Introducción: Hasta hace poco tiempo no existía una terapia adyuvante recomendada para pacientes con metástasis en los ganglios linfáticos (ypN+) después de la quimioterapia neoadyuvante (QNA) y la cistectomía radical (CR) para el cáncer de vejiga músculo invasor (CVMI). El objetivo del estudio fue describir los resultados oncológicos de los pacientes ypN+ tras QNA y CR para CVMI.Métodos: Este estudio retrospectivo colaborativo incluyó a 195 pacientes con enfermedad ypN+ después de QNA seguida de CR y disección bilateral de ganglios linfáticos pélvicos para el CVMI en 7 centros entre 2000 y 2019. Se recopilaron los datos demográficos y las características clínicas y patológicas de los pacientes. Se realizaron análisis de supervivencia con estimaciones de Kaplan-Meier y se generó un modelo de Cox.Resultados: En total, 120 (62%) pacientes fueron pN1, 51 (26%) pN2 y 24 (12%) pN3. Se realizó radioterapia adyuvante en 18 (9%), quimioterapia adyuvante en 40 (21%), y los 137 pacientes restantes (70%) fueron sometidos a observación. La mediana del tiempo de seguimiento fue de 51 meses (IC 95%: 44-62). La mediana de la supervivencia libre de recurrencia, la supervivencia específica al cáncer y la supervivencia global (SG) fue de 18 meses (IC del 95%: 16-21), 47 meses (IC del 95%: 31-70) y 28 meses (IC del 95%: 22-34), respectivamente. En el análisis multivariable, el sexo femenino (HR=1,5; IC 95%: 1,002-2,21; p=0,049) y los márgenes quirúrgicos positivos (HR=1,6; IC 95%: 1,06-2,38; p=0,026) fueron los únicos factores predictivos independientes de la SG. El tipo de tratamiento adyuvante no influyó en la SG (quimioterapia adyuvante, p=0,44; radioterapia adyuvante, p=0,40).Conclusión: Los resultados de supervivencia de los pacientes con CVMI y afectación ganglionar residual tras la QNA y la CR son desfavorecedores. El sexo femenino y los márgenes positivos en la CR se asocian a un pronóstico peor. Estos resultados pueden ser útiles para el diseño de ensayos clínicos a futuro.

INTRODUCTION:Until recently there was no recommended adjuvant therapy for patients with lymph nodes metastasis (ypN+) following neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). The aim of the study was to describe the oncological outcomes of ypN+ patients following NAC and RC for MIBC. METHODS:This collaborative retrospective study included 195 patients with ypN+ disease after NAC followed by RC and bilateral pelvic lymph node dissection for MIBC between 2000 and 2019 in seven centers. Patients' demographics, clinical and pathological features were collected. Survival analyses were carried out with Kaplan-Meier estimates and a Cox model was generated. RESULTS:A total of 120 patients (62%) were pN1, 51 pN2 (26%) and 24 pN3 (12%). Adjuvant radiation therapy was performed in 18 (9%), adjuvant chemotherapy in 40 (21%) and the remaining 137 (70%) patients were observed. The median follow-up time was 51 months (95%CI 44-62). Median times for recurrence-free survival, cancer-specific survival and overall survival (OS) were 18 months (95%CI 16-21), 47 months (95%CI 31-70) and 28 months (95%CI 22-34) respectively. On multivariable analysis, female gender (HR = 1.5, 95%CI 1.002-2.21, p = 0.049) and positive surgical margins (HR = 1.6, 95%CI 1.06-2.38, p = 0.026) were the only independent predictor of OS. The type of adjuvant therapy did not impact OS (adjuvant chemotherapy, p = 0.44; adjuvant radiotherapy p = 0.40). CONCLUSION:MIBC patients with residual node positive disease following NAC and RC have poor survival outcomes. Females and patients with positive margin status at RC carry a poorer prognosis. These results may be beneficial for clinical trial design.

Las mutaciones del FGFR3, asociadas principalmente al subtipo papilar luminal (LumP) se encuentran entre las alteraciones genómicas más comunes en el cáncer urotelial (CU)). Gracias al desarrollo de los inhibidores del FGFR (receptor del factor de crecimiento de fibroblastos), el tratamiento del CU se acerca cada vez más a la medicina personalizada. Se realizó una revisión sistemática utilizando Medline y publicaciones de congresos científicos según las directrices PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) para evaluar el papel potencial de los inhibidores del FGFR utilizados en combinación con otras terapias para el tratamiento del CU. Se llevó a cabo una búsqueda sistemática en ClinicalTrials.gov para identificar ensayos clínicos en curso. En total, once artículos a texto completo, diez resúmenes de congresos y cinco ensayos fueron identificados. Según los estudios BLC2001 y THOR, erdafitinib es el único inhibidor de FGFR1-4 aprobado para el CU metastásico con alteraciones susceptibles en FGFR2/3 tras quimioterapia basada en platino. Según los datos correspondientes a la cohorte 2 del ensayo THOR, erdafitinib no debe recomendarse en pacientes aptos para recibir tratamiento con inhibidores de puntos de control inmunitario (ICI) y que no lo hayan recibido previamente. Dos ensayos de fase 3 están evaluando actualmente el sistema de administración intravesical (TAR210) en el cáncer de vejiga no-músculo invasor (CVNMI) de grado intermedio con alteraciones en FGFR (MoonRISe-1) y tratamiento adyuvante con infigratinib en pacientes con CVNMI o carcinoma urotelial de tracto superior (CUTS) y riesgo elevado de recurrencia (PROOF-302). Los estudios preclínicos sugieren que podrían considerarse estrategias basadas en terapias combinadas para mejorar la eficacia de los inhibidores del FGFR en pacientes con CU. Nueve ensayos de fase 1b/2 están enfocados a evaluar el papel de los inhibidores del FGFR en combinación con ICI, quimioterapia o enfortumab vedotina. En el contexto de la enfermedad metastásica, estudios preliminares han revelado resultados prometedores de estas combinaciones (por ejemplo, los ensayos NORSE y FORT-2). Sin embargo, ningún ensayo de fase 3 ha finalizado, por lo que actualmente no existen datos de nivel 1 con resultados a largo plazo que respalden la combinación de inhibidores del FGFR con ICI, quimioterapia o terapias dirigidas. Aún se requiere un mejor entendimiento de los diferentes mecanismos de acción de los inhibidores de las vías de señalización del FGFR, la selección óptima de pacientes y los enfoques terapéuticos.

INTRODUCTION:Collaboration between pathologists and urologists is crucial for accurate diagnostic reporting and patient management, particularly in urology. This study aims to evaluate international practices regarding pathology reporting of bladder specimens to identify areas for improvement. MATERIALS AND METHODS:A web-based survey with 32 questions was developed in collaboration with the EAU Young Academic Urologists Urothelial Cancer Working Party. It was sent to urologists with more than five years of experience across different institutions globally. Descriptive statistics were used to evaluate the responses. RESULTS:A total of 157 responses were received from urologists, representing a response rate of 65%. Most respondents (64.3%) found pathological reports comprehensive, although 36% reported unclear reports in some cases. Pathologists were contacted for clarification in less than 20% of cases. Notably, the reporting of pathological subtypes and depth of invasion was inconsistent among institutions. CONCLUSION:The survey highlights variability in pathology report quality across centers. Standardized reporting, increased pathologist involvement in multidisciplinary teams, and adherence to international guidelines are necessary to improve the accuracy and clarity of pathology reports in urology.

FGFR3 mutations are among the most frequent genomic alterations in urothelial cancer (UC) being mainly associated with the luminal papillary (LumP) subtype. With the establishment of fibroblast growth factor receptor (FGFR) inhibitors, the treatment of UC is now shifting more and more towards personalized medicine. A systematic review using Medline and scientific meeting records was carried out according to the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines to assess the potential role of FGFR inhibitors in combination with additional therapies for the management of UC. Ongoing trials were identified via a systematic search on ClinicalTrials.gov. A total of eleven full-text papers, ten congress abstracts, and 5 trials on ClinicalTrials.gov were identified. Following the BLC2001 and THOR study, erdafitinib is the only approved FGFR1-4 inhibitor for metastatic UC with susceptible FGFR2/3 alterations following platinum-based chemotherapy. According to the THOR data of cohort 2, erdafitinib should not be recommended in patients who are eligible for and have not received prior immune checkpoint inhibitors (ICIs). One phase 3 trial is currently evaluating the intravesical device system (TAR210) in FGFR-altered intermediate non-muscle invasive bladder cancer (MoonRISe-1). Preclinical evidence suggests that combination-based approaches could be considered to improve the efficacy of FGFR inhibitors in patients with UC. Nine phase 1b/2 trials are focusing on the combination of FGFR inhibitors with ICIs, chemotherapy, or enfortumab vedotin. In metastatic disease, some preliminary analyses have reported promising results from these combinations (e.g. NORSE and FORT-2 trial). However, no phase 3 trial is terminated, so there is currently no level 1 evidence with long-term outcomes to support the combination of FGFR inhibitors with ICIs, chemotherapy, or targeted therapies. A better understanding of the different mechanisms of action to inhibit FGFR signaling pathways, optimal patient selection and treatment approaches is still needed.

You have accessJournal of UrologyCME1 May 2022MP27-02 NOT ALL ADVERSE PATHOLOGY FEATURES ARE EQUAL: IDENTIFYING OPTIMAL CANDIDATES FOR ADJUVANT RADIOTHERAPY AMONG PATIENTS WITH ADVERSE PATHOLOGY AT RADICAL PROSTATECTOMY Elio Mazzone, Giorgio Gandaglia, Armando Stabile, Nicola Fossati, Andrea Gallina, Emanuele Zaffuto, Marta Picozzi, Francesco Barletta, Simone Scuderi, Riccardo Leni, Luigi Nocera, Gabriele Sorce, Francesco Pellegrino, Giuseppe Rosiello, Umberto Capitanio, Alessandro Larcher, Roberta Lucianò, Alessia Cimadamore, Federico Dehò, Rodolfo Montironi, Pierre I. Karakiewicz, Shahrokh F. Shariat, Francesco Montorsi, and Alberto Briganti Elio MazzoneElio Mazzone More articles by this author , Giorgio GandagliaGiorgio Gandaglia More articles by this author , Armando StabileArmando Stabile More articles by this author , Nicola FossatiNicola Fossati More articles by this author , Andrea GallinaAndrea Gallina More articles by this author , Emanuele ZaffutoEmanuele Zaffuto More articles by this author , Marta PicozziMarta Picozzi More articles by this author , Francesco BarlettaFrancesco Barletta More articles by this author , Simone ScuderiSimone Scuderi More articles by this author , Riccardo LeniRiccardo Leni More articles by this author , Luigi NoceraLuigi Nocera More articles by this author , Gabriele SorceGabriele Sorce More articles by this author , Francesco PellegrinoFrancesco Pellegrino More articles by this author , Giuseppe RosielloGiuseppe Rosiello More articles by this author , Umberto CapitanioUmberto Capitanio More articles by this author , Alessandro LarcherAlessandro Larcher More articles by this author , Roberta LucianòRoberta Lucianò More articles by this author , Alessia CimadamoreAlessia Cimadamore More articles by this author , Federico DehòFederico Dehò More articles by this author , Rodolfo MontironiRodolfo Montironi More articles by this author , Pierre I. KarakiewiczPierre I. Karakiewicz More articles by this author , Shahrokh F. ShariatShahrokh F. Shariat More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , and Alberto BrigantiAlberto Briganti More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002570.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The role of adjuvant radiotherapy (aRT) in patients with adverse pathology features is still debated due to the low rate of enrolment of such patients in RCT comparing aRT vs. early salvage radiotherapy (sRT). A recent retrospective analysis reported a potential benefit associated with aRT for patients with adverse pathology features. We hypothesized that not all the patients with adverse pathology may benefit from aRT and sRT may be considered in a subgroup of men without aggressive features. METHODS: Overall, 1,328 with adverse pathology features (i.e. Gleason Grade [GG] 4-5 with ≥pT3a stage and/or lymph node invasion [LNI]) out of 8,362 patients treated with RP at a single center between 1987 and 2020 were identified. Only patients with follow-up >36 months, absence of PSA persistence and ≤6 positive nodes were included (n=682). Patients were stratified according to aRT vs. observation with or without sRT. The primary endpoint was overall mortality (OM). Multivariable Cox regression model tested the impact of adverse pathology features on OM. Based on Cox-derived coefficients, a score was assigned to each adverse pathology feature (1 point for pT3b; 2 for GG 5 or 1-2 positive nodes; 3 for >2 positive nodes). Patients were stratified in low (0-1 points), intermediate (2-3 points) and high (4-5 points) risk groups. The probability of receiving aRT was weighted trough an inverse-probability of treatment weighting propensity score adjusted for the presence of positive surgical margins, PSA, year of surgery and age. The resulting weight was used as propensity adjustment in multivariable Cox regression models examining the impact of aRT on OM after adjusting for age, sRT and adjuvant or salvage hormonal therapy (HT). The impact of aRT was tested for each risk subgroup. RESULTS: Of 682 patients, 438 (64%) vs. 79 (12%) vs 167 (24%) patients received aRT vs sRT vs observation. Median follow-up for survivors was 116 months. A total of 65 patients died during follow-up. The overall 10-year OM-free survival rate was 90%. At multivariable Cox regression models, the presence of >2 positive nodes was the strongest predictor of OM (HR 2.8, p<0.001). After stratification according to risk groups, 75 (11%), 434 (63%) and 175 (26%) patients were included in low, intermediate and high-risk groups. Cox-derived KM depicted comparable 10-year OM-free survival in low and intermediate risk patients (all p=0.2) treated with aRT or observation +/- sRT. In the high-risk group, use of aRT was associated with significant improvement in 10-yr OM-free survival compared to observation +/- sRT (86 vs 73%, p=0.04). CONCLUSIONS: Among patients with adverse pathology features, we identified three subclassification of risk. When testing the effect of aRT vs. observation +/- sRT on survival, only patients included in the high-risk group seemed to benefit from aRT. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e449 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Elio Mazzone More articles by this author Giorgio Gandaglia More articles by this author Armando Stabile More articles by this author Nicola Fossati More articles by this author Andrea Gallina More articles by this author Emanuele Zaffuto More articles by this author Marta Picozzi More articles by this author Francesco Barletta More articles by this author Simone Scuderi More articles by this author Riccardo Leni More articles by this author Luigi Nocera More articles by this author Gabriele Sorce More articles by this author Francesco Pellegrino More articles by this author Giuseppe Rosiello More articles by this author Umberto Capitanio More articles by this author Alessandro Larcher More articles by this author Roberta Lucianò More articles by this author Alessia Cimadamore More articles by this author Federico Dehò More articles by this author Rodolfo Montironi More articles by this author Pierre I. Karakiewicz More articles by this author Shahrokh F. Shariat More articles by this author Francesco Montorsi More articles by this author Alberto Briganti More articles by this author Expand All Advertisement PDF downloadLoading ...

Prostate cancer is the most common cancer and second leading cause of cancer-related death in American men. Antiandrogen therapies are part of the standard of therapeutic regimen for advanced or metastatic prostate cancers; however, patients who receive these treatments are more likely to develop castration-resistant prostate cancer (CRPC) or neuroendocrine prostate cancer (NEPC). In the development of CRPC or NEPC, numerous genetic signaling pathways have been under preclinical investigations and in clinical trials. Accumulated evidence shows that DNA methylation, chromatin integrity, and accessibility for transcriptional regulation still play key roles in prostate cancer initiation and progression. Better understanding of how epigenetic change regulates the progression of prostate cancer and the interaction between epigenetic and genetic modulators driving NEPC may help develop a better risk stratification and more effective treatment regimens for prostate cancer patients.

Bernardo Rocco*, Maria Chiara Sighinolfi, Maurizio Paterlini, Modena, Italy; Roberta Mazzucchelli, Ancona, Italy; Antonio Lopez-Beltran, Barcelona, Spain; Alessia Cimadamore, Ancona, Italy; Stefnao Puliatti, Modena, Italy; Ahmed Eissa, Tanta, Egypt; Metka Volavsek, Lubjiana, Slovenia; Luca Reggiani Bonetti, Antonino Maiorana, Modena, Italy; Giorgio Bozzini, Busto Arsizio, Italy; Marco Sandri, Brescia, Italy; Andrea Iseppi, Valentina Spandri, Laura Bertoni, Paola Azzoni, Salvatore Micali, Giampaolo Bianchi, Giovanni Pellacani, Modena, Italy; Rodolfo Montironi, Ancona, Italy