Performance of a Region of Interest-based Algorithm in Diagnosing International Society of Urological Pathology Grade Group ≥2 Prostate Cancer on the MRI-FIRST Database-CAD-FIRST Study.

BACKGROUND AND OBJECTIVE: Prostate multiparametric magnetic resonance imaging (MRI) shows high sensitivity for International Society of Urological Pathology grade group (GG) ≥2 cancers. Many artificial intelligence algorithms have shown promising results in diagnosing clinically significant prostate cancer on MRI. To assess a region-of-interest-based machine-learning algorithm aimed at characterising GG ≥2 prostate cancer on multiparametric MRI. METHODS: The lesions targeted at biopsy in the MRI-FIRST dataset were retrospectively delineated and assessed using a previously developed algorithm. The Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) score assigned prospectively before biopsy and the algorithm score calculated retrospectively in the regions of interest were compared for diagnosing GG ≥2 cancer, using the areas under the curve (AUCs), and sensitivities and specificities calculated with predefined thresholds (PIRADSv2 scores ≥3 and ≥4; algorithm scores yielding 90% sensitivity in the training database). Ten predefined biopsy strategies were assessed retrospectively. KEY FINDINGS AND LIMITATIONS: After excluding 19 patients, we analysed 232 patients imaged on 16 different scanners; 85 had GG ≥2 cancer at biopsy. At patient level, AUCs of the algorithm and PI-RADSv2 were 77% (95% confidence interval [CI]: 70-82) and 80% (CI: 74-85; p = 0.36), respectively. The algorithm's sensitivity and specificity were 86% (CI: 76-93) and 65% (CI: 54-73), respectively. PI-RADSv2 sensitivities and specificities were 95% (CI: 89-100) and 38% (CI: 26-47), and 89% (CI: 79-96) and 47% (CI: 35-57) for thresholds of ≥3 and ≥4, respectively. Using the PI-RADSv2 score to trigger a biopsy would have avoided 26-34% of biopsies while missing 5-11% of GG ≥2 cancers. Combining prostate-specific antigen density, the PI-RADSv2 and algorithm's scores would have avoided 44-47% of biopsies while missing 6-9% of GG ≥2 cancers. Limitations include the retrospective nature of the study and a lack of PI-RADS version 2.1 assessment. CONCLUSIONS AND CLINICAL IMPLICATIONS: The algorithm provided robust results in the multicentre multiscanner MRI-FIRST database and could help select patients for biopsy. PATIENT SUMMARY: An artificial intelligence-based algorithm aimed at diagnosing aggressive cancers on prostate magnetic resonance imaging showed results similar to expert human assessment in a prospectively acquired multicentre test database.

Multiparametric Magnetic Resonance Imaging in the follow-up of non-muscle-invasive bladder tumors after intravesical instillations: a promising tool.

PURPOSE: The standard follow-up for non-muscle-invasive bladder cancer is based on cystoscopy. Unfortunately, post-instillation inflammatory changes can make the interpretation of this exam difficult, with lower specificity. This study aimed to evaluate the interest of bladder MRI in the follow-up of patients following intravesical instillation. METHODS: Data from patients who underwent cystoscopy and bladder MRI in a post-intravesical instillation setting between February 2020 and March 2023 were retrospectively collected. Primary endpoint was to evaluate and compare the diagnostic performance of cystoscopy and bladder MRI in the overall cohort (n = 67) using the pathologic results of TURB as a reference. The secondary endpoint was to analyze the diagnostic accuracy of cystoscopy and bladder MRI according to the appearance of the lesion on cystoscopy [flat (n = 40) or papillary (n = 27)]. RESULTS: The diagnostic performance of bladder MRI was better than that of cystoscopy, with a specificity of 47% (vs. 6%, p < 0.001), a negative predictive value of 88% (vs. 40%, p = 0.03), and a positive predictive value of 66% (vs. 51%, p < 0.001), whereas the sensitivity did not significantly differ between the two exams. In patients with doubtful cystoscopy and negative MRI findings, inflammatory changes were found on TURB in most cases (17/19). The superiority in MRI bladder performance prevailed for "flat lesions", while no significant difference was found for "papillary lesions". CONCLUSIONS: In cases of doubtful cystoscopy after intravesical instillations, MRI appears to be relevant with good performance in differentiating post-therapeutic inflammatory changes from recurrent tumor lesions and could potentially allow avoiding unnecessary TURB.

An optimised liver-first strategy for synchronous metastatic rectal cancer leads to higher protocol completion and lower surgical morbidity.

INTRODUCTION: The optimal management of rectal cancer with synchronous liver metastases remains debatable. Thus, we propose an optimised liver-first (OLF) strategy that combines concomitant pelvic irradiation with hepatic management. This study aimed to evaluate the feasibility and oncological quality of the OLF strategy. MATERIALS AND METHODS: Patients underwent systemic neoadjuvant chemotherapy followed by preoperative radiotherapy. Liver resection was performed in one step (between radiotherapy and rectal surgery) or in two steps (before and after radiotherapy). The data were collected prospectively and analysed retrospectively as intent to treat. RESULTS: Between 2008 and 2018, 24 patients underwent the OLF strategy. The rate of treatment completion was 87.5%. Three patients (12.5%) did not proceed to the planned second-stage liver and rectal surgery because of progressive disease. The postoperative mortality rate was 0%, and the overall morbidity rates after liver and rectal surgeries were 21% and 28.6%, respectively. Only two patients developed severe complications. Liver and rectal complete resection was performed in 100% and 84.6%, respectively. A rectal-sparing strategy was performed in 6 patients who underwent local excision (n = 4) or a watch and wait strategy (n = 2). Among patients who completed treatment, the median overall and disease-free survivals were 60 months (range 12-139 months) and 40 months (range 10-139 months), respectively. Eleven patients (47.6%) developed recurrence, among whom five underwent further treatment with curative intent. CONCLUSION: The OLF approach is feasible, relevant, and safe. Organ preservation was feasible for a quarter of patients and may be associated with reduced morbidity.

MRI restaging of rectal cancer: The RAC (Response-Anal canal-CRM) analysis joint consensus guidelines of the GRERCAR and GRECCAR groups.

PURPOSE: To develop guidelines by international experts to standardize data acquisition, image interpretation, and reporting in rectal cancer restaging with magnetic resonance imaging (MRI). MATERIALS AND METHODS: Evidence-based data and experts' opinions were combined using the RAND-UCLA Appropriateness Method to attain consensus guidelines. Experts provided recommendations for reporting template and protocol for data acquisition were collected; responses were analysed and classified as "RECOMMENDED" versus "NOT RECOMMENDED" (if ≥ 80% consensus among experts) or uncertain (if < 80% consensus among experts). RESULTS: Consensus regarding patient preparation, MRI sequences, staging and reporting was attained using the RAND-UCLA Appropriateness Method. A consensus was reached for each reporting template item among the experts. Tailored MRI protocol and standardized report were proposed. CONCLUSION: These consensus recommendations should be used as a guide for rectal cancer restaging with MRI.

External validation of the computerized analysis of TRUS of the prostate with the ANNA/C-TRUS system: a potential role of artificial intelligence for improving prostate cancer detection.

PURPOSE: Prostate cancer (PCa) imaging has been revolutionized by the introduction of multi-parametric Magnetic Resonance Imaging (mpMRI). Transrectal ultrasound (TRUS) has always been considered a low-performance modality. To overcome this, a computerized artificial neural network analysis (ANNA/C-TRUS) of the TRUS based on an artificial intelligence (AI) analysis has been proposed. Our aim was to evaluate the diagnostic performance of the ANNA/C-TRUS system and its ability to improve conventional TRUS in PCa diagnosis. METHODS: We retrospectively analyzed data from 64 patients with PCa and scheduled for radical prostatectomy who underwent TRUS followed by ANNA/C-TRUS analysis before the procedure. The results of ANNA/C-TRUS analysis with whole mount sections from final pathology. RESULTS: On a per-sectors analysis, sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy were 62%, 81%, 80%, 64% and 78% respectively. The values for the detection of clinically significant prostate cancer were 69%, 77%, 88%, 50% and 75%. The diagnostic values for high grade tumours were 70%, 74%, 91%, 41% and 74%, respectively. Cancer volume (≤ 0.5 or greater) did not influence the diagnostic performance of the ANNA/C-TRUS system. CONCLUSIONS: ANNA/C-TRUS represents a promising diagnostic tool and application of AI for PCa diagnosis. It improves the ability of conventional TRUS to diagnose prostate cancer, preserving its simplicity and availability. Since it is an AI system, it does not hold the inter-observer variability nor a learning curve. Multicenter biopsy-based studies with the inclusion of an adequate number of patients are needed to confirm these results.

Nomogram to predict disease recurrence in patients with locally advanced rectal cancer undergoing rectal surgery after neoadjuvant therapy: retrospective cohort study.

INTRODUCTION: Prognostic models can be used for predicting survival outcomes and guiding patient management. TNM staging alone is insufficient for predicting recurrence after chemoradiotherapy (CRT) and surgery for locally advanced rectal cancer. This study aimed to develop a nomogram to better predict cancer recurrence after CRT followed by total mesorectal excision (TME) and tailor postoperative management and follow-up. MATERIALS AND METHODS: Between 2002 and 2019, data were retrospectively collected on patients with rectal adenocarcinoma. Data on sex, age, carcinoembryonic antigen (CEA) level, tumour location, induction chemotherapy, adjuvant chemotherapy, tumour downsizing, perineural invasion, lymphovascular invasion, pathological stage, resection margins (R0 versus R1), and pelvic septic complications were analysed. The variables significantly associated with cancer recurrence were used to build a nomogram that was validated in both the training and validation cohorts. Model performance was evaluated by receiver operating characteristic curve and area under the curve (AUC) analyses. RESULTS: After applying exclusion criteria, 634 patients with rectal adenocarcinoma were included in this study. Eight factors (CEA level, adjuvant chemotherapy, tumour downsizing, perineural invasion, lymphovascular invasion, pathological stage, resection margins (R0 versus R1), and pelvic septic complications) were identified as nomogram variables. Our nomogram showed good performance with an AUC of 0.74 and 0.75 in the training and validation cohorts respectively. CONCLUSION: Our nomogram is a simple tool for predicting cancer recurrence in patients with locally advanced rectal cancer after neoadjuvant CRT followed by TME. It provides an individual risk prediction of recurrence to tailor surveillance.

Impact of long-term indwelling JJ stent on renal volume and renal function.

BACKGROUND: Data is lacking about long-term impact of JJ stents (JJst) on renal parenchyma. The aim of the study was to assess the evolution of renal parenchyma in patients with JJst indwelling for more than two years, and to find predictive factors for the development of renal atrophy. METHODS: Consecutive patients with JJst indwelled for more than 24 months, with a history of cancer, were retrospectively included. Replacements of JJst were scheduled every six months, or earlier in case of premature obstruction. Patient characteristics at the time of insertion of JJst, history of indwelling JJst and most recent data (serum creatinine, cancer status, definite JJst removal, renal volume (RV) with3D software) were recorded. RESULTS: With a median follow-up of 4 years, 73 patients were included. The indication of JJst insertion was mostly external compression (65.8%). CT scans were available to assess RV evolution in 66 patients (90.4%). Median shrinkage of RV was higher when JJ stenting was unilateral versus bilateral: -40% (-63; -15) versus -16% (-36; -3), P<0.001. The duration of indwelling JJst was the only statistically significative predictive factor of renal shrinkage in multivariate analysis (OR [CI 95%]: 1.35 [1.10-1.66] P=0.004). Median relative change from baseline in eGFR was -22% (-45%; -5%.). No statistically significant predictive factors of eGFR evolution were found in univariate and multivariate analysis. CONCLUSIONS: Unilateral JJst for more than 2 years was associated with a significant shrinkage of renal parenchyma, especially since the duration of the indwelling stent was long.

Case-Matched Comparison of Functional and Quality of Life Outcomes of Local Excision and Total Mesorectal Excision Following Chemoradiotherapy for Rectal Cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery is the standard curative treatment for mid- to low-rectal cancer. However, the combination of these treatments may affect patients' GI and genitourinary functions and their quality of life. In the cases of good clinical response to neoadjuvant treatment, local excision is a rectal sparing strategy that would limit these side effects. OBJECTIVE: The aim of this study is to compare the effects of local excision or conventional laparoscopic total mesorectal excision after chemoradiotherapy in patients with rectal cancer. DESIGN: The design is a retrospective study. SETTING: The setting used is a single tertiary center. PATIENTS: Patients with mid- to low-rectal cancer treated with chemoradiotherapy and accessible via conservative surgery at our hospital between January 2010 and December 2018 were included. Patients undergoing local excision were matched 1 to 1 with the patients undergoing total mesorectal excision by age, sex, body mass index, tumor height, and year of surgery. MAIN OUTCOME MEASURES: Quality of life and digestive and genitourinary functions were measured using validated questionnaires. The socioeconomic impact was also assessed. RESULTS: Forty-four patients undergoing local excision agreed to participate and were matched with 44 patients undergoing total mesorectal excision. Patients who underwent local excision reported a more favorable global health status ( p < 0.01), emotional function ( p = 0.035), social function ( p = 0.04), and body image ( p = 0.04). The low anterior resection syndrome score (rate of major syndrome, 23.8% vs 54.5%; p < 0.01) and the specific fecal incontinence subscale score ( p < 0.01) were more favorable in the local excision group. Sexual and urinary outcomes were comparable between the 2 groups. Local excision had a lower impact on the professional status (35.7% vs 76.5%; p = 0.03). LIMITATIONS: The study limitations include its retrospective design and small sample size. CONCLUSIONS: When indicated, local excision improves the bowel function and quality of life of patients undergoing surgery for rectal cancer after chemoradiotherapy compared with total mesorectal excision. See Video Abstract at http://links.lww.com/DCR/B997 . COMPARACIN DE CASOS EMPAREJADOS DE LOS RESULTADOS FUNCIONALES Y DE CALIDAD DE VIDA DE LA ESCISIN LOCAL Y LA ESCISIN TOTAL DE MESORECTO DESPUS DE QUIMIORRADIOTERAPIA EN CNCER DE RECTO: ANTECEDENTES:La quimiorradioterapia neoadyuvante seguida de cirugía radical es el tratamiento curativo estándar para el cáncer de recto medio-bajo. Sin embargo, la combinación de estos tratamientos puede afectar las funciones gastrointestinales y genitourinarias de los pacientes y su calidad de vida. En casos de buena respuesta clínica al tratamiento neoadyuvante, la escisión local es una estrategia conservadora del recto que limitaría estos efectos secundarios.OBJETIVO:Este estudio comparó los efectos de la escisión local o escisión total de mesorecto laparoscópica convencional después de quimiorradioterapia en pacientes con cáncer de recto.DISEÑO:Estudio retrospectivo.ENTORNO CLINICO:Centro terciario único.PACIENTES:Se incluyeron pacientes con cáncer de recto medio-bajo tratados con quimiorradioterapia y accesibles mediante cirugía conservadora en nuestro hospital entre enero del 2010 y diciembre del 2018. Los pacientes sometidos a escisión local se emparejaron uno a uno con los sometidos a escisión total de mesorecto por edad, sexo, índice de masa corporal, altura del tumor y año de cirugía.PRINCIPALES MEDIDAS DE RESULTADO:La calidad de vida, las funciones digestivas y genitourinarias se midieron mediante cuestionarios validados. También se evaluó el impacto socioeconómico.RESULTADOS:Cuarenta y cuatro pacientes sometidos a escisión local aceptaron participar y fueron emparejados con 44 pacientes sometidos a escisión mesorrectal total. Los pacientes que se sometieron a escisión local informaron un estado de salud global más favorable ( p <0,01), función emocional ( p = 0,035), función social ( p = 0,04) e imagen corporal ( p = 0,04). La puntuación baja del síndrome de resección anterior (tasa de síndrome mayor: 23,8 % frente a 54,5 %; p <0,01) y la puntuación de la subescala de incontinencia fecal específica ( p <0,01) fueron más favorables en el grupo de escisión local. Los resultados sexuales y urinarios fueron comparables entre los dos grupos. La escisión local tuvo un menor impacto en el estatus profesional (35,7% vs 76,5%; p = 0,03).LIMITACIONES:Diseño retrospectivo, tamaño de muestra pequeño.CONCLUSIONES:Cuando está indicada, la escisión local mejora la función intestinal y la calidad de vida de los pacientes sometidos a cirugía por cáncer de recto después de quimiorradioterapia en comparación con escisión total de mesorecto. Consulte Video Resumen en http://links.lww.com/DCR/B997 . (Traducción-Dr. Francisco M. Abarca-Rendon ).

Molecular Profiles of Advanced Urological Cancers in the PERMED-01 Precision Medicine Clinical Trial.

INTRODUCTION: The prognosis of advanced urological cancers (AUC) remains unfavorable, and few data are available regarding precision medicine. METHODS: the PERMED-01 prospective clinical trial assessed the impact of molecular profiling in adults with refractory advanced solid cancer, in terms of number of patients with tumor actionable genetic alterations (AGA), feasibility, description of molecular alterations, treatment, and clinical outcome. We present here those results in the 64 patients enrolled with AUC. DNA extracted from a new tumor biopsy was profiled in real-time (targeted NGS, whole-genome array-comparative genomic hybridization), and the results were discussed during a weekly molecular tumor board meeting. RESULTS: a complete molecular profile was obtained in 49 patients (77%). Thirty-eight (59%) had at least one AGA. Twelve (19%) received a matched therapy on progression, of which 42% had a PFS2/PFS1 ratio ≥ 1.3 versus 5% in the "non-matched therapy group" (n = 25). The objective response and disease control rates were higher in the "matched therapy group" (33% and 58%, respectively) than in the "non-matched therapy group" (13% and 22%), as was the 6-month OS (75% vs. 42%). CONCLUSION: the profiling of a newly biopsied tumor sample identified AGA in 59% of patients with AUC, led to "matched therapy" in 19%, and provided clinical benefit in 8%.

Comparison Between Micro-Ultrasound and Multiparametric MRI Regarding the Correct Identification of Prostate Cancer Lesions.

INTRODUCTION: Multiparametric MRI (mpMRI) has become the standard imaging technique for the diagnosis of prostate cancer. However, mpMRI pathways are depending on experience, expertise, and information transfer from radiology to urology. Micro-ultrasound (Micro-US) is a new system, using high frequency (up to 29 MHz) and high resolution (down to 75 µm) ultrasound images. We evaluated the diagnostic performance of Micro-US in the detection of the prostate cancer index lesion and compared its performance to mpMRI using pathological whole mount sections as the reference. MATERIALS AND METHODS: We retrospectively reviewed the data of 32 patients with diagnosis of prostate cancer and scheduled for radical prostatectomy and who underwent Micro-US before surgery. Still images and cineloops of Micro-US were recorded. Sixteen patients had also mpMRI images with acceptable quality and complete sequences available. For validation purposes each prostate was partitioned into 12 sectors for a total of 192 sectors evaluated. Micro-US and mpMRI images were both scored according to a validated system (PRI-MUS and Pi-RADS) where a score ≥3 was suspicious for both scores. Preoperative and postoperative results regarding the identification of the index lesion, the biggest lesion visible, were then compared and sensitivity, specificity, negative and positive predictive values, and accuracy were calculated. RESULTS: Median age was 67 years, median PSA was 6.2ng/ml, and median cancer volume of the index lesion was 3.1cc. The sensitivity of Micro-US in the index lesion detection was 76.5%, specificity 76.6%, negative predictive value 85.6%, positive predictive value 64.1% and 76.6% of accuracy. The sensitivity of mpMRI was 65.1%, specificity 93.4%, negative predictive value 83.2%, positive predictive value 84.3%, and 81.8% of accuracy (all p> .05). CONCLUSION: Micro-US showed good reliability in identifying prostate cancer index lesions. Its performance is comparable to that of mpMRI.

Structured and shared MRI staging lexicon and report of rectal cancer: A consensus proposal by the French Radiology Group (GRERCAR) and Surgical Group (GRECCAR) for rectal cancer.

PURPOSE: To develop French guidelines by experts to standardize data acquisition, image interpretation, and reporting in rectal cancer staging with magnetic resonance imaging (MRI). MATERIALS AND METHODS: Evidence-based data and opinions of experts of GRERCAR (Groupe de REcherche en Radiologie sur le CAncer du Rectum [i.e., Rectal Cancer Imaging Research Group]) and GRECCAR (Groupe de REcherche en Chirurgie sur le CAncer du Rectum [i.e., Rectal Cancer Surgery Research Group]) were combined using the RAND-UCLA Appropriateness Method to attain consensus guidelines. Experts scoring of reporting template and protocol for data acquisition were collected; responses were analyzed and classified as "Recommended" versus "Not recommended" (when ≥ 80% consensus among experts) or uncertain (when < 80% consensus among experts). RESULTS: Consensus regarding patient preparation, MRI sequences, staging and reporting was attained using the RAND-UCLA Appropriateness Method. A consensus was reached for each reporting template item among the experts. Tailored MRI protocol and standardized report were proposed. CONCLUSION: These consensus recommendations should be used as a guide for rectal cancer staging with MRI.

Endoscopic Ultrasound-Guided Radiofrequency Ablation as an Future Alternative to Pancreatectomy for Pancreatic Metastases from Renal Cell Carcinoma: A Prospective Study.

BACKGROUND: Pancreatic metastases (PM) from renal cell carcinoma (RCC) are rare, are associated with favorable outcomes and are usually handled by surgery or VEGFR inhibitors, which both have side effects. Endoscopic Ultrasound (EUS)-guided radiofrequency ablation (RFA) is an innovative approach to treat focally deep metastases and could be a relevant technique to control PM from RCC. METHODS: This monocentric, prospective study aimed to evaluate the safety and efficacy of EUS-RFA to treat PM. We included patients with confirmed and progressive PM from RCC. PM was ablated under general anesthesia with a linear EUS scope and a EUS-RFA 19-gauge needle electrode placed into the tumor. RESULTS: Twelve patients from Paoli-Calmettes Institute were recruited between May 2017 and December 2019. Median age was 70.5 years (range 61-75), 50% were female, 100% were ECOG 0-1. At inclusion, mean PM size was 17 mm (range 3-35 mm); and all were progressive before EUS-RFA. Seven patients had EUS-RFA as the only treatment for RCC. We performed 26 EUS-RFA procedures and 21 PM was ablated. Median follow up was 27.7 months (range 6.4-57.1). For evaluable PM, the 6- and 12-month focal control rates were 84% and 73% respectively. One patient treated with TKI developed a paraduodenal abscess 2 months after EUS-RFA and another patient with biliary stent developed hepatic abscesses few days after EUS-RFA. No other severe side effects were experienced. CONCLUSIONS: in this series, which is the largest ever reported, we showed that EUS-RFA is feasible and yields an excellent local control rate for PM from mRCC. With manageable complications, it could be a valuable alternative to pancreatic surgery in well-selected patients.

Corrigendum: Gastrointestinal Metastases From Primary Renal Cell Cancer: A Single Center Review.

[This corrects the article DOI: 10.3389/fonc.2021.644301.].

Prospective high-throughput genome profiling of advanced cancers: results of the PERMED-01 clinical trial.

BACKGROUND: The benefit of precision medicine based on relatively limited gene sets and often-archived samples remains unproven. PERMED-01 (NCT02342158) was a prospective monocentric clinical trial assessing, in adults with advanced solid cancer, the feasibility and impact of extensive molecular profiling applied to newly biopsied tumor sample and based on targeted NGS (t-NGS) of the largest gene panel to date and whole-genome array-comparative genomic hybridization (aCGH) with assessment of single-gene alterations and clinically relevant genomic scores. METHODS: Eligible patients with refractory cancer had one tumor lesion accessible to biopsy. Extracted tumor DNA was profiled by t-NGS and aCGH. We assessed alterations of 802 "candidate cancer" genes and global genomic scores, such as homologous recombination deficiency (HRD) score and tumor mutational burden. The primary endpoint was the number of patients with actionable genetic alterations (AGAs). Secondary endpoints herein reported included a description of patients with AGA who received a "matched therapy" and their clinical outcome, and a comparison of AGA identification with t-NGS and aCGH versus whole-exome sequencing (WES). RESULTS: Between November 2014 and September 2019, we enrolled 550 patients heavily pretreated. An exploitable complete molecular profile was obtained in 441/550 patients (80%). At least one AGA, defined in real time by our molecular tumor board, was found in 393/550 patients (71%, two-sided 90%CI 68-75%). Only 94/550 patients (17%, 95%CI 14-21) received an "AGA-matched therapy" on progression. The most frequent AGAs leading to "matched therapy" included PIK3CA mutations, KRAS mutations/amplifications, PTEN deletions/mutations, ERBB2 amplifications/mutations, and BRCA1/2 mutations. Such "matched therapy" improved by at least 1.3-fold the progression-free survival on matched therapy (PFS2) compared to PFS on prior therapy (PFS1) in 36% of cases, representing 6% of the enrolled patients. Within patients with AGA treated on progression, the use of "matched therapy" was the sole variable associated with an improved PFS2/PFS1 ratio. Objective responses were observed in 19% of patients treated with "matched therapy," and 6-month overall survival (OS) was 62% (95%CI 52-73). In a subset of 112 metastatic breast cancers, WES did not provide benefit in term of AGA identification when compared with t-NGS/aCGH. CONCLUSIONS: Extensive molecular profiling of a newly biopsied tumor sample identified AGA in most of cases, leading to delivery of a "matched therapy" in 17% of screened patients, of which 36% derived clinical benefit. WES did not seem to improve these results. TRIAL REGISTRATION: ID-RCB identifier: 2014-A00966-41; ClinicalTrials.gov identifier: NCT02342158 .

Impact of sarcopenia status of muscle-invasive bladder cancer patients on kidney function after neoadjuvant chemotherapy.

BACKGROUND: Sarcopenia is suspected to influence the complication rates in patients undergoing radical cystectomy (RC). The aim of our study was to assess variations in sarcopenia in patients scheduled for neoadjuvant cisplatin-based chemotherapy (NAC) and RC for muscle invasive bladder cancer (MIBC) and to explore the impact of sarcopenia on complications linked to NAC or surgery. METHODS: Between 2012 and 2017, 82 consecutive patients who underwent NAC and RC for cT2-T4 N0 MIBC were retrospectively selected. Using CT scan before and after NAC, Lumbar Skeletal Muscle Index (SMI) was assessed by two observers. We defined severe sarcopenia as SMI <50 cm2/m2 for men and SMI <35 cm2/m2 for women. We evaluated pre- and post-NAC cisplatin-based chemotherapy renal function and post-operative complication rates after cystectomy using the Clavien-Dindo classification. We explored risk factors of complications by logistic regression models. RESULTS: According to the SMI, 47 patients (57.3%) were classified as sarcopenic and 35 patients (42.7%) non-sarcopenic. Patients' characteristics between sarcopenic and non-sarcopenic patients were not significantly different except for BMI (P<0.001). Among patients non-sarcopenic before NAC, nine (25.7%) became sarcopenic after NAC. In multivariate analysis, sarcopenia was an independent significant predictor of renal impairment after NAC (P=0.02). Moreover, sarcopenia and ASA score were independent significant predictors of postoperative early complications (P=0.01 and P=0.03, respectively). CONCLUSIONS: We observed significant changes in sarcopenic status during NAC. Sarcopenia, estimated by the lumbar SMI measurement, was an independent predictor associated with the risk of renal impairment during NAC and early postoperative complications after RC.

PD-L1 expression and pattern of immune cells in pre-treatment specimens are associated with disease-free survival for HR-NMIBC undergoing BCG treatment.

PURPOSE: To assess the association between PD-L1 expression and disease-free survival (DFS) in High-Risk Non-Muscle Invasive Bladder Cancer (HR-NMIBC) patients treated with intravesical Bacillus Calmette-Guerin (BCG) instillations (IBI). METHODS: Retrospective study in five French centres between 2001 and 2015. Participants were 140 patients with histologically confirmed HR-NMIBC. All patients received induction and maintenance IBI. Pathological stage/grade, concomitant carcinoma in situ, lesion number and tumour size were recorded. CD3, CD8 and PD-L1 expression in tumour cells and in T cells in the tumour microenvironment (TME) was determined immunohistochemically. Median follow-up was 54.2 months. The primary outcome measure was DFS. Univariable and multivariable analyses were performed using the log rank test and Cox proportional hazards model. RESULTS: Of the 140 NMIBC, 52 (37.1%) were Ta, 88 (62.9%) were T1 and 100% were high grade. Median number of maintenance IBI was six (range 1-30). Twenty-five (17.9%) patients had recurrence/progression. In multivariable analysis, age (HR 1.07 [95% CI 1.02-1.13], p = 0.009), PD-L1 expression in tumour cells (HR per 10 units = 1.96 [95% CI 1.28-3.00], p = 0.02) and CD3/CD8 ratio (HR per 10 units = 3.38 [95% CI 1.61-7.11], p = 0.01) were significantly associated with DFS. However, using the cut-off corresponding for each PD-L1 antibodies, PD-L1 + status was not associated with DFS. CONCLUSION: Despite an association between PD-L1 expression and BCG failure in HR-NMIBC, the PD-L1 + status was not a prognostic factor in the response of BCG. Moreover, we confirmed the key role played by the IC within the microenvironment in BCG treatment. These findings highlighted the rationale to combine BCG and PD-L1/PD-1 antibodies in early bladder cancer.

Metastatic hormone sensitive prostate cancer: local treatment strategies.

PURPOSE: The landscape of the management of metastatic prostate cancer is changing rapidly and there is growing interest in the local treatment of the primary in these patients. The effect of local treatment on the outcome of metastatic prostate cancer patients was addressed based on retrospective analysis but now also based on prospective randomized trials. This article provides an overview of the currently available literature in this field. METHODS: A literature review was done searching the Medline database for English language articles using the keywords "metastatic prostate cancer", and "local treatment", "radiotherapy", "prostatectomy". The data of prospective randomized studies and the data of case-control studies or retrospective analysis were summarized in a narrative fashion. RESULTS: Data from two prospective randomized trials exploring the effect of local treatment of the prostate in hormone-sensitive metastatic prostate cancer showed no improvement of overall survival in the individual overall cohorts as well as in the pooled analysis (HR 0.92, 95% CI 0.81-1.04). There was an improvement of failure-free survival (pooled analysis HR 0.76, 95% CI 0.69-0.0.84). There was also an improved overall survival associated with radiotherapy in patients with < 5 metastases and with low volume disease. Data from prospective non-randomized or retrospective studies are inconclusive and underlies major selection biases. CONCLUSION: Based on prospective randomized trials, local treatment by radiotherapy does not improve the overall survival in unselected metastatic prostate cancer patients. An effect can be seen in low volume patients or patients with < 5 metastases.

Imaging protocols for renal multiparametric MRI and MR urography: results of a consensus conference from the French Society of Genitourinary Imaging.

OBJECTIVES: To develop technical guidelines for magnetic resonance imaging aimed at characterising renal masses (multiparametric magnetic resonance imaging, mpMRI) and at imaging the bladder and upper urinary tract (magnetic resonance urography, MRU). METHODS: The French Society of Genitourinary Imaging organised a Delphi consensus conference with a two-round Delphi survey followed by a face-to-face meeting. Two separate questionnaires were issued for renal mpMRI and for MRU. Consensus was strictly defined using a priori criteria. RESULTS: Forty-two expert uroradiologists completed both survey rounds with no attrition between the rounds. Fifty-six of 84 (67%) statements of the mpMRI questionnaire and 44/71 (62%) statements of the MRU questionnaire reached final consensus. For mpMRI, there was consensus that no injection of furosemide was needed and that the imaging protocol should include T2-weighted imaging, dual chemical shift imaging, diffusion-weighted imaging (use of multiple b-values; maximal b-value, 1000 s/mm2) and fat-saturated single-bolus multiphase (unenhanced, corticomedullary, nephrographic) contrast-enhanced imaging; late imaging (more than 10 min after injection) was judged optional. For MRU, the patients should void their bladder before the examination. The protocol must include T2-weighted imaging, anatomical fast T1/T2-weighted imaging, diffusion-weighted imaging (use of multiple b-values; maximal b-value, 1000 s/mm2) and fat-saturated single-bolus multiphase (unenhanced, corticomedullary, nephrographic, excretory) contrast-enhanced imaging. An intravenous injection of furosemide is mandatory before the injection of contrast medium. Heavily T2-weighted cholangiopancreatography-like imaging was judged optional. CONCLUSION: This expert-based consensus conference provides recommendations to standardise magnetic resonance imaging of kidneys, ureter and bladder. KEY POINTS: • Multiparametric magnetic resonance imaging (mpMRI) aims at characterising renal masses; magnetic resonance urography (MRU) aims at imaging the urinary bladder and the collecting systems. • For mpMRI, no injection of furosemide is needed. • For MRU, an intravenous injection of furosemide is mandatory before the injection of contrast medium; heavily T2-weighted cholangiopancreatography-like imaging is optional.

Computed tomography-guided percutaneous cryoablation of T1b renal tumors: safety, functional and oncological outcomes.

Purpose: To evaluate the safety, functional and oncological outcomes associated with percutaneous cryoablation of stage T1b renal cell carcinoma (RCC). Materials and methods: Institutional database was reviewed to identify patients treated by percutaneous CT-guidance cryoablation between 2013 and 2018 for biopsy-proven RCC tumors measuring 4.1-7.0 cm. The main outcome parameters analyzed were primary and secondary technique efficacy, progression-free survival (PFS), cancer-specific survival (CSS), loss of estimated glomerular filtration rate (eGFR) and complications. PFS and CSS were estimated by the Kaplan-Meier method. Complications were graded by the Clavien-Dindo system. Results: Twenty-three consecutive patients were included (mean tumor diameter: 45.6 ± 6.2 mm; mean RENAL score: 8.1 ± 1.8). The technical success rate was 95.7%. Primary and secondary technique efficacy rates were 86.3 and 100%, respectively. Three patients found to have incomplete ablations at 3 months were successfully treated by repeat cryoablation. Median duration follow-up was 11 months (range: 3-33). Imaging showed PFS to be 85.7% at 6 months, 66.7% at 12 months and 66.7% at 24 months. One patient with a local recurrence at 12 months was treated by radical nephrectomy. One patient died from progression of disease within 12 months. One patient reported a complication grade ≥ II (4.3%). Mean eGFR loss was 4.4 ± 8.5 ml/min/1.73m2, which was significantly higher among those treated for central tumors (p < .05). Conclusion: Cryoablation for stage T1b renal tumors is technically feasible, with favorable oncological and perioperative outcomes. Longer-term studies are needed to verify our findings.

Vitiligo Adverse Event Observed in a Patient With Durable Complete Response After Nivolumab for Metastatic Renal Cell Carcinoma.

Background: Renal cell carcinoma is the third most prevalent urological cancer worldwide and about 30% of patients present with metastatic disease at the time of diagnosis. Systemic treatments for metastatic renal cell carcinoma have improved recently. Vascular endothelial growth factor targeting therapies were the previous standard of care. However, immune checkpoint inhibitors used in second line therapy have now been shown to improve patient survival. We report a case of metastatic renal cell carcinoma with nivolumab as a second-line therapy after progression with tyrosine kinase inhibitor therapy. Unusual adverse events in metastatic renal cell carcinoma, such as vitiligo, were observed in this patient who developed a remarkable documented pathological complete response to his renal tumor. Case presentation: A 60-year-old caucasian male was diagnosed with a pulmonary metastatic clear cell renal cell carcinoma. Sunitinib was used as first line treatment without success. He received nivolumab in second-line treatment. He developed several immune-related adverse events, most notably vitiligo. The patient had a radiological complete response on metastatic sites, with a significant decrease of renal tumor volume and underwent cytoreductive nephrectomy after 2 years of treatment, confirming the pathological complete response. The patient remains disease-free for 10 months without further systemic therapy after nivolumab discontinuation. Conclusions: Pathological complete response with nivolumab in metastatic renal cell carcinoma is rare. This case further highlights the potentially predictive role of immune-related adverse events during nivolumab therapy for metastatic renal cell carcinoma and raises questions concerning the role of nephrectomy after immune checkpoint inhibitor therapy. Further studies are needed to better identify predictive factors for treatment response to immunotherapy in metastatic renal cell carcinoma, and to better understand the role of nephrectomy after nivolumab treatment.