Erdafitinib in BCG-treated high-risk non-muscle-invasive bladder cancer.

BACKGROUND: Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) with disease recurrence after bacillus Calmette-Guérin (BCG) treatment and who are ineligible for/refuse radical cystectomy. FGFR alterations are commonly detected in NMIBC. We evaluated the activity of oral erdafitinib, a selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, versus intravesical chemotherapy in patients with high-risk NMIBC and select FGFR3/2 alterations following recurrence after BCG treatment. PATIENTS AND METHODS: Patients aged ≥18 years with recurrent, BCG-treated, papillary-only high-risk NMIBC (high-grade Ta/T1) and select FGFR alterations refusing or ineligible for radical cystectomy were randomized to 6 mg daily oral erdafitinib or investigator's choice of intravesical chemotherapy (mitomycin C or gemcitabine). The primary endpoint was recurrence-free survival (RFS). The key secondary endpoint was safety. RESULTS: Study enrollment was discontinued due to slow accrual. Seventy-three patients were randomized 2 : 1 to erdafitinib (n = 49) and chemotherapy (n = 24). Median follow-up for RFS was 13.4 months for both groups. Median RFS was not reached for erdafitinib [95% confidence interval (CI) 16.9 months-not estimable] and was 11.6 months (95% CI 6.4-20.1 months) for chemotherapy, with an estimated hazard ratio of 0.28 (95% CI 0.1-0.6; nominal P value = 0.0008). In this population, safety results were generally consistent with known profiles for erdafitinib and chemotherapy. CONCLUSIONS: Erdafitinib prolonged RFS compared with intravesical chemotherapy in patients with papillary-only, high-risk NMIBC harboring FGFR alterations who had disease recurrence after BCG therapy and refused or were ineligible for radical cystectomy.

[Results of subinguinal microsurgical varicocelectomy]. / Résultats des cures de varicocèles microchirurgicales sous-inguinales.

INTRODUCTION: The subinguinal microsurgical varicocelectomy is considered as the gold standard surgical technique for the treatment of varicocele. The objective of this study is to evaluate the results of this technique on the resolution of pain and the parameters of sperm analysis. METHODS: Single-center, retrospective study that includes 22 patients who have been operated over a period of six months for a clinically palpable varicocele via the microsurgical subinguinal technique. Nine patients were operated for pain and 13 patients for infertility with an abnormality of their sperm analysis. RESULTS: All the patients operated for pain had a complete resolution of pain at the postoperative follow-up (3 months). Concerning the patients operated for infertility, 76.92% of the patients had a normal sperm analysis, 7.69% of the patients presented a partial improvement, and 15.39% of the patients without any improvement. Analysis of sperm's parameters at 3 months showed a significant improvement in the morphology (4.3% vs 6.69% of typical forms according to Kruger ; P<0.05) and mobility (progressive mobility 15.6% vs 23% postoperatively; P<0.01). A non-significant improvement (low sample) in the concentration was noted (21.58 million/mL preoperative vs 34.9 million/mL postoperative, P=0.08). Pregnancies are noted in 38.5% of patients. A postoperative complication was noted with surgical site infection resolved with antibiotics. CONCLUSION: This single-center study confirms that the treatment of varicocele by subinguinal microsurgical route is an effective therapeutic strategy on symptomatic varicocele and in infertile men. This technique is associated with few complications.

Ureteropelvic junction obstruction and renal calculi: Simultaneous treatment by robot-assisted laparoscopic pyeloplasty and transcutaneous retrograde flexible ureteroscopy. Technique description and early outcomes.

BACKGROUND: Ureteropelvic junction obstruction (UPJO) and renal calculi are associated in 20 to 30% of cases and treatment is mandatory. The simultaneous surgical management is a therapeutic challenge that is still a source of controversy. We describe our technique combining robot-assisted laparoscopic pyeloplasty and transcutaneous retrograde flexible ureteroscopy (fURS), assessing the feasibility of simultaneous treatment through an original technique. METHODS: This single centre series reports our initial experience with 12 patients. From January 2014 to September 2018, 12 patients underwent robot-assisted laparoscopic pyeloplasty with simultaneous fURS for UPJO and renal calculi. Mean age was 46 years (24-68). 92% had multiple renal stones and the mean cumulative stone diameter was 31,3mm. Robot-assisted pyeloplasty was performed with peroperative transcutaneous retrograde fURS through a ureteral access sheath introduced in an incision on the bassinet through a subcostal trocar. Stone extraction was performed using a basket. RESULTS: All patients underwent surgery successfully, achieving UPJ repair and complete stone extraction. Mean operating time was 92,5min (85-110). All reported Clavien-Dindo complications were grade 1. Non-contrast enhanced abdominal CT performed 1 month after surgery confirmed the absence of residual stones in all patients. Mean follow-up time was 10 months with no recurrence of UPJO. CONCLUSION: This small series confirms the feasibility with good surgical results of concomitant robot-assisted laparoscopic pyeloplasty and transcutaneous retrograde fURS stone extraction. No major complications were observed. This technique is easily reproducible but requires 2 experienced urologists to be achieved in a contained operative time.

[Pathological pelvic lymph node involvement in muscle-invasive bladder cancer patients treated with radical cystectomy: A narrative review]. / Envahissement ganglionnaire pelvien anatomopathologique après cystectomie totale pour le traitement des tumeurs de vessie infiltrant le muscle : une revue narrative de la littérature.

OBJECTIVE: To perform a narrative review of the contemporary literature on the diagnosis, prognosis and adjuvant management of muscle-invasive bladder cancer (MIBC) patients with pathological pelvic lymph node involvement (pN+) at radical cystectomy. METHOD: A narrative review of the contemporary literature available on Medline was conducted to report studies evaluating the diagnosis, prognosis and/or adjuvant treatments for MIBC patients with pN+ disease at radical cystectomy. RESULTS: Open or robotic extended pelvic lymph node dissection up to the crossing of the ureter with common iliac vessels can enhance the diagnosis of pN+ MIBC, especially using separate packages for the submission of a maximum number of lymph nodes. The main prognosis factors for pN+ patients are the number of positive and retrieved lymph nodes, lymph node density, extranodal extension as well as lymph node metastasis diameter. Adjuvant chemotherapy is likely to prolong overall survival in pN+ patients treated with radical cystectomy alone while adjuvant immunotherapy using nivolumab has been shown to decrease the risk of recurrence in all pN+ patients, especially those with ypN+ disease after neoadjuvant chemotherapy followed by radical cystectomy. However, few data are currently available on the role of adjuvant radiation therapy, which remains currently experimental for these patients. CONCLUSION: Multiple parameters have been reported to impact the diagnosis and prognosis of patients with pN+ MIBC at radical cystectomy. Adjuvant management is currently based on chemotherapy and immunotherapy with preliminary data on radiation therapy.

Photodynamic cystoscopy for bladder cancer diagnosis and for NMIBC follow-up: An overview of systematic reviews and meta-analyses.

INTRODUCTION: Currently, bladder cancer detection is based on cytology and cystoscopy. White light cystoscopy (WLC) is an invasive procedure and may under-detect flat lesions. Blue light cystoscopy (BLC) and narrow band imaging (NBI) cystoscopy are new modalities that could improve the detection of non-muscle invasive bladder cancer (NMIBC) and its recurrence or progression to muscle invasive bladder cancer. We present a systematic review on BLC and NBI cystoscopy for bladder cancer diagnosis and NMIBC follow-up. MATERIAL AND METHODS: All available systematic reviews and meta-analyses on cystoscopy published in PubMed® between May 2010 and March 2021 were identified and reviewed. The main endpoints were clinical performance for bladder cancer diagnosis and for recurrence or progression detection during NMIBC follow-up, and additional value compared with cytology and/or WLC. RESULTS: Most of the meta-analyses and systematic reviews published suggest a better sensitivity of BLC and NBI cystoscopy compared to WLC, particularly for the detection of flat lesions (CIS). NBI- and BLC-guided TURBT could decrease the recurrence rates. However, their clinical utility to reduce progression rate and increase survival is still unclear. CONCLUSIONS: BLC and NBI cystoscopy are efficient techniques for bladder cancer diagnosis and NMIBC follow-up. However, their clinical benefit remains to be confirmed.

[Early detection of prostate cancer: Towards a new paradigm?] / Détection précoce du cancer de la prostate : vers un nouveau paradigme ?

Prostate cancer (PCa) is a public health issue. The diagnostic strategy for PCa is well codified and assessed by digital rectal examination, PSA testing and multiparametric MRI, which may or may not lead to prostate biopsies. The formal benefit of organized PCa screening, studied more than 10 years ago at an international scale and for all incomers, is not demonstrated. However, diagnostic and therapeutic modalities have evolved since the pivotal studies. The contribution of MRI and targeted biopsies, the widespread use of active surveillance for unsignificant PCa, the improvement of surgical techniques and radiotherapy… have allowed a better selection of patients and strengthened the interest for an individualized approach, reducing the risk of overtreatment. Aiming to enhance coverage and access to screening for the population, the European Commission recently promoted the evaluation of an organized PCa screening strategy, including MRI. The lack of screening programs has become detrimental to the population and must shift towards an early detection policy adapted to the risk of each individual.

Biochemical relapse predictive factors in patients with lymph node metastases during radical prostatectomy.

INTRODUCTION: There are no clear recommendations for the management of patients with lymph node invasion discovered during radical prostatectomy for prostate cancer (PCa). Adequate risk stratification could personalize post-surgical adjuvant treatment. Our objective was to identify predictive factors for biochemical relapse (BCR) in patients with lymph node (LN) invasion at the time of radical prostatectomy(RP). MATERIALS AND METHODS: Patients who underwent RP for high-risk PCa with LN invasion in two academic centres between 2008 and 2019 were included. Patients with metastatic disease or extrapelvic LN involvement were excluded. Following data were collected retrospectively: age, preoperative prostate-specific antigen level, Gleason score, clinical and pathological stage, number of metastatic LN and LN density. Outcome was BCR during follow-up. BCR-free survival was assessed by Kaplan-Meier method and its association with relevant variables was determined with log-rank test. RESULTS: Twenty-six patients were included. Median (IQR) age, PSA and follow-up were 64.5 years (55-78), 9.2ng/mL (4.4-20) and 16.1 months (6-27.5), respectively. Twenty patients (77%) had BCR after surgery, accounting for 24-month BCR-free survival of 65%. Patients with LN density > 15% had better survival rates than those with ≤ 15% (40% vs. 0%, respectively, at 24 months; P=0.06) without reaching significance. Cox proportional Hazards analysis could not evidence predictive factors of BCR free-survival. CONCLUSIONS: LN density seemed associated with BCR-free survival within patients with high-risk PCa and positive LN at RP. However, extraprostatic extension, number of positive LN and positive surgical margins were not independent risk factors for BCR. Larger prospective studies with centralized pathological reviews are needed. LEVEL OF PROOF: 3.

French AFU Cancer Committee Guidelines - Update 2022-2024: penile cancer.

OBJECTIVE: To update French oncology guidelines concerning penile cancer. METHODS: Comprehensive Medline search between 2020 and 2022 upon diagnosis, treatment and follow-up of testicular germ cell cancer to update previous guidelines. Level of evidence was evaluated according to AGREE-II. RESULTS: Epidermoid carcinoma is the most common penile cancer histology. Physical examination is mandatory to define local and inguinal nodal cancer stage. MRI with artificial erection can help to assess deep infiltration in cases of organsparing intention. Node negative patients (defined by palpation and imaging) will present micro nodal metastases in up to 25% of cases. Invasive lymph node assessment is thus advocated except for low risk patients. Sentinel node dynamic biopsy is the first line technique. Modified bilateral inguinal lymphadenectomy is an option with higher morbidity. 18-FDG-PET is recommended in patients with palpable nodes. Chest, abdominal and pelvis computerized tomography is an option. Fine needle aspiration (when positive) is an easy way to assess inguinal palpable node pathological involvement. Its results determine the type of lymphadenectomy to be performed (for diagnostic or curative purposes). Treatment is mostly surgical. Free margins status is essential, but it also has to be organ-sparing when possible. Brachytherapy and topic agents can cure in selected cases. Lymph node assessment should be synchronous to the removal of the tumour when possible. Limited inguinal lymph node involvement (pN1 stage) can be cured with the only lymphadenectomy. In case of larger lymph node stage, one should consider multidisciplinary treatment including chemotherapy and inclusion in a trial. CONCLUSIONS: Penile cancer needs demanding surgery to be cured, surrounded by chemotherapy in node positive patients. Lymph nodes involvement is a major prognostic factor. Thus, inguinal node assessment cannot be neglected.

French AFU Cancer Committee Guidelines Update 2022-2024: Adrenal tumor - Assessment of an adrenal incidetaloma and oncological management.

INTRODUCTION: The objective of this publication is to recall the initial work-up when faced with an adrenal incidentaloma and, if necessary, to establish the oncological management of an adrenal malignant tumor. MATERIAL AND METHODS: The multidisciplinary working group updated French urological guidelines about oncological assessment of the adrenal incidentaloma, established by the CCAFU in 2020, based on an exhaustive literature review carried out on PubMed. RESULTS: Although the majority of the adrenal masses are benign and non-functional, it is important to investigate them, as a percentage of these can cause serious endocrine diseases or be cancers. Malignant adrenal tumors are mainly represented by adrenocortical carcinomas (ACC), malignant pheochromocytomas (MPC) and adrenal metastases (AM). The malignancy assessment of an adrenal incident includes a complete history, a physical examination, a biochemical/hormonal assessment to look for subclinical hormonal secretion. Diagnostic hypotheses are sometimes available at this stage, but it is the morphological and functional imaging and the histological analysis, which will make it possible to close the malignancy assessment and make the oncological diagnosis. CONCLUSIONS: ACC and MPC are mainly sporadic but a hereditary origin is always possible. ACC is suspected preoperatively but the diagnosis of certainty is histological. The diagnosis of MPC is more delicate and is based on clinic, biology and imagery. The diagnosis of certainty of AM requires a percutaneous biopsy. At the end, the files must be discussed within the COMETE - adrenal cancer network (Appendix 1).

French AFU Cancer Committee Guidelines - Update 2022-2024: testicular germ cell cancer.

OBJECTIVE: Updated Recommendations for the management of testicular germ cell cancer. MATERIALS AND METHODS: Comprehensive review of the literature on PubMed since 2020 concerning the diagnosis, treatment and follow-up of testicular germ cell cancer (TGCT), and the safety of treatments. The level of evidence of the references was evaluated. RESULTS: The initial work-up for patients with testicular germ cell cancer is based on a clinical examination, biochemical (AFP, total hCG and LDH serum markers) and radiological assessment (scrotal ultrasound and thoracic-abdominal-pelvic [TAP] CT). Inguinal orchiectomy is the first therapeutic step whereby the histological diagnosis can be made, and the local stage and risk factors for stage I non-seminomatous germ cell tumours (NSGCT) can be determined. For patients with pure stage-I seminoma, the risk of progression is 15 to 20%. Therefore, surveillance in compliant patients is preferable; adjuvant chemotherapy with carboplatin AUC 7 is an option; and indications for para-aortic radiotherapy are limited. For patients with stage I NSGCT, there are various options between surveillance and a risk-adapted strategy (surveillance or 1 cycle of BEP [Bleomycin Etoposide Cisplatin] depending on the absence or presence of vascular emboli within the tumour). Retroperitoneal lymph node dissection for staging has a very limited role. The treatment for metastatic TGCT is BEP chemotherapy in the absence of any contraindication to bleomycin, for which the number of cycles is determined according to the prognostic risk group of the International Germ Cell Cancer Consortium Group (IGCCCG). Para-aortic radiotherapy is still a standard in stage IIA seminomatous germ cell tumours (SGCT). After chemotherapy, the size of residual masses should be assessed by TAP scan for NSGCT: retroperitoneal lymph node dissection is recommended for any residual mass of more than 1 cm, and all other metastatic sites should be excised. For SGCT, reassessment by 18F-FDG PET is required to specify the surgical indication for residual masses>3cm. Surgery is still rare in these situations. CONCLUSION: By adhering to TGCT management recommendations, excellent disease-specific survival rates are achieved; 99% for stage I and over 85% for metastatic stages.

French AFU Cancer Committee Guidelines - Update 2022-2024: Non-muscle-invasive bladder cancer (NMIBC).

OBJECTIVE: To update the ccAFU recommendations for the management of bladder tumours that do not infiltrate the bladder muscle (NBMIC). METHODS: A systematic review (Medline) of the literature from 2020 to 2022 was performed, taking account of the diagnosis, treatment options and surveillance of NMIBC, while evaluating the references with their levels of evidence. RESULTS: The diagnosis of NMIBC (Ta, T1, CIS) is made after complete full-thickness tumour resection. The use of bladder fluorescence and the indication of a second look (4-6 weeks) help to improve the initial diagnosis. The EORTC score is used to assess the risk of recurrence and/or tumour progression. Through the stratification of patients in low, intermediate and high-risk categories, adjuvant treatment can be proposed: intravesical chemotherapy (immediate postoperative, initiation regimen) or BCG (initiation and maintenance regimen) instillations, or even the indication of cystectomy for BCG-resistant patients. CONCLUSION: Updating the ccAFU recommendations should contribute to improving patient management, as well as the diagnosis and treatment of NMIBC.

French AFU Cancer Committee Guidelines - Update 2022-2024: Muscle-Invasive Bladder Cancer (MIBC).

OBJECTIVE: To update the CCAFU recommendations for the management of muscle invasive bladder carcinoma (MIBC). METHODS: A systematic review (Medline) of the literature from 2020 to 2022 was performed taking account of the diagnosis, treatment options and surveillance of NMIBC and MIBC, while evaluating the references with their levels of evidence. RESULTS: MIBC is diagnosed after the most complete tumour resection possible. MIBC grading is based on CTU along with chest CT. Multiparametric pelvic MRI could be an alternative. Cystectomy with extensive lymphadenectomy is the gold standard treatment for non-metastatic MIBC. It should be preceded by platinum-based neoadjuvant chemotherapy in patients in good general health with satisfactory renal function. Enterocystoplasty is proposed in men and women in the absence of contraindications and when the urethral resection is negative on extemporaneous examination. Otherwise, transileal cutaneous ureterostomy is the recommended method of urinary diversion. Inclusion of all patients in an ERAS (Enhanced Recovery After Surgery) protocol is recommended. For metastatic MIBC, first line treatment with platinum-based chemotherapy (GC or MVAC) is recommended, if general health (PS>1) and renal function (clearance>60mL/min) so allow (only 50% of the cases). Pembrolizumab immunotherapy has demonstrated an overall survival benefit in second-line treatment. CONCLUSION: Updating the ccAFU recommendations should contribute to improving patient management, as well as the diagnosis and decision-making concerning MIBC treatment.

French AFU Cancer Committee Guidelines - Update 2022-2024: Upper urinary tract urothelial cancer (UTUC).

INTRODUCTION: The aim was to propose an update of the French Urology Association Cancer Committee (ccAFU) Recommendations on the management of upper urinary tract urothelial carcinomas (UUT-UC). METHODS: A systematic Medline search was performed between 2020 and 2022, taking account of the diagnosis, treatment options and follow-up of UUT-UC, while evaluating the references with their levels of evidence. RESULTS: The diagnosis of this rare pathology is based on CTU acquisition during excretion and flexible ureterorenoscopy with histological biopsies. Radical nephroureterectomy (RNU) remains the gold standard for surgical treatment. Nevertheless conservative treatment can be discussed for low risk lesions: tumour of low-grade, with no infiltration on imaging, unifocal<2cm, eligible for full treatment therefore requiring close endoscopic surveillance by flexible ureteroscopy in compliant patients. After RNU, postoperative instillation of chemotherapy is recommended to reduce the risk of recurrence in the bladder. Adjuvant chemotherapy has shown clinical benefits compared to surveillance after RNU for tumours (pT2-T4 N0-3 M0). CONCLUSION: These updated recommendations should contribute to improving not only patients' level of care, but also the diagnosis and decision-making concerning treatment for UUT-UC.

[Intravesical adjuvant regimen of epitubicin for intermediate risk NMIBC: Feasability study from CC-AFU vessie]. / Instauration du traitement adjuvant endovésical par épirubicine des tumeurs de vessie n'infiltrant pas le muscle : premier retour national d'expérience du CC-AFU vessie.

INTRODUCTION: Mitomycin C is the gold standard intravesical adjuvant therapy for intermediate-risk non-muscle-invasive bladder cancer (NMIBC). Tensions in the supply of mitomycin have emerged in France since late 2019. The ANSM in agreement with the AFU proposed to use epirubicin, already available in other European countries in this indication. The objective of our study was to report the initial French experience with the use of epirubicin in adjuvant treatment of NMIBC. MATERIALS AND METHODS: We undertook a French multicenter retrospective descriptive study to collect, from the centers of the members of the CC-AFU bladder, the clinico-pathological data of the patients, the indications, the modalities of use (dose, indication, circuit in the pharmacy) and the tolerance data of epirubicin. The impact of the COVID-19 epidemic on treatment interruptions was also identified. Of the 20 centers contacted, 5 (25%) had implemented the epirubicin administration protocol developed by the CC-AFU bladder subcommittee. A total of 61 patients were treated with endovesical instillations of epirubicin between November 2019 and November 2020 for NMIBC at a single dose of 50mg. RESULTS: A total of 61 patients (mean age 67 years, 64-77 years) were treated with epirubicin, of which 45 (73.8%) were male. The patients had intermediate-risk NMIBC in 88.5%, the rest had high-risk disease. Induction therapy without or with maintenance was planned for 48 (78.7%) and 13 patients (21.3%), respectively. The preparation and administration of epirubicin was similar to that of mitomycin: central pharmacy preparation for same-day dispensing with immediate outpatient instillation. Unlike mitomycin, urinary alkalinization was not required. Of the 498 total instillations scheduled, 345 were performed (69.3%). The COVID-19 epidemic significantly impacted epirubicin delivery: one patient could not start treatment (1.6%), 8 patients (13.1%) had to discontinue it permanently; the rest of the patients underwent delayed instillations (18%). Other causes of discontinuation included infectious complications (9.8%). No major toxicities were reported. CONCLUSION: The implementation of an adjuvant epirubicin treatment protocol presented a good feasibility with low toxicity, without modifying the organization of the patients' care pathway. In the context of unpredictable mitomycin shortage, epirubicin represents a good therapeutic alternative in the endovesical adjuvant treatment of intermediate-risk NMIBC. LEVEL OF PROOF: 3.

[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]. / Recommandations du Comité de cancérologie de l'Association Française d'Urologie (CC-AFU) pour la bonne pratique des instillations intravésicales de mitomycine C, d'épirubicine et de BCG pour le traitement des tumeurs de la vessie n'infiltrant pas le muscle (TVNIM).

INTRODUCTION: 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. 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® and Embase® with the keywords "BCG"; "mitomycin C"; "epirubicin"; "bladder"; "complication"; "toxicity"; "adverse reaction"; "prevention" and "treatment" was performed November 2021. 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 6hours 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. CONCLUSION: The delivery of intravesical instillations of mitomycin C, epirubicin and BCG should follow a standardized procedure for better efficacy and lower morbidity.

[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]. / Recommandations des Comités de cancérologie (CC-AFU) et d'infectiologie (CI-AFU) de l'Association française d'urologie pour la prise en charge effets indésirables et complications du BCG.

INTRODUCTION: 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.

[DNA repair gene alterations testing in prostate cancer : A practical update by the prostate cancer committee of the french association of urology]. / Recherche d'altérations des gènes de réparation de l'ADN dans le cancer de la prostate : mise au point pratique du Comité de cancérologie de l'association française d'urologie.

INTRODUCTION: Current therapeutic developments in prostate cancer (PCa) tend to increasingly personalize the treatment strategy, in particular as a function of tumor genomics. Recently, poly ADP-ribose polymerase (PARPi) inhibitors have shown their efficacy at the stage of castration resistance, in case of alteration of DNA repair genes in tumor tissue. MATERIAL AND METHODS: A narrative review was carried out on recent data in the literature since 2000. A consensus among the members of the Committee was obtained in order to synthesize the current data, with a particular focus on the practical considerations regarding indications and developments of molecular testing circuits concerning DNA repair genes, for theranostics purpose. RESULTS: The establishment of an efficient molecular testing network is based on the multidisciplinary organization of the various actors and the coordination of all material resources. Its goal is the routine search for somatic mutations (in tumor tissue) of BRCA1/2 genes in patients who may benefit from PARPi. The current indications are for BRCA1 or 2 mutated castration-resistant metastatic PCa after next-generation hormone therapy failure. The demand for molecular testing must be decided in the tumor board, giving priority to archived tissue less than 10 years old. In case of unsuccess, biopsies of the primary or metastases, or even analysis of circulating tumor DNA, may be necessary. Any demand for a genetic test on tumor tissue must be accompanied by detailed information for the patient on the possible familial consequences, in case of associated germline mutation. CONCLUSION: This article aims to guide the practical implementation of molecular testing circuits for DNA repair genes alterations, in order to guide the therapeutic management of patients with advanced PCa.

Narrative review of PET/CT performances at biochemical recurrence in prostate cancer after radical prostatectomy and impact on patient disease management: Revue narrative à propos des performances de la TEP/TDM en cas de récidive biochimique après prostatectomie radicale dans le cancer de la prostate et impact sur la prise en charge des patients.

Patients treated by radical prostatectomy (RP) for localized prostate cancer (PCa) may experience biochemical recurrence (BCR) in approximately 30% of cases. Recently, advances in imaging modalities and in particular Positron-Emission Tomography with computed tomography (PET/CT) imaging allow for better detection and characterization of lesions outside the prostatic bed at recurrence. Thus, treatment at BCR can be significantly improved by a tailored strategy based on new generation imaging. A more precise and accurate staging of the disease at recurrence paves the way to more appropriate treatment, potentially translating into better survival outcomes of these patients. This review therefore highlights the interest of PET/CT at the time of BCR, its superiority over standard imaging in terms of staging, and its impact on guiding the different therapeutic possibilities depending on the site, number, and volumes of recurrence. Indeed, we will discuss below about different strategies and their indications: salvage radiotherapy of the prostate bed, systemic therapies, stereotactic body radiotherapy and others therapeutical strategies. The various innovative approaches based on PET/CT implementation are partly underway within protocol trials to prove their benefits on clinically meaningful endpoints. © 2022 Elsevier Masson SAS. All rights reserved.

How PET-CT is Changing the Management of Non-metastatic Castration-resistant Prostate Cancer?: Comment la TEP-TDM Peut Modifier la Prise en Charge du Cancer de la Prostate Non Métastatique Résistant à la Castration ?

INTRODUCTION: The aim of this narrative review conducted by the Prostate Cancer Committee of the French Association of Urology (CC-AFU) was to provide an update on the current evidence for the impact of PET/CT in the management of men with non-metastatic castration-resistant prostate cancer (nmCRPC). MATERIAL AND METHODS: This review is based on data available in the literature on PET/CT imaging for staging nmCRPC patients. A PubMed search and narrative review of the data were performed in March 2022. Only articles in French or English were considered. RESULTS: Current guidelines recommend bone scan and CT scan as standard imaging modalities for staging and follow-up of patients with nmCRPC. Nearly one-third of asymptomatic patients with presumed nmCRPC ultimately have metastatic disease on conventional imaging. Increasing reports have shown that conventional imaging has limited accuracy in detecting metastatic disease in nmCRPC patients, leading to the development of next-generation imaging techniques. In a retrospective study, 18F-choline PET/CT detected distant metastases in 27/58 high-risk nmCRPC patients with prior negative conventional imaging. The implementation of radiolabeled ligands of the prostate-specific membrane antigen (PSMA) PET/CT in staging strategy has resulted in metastasis detection in 45% to 98% of patients with presumptive nmCRPC on conventional imaging. Such an early diagnosis of metastatic CRPC may allow patients to be referred for metastasis-directed therapies (i.e. stereotactic body radiotherapy), aimed at prolonging the efficacy of systemic therapies and improving clinical outcomes. However, current data are not strong enough to recommend this strategy, which must be properly evaluated in clinical trials. Indeed, the use of molecular imaging may lead to inappropriate undertreatment if the second-generation androgen receptor inhibitors (darolutamide, enzalutamide, apalutamide), which prolong life, are not used in the subgroup of patients with high PSA velocity (PSA doubling time <10 months). CONCLUSION: Implementation of PSMA-PET/CT in the staging strategy would result in a migration of disease stage to extra-pelvic, M1 disease in at least half of presumed nmCRPC patients. The unprecedented accuracy of PSMA-PET/CT may pave the way for a more personalized treatment strategy. However, no data yet support this strategy for all nmCRPC patients as no oncologic benefit of early detection of M1 disease or MDT has been demonstrated. © 2022 Elsevier Masson SAS. All rights reserved.

[Recent advances in the management of localized high-risk prostate cancer: An update by the Prostate Cancer Committee of the French Association of Urology]. / Avancées récentes dans la prise en charge du cancer de la prostate localisé à haut risque : mise au point par le Comité Prostate de l'Association française d'urologie.

INTRODUCTION: The risk of recurrence is increased in localized high-risk prostate cancer (PCa). The implementation of an appropriate diagnostic and therapeutic strategy is essential. The objective of this update by the Prostate Committee of the French Association of Urology was to report the most recent data in the management of localized high-risk PCa. MATERIAL AND METHODS: This update is based on the data available in the literature on localized high-risk PCa. A PubMed search and narrative review of the recent data were performed in March 2022. RESULTS: Compared with conventional imaging, PET-PSMA is more effective for the diagnosis of lymph nodes and distant metastases. Two recent randomized clinical trials have failed to prove the oncologic benefit of extended pelvic lymph node dissection during radical prostatectomy (RP). Postoperatively, early salvage radiotherapy is the standard of care, with adjuvant radiotherapy becoming an option in case of unfavorable pathological criteria (ISUP 4-5, pT3±positive margins) in young patients. Although promising, perioperative systemic therapies (chemotherapy, second-generation hormonotherapy) cannot be recommended at this time when the patient is treated by RP. Regarding radiotherapy, prophylactic lymph node irradiation during prostatic irradiation was associated with improved biochemical and metastasis-free survival in a recent randomized trial but it is still controversial. Since the publication of the results of the STAMPEDE trial, the addition of abiraterone acetate to radiation-hormone therapy should be considered the new standard of care for patients with localized (very) high-risk PCa, according to the inclusion criteria of the study. CONCLUSION: The most recent data of the literature regarding the management of high-risk localized PCa redefine the diagnostic performance of molecular imaging, the timing of postoperative radiotherapy, the oncologic benefit of pelvic lymph node treatment, and the intensification of systemic therapies.