Circulating Biomarkers Predictive of Treatment Response in Patients with Hormone-sensitive or Castration-resistant Metastatic Prostate Cancer: A Systematic Review.

BACKGROUND AND OBJECTIVE: Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also directly in biologic fluids (ie, liquid biopsies), mainly blood. Liquid biopsies may represent a safer and less invasive alternative for monitoring patients treated for mPCa. Current research focuses on the description and validation of novel predictive biomarkers to improve precision medicine in mPCa. Our aim was to systematically review the current evidence on liquid biopsy biomarkers for predicting treatment response in mPCa. METHODS: We systematically searched Medline, Web of Science, and evidence-based websites for publications on circulating biomarkers in mPCa between March 2013 and February 2024 for review. Endpoints were: prediction of overall survival, biochemical or radiographic progression-free survival after treatment (chemotherapy, androgen deprivation therapy, androgen receptor pathway inhibitors [ARPIs], immunotherapy, or PARP inhibitors [PARPIs]). For each biomarker, the level of evidence (LOE) for clinical validity was attributed: LOE IA and IB, high level of evidence; LOE IIB and IIC, intermediate level; and LOE IIIC and LOE IV-VD, weak level. KEY FINDINGS AND LIMITATIONS: The predictive value of each biomarker for the response to several therapies was evaluated in both metastatic hormone-sensitive (mHSPC) and castration-resistant prostate cancer (mCRPC). In patients with mCRPC, BRCA1/2 or ATM mutations predicted response to ARPIs (LOE IB) and PARPIs (LOE IIB), while AR-V7 transcripts or AR-V7 protein levels in circulating tumor cells (CTCs) predicted response to ARPIs and taxanes (LOE IB). CTC quantification predicted response to cabazitaxel, abiraterone, and radium-223 (LOE IIB), while TP53 alterations predicted response to 177Lu prostate-specific membrane antigen radioligand treatment (LOE IIB). AR copy number in circulating tumor DNA before the first treatment line and before subsequent lines predicted response to docetaxel, cabazitaxel, and ARPIs (LOE IIB). In mHSPC, DNA damage in lymphocytes was predictive of the response to radium-223 (LOE IIB). CONCLUSIONS AND CLINICAL IMPLICATIONS: BRCA1/2, ATM, and AR alterations detected in liquid biopsies may help clinicians in management of patients with mPCa. The other circulating biomarkers did not reach the LOE required for routine clinical use and should be validated in prospective independent studies. PATIENT SUMMARY: We reviewed studies assessing the value of biomarkers in blood or urine for management of metastatic prostate cancer. The evidence indicates that some biomarkers could help in selecting patients eligible for specific treatments.

Clinical and pathological characteristics of renal cell carcinomas with MiTF translocation.

INTRODUCTION: Microphthalmia Transfactor Family (MiTF) translocation renal cell carcinomas (RCCs) represent a rare subtype of renal cell cancers. They are diagnosed in young patients and have a poor prognosis. The aim of our study was to analyze the clinical and pathological features of patients with MiTF RCC. MATERIAL AND METHOD: We performed a retrospective, monocentric, descriptive study including all patients operated for RCC between January 2015 and January 2023. The diagnosis of MiTF RCC was suspected by immunohistochemistry (IHC) and confirmed by fluorescent in situ hybridization (FISH). Survival data according to histological subtype (MiTF versus ccRCC) were analyzed using the Kaplan-Meier method and compared using a log-rank test. The primary endpoint was recurrence-free survival (RFS). A descriptive cohort analysis was performed. RESULTS: Of the 960 patients included, 19 (2%) had FISH-confirmed MiTF tumors. The median age at diagnosis was 42 years [18-75], the sex ratio was 1.11 females for 1 male, and 4 (21%) patients were immediately metastatic. Median RFS was 21months for patients in the MiTF group and was significantly lower than that of ccRCC patients, HR=4.33 [CI95% 2.06; 9.10; P<0.001]. Of the 11 patients with cT1-T2 tumors, 9 (81.8%) were treated with nephron sparing-surgery, with 2 (22.2%) harbored local recurrence. CONCLUSION: Our study shows that patients with MiTF translocation RCC have a significantly lower RFS than non-MiTF RCC patients. Nephron sparing surgery must be weighted by the high risk of recurrence in this particularly young population.

Primary angiosarcoma of the kidney: A challenging diagnosis.

Angiosarcoma is a rare malignancy derived from endothelial cells, which behaves aggressively. Primary angiosarcoma of the kidney is even rarer, and its clinical and radiological presentations do not differ from clear cells renal cell carcinoma (ccRCC). Management protocols are not standardized, although nephrectomy is usually performed. Subsequent treatments (chemotherapy, radiotherapy, and lately, targeted therapies) vary considerably. Herein, we report the case of a middle-aged patient harboring primary angiosarcoma of the left kidney and discuss its presentation and management in light of current guidelines. The case is described for its rarity and masquerading nature.

[Current state of knowledge of urology residents and fellows on the neuro-urological management of spina bifida patients in France]. / État des lieux des connaissances des internes et chefs de clinique d'urologie sur la prise en charge neuro-urologique des patients spina bifida en France.

OBJECTIVE: To assess the current knowledge of French urology residents and fellows about neurogenic lower urinary tract dysfunction and their management in patients with spina bifida. MATERIAL AND METHOD: A 7-question questionnaire, covering the responder's experience and the various stages in the neuro-urological management of spina bifida, was drafted by an expert urologist. Responses were collected within 5days of being e-mailed to members of the Association française des urologues en formation (AFUF), and a descriptive analysis was carried out. RESULTS: Of the 448 members, 155 completed the questionnaire. Of the participants, 83.8% said they knew the definition of spina bifida, and 76.8% had already had to care for a spina bifida patient. Of the participants, 48.4% correctly estimated the number of spina bifida patients in France. Neurogenic lower urinary tract dysfunction to look for and the specificities of management seemed to have been acquired by a majority of respondents (correct response rates of 70.7% and 75.4%, respectively), unlike the extra-urological aspects (53.9%), and the choice of examinations useful for the initial work-up and follow-up (55.8%). CONCLUSION: While the expected neurogenic lower urinary tract dysfunction and the specificities of therapeutic management of spina bifida patients appear to be well known to urologists in training, knowledge of extra-urological symptoms and the choice of examinations could be improved. These results could be used to adjust the teaching given to French urologists in training on the urological management of spina bifida patients. LEVEL OF EVIDENCE: Grade 4.

Clinical Reproducibility of the Stone Volume Measurement: A "Kidney Stone Calculator" Study.

BACKGROUND: An accurate estimation of the stone burden is the key factor for predicting retrograde intra-renal surgical outcomes. Volumetric calculations better stratify stone burden than linear measurements. We developed a free software to assess the stone volume and estimate the lithotrity duration according to 3D-segmented stone volumes, namely the Kidney Stone Calculator (KSC). The present study aimed to validate the KSC's reproducibility in clinical cases evaluating its inter-observer and intra-observer correlations. METHODS: Fifty patients that harbored renal stones were retrospectively selected from a prospective cohort. For each patient, three urologists with different experience levels in stone management made five measurements of the stone volume on non-contrast-enhanced computed tomography (NCCT) images using the KSC. RESULTS: the overall inter-observer correlation (Kendall's concordance coefficient) was 0.99 (p < 0.0001). All three paired analyses of the inter-observer reproducibility were superior to 0.8. The intra-observer variation coefficients varied from 4% to 6%, and Kendall's intra-observer concordance coefficient was found to be superior to 0.98 (p < 0.0001) for each participant. Subgroup analyses showed that the segmentation of complex stones seems to be less reproductible. CONCLUSIONS: The Kidney Stone Calculator is a reliable tool for the stone burden estimation. Its extension for calculating the lithotrity duration is of major interest and could help the practitioner in surgical planning.

Lymph Node Dissection During Radical Nephro-Ureterectomy for Upper Tract Urothelial Carcinoma: A Review.

Although lymphonodal dissection is well-accepted for muscle-invasive bladder cancer management, its role is still debated during radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). The aim of this study was to summarize the current knowledge concerning the indication, anatomical template, prognostic, and therapeutic roles of lymph node dissection (LND) performed at the time of RNU. Quality control markers, such as the number of lymph nodes (LN) removed, lymph node density, and safety of the different surgical approaches, were assessed. We performed a narrative review using the PubMed and ClinicalTrials.gov databases. We identified and analyzed articles based on the practice and the role of lymph node dissection for non-metastatic UTUC. There are no clear guidelines regarding the indication of LND for UTUC, but aggressive tumors may beneficiate from lymphadenectomy since lymph node invasion is a clear independent poor prognostic factor, allowing for adjuvant treatments. It seems that an extended lymphadenectomy may provide therapeutic advantages as a higher number of nodes removed may be related to the removal of undetected LNs micrometastases and a subsequent improvement in recurrence rate and cancer-specific survival. Clear anatomical templates are thus needed based on the location and the laterality of the primary tumor.

Current Advances in Immune Checkpoint Inhibition and Clinical Genomics in Upper Tract Urothelial Carcinoma: State of the Art.

Upper tract urothelial carcinoma (UTUC) is a rare and challenging-to-treat malignancy. In most patients it is a sporadic tumor entity, less commonly it falls on the spectrum of Lynch syndrome, an autosomal dominant familial tumor syndrome. Localized UTUC with high-risk features as well as the metastatic disease scenario might require systemic therapy. Platinum-based combination chemotherapy is currently the recommended management option. However, the introduction of immune checkpoint inhibitors into the therapeutic armamentarium has led to a paradigm shift in treatment standards. Immunotherapy has been shown to be safe and effective in treating at least metastatic UTUC, although UTUC-specific high-level evidence is still lacking. Recent technological advances and noteworthy research efforts have greatly improved the general understanding of the biological landscape of UTUC. According to the main findings, UTUC represent a particular subtype of urothelial carcinoma frequently associated with activated FGFR3 signaling, a luminal-papillary phenotype and a T-cell-depleted microenvironment. This improved knowledge promises precision oncology approaches that match treatment decision strategies and genomic profile to ultimately result in better clinical outcomes. The aim of this review was to summarize the main currently available evidence on immune checkpoint inhibition and clinical genomics in UTUC.

Neoadjuvant Immunotherapy for Muscle-Invasive Bladder Cancer.

Background and Objectives: Facing neoadjuvant chemotherapy followed by surgery, neoadjuvant immunotherapy is an innovative concept in localized muscle-invasive bladder cancer. Herein, we performed a review of the available and ongoing evidence supporting immune checkpoint inhibitor (ICI) administration in the early stages of bladder cancer treatment. Materials and Methods: A literature search was performed on Medline and clinical trials databases, using the terms: "bladder cancer" OR "urothelial carcinoma", AND "neoadjuvant immunotherapy" OR "preoperative immunotherapy". We restricted our investigations to prospective clinical trials evaluating anti-PD-(L)1 and anti-CTLA-4 monoclonal antibodies. Data on efficacy, toxicity and potential biomarkers of response were retrieved. Results: The search identified 6 ICIs that were tested in the neoadjuvant setting for localized bladder cancer-4 anti-PD-(L)1 inhibitors (Pembrolizumab, Atezolizumab, Nivolumab and Durvalumab) and 2 anti-CTLA-4 inhibitors (Ipilimumab and Tremelimumab). Most of the existing literature was based on single-arm phase 2 clinical trials that included from 23 to 143 patients. The pathological complete response rate (pCR) and pathological response rate (pRR) ranged from 31% to 46% and from 55.9% to 66%, respectively. Survival data were immature at this time. The safety profile was acceptable, with severe treatment-related adverse events ranging from 6% to 41%. Conclusions: The results of early phase trials are encouraging, and more investigations are needed to strengthen the rationale for immune checkpoint inhibitor administration in localized muscle-invasive bladder cancer.