Radium 223 dichloride for prostate cancer treatment

Emmanuel Deshayes,1,2 Mathieu Roumiguie,3 Constance Thibault,4 Philippe Beuzeboc,5 Florent Cachin,6 Christophe Hennequin,7 Damien Huglo,8 François Rozet,9 Diana Kassab-Chahmi,10 Xavier Rebillard,11 Nadine Houédé1,12 1Radiobiology Unit, INSERM U1194, Institut du Cancer de Montpellier (ICM), 2Department of Nuclear Medicine, Institut du Cancer de Montpellier (ICM), Montpellier, 3Urology Department, Andrology and Renal Transplantation, CHU Rangueil, Toulouse, 4Medical Oncology Department, Hôpital Européen Georges Pompidou, 5Oncology Department, Institut Curie, 6Department of Nuclear Medicine, CHU, Clermont-Ferrand, 7Radiotherapy Department, Hôpital Saint Louis, Paris, 8Department of Nuclear Medicine, CHRU, Lille, 9Urology Department, Institut Mutualiste Montsouris, 10Intergroupe coopérateur francophone de recherche en onco-urologie, Paris, 11Urology Department, Clinique BeauSoleil, Montpellier, 12Medical Oncology Department, Institut de Cancérologie du Gard – CHU Caremeau, Nîmes, France Abstract: Prostate cancer is the most common malignant disease in men. Several therapeutic agents have been approved during the last 10 years. Among them, radium-223 dichloride (Xofigo®) is a radioactive isotope that induces irreversible DNA double-strand breaks and consequently tumor cell death. Radium-223 dichloride is a calcium-mimetic agent that specifically targets bone lesions. Radium-223 dichloride has been approved for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases, without known visceral metastases. In this review, first we summarize the interplay between prostate tumor cells and bone microenvironment; then, we discuss radium-223 dichloride mechanism of action and present the results of the available clinical trials and future developments for this new drug. Keywords: bone metastasis, mCRPC, mechanism, drug, agents, development&nbsp

<p>Guidelines from the cancer committee of the French Association of Urology (CC-AFU) for adequate intravesical instillations of Mitomycin C, Epirubicin, and BCG for non-muscle invasive bladder cancer</p>

International audienceIntroduction. - Intravesical instillations of mitomycin C, epirubicin and BCG are considered as the standard treatment for most patients diagnosed with non-muscle invasive bladder cancer. These guidelines aim to optimize the adjuvant intravesical treatment in order to increase the efficacy and lower the morbidity associated with its administration.& nbsp;Methods. - We conducted a daily practice survey, an online search of available national regulation recommendations and of published guidelines. A bibliography search in French and English using Medline (R) and Embase (R) with the keywords ``BCG ``; ``mitomycin C ``; ``epirubicin ``; ``bladder ``; ``complication ``; ``toxicity ``; ``adverse reaction ``; ``prevention `` and ``treatment `` was performed November 2021.& nbsp;Results. - Patient information should be given by the attending physician before the first intravesical instillation. A medical exam to look for specific contraindications is also mandatory to select adequate candidates. Intravesical instillations should be delivered in health-care centers where urologic endoscopic procedures are routinely performed. Attending urologist or specialized nurse should check for negative pretreatment urine test. Intravesical instillation can only be delivered after bladder catheter has been inserted in the bladder without any injury of the lower urinary tract. The pharmaceutical agent should be kept in the bladder for two hours. Finally, voiding within the 6 hours following intravesical instillations should be done in the sitting position and the patient should drink at least 2 liters of water per day for 2 days.& nbsp;Conclusion. - The delivery of intravesical instillations of mitomycin C, epirubicin and BCG should follow a standardized procedure for better efficacy and lower morbidity. (C) 2022 Elsevier Masson SAS. All rights reserved

<p>Guidelines from the cancer committee of the French Association of Urology (CC-AFU) for adequate intravesical instillations of Mitomycin C, Epirubicin, and BCG for non-muscle invasive bladder cancer</p>

International audienceIntroduction. - Intravesical instillations of mitomycin C, epirubicin and BCG are considered as the standard treatment for most patients diagnosed with non-muscle invasive bladder cancer. These guidelines aim to optimize the adjuvant intravesical treatment in order to increase the efficacy and lower the morbidity associated with its administration.& nbsp;Methods. - We conducted a daily practice survey, an online search of available national regulation recommendations and of published guidelines. A bibliography search in French and English using Medline (R) and Embase (R) with the keywords ``BCG ``; ``mitomycin C ``; ``epirubicin ``; ``bladder ``; ``complication ``; ``toxicity ``; ``adverse reaction ``; ``prevention `` and ``treatment `` was performed November 2021.& nbsp;Results. - Patient information should be given by the attending physician before the first intravesical instillation. A medical exam to look for specific contraindications is also mandatory to select adequate candidates. Intravesical instillations should be delivered in health-care centers where urologic endoscopic procedures are routinely performed. Attending urologist or specialized nurse should check for negative pretreatment urine test. Intravesical instillation can only be delivered after bladder catheter has been inserted in the bladder without any injury of the lower urinary tract. The pharmaceutical agent should be kept in the bladder for two hours. Finally, voiding within the 6 hours following intravesical instillations should be done in the sitting position and the patient should drink at least 2 liters of water per day for 2 days.& nbsp;Conclusion. - The delivery of intravesical instillations of mitomycin C, epirubicin and BCG should follow a standardized procedure for better efficacy and lower morbidity. (C) 2022 Elsevier Masson SAS. All rights reserved

Pathological features of Prostate Imaging Reporting and Data System (PI-RADS) 3 MRI lesions in biopsy and radical prostatectomy specimens

Objective To assess the whole pathology spectrum of Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, identified on magnetic resonance imaging, using systematic (SB), targeted biopsy (TB) and radical prostatectomy (RP) specimen analysis. Methods From a prospective database of patients undergoing RP after a combination of SB (median 12 cores) and fusion TB (median 3 cores), we included 150 PI-RADS 3 cases. Clinically significant prostate cancer (csPCa) was defined by a Grade Group 2 or more. The primary endpoints were unfavourable features in RP specimens. Results Targeted biopsy was negative in 20.7% of patients. Final Grade Group 3 or more and a pT3 stage was reported in 36.7% and 38.7% of RP specimens. The upgrading rate was 38.2% between biopsy and RP specimens. The concordance rate between Grade Group on TB and RP was only 38.0%. The two independent predictive factors for unfavourable disease (pT3-4 and/or final Grade Group 3-5) were prostate-specific antigen density (PSAD; P = 0.001) and presence of csPCa on TB (odds ratio 3.7; P = 0.001). The risk of unfavourable disease was increased 2.3-fold and 5.8-fold, respectively, for patients with a PSAD between 0.15 and 0.20, and a PSAD &gt;0.20 ng/mL/g. The 5-year biochemical recurrence-free survival rate was 93.2%. Conclusions PI-RADS 3 lesions exhibited aggressive features in almost 40% of cases. PSAD and presence of csPCa on TB are independent predictive factors for high-grade and/or extraprostatic disease. A combination of SB and TB improve grade prediction compared to use of TB alone

Multicenter external validation of the radical cystectomy pentafecta in a European cohort of patients undergoing robot-assisted radical cystectomy with intracorporeal urinary diversion for bladder cancer

International audienceObjective To perform an external validation of this RC-pentafecta. Method Between January 2014 and December 2019, 104 consecutive patients who underwent RARC with ICUD within 6 urological centers were analyzed retrospectively. Patients who simultaneously demonstrated negative soft tissue surgical margins (STSMs), a lymph node (LN) yield ≥ 16, absence of major (Clavien-Dindo grade III-V) 90-day postoperative complications, absence of UD-related long-term sequelae, and absence of 12-month clinical recurrence were considered to have achieved RC-pentafecta. A multivariable logistic regression model was used to measure predictors for achieving RCpentafecta. We analyzed the influence of this RC-pentafecta on survival, and the impact ofthe surgical experience. Results Since 2014, 104 patients who had completed at least 12 months of follow-up were included. Over a mean follow-up of 18 months, a LN yield ≥ 16, negative STSMs, absence of major complications at 90 days, and absence of UD-related surgical sequelae and clinical recurrence at ≤ 12 months were observed in 56%, 96%, 85%, 81%, and 91% of patients, respectively, resulting in a RC-pentafecta rate of 39.4%. Multivariate analysis showed that age was an independent predictor of pentafecta achievement (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.90. 0.99; p = 0.04). The surgeon experience had an impact on the validation of the criteria. Conclusion This study confirmed that the RC-pentafecta is reproducible and could be externally used for the outcome assessment after RARC with ICUD. Therefore, the RC-pentafecta could be a useful tool to assess surgical success and its impact on different outcomes

Guidelines from the cancer (CC-AFU) and infection disease (CI-AFU) committees of the French Association of Urology for the management of adverse events and complications of BCG

International audienceIntroduction. - Intravesical instillations of BCG are recommended for the treatment of high risk non-muscle-invasive bladder cancer. However, their prolonged use remains limited by the associated potentially serious adverse effects or complications. The purpose of this article was to provide updated recommendations for the diagnosis and management of adverse events (AEs) or complications of intravesical BCG instillations. Materials and methods. - Review of the literature in Medline (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using the following MeSH keywords or a combination of these keywords: ``bladder,'' ``BCG,'' ``complication,'' ``toxicity,'' ``adverse events,''''prevention,'' and ``treatment''. Results. - AEs or complications of BCG included genitourinary and systemic symptoms. The most common complications (cystitis, moderate fever) should be treated symptomatically and may require adjustment to allow patients to have the most complete BCG treatment possible. Serious complications are rare but must be identified promptly because of the life-threatening nature of the disease. Their management is based on the combination of anti-tuberculosis treatments, anti-inflammatory drugs and the definitive discontinuation of BCG. Conclusion. - The management of BCG AEs requires early identification, rational and effective treatment if necessary, and discussion of the continuation of treatment for each situation. (C) 2022 Elsevier Masson SAS. All rights reserved