BACKGROUND AND OBJECTIVE:Given the uncertainty regarding the role of radical nephroureterectomy (RNU) as part of a multimodal treatment strategy for upper tract urothelial carcinoma (UTUC) patients with cN+ disease, we aimed to perform a systematic review and meta-analysis of the corresponding literature. METHODS:Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we identified 17 observational comparative and noncomparative studies, published between January 2000 and September 2024, evaluating UTUC patients with cTanyN+M0 disease (P) who received RNU as part of a multimodal treatment strategy (I), as compared with any treatment strategy if applicable (C), to assess oncological or postoperative outcomes (O). Meta-analyses were further performed, as appropriate. KEY FINDINGS AND LIMITATIONS:Overall, 15 studies evaluated the effectiveness of adding chemotherapy to RNU in the perioperative setting without specifying the exact timing of delivery (n = 1), in the induction setting (n = 14), or in the adjuvant setting (n = 5), while two studies evaluated the effectiveness of adding RNU to chemotherapy. Meta-analyses showed that the use of induction chemotherapy plus RNU versus RNU alone was associated with greater odds of pathological downstaging (risk ratio [RR] = 3.06; 95% confidence interval [CI] = [2.48-3.77]; p < 0.001; I2 = 0%; p = 0.44) and pathological complete nodal response (RR = 2.80; 95% CI = [2.03-3.86]; p < 0.001; I2 = 0%; p = 0.47) as well as prolonged overall survival (HR = 0.52; 95% CI = [0.42-0.64]; p < 0.001; I2 = 14%; p = 0.33) without any significant impact on the risk of overall (RR = 1.14; 95% CI = [0.79-1.64]; p = 0.48; I2 = 0%; p = 0.76) and major (RR = 0.48; 95% CI = [0.18-1.24]; p = 0.13; I2 = 0%; p = 0.87) postoperative complications. In addition, the use of induction chemotherapy plus RNU versus RNU plus adjuvant chemotherapy (HR = 0.58; 95% CI = [0.38-0.89]; p = 0.01) or chemotherapy alone (HR = 0.49; 95% CI = [0.32-0.76]; p = 0.001; I2 = 46%; p = 0.17) was associated with prolonged overall survival. Limitations include the observational design of all included studies. CONCLUSIONS AND CLINICAL IMPLICATIONS:The use of RNU could provide the greatest oncological benefits without any significant harm in selected UTUC patients with fit general condition and resectable cN+ disease responding to induction chemotherapy. PATIENT SUMMARY:In this report, we looked at the outcomes of radical surgery in combination with systemic chemotherapy for upper tract urothelial carcinoma with clinical evidence of dissemination to the surrounding lymph nodes. We observed that the use of radical surgery was associated with the greatest oncological benefits without any increased risk of postoperative complications in patients with fit general condition and resectable disease responding to induction chemotherapy. We conclude that the use of induction chemotherapy plus radical surgery could be the best multimodal treatment strategy for these patients.

BJU InternationalEarly View Research Letter The FocAL therapy CONsensus (FALCON): enhancing partial gland ablation for localised prostate cancer Lara Rodríguez-Sánchez, Corresponding Author Lara Rodríguez-Sánchez [email protected] orcid.org/0000-0001-6939-2645 Urology Department, Institut Mutualiste Montsouris, Paris, France Correspondence: Lara Rodríguez-Sánchez, Urology Department, Institut Mutualiste Montsouris, Paris, France. e-mail: [email protected]Search for more papers by this authorRobert Reiter, Robert Reiter Department of Urology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USASearch for more papers by this authorAlejandro Rodríguez, Alejandro Rodríguez orcid.org/0000-0001-8954-153X Department of Urology, Atrium Health Wake Forest Baptist Medical Center, Winston Salem, North Carolina, USASearch for more papers by this authorMark Emberton, Mark Emberton orcid.org/0000-0003-4230-0338 Division of Surgery and Interventional Science, University College London, London, UKSearch for more papers by this authorTheo de Reijke, Theo de Reijke Amsterdam UMC, department of Urology, University of Amsterdam, Amsterdam, The NetherlandsSearch for more papers by this authorEva M. Compérat, Eva M. Compérat Department of Pathology, Medical University of Vienna, General Hospital of Vienna, Vienna, AustriaSearch for more papers by this authorAlberto Bossi, Alberto Bossi Genitourinary Oncology, Prostate Brachytherapy Unit, Gustave Roussy, Paris, FranceSearch for more papers by this authorRafael Sanchez-Salas, Rafael Sanchez-Salas Department of Surgery, Division of Urology, McGill University, Montreal, Quebec, CanadaSearch for more papers by this author Lara Rodríguez-Sánchez, Corresponding Author Lara Rodríguez-Sánchez [email protected] orcid.org/0000-0001-6939-2645 Urology Department, Institut Mutualiste Montsouris, Paris, France Correspondence: Lara Rodríguez-Sánchez, Urology Department, Institut Mutualiste Montsouris, Paris, France. e-mail: [email protected]Search for more papers by this authorRobert Reiter, Robert Reiter Department of Urology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USASearch for more papers by this authorAlejandro Rodríguez, Alejandro Rodríguez orcid.org/0000-0001-8954-153X Department of Urology, Atrium Health Wake Forest Baptist Medical Center, Winston Salem, North Carolina, USASearch for more papers by this authorMark Emberton, Mark Emberton orcid.org/0000-0003-4230-0338 Division of Surgery and Interventional Science, University College London, London, UKSearch for more papers by this authorTheo de Reijke, Theo de Reijke Amsterdam UMC, department of Urology, University of Amsterdam, Amsterdam, The NetherlandsSearch for more papers by this authorEva M. Compérat, Eva M. Compérat Department of Pathology, Medical University of Vienna, General Hospital of Vienna, Vienna, AustriaSearch for more papers by this authorAlberto Bossi, Alberto Bossi Genitourinary Oncology, Prostate Brachytherapy Unit, Gustave Roussy, Paris, FranceSearch for more papers by this authorRafael Sanchez-Salas, Rafael Sanchez-Salas Department of Surgery, Division of Urology, McGill University, Montreal, Quebec, CanadaSearch for more papers by this author First published: 13 April 2024 https://doi.org/10.1111/bju.16360Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1Hopstaken JS, Bomers JGR, Sedelaar MJP, Valerio M, Fütterer JJ, Rovers MM. An updated systematic review on focal therapy in localized prostate cancer: what has changed over the past 5 years? Eur Urol 2022; 81: 5–33 10.1016/j.eururo.2021.08.005 PubMedWeb of Science®Google Scholar 2Ong S, Chen K, Grummet J et al. Guidelines of guidelines: focal therapy for prostate cancer, is it time for consensus? BJU Int 2023; 131: 20–31 10.1111/bju.15883 PubMedWeb of Science®Google Scholar 3Nasa P, Jain R, Juneja D. Delphi methodology in healthcare research: how to decide its appropriateness. World J Methodol 2021; 11: 116–129 10.5662/wjm.v11.i4.116 PubMedGoogle Scholar 4 COMET. Initiative. DelphiManager. Available at: https://www.comet-initiative.org/delphimanager/ [Accessed November 28, 2023]. Google Scholar 5Rodríguez-Sánchez L, Emberton M, de Reijke T et al. 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The authors regret that the author 'Maurizio Colecchia' was not included in the author list. This has now been corrected as above. The authors would like to apologise for any inconvenience caused. Proposal for a Novel Histological Scoring System as a Potential Grading Approach for Muscle-invasive Urothelial Bladder Cancer Correlating with Disease Aggressiveness and Patient OutcomesEuropean Urology OncologyPreviewTake Home Message Grading of muscle-invasive bladder cancer according to the current World Health Organization criteria is controversial due to its limited prognostic value. We propose a specific, prognostically relevant scoring system for muscle-invasive bladder cancer integrating histomorphological phenotype, stromal tumor infiltrating lymphocytes, tumor budding, and growth and spreading patterns. Full-Text PDF Open Access

BackgroundGrading of muscle-invasive bladder cancer (MIBC) according to the current World Health Organization (WHO) criteria is controversial due to its limited prognostic value. All MIBC cases except a tiny minority are of high grade.ObjectiveTo develop a prognostic histological scoring system for MIBC integrating histomorphological phenotype, stromal tumor-infiltrating lymphocytes (sTILs), tumor budding, and growth and spreading patterns.Design, setting, and participantsTissue specimens and clinical data of 484 patients receiving cystectomy and lymphadenectomy with curative intent with or without adjuvant chemotherapy. Histomorphological phenotypes, sTILs, tumor budding, and growth and spreading patterns were evaluated and categorized into four grade groups (GGs). GGs were correlated with molecular subtypes, immune infiltration, immune checkpoint expression, extracellular matrix (ECM) remodeling, and epithelial-mesenchymal transition (EMT) activity.Outcome measurements and statistical analysisGGs were associated with overall (OS), disease-specific (DSS), and progression-free (PFS) survival in univariable and multivariable analyses. Association with biological features was analyzed with descriptive statistics.Results and limitationsIntegration of two histomorphological tumor groups, three sTILs groups, three tumor budding groups, and four growth/spread patterns yielded four novel GGs that had high significance in the univariable survival analysis (OS, DSS, and PFS). GGs were confirmed as independent prognostic predictors with the greatest effect in the multivariable Cox regression analysis. Correlation with molecular data showed a gradual transition from basal to luminal subtypes from GG1 to GG4; a gradual decrease in survival, immune infiltration, and immune checkpoint activity; and a gradual increase in ECM remodeling and EMT activity.ConclusionsWe propose a novel, prognostically relevant, and biologically based scoring system for MIBC in cystectomies applicable to routine pathological sections.Patient summaryWe developed a novel approach to assess the aggressiveness of advanced bladder cancer, which allows improved risk stratification compared with the method currently proposed by the World Health Organization.

The fifth-edition of World Health Organization (WHO) Classification of Tumors series for urinary and male genital tract tumors has been published, six years later the fourth-edition. In these years, new treatment approaches have been implemented and new molecular data on urological cancers are known.Morphology remains the groundwork for taxonomy of the urinary tract tumors. However, a molecular approach to classification of urothelial carcinomas and the management of selected neoplasms with new therapeutic modalities such as immunotherapy are emerging. More data are needed for the application of these advances in routine pathology practice and patient management.The 2022 World Health Organization (WHO) Classification of Tumors of the Urinary System and Male Genital Organs represents an update in classification on urinary tract tumors. It also offers new insights with regards to the grading of heterogeneous non-invasive urothelial neoplasms, the definition of inverted neoplasms, the grading of invasive urothelial carcinomas, the diversity of morphological appearance of urothelial carcinomas, the definition of precursor lesions and the lineage of differentiation of the tumors.

Background: Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC) is a rela-tively rare diagnosis with an ambiguous character owing to the presence of an aggres-sive G3 component together with the lower malignant potential of the Ta component. The European Association of Urology (EAU) NMIBC guidelines recently changed the risk stratification for Ta G3 from high risk to intermediate, high, or very high risk. However, prognostic studies on Ta G3 carcinomas are limited and inconclusive.Objective: To evaluate the prognostic value of categorizing Ta G3 compared to Ta G2 and T1 G3 carcinomas.Design, setting, and participants: Individual patient data for 5170 primary Ta-T1 blad-der tumors from 17 hospitals were analyzed. Transurethral resection of the tumor was performed between 1990 and 2018.Outcome measurements and statistical analysis: Time to recurrence and time to progres-sion were analyzed using cumulative incidence functions, log-rank tests, and multivari-able Cox-regression models with interaction terms stratified by institution.Results and limitations: Ta G3 represented 7.5% (387/5170) of Ta-T1 carcinomas of which 42% were classified as intermediate risk. Time to recurrence did not differ between Ta G3 and Ta G2 (p = 0.9) or T1 G3 (p = 0.4). Progression at 5 yr occurred for 3.6% (95% confidence interval [CI] 2.7-4.8%) of Ta G2, 13% (95% CI 9.3-17%) of Ta G3, and 20% (95% CI 17-23%) of T1 G3 carcinomas. Time to progression for Ta G3 was shorter than for Ta G2 (p < 0.001) and longer than for T1 G3 (p = 0.002). Patients with Ta G3 NMIBC with concomitant carcinoma in situ (CIS) had worse prognosis and a similar time to progression as for patients with T1 G3 NMIBC with CIS (p = 0.5). Multivariable anal-yses for recurrence and progression showed similar results. Conclusions: The prognosis of Ta G3 tumors in terms of progression appears to be in between that of Ta G2 and T1 G3. However, patients with Ta G3 NMIBC with concomi-tant CIS have worse prognosis that is comparable to that of T1 G3 with CIS. Our results support the recent EAU NMIBC guideline changes for more refined risk stratification of Ta G3 tumors because many of these patients have better prognosis than previously thought.Patient summary: We used data from 17 centers in Europe and Canada to assess the prognosis for patients with stage Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC). Time to cancer progression for Ta G3 cancer differed from both Ta G2 and T1 G3 tumors. Our results support the recent change in the European Association of Urology guidelines for more refined risk stratification of Ta G3 NMIBC because many patients with this tumor have better prognosis than previously thought.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

We present the rationale for keeping the "cancer" label for grade group 1 (GG1) prostate cancer. Maintaining GG1 as the lowest grade outweighs the potential benefits that a benign designation may bring. Patient and surgeon education on the vital role of active surveillance for GG1 cancers and avoidance of overtreatment should be the focus rather than such a drastic change in nomenclature.

Context: The European Association of Urology (EAU) guidelines panel on upper urinary tract urothelial carcinoma (UTUC) has updated the guidelines to aid clinicians in evidence-based management of UTUC. Objective: To provide an overview of the EAU guidelines on UTUC as an aid to clinicians. Evidence acquisition: The recommendations provided in these guidelines are based on a review of the literature via a systematic search of the PubMed, Ovid, EMBASE, and Cochrane databases. Data were searched using the following keywords: urinary tract cancer, urothelial carcinomas, renal pelvis, ureter, bladder cancer, chemotherapy, ure-teroscopy, nephroureterectomy, neoplasm, (neo)adjuvant treatment, instillation, recur-rence, risk factors, metastatic, immunotherapy, and survival. The results were assessed by a panel of experts. Evidence synthesis: Even though data are accruing, for many areas there is still insuffi-cient high-level evidence to provide strong recommendations. Patient stratification on the basis of histology and clinical examination (including imaging) and assessment of patients at risk of Lynch syndrome will aid management. Kidney-sparing management should be offered as a primary treatment option to patients with low-risk UTUC and two functional kidneys. In particular, for patients with high-risk or metastatic UTUC, new treatment options have become available. In high-risk UTUC, platinum-based chemotherapy after radical nephroureterectomy, and adjuvant nivolumab for unfit or patients who decline chemotherapy, are options. For metastatic disease, gemcitabine/carboplatin chemotherapy is recommended as first-line treatment for cisplatinineligible patients. Patients with PD-1/PD-L1-positive tumours should be offered a checkpoint inhibitor (pembrolizumab or atezolizumab). Conclusions: These guidelines contain information on the management of individual patients according to the current best evidence. Urologists should take into account the specific clinical characteristics of each patient when determining the optimal treatment regimen according to the risk stratification of these tumours. Patient summary: Cancer of the upper urinary tract is rare, but because 60% of these tumours are invasive at diagnosis, timely and appropriate diagnosis is most important. A number of known risk factors exist. & COPY; 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.

A re-transurethral resection of the bladder (re-TURB) is a well-established approach in managing non-muscle invasive bladder cancer (NMIBC) for various reasons: repeat-TURB is recommended for a macroscopically incomplete initial resection, restaging-TURB is required if the first resection was macroscopically complete but contained no detrusor muscle (DM) and second-TURB is advised for all completely resected T1-tumors with DM in the resection specimen. This study assessed the long-term outcomes after repeat-, second-, and restaging-TURB in T1-NMIBC patients. Individual patient data with tumor characteristics of 1660 primary T1-patients (muscle-invasion at re-TURB omitted) diagnosed from 1990 to 2018 in 17 hospitals were analyzed. Time to recurrence, progression, death due to bladder cancer (BC), and all causes (OS) were visualized with cumulative incidence functions and analyzed by log-rank tests and multivariable Cox-regression models stratified by institution. Median follow-up was 45.3 (IQR 22.7–81.1) months. There were no differences in time to recurrence, progression, or OS between patients undergoing restaging (135 patients), second (644 patients), or repeat-TURB (84 patients), nor between patients who did or who did not undergo second or restaging-TURB. However, patients who underwent repeat-TURB had a shorter time to BC death compared to those who had second- or restaging-TURB (multivariable HR 3.58, P = 0.004). Prognosis did not significantly differ between patients who underwent restaging- or second-TURB. However, a worse prognosis in terms of death due to bladder cancer was found in patients who underwent repeat-TURB compared to second-TURB and restaging-TURB, highlighting the importance of separately evaluating different indications for re-TURB.

Context: The European Association of Urology (EAU) has released an updated version of the guidelines on non-muscle-invasive bladder cancer (NMIBC). Objective: To present the 2021 EAU guidelines on NMIBC. Evidence acquisition: A broad and comprehensive scoping exercise covering all areas of the NMIBC guidelines since the 2020 version was performed. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries. Previous guidelines were updated, and the level of evidence and grade of recommendation were assigned. Evidence synthesis: Tumours staged as Ta, T1 and carcinoma in situ (CIS) are grouped under the heading of NMIBC. Diagnosis depends on cystoscopy and histological evaluation of tissue obtained via transurethral resection of the bladder (TURB) for papillary tumours or via multiple bladder biopsies for CIS. For papillary lesions, a complete TURB is essential for the patient's prognosis and correct diagnosis. In cases for which the initial resection is incomplete, there is no muscle in the specimen, or a T1 tumour is detected, a second TURB should be performed within 2-6 wk. The risk of progression may be estimated for individual patients using the 2021 EAU scoring model. On the basis of their individual risk of progression, patients are stratified as having low, intermediate, high, or very high risk, which is pivotal to recommending adjuvant treatment. For patients with tumours presumed to be at low risk and for small papillary recurrences detected more than 1 yr after a previous TURB, one immediate chemotherapy instillation is recommended. Patients with an intermediate-risk tumour should receive 1 yr of full-dose intravesical bacillus Calmette-Guerin (BCG) immunotherapy or instillations of chemo therapy for a maximum of 1 yr. For patients with high-risk tumours, full-dose intravesical BCG for 1-3 yr is indicated. For patients at very high risk of tumour progression, immediate radical cystectomy should be considered. Cystectomy is also recommended for BCG-unresponsive tumours. The extended version of the guidelines is available on the EAU website at https://uroweb.org/guideline/non-muscle-invasive-bladder-cancer/. Conclusions: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice. Patient summary: The European Association of Urology has released updated guidelines on the classification, risk factors, diagnosis, prognostic factors, and treatment of non- muscle-invasive bladder cancer. The recommendations are based on the literature up to 2020, with emphasis on the highest level of evidence. Classification of patients as having low, intermediate, or and high risk is essential in deciding on suitable treatment. Surgical removal of the bladder should be considered for tumours that do not respond to bacillus Calmette-Guerin (BCG) treatment and tumours with the highest risk of progression. (c) 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.

The fifth edition of the WHO Classification of Tumours of the Urinary and Male Genital Systems encompasses several updates to the classification and diagnosis of prostatic carcinoma as well as incorporating advancements in the assessment of its prognosis, including recent grading modifications. Some of the salient aspects include: (1) recognition that prostatic intraepithelial neoplasia (PIN)‐like carcinoma is not synonymous with a pattern of ductal carcinoma, but better classified as a subtype of acinar adenocarcinoma; (2) a specific section on treatment‐related neuroendocrine prostatic carcinoma in view of the tight correlation between androgen deprivation therapy and the development of prostatic carcinoma with neuroendocrine morphology, and the emerging data on lineage plasticity; (3) a terminology change of basal cell carcinoma to “adenoid cystic (basal cell) cell carcinoma” given the presence of an underlying MYB::NFIB gene fusion in many cases; (4) discussion of the current issues in the grading of acinar adenocarcinoma and the prognostic significance of cribriform growth patterns; and (5) more detailed coverage of intraductal carcinoma of prostate (IDC‐P) reflecting our increased knowledge of this entity, while recommending the descriptive term atypical intraductal proliferation (AIP) for lesions falling short of IDC‐P but containing more atypia than typically seen in high‐grade prostatic intraepithelial neoplasia (HGPIN). Lesions previously regarded as cribriform patterns of HGPIN are now included in the AIP category. This review discusses these developments, summarising the existing literature, as well as the emerging morphological and molecular data that underpins the classification and prognostication of prostatic carcinoma.

The 5th edition of the WHO Classification of Tumours of the Urinary and Male Genital Systems contains relevant revisions and introduces a group of molecularly defined renal tumour subtypes. Herein we present the World Health Organization (WHO) 2022 perspectives on papillary and chromophobe renal cell carcinoma with emphasis on their evolving classification, differential diagnosis, and emerging entities. The WHO 2022 classification eliminated the type 1/2 papillary renal cell carcinoma (pRCC) subcategorization, given the recognition of frequent mixed tumour phenotypes and the existence of entities with a different molecular background within the type 2 pRCC category. Additionally, emerging entities such as biphasic squamoid alveolar RCC, biphasic hyalinising psammomatous RCC, papillary renal neoplasm with reverse polarity, and Warthin-like pRCC are included as part of the pRCC spectrum, while additional morphological and molecular data are being gathered. In addition to oncocytomas and chromophobe renal cell carcinoma (chRCC), a category of 'other oncocytic tumours' with oncocytoma/chRCC-like features has been introduced, including emerging entities, most with TSC/mTOR pathway alterations (eosinophilic vacuolated tumour and so-called 'low-grade' oncocytic tumour), deserving additional research. Eosinophilic solid and cystic RCC was accepted as a new and independent tumour entity. Finally, a highly reproducible and clinically relevant universal grading system for chRCC is still missing and is another niche of ongoing investigation. This review discusses these developments and highlights emerging morphological and molecular data relevant for the classification of renal cell carcinoma.

The 5th edition of the World Health Organisation Blue Book was published recently and includes a comprehensive update on testicular tumours. This builds upon the work of the 4th edition, retaining its structure and main nomenclature, including the use of the term ‘germ cell neoplasia in situ’ (GCNIS) for the pre‐invasive lesion of most germ cell tumours and division from those not derived from GCNIS. While there have been important developments in understanding the molecular underpinnings of testicular cancer, this updated classification paradigm and approach remains rooted in morphology. Nomenclature changes include replacement of the term ‘primitive neuroectodermal tumour’ by ‘embryonic neuroectodermal tumour’ based on the non‐specificity of the former term and to separate these tumours clearly from Ewing sarcoma. Seminoma is placed in a germinoma family of tumours emphasising relation to those tumours at other sites. Criteria for the diagnosis of ‘teratoma with somatic transformation’ have been modified to not include variable field size assessments. The word ‘carcinoid’ has been changed to ‘neuroendocrine tumour’, with most examples in the testis now classified as ‘prepubertal type testicular neuroendocrine tumour’. For sex cord‐stromal tumours, the use of mitotic counts per high‐power field has been changed to per mm2 for malignancy assessments, and the new entities, ‘signet ring stromal tumour’ and ‘myoid gonadal stromal tumour’, are defined. Well‐differentiated papillary mesothelial tumour has now been defined as tumour type with a favourable prognosis. Sertoliform cystadenoma has been removed as an entity from testicular adnexal tumours and placed with Sertoli cell tumours.

Purpose of review Due to the limited number of cases, there are no guidelines for basal cell carcinoma (BCC) of the prostate. This review combines an unpublished case report of a 55-year-old patient with BCC with an assessment of the latest literature. Recent findings BCC of the prostate has previously been described in only approximately 140 cases. We describe the diagnostic process, including the uropathological and DNA-sequencing results, which allowed us to start an experimental treatment with pemigatinib. BCC of the prostate is associated with an aggressive biological and clinical behavior, such as recurrence and metastasis. Several immunohistochemical stainings are available to differentiate BCC from adenocarcinoma of the prostate. Based on pathology and results from next-generation sequencing (NGS), patients can be offered targeted therapies. Summary With the aid of histological work-up and immunostaining, prostatic BCC can be accurately diagnosed. Our patient underwent radical prostatectomy and staged extended lymphadenectomy due to lymph node recurrence. The patient subsequently developed progressive disease and was treated with the FGFR-inhibitor pemigatinib. The patient's liver metastasis significantly responded. The present case confirms the possibility of aggressive behavior of prostatic BCC and highlights the importance of a thorough uropathological and molecular biological analysis with a precision medicine strategy.

Context: Treatment of metastatic urothelial carcinoma is currently undergoing a rapid evolution. Objective: This overview presents the updated European Association of Urology (EAU) guidelines for metastatic urothelial carcinoma. Evidence acquisition: A comprehensive scoping exercise covering the topic of metastatic urothelial carcinoma is performed annually by the Guidelines Panel. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. Evidence synthesis: Platinum-based chemotherapy is the recommended first-line standard therapy for all patients fit to receive either cisplatin or carboplatin. Patients positive for programmed death ligand 1 (PD-L1) and ineligible for cisplatin may receive immunotherapy (atezolizumab or pembrolizumab). In case of nonprogressive disease on platinum-based chemotherapy, subsequent maintenance immunotherapy (avelumab) is recommended. For patients without maintenance therapy, the recommended second-line regimen is immunotherapy (pembrolizumab). Later-line treatment has undergone recent advances: the antibody-drug conjugate enfortumab vedotin demonstrated improved overall survival and the fibroblast growth factor receptor (FGFR) inhibitor erdafitinib appears active in case of FGFR3 alterations. Conclusions: This 2021 update of the EAU guideline provides detailed and contemporary information on the treatment of metastatic urothelial carcinoma for incorporation into clinical practice. Patient summary: In recent years, several new treatment options have been introduced for patients with metastatic urothelial cancer (including bladder cancer and cancer of the upper urinary tract and urethra). These include immunotherapy and targeted treatments. This updated guideline informs clinicians and patients about optimal tailoring of treatment of affected patients. (c) 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Context: Active surveillance (AS) of biopsy-proven renal oncocytomas may reduce overtreatment. However, on biopsy, the risk of misdiagnosis owing principally to entities with peculiar hybrids and overlap morphology, and phenotypes argues for early intervention. Objective: To assess the benefit and harm of AS in biopsy-proven renal oncocytoma. Evidence acquisition: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). We systematically searched PubMed, Scopus, and Web of Science databases from September 26 up to October 2021, for studies that analyzed the outcomes of AS in patients with biopsy-proven renal oncocytoma. Evidence synthesis: A total of ten studies with 633 patients met our inclusion criteria and were included for analysis. After a median follow-up of 34.5 mo (95% confidence interval [CI] 30.6-38.4), the overall definitive treatment rate from AS to definitive treatment was 17.3% (n = 75/433, six studies). The pooled pathological agreement between the initial renal mass biopsy and the surgical pathology report was 91.1%. The main indications for surgery during follow-up were rapid tumor growth and patient request. The pooled median growth rate was 1.55 mm/yr (95% CI 0.9-2.2). No metastasis or death related to renal oncocytoma was reported. Conclusions: Annual tumor growth of biopsy-proven renal oncocytoma is low. AS is oncologically safe, with favorable compliance of patients. Crossover to definitive treatment revealed a strong concordance between biopsy and final pathology. Further studies on the long-term outcomes of AS are needed. Patient summary: In this study, we examined the benefit and harm of active surveillance (AS) in biopsy-proven oncocytoma. Based on the available data, AS appears oncologically safe and may represent a promising alternative to immediate treatment. Patients should be included in AS decision discussions. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.

The fifth edition of the World Health Organization (WHO) classification of urogenital tumours (WHO "Blue Book"), published in 2022, contains significant revisions. This review summarises the most relevant changes for renal, penile, and testicular tumours. In keeping with other volumes in the fifth edition series, the WHO classification of urogenital tumours follows a hierarchical classification and lists tumours by site, category, family, and type. The section "essential and desirable diagnostic criteria" included in the WHO fifth edition represents morphologic diagnostic criteria, combined with immunohistochemistry and relevant molecular tests. The global introduction of massive parallel sequencing will result in a diagnostic shift from morphology to molecular analyses. Therefore, a molecular-driven renal tumour classification has been introduced, taking recent discoveries in renal tumour genomics into account. Such novel molecularly defined epithelial renal tumours include SMARCB1-deficient medullary renal cell carcinoma (RCC), TFEB-altered RCC, Alk-rearranged RCC, and ELOC-mutated RCC. Eosinophilic solid and cystic RCC is a novel morphologically defined RCC entity. The diverse morphologic patterns of penile squamous cell carcinomas are grouped as human papillomavirus (HPV) associated and HPV independent, and there is an attempt to simplify the morphologic classification. A new chapter with tumours of the scrotum has been introduced. The main nomenclature of testicular tumours is retained, including the use of the term "germ cell neoplasia in situ" (GCNIS) for the preneoplastic lesion of most germ cell tumours and division from those not derived from GCNIS. Nomenclature changes include replacement of the term "primitive neuroectodermal tumour" by "embryonic neuroectodermal tumour" to separate these tumours clearly from Ewing sarcoma. The term "carcinoid" has been changed to "neuroendocrine tumour", with most examples in the testis now classified as "prepubertal type testicular neuroendocrine tumour".

Background: The pathological existence and clinical consequence of stage T1 grade 1 (T1G1) bladder cancer are the subject of debate. Even though the diagnosis of T1G1 is controversial, several reports have consistently found a prevalence of 2-6% G1 in their T1 series. However, it remains unclear if T1G1 carcinomas have added value as a separate category to predict prognosis within the non-muscle-invasive bladder cancer (NMIBC) spectrum. Objective: To evaluate the prognostic value of T1G1 carcinomas compared to TaG1 and T1G2 carcinomas within the NMIBC spectrum. Design, setting, and participants: Individual patient data for 5170 primary Ta and T1 bladder tumors from 17 hospitals in Europe and Canada were analyzed. Transurethral resection (TUR) was performed between 1990 and 2018. Outcome measurements and statistical analysis: Time to recurrence and progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox regression models stratified by institution. Results and limitations: T1G1 represented 1.9% (99/5170) of all carcinomas and 5.3% (99/1859) of T1 carcinomas. According to primary TUR dates, the proportion of T1G1 varied between 0.9% and 3.5% per year, with similar percentages in the early and later calendar years. We found no difference in time to recurrence between T1G1 and TaG1 (p = 0.91) or between T1G1 and T1G2 (p = 0.30). Time to progression significantly differed between TaG1 and T1G1 (p < 0.001) but not between T1G1 and T1G2 (p = 0.30). Multivariable analyses for recurrence and progression showed similar results. Conclusions: The relative prevalence of T1G1 diagnosis was low and remained constant over the past three decades. Time to recurrence of T1G1 NMIBC was comparable to that for other stage/grade NMIBC combinations. Time to progression of T1G1 NMIBC was comparable to that for T1G2 but not for TaG1, suggesting that treatment and surveillance of T1G1 carcinomas should be more like the approaches for T1G2 NMIBC in accordance with the intermediate and/or high risk categories of the European Association of Urology NMIBC guidelines. Patient summary: Although rare, stage T1 grade 1 (T1G1) bladder cancer is still diagnosed in daily clinical practice. Using individual patient data from 17 centers in Europe and Canada, we found that time to progression of T1G1 cancer was comparable to that for T1G2 but not TaG1 cancer. Therefore, our results suggest that primary T1G1 bladder cancers should be managed with more aggressive treatment and more frequent follow-up than for low-risk bladder cancer. (C) 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Context: This overview presents the updated European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC). Objective: To provide practical evidence-based recommendations and consensus statements on the clinical management of MMIBC with a focus on diagnosis and treatment. Evidence acquisition: A broad and comprehensive scoping exercise covering all areas of the MMIBC guideline has been performed annually since its 2017 publication (based on the 2016 guideline). Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. A level of evidence and a grade of recommendation were assigned. Additionally, the results of a collaborative multistakeholder consensus project on advanced bladder cancer (BC) have been incorporated in the 2020 guidelines, addressing those areas where it is unlikely that prospective comparative studies will be conducted. Evidence synthesis: Variant histologies are increasingly reported in invasive BC and are relevant for treatment and prognosis. Staging is preferably done with (enhanced) computerised tomography scanning. Treatment decisions are still largely based on clinical factors. Radical cystectomy (RC) with lymph node dissection remains the recommended treatment in highest-risk non-muscle-invasive and muscle-invasive nonmetastatic BC, preceded by cisplatin-based neoadjuvant chemotherapy (NAC) for invasive tumours in "fit" patients. Selected men and women benefit from sexuality sparing RC, although this is not recommended as standard therapy. Open and robotic RC show comparable outcomes, provided the procedure is performed in experienced centres. For open RC 10, the minimum selected case load is 10 procedures per year. If bladder preservation is considered, chemoradiation is an alternative in well-selected patients without carcinoma in situ and after maximal resection. Adjuvant chemotherapy should be considered if no NAC was given. Perioperative immunotherapy can be offered in clinical trial setting. For fit metastatic patients, cisplatin-based chemotherapy remains the first choice. In cisplatin-ineligible patients, immunotherapy in Programmed Death Ligand 1 (PD-L1)-positive patients or carboplatin in PD-L1-negative patients is recommended. For second-line treatment in metastatic disease, pembrolizumab is recommended. Postchemotherapy surgery may prolong survival in responders. Quality of life should be monitored in all phases of treatment and follow-up. The extended version of the guidelines is available at the EAU website: https://uroweb.org/guideline/ bladder-cancer-muscle-invasive-and-metastatic/. Conclusions: This summary of the 2020 EAU MMIBC guideline provides updated information on the diagnosis and treatment of MMIBC for incorporation into clinical practice. Patient summary: The European Association of Urology Muscle-invasive and Metastatic Bladder Cancer (MMIBC) Panel has released an updated version of their guideline, which contains information on histology, staging, prognostic factors, and treatment of MMIBC. The recommendations are based on the current literature (until the end of 2019), with emphasis on high-level data from randomised clinical trials and meta-analyses and on the findings of an international consensus meeting. Surgical removal of the bladder and bladder preservation are discussed, as well as the use of chemotherapy and immunotherapy in localised and metastatic disease. (C) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.