outbreak. Furthermore, both personal and societal considerations may favor continued use of telemedicine, even beyond the COVID-19 pandemic.

Patient Summary: Telemedicine in urology offers specialized remote clinical support to patients, similar to face-to-face visits. It is very useful for reducing unnecessary visits to the clinic, as well as reducing the risk of contagion in the current coronavirus disease 2019 (COVID-19) pandemic.
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http://dx.doi.org/10.1016/j.eururo.2020.06.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347487PMC
December 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

Long-term Outcomes of Salvage Lymph Node Dissection for Nodal Recurrence of Prostate Cancer After Radical Prostatectomy: Not as Good as Previously Thought.

Eur Urol 2020 11 2;78(5):661-669. Epub 2020 Jul 2.

Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy. Electronic address:

Background: Long-term outcomes of patients treated with salvage lymph node dissection (sLND) for nodal recurrence of prostate cancer (PCa) remain unknown.

Objective: To investigate long-term oncological outcomes after sLND in a large multi-institutional series.

Design, Setting, And Participants: The study included 189 patients who experienced prostate-specific antigen (PSA) rise and nodal-only recurrence after radical prostatectomy (RP) and underwent sLND at 11 tertiary referral centers between 2002 and 2011. Lymph node recurrence was documented by positron emission tomography/computed tomography (PET/CT) scan using either C-choline or Ga prostate-specific membrane antigen ligand.

Outcome Measurements And Statistical Analysis: The primary outcome of the study was cancer-specific mortality (CSM). The secondary outcomes were overall mortality, clinical recurrence (CR), biochemical recurrence (BCR), and androgen deprivation therapy (ADT)-free survival after sLND. The probability of freedom from each outcome was calculated using Kaplan-Meier analyses. Cox regression analysis was used to predict the risk of prostate CSM after accounting for several parameters, including the use of additional treatments after sLND.

Results And Limitations: At long term, 110 and 163 patients experienced CR and BCR, respectively, with CR-free and BCR-free survival at 10 yr of 31% and 11%, respectively. After sLND, a total of 145 patients received ADT, with a median time to ADT of 41 mo. At a median (interquartile range) follow-up for survivors of 87 (51, 104) mo, 48 patients died. Of them, 45 died from PCa. The probabilities of freedom from cancer-specific and all-cause death at 10 yr were 66% and 64%, respectively. Similar results were obtained in sensitivity analyses in patients with pelvic-only positive PET/CT scan, as well as after excluding men on ADT at PET/CT scan and patients with PSA level at sLND higher than the 75th percentile. At multivariable analyses, patients who had PSA response after sLND (hazard ratio [HR]: 0.45; p = 0.001), and those receiving ADT within 6 mo from sLND (HR: 0.51; p = 0.010) had lower risk of death from PCa.

Conclusions: A third of men treated with sLND for PET-detected nodal recurrence of PCa died at long term, with PCa being the main cause of death. Salvage LND alone was associated with durable long-term outcomes in a minority of men who significantly benefited from additional treatments after surgery. Taken together, all these data argue against the use of metastasis-directed therapy alone for patients with node-only recurrent PCa. These men should instead be considered at high risk of systemic dissemination already at the time of sLND.

Patient Summary: We assessed long-term outcomes of patients treated with salvage lymph node dissection (sLND) for node-recurrent prostate cancer (PCa). In contrast with prior evidence, we found that the majority of these men recurred after sLND and eventually died from PCa. A significant survival benefit associated with the administration of androgen deprivation therapy after sLND suggests that sLND should be considered part of a multimodal approach rather than an exclusive treatment strategy.
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http://dx.doi.org/10.1016/j.eururo.2020.06.043DOI Listing
November 2020

Assessing the Best Surgical Template at Salvage Pelvic Lymph Node Dissection for Nodal Recurrence of Prostate Cancer After Radical Prostatectomy: When Can Bilateral Dissection be Omitted? Results from a Multi-institutional Series.

Eur Urol 2020 12 2;78(6):779-782. Epub 2020 Jul 2.

Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.

The best surgical template for salvage pelvic lymph node dissection (sLND) in patients with nodal recurrence from prostate cancer (PCa) after radical prostatectomy (RP) is currently unknown. We analyzed data of 189 patients with a unilateral positive positron emission tomography (PET) scan of the pelvic lymph node areas, who were treated with bilateral pelvic sLND after RP at 11 high-volume centers. The primary endpoint was missed contralateral disease at final pathology, defined as lymph node positive for PCa in the side opposite to the positive spot(s) at the PET scan. Overall, 93 (49%) and 96 (51%) patients received a C-choline and a Ga prostate-specific membrane antigen (PSMA) PET scan, respectively, and 171 (90%) and 18 (10%) men had one and two positive spots, respectively. The rate of missed contralateral PCa was 18% (34/189), with the rates being 17% (29/171) and 28% (5/18) in men with one and two positive spots, respectively. While the rate of contralateral disease did not differ between Ga-PSMA and C-choline (29% and 27%, respectively) among men with two positive spots, the rate of contralateral PCa was only 6% with Ga-PSMA versus 28% with C-choline in patients with a single positive spot. This finding was confirmed at multivariable logistic regression analysis predicting missed disease at final pathology after accounting for confounders (odds ratio: 0.24; p =  0.001). However, in men with a single positive spot at Ga-PSMA PET/computed tomography, the rate of single confirmed lymph node metastasis at final pathology was only 33%, suggesting the need for extended template even if unilateral dissection is performed. Awaiting confirmatory studies, patients diagnosed with a single positive spot at the Ga-PSMA PET scan might be considered for unilateral extended pelvic sLND. PATIENT SUMMARY: We assessed the risk of missing contralateral disease in patients with a positron emission tomography (PET) scan suggestive of unilateral nodal recurrence from prostate cancer (PCa) after radical prostatectomy and who were treated with bilateral salvage lymph node dissection (sLND). Variability exists according to the number of positive spots and PET tracer, with the lowest rate of missed PCa in men diagnosed with a single positive spot at a Ga prostate-specific membrane antigen PET scan (6%). If replicated, our data suggest that these patients might be considered for unilateral extended pelvic sLND.
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http://dx.doi.org/10.1016/j.eururo.2020.06.047DOI Listing
December 2020

Upstaging to pT3a in Patients Undergoing Partial or Radical Nephrectomy for cT1 Renal Tumors: A Systematic Review and Meta-analysis of Outcomes and Predictive Factors.

Eur Urol Focus 2021 May 19;7(3):574-581. Epub 2020 Jun 19.

Division of Urology, VCU Health System, Richmond, VA, USA. Electronic address:

Context: Predictors of upstaging from cT1 to pT3a renal masses are poorly inquired, and this remains an area of controversial findings.

Objective: To evaluate predictors and outcomes of upstaging from cT1 to pT3a in patients undergoing surgical removal of a renal tumor.

Evidence Acquisition: A systematic literature search was performed to identify relevant articles using three electronic engines (PubMed, Embase, and Web of Science). Only studies looking at upstaging to pT3a in patients undergoing either partial nephrectomy (PN) or radical nephrectomy (RN) for cT1 renal tumor were included. Study selection was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement.

Evidence Synthesis: Thirteen studies, including 21869 patients (cT1/pT3a: 1256 [5.7%]; cT1/pT1: 20613 [93.3%]), were identified. Patients in the upstaged group were older (weighted mean difference [WMD]: 3.89; p < 0.00001) and mostly male (odds ratio [OR]: 1.23; p = 0.04). Renal tumors were larger (WMD: 0.98; p < 0.00001), more complex (OR: 2.38; p < 0.0001), and with a higher rate of cT1b masses (OR: 3.36; p < 0.00001). The cT1/pT3a group had a higher rate of other renal cell carcinoma histological subtypes (OR: 1.59; p = 0.04), as well as higher odds of Fuhrman grade ≥3 (OR: 2.57; p < 0.00001) and positive surgical margins (OR: 1.85; p = 0.007). Five-year recurrence-free survival (RFS) was worse in the upstaged group (OR: 0.31; p = 0.02). Age (OR: 1.03; p < 0.00001), tumor size (OR: 1.51; p < 0.00001), and RENAL score (OR: 2.80; p = 0.0004) were predictors of upstaging. Upstaging was associated with overall survival (hazard ratio [HR]: 1.94; p = 0.05), cancer-specific survival (HR: 2.24; p = 0.007), and RFS (HR: 2.17; p < 0.00001).

Conclusions: Upstaging to pT3a in case of surgical removal of a cT1 renal tumor is an uncommon event, which however can translate into worse oncological outcomes. Both patient (older age) and tumor (larger size and higher complexity) characteristics are associated with a higher risk of upstaging. There is very limited evidence regarding whether RN would be better than PN in these cases. There remains an unmet need for tools to better characterize renal masses in the preoperative setting.

Patients Summary: About 6% of surgically treated localized renal tumors can be found to be locally advanced on final pathology after surgery. This "upstaging" can translate into worse oncological outcomes. There are patient and tumor characteristics that are associated with an increased the risk of upstaging.
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http://dx.doi.org/10.1016/j.euf.2020.05.013DOI Listing
May 2021

Undergraduate Education for Urology in Europe. Where Do We Stand?

Eur Urol 2020 09 13;78(3):381-384. Epub 2020 Jun 13.

Department of Urology, Fundació Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain.

Regardless of career intentions, junior doctors will meet patients with urological problems. There are no studies on the status of undergraduate education for urology in Europe. We designed an 18-item online survey using the platform www.surveymonkey.com to assess the current status of undergraduate education in urology. A total of 347 medical students, trainees, and urologists responded to the survey. Medical students' exposure to urology during their undergraduate career was heterogeneous. Although the quality of urology education was valued from moderate to high, urology as a speciality did not influence their future training decision making. Decision making in relation to residency training correlated with the number of hours spent on practical training, duration of urology rotation, and year of medical school in which urological exposure was introduced. The current European exposure to urology at undergraduate level is heterogeneous, with various factors influencing future decisions regarding training and specialisation. A uniform undergraduate curriculum would eliminate such heterogeneous exposure and facilitate a workforce fit for the future urological needs. PATIENT SUMMARY: Junior doctors will meet patients with urological problems in the wards, emergency departments, and primary care. Institutions should work together for a urological curriculum that fits the future clinical requirements.
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http://dx.doi.org/10.1016/j.eururo.2020.05.037DOI Listing
September 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

European Association of Urology Guidelines Office Rapid Reaction Group: An Organisation-wide Collaborative Effort to Adapt the European Association of Urology Guidelines Recommendations to the Coronavirus Disease 2019 Era.

Eur Urol 2020 Jul 27;78(1):21-28. Epub 2020 Apr 27.

Department of Urology, Medical University of Innsbruck, Innsbruck, Austria.

The coronavirus disease 2019 (COVID-19) pandemic is unlike anything seen before by modern science-based medicine. Health systems across the world are struggling to manage it. Added to this struggle are the effects of social confinement and isolation. This brings into question whether the latest guidelines are relevant in this crisis. We aim to support urologists in this difficult situation by providing tools that can facilitate decision making, and to minimise the impact and risks for both patients and health professionals delivering urological care, whenever possible. We hope that the revised recommendations will assist urologist surgeons across the globe to guide the management of urological conditions during the current COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.eururo.2020.04.056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183974PMC
July 2020

Preoperative Risk-Stratification of High-Risk Prostate Cancer: A Multicenter Analysis.

Front Oncol 2020 6;10:246. Epub 2020 Mar 6.

Urology, Department of Development and Regeneration, University Hospitals Leuven, Leuven, Belgium.

Cancer-specific survival (CSS) within high-risk non-metastatic prostate cancer varies dramatically. It is likely that within this heterogenous population there are subgroup(s) at extraordinary risk, burdened with an exaptational poor prognosis. Establishing the characteristics of these group(s) would have significant clinical implications since high quality preoperative risk stratification remains the cornerstone of therapeutic decision making to date. To stratify high-risk prostate cancer based on preoperative characteristics and evaluate cancer specific survival after radical prostatectomy. The EMPaCT multi-center database offers an international population of non-metastatic high-risk prostate cancer. Preoperative characteristics such as age, biopsy Gleason score, PSA and clinical stage were subcategorized. A multivariate analysis was performed using predictors showing significant survival heterogeneity after stratification, as observed by a univariate analysis. Based upon the hazard ratios of this multivariate analysis, a proportional score system was created. The most ideal group distribution was evaluated trough different score cut-off's. The predictive value was tested by the herald C index. An overall 5-years CSS of 94% was noted within the entire high-risk cohort ( = 4,879). Except for age, all preoperative risk factors showed a significantly differing CSS. Multivariate analysis indicated, T4 stage as being the strongest predictor of CSS (HR: 3.31), followed by ISUP grade 5 group (HR 3,05). A score system was created by doubling the hazard ratios of this multivariate analysis and rounding off to the nearest complete number. Multivariate analysis suggested 0, 4, 8, and 12 pts as being the most optimal group distribution (-value: 0.0015). Five-years CSS of these groups were 97, 93, 87, and 70%, respectively. The calculated Herald C-index of the model was 0.77. An easy-to-use pre-operative model for risk stratification of newly diagnosed high-risk prostate cancer is presented. The heterogeneous CSS of high-risk non-metastatic prostate cancer after radical prostatectomy is illustrated. The model is clinically accessible through an online calculator, presenting cancer specific survival based on individualized patient characteristics.
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http://dx.doi.org/10.3389/fonc.2020.00246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068909PMC
March 2020

Underestimation of Positron Emission Tomography/Computerized Tomography in Assessing Tumor Burden in Prostate Cancer Nodal Recurrence: Head-to-Head Comparison of Ga-PSMA and C-Choline in a Large, Multi-Institutional Series of Extended Salvage Lymph Node Dissections.

J Urol 2020 Aug 18;204(2):296-302. Epub 2020 Feb 18.

Division of Oncology/Unit of Urology, URI; IRCCS Ospedale San Raffaele, Milan, Italy.

Purpose: We compared the use of C-choline and Ga-prostate specific membrane antigen in men undergoing salvage lymph node dissection for nodal recurrent prostate cancer.

Materials And Methods: The study included 641 patients who experienced prostate specific antigen rise and nodal recurrence after radical prostatectomy and underwent salvage lymph node dissection. Lymph node recurrence was documented by positron emission tomography/computerized tomography using C-choline (407, 63%) or Ga-PSMA ligand (234, 37%). The outcome was underestimation of tumor burden (difference between number of positive nodes on final pathology and number of positive spots at positron emission tomography/computerized tomography). Multivariable analysis tested the association between positron emission tomography/computerized tomography tracer (C-choline vs Ga-PSMA) and tumor burden underestimation.

Results: Overall the extent of tumor burden underestimation was significantly higher in the C-choline group compared to the Ga-PSMA group (p <0.0001), which was confirmed on multivariable analysis (p=0.028). Repeating these analyses according to prostate specific antigen, tumor burden underestimation was lower with Ga-PSMA only when prostate specific antigen was 1.5 ng/ml or less. Conversely, the underestimation of the 2 tracers became similar when prostate specific antigen was greater than 1.5 ng/ml. Furthermore, we evaluated the risk of underestimation by number of positive spots on positron emission tomography/computerized tomography. The higher the number of positive spots the higher the underestimation of tumor burden regardless of the tracer used (p=0.2).

Conclusions: Positron emission tomography/computerized tomography significantly underestimates the burden of prostate cancer recurrence, regardless of the tracer used. Ga-PSMA was associated with a lower rate of underestimation in patients with a prostate specific antigen below 1.5 ng/ml and a limited nodal tumor load. In all other men there was no benefit from Ga-PSMA over C-choline in assessing the extent of nodal recurrence.
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http://dx.doi.org/10.1097/JU.0000000000000800DOI Listing
August 2020
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