BACKGROUND AND OBJECTIVE:Management of local prostate cancer (PCa) recurrence after primary radiotherapy (RT) remains challenging in daily practice. Salvage high-intensity focused ultrasound (S-HIFU) represents a valid option, but large prospective data are missing. METHODS:A prospective, nationwide study was conducted in 32 French centers assessing S-HIFU as a local treatment after RT failure in patients with biopsy-confirmed intraprostatic recurrence without regional or distant metastases. The primary endpoint was androgen deprivation therapy-free survival (ADT-FS). Secondary endpoints were PCa-specific survival and overall survival, and functional outcomes. KEY FINDINGS AND LIMITATIONS:From 2015 to 2019, 531 patients were included. Median age and prostate-specific antigen (PSA) at S-HIFU were 75 yr and 4.5 ng/ml, respectively. Median PSA was 0.7 and 1.02 ng/ml at 12 and 30 mo after HIFU, respectively. The 30-mo ADT-FS was 71% in the overall cohort (95% CI, 67-76). A pre-S-HIFU PSA level ≤ 4.5 ng/ml and Gleason score 6-7 had the most favorable ADT- FS rates at 30-mo: 84% (95% CI, 78-91). High-grade (>IIIa) complications graded with the Dindo-Clavien classification were reported in 19/531 patients. The number of cases with severe incontinence increased from 7% to 12% after S-HIFU. The quality-of-life study showed no deterioration in the EORTC QLQC-30 median score at 12 mo. CONCLUSION AND CLINICAL IMPLICATIONS:This large prospective trial demonstrates good oncologic and functional outcomes after S-HIFU for treating local PCa recurrence after RT. The importance of pre-S-HIFU PSA for efficacy prediction highlights the need for earlier detection of recurrence in patients eligible for local salvage treatment. Further studies should focus on comparisons between different salvage local treatment options within high-level evidence trials. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT04307056.

BACKGROUND:Androgen-deprivation therapy (ADT) plus radiotherapy is a standard of care for men with high-risk localized prostate cancer (PC). Adding docetaxel in this setting demonstrated better relapse-free survival (RFS) but not survival. Few data are available on relapse patterns. Our aim was to investigate whether different patterns of relapses exist in men with high-risk localized PC. PATIENTS AND METHODS:Prospective data from the GETUG12 phase 3 randomized controlled trial comparing ADT alone vs ADT + docetaxel and estramustine (DE) was examined. RFS (main endpoint) was analysed using parametric survival models and second event-free survival (SEFS) defined from biochemical progression (BP) was analysed using a competing-risk approach. RESULTS:Overall, 413 patients were randomized from 2002 to 2006, 206 treated with ADT and 207 with ADT+DE, in addition to local treatment. First analysis showed that the piecewise-exponential model with two time-intervals ([0-3[; ≥3 years) was the model that best characterized RFS with no time-dependent effect of risk factors and treatment. Second analyses limited to patients with a BP showed that the risk of a second event was significantly lower in patients with a longer time-interval from randomization to BP (hazard ratio (HR≥ 3 versus < 3 years): 0.49 [95% CI 0.30-0.79]). In competing-risk analysis, a significant and protective effect of this time-interval was observed for metastases (sub-HR≥ 3 versus < 3 years: 0.41 [0.23-0.73] accounting for salvage treatment. CONCLUSION:Time-interval from randomization to BP is a major prognostic factor for developing local or distant recurrences for patients with high-risk localized PC.

Background and objective Docetaxel has become a standard component of care for advanced prostate cancer (PC); however, its benefits are not universal among patients. A subset of PC cases exhibit TMPRSS2-ERG gene fusion, resulting in ERG overexpression in tumors. Our aim was to assess biomarkers for docetaxel efficacy in men with hormone-sensitive PC (HSPC). Methods Pretreatment prostate biopsies were obtained from participants in two randomized phase 3 clinical trials investigating docetaxel in high-risk localized PC (GETUG 12) and metastatic HSPC (GETUG 15). Immunohistochemistry staining for Ki67, PTEN, RB, and phosphorylated RB was conducted for GETUG 12 samples, and ERG staining for GETUG 12 and GETUG 15 samples. We examined biomarker association with outcomes using univariate and multivariable analyses adjusted for other validated prognostic factors. Key findings and limitations Among GETUG 12 patients, Ki67 was associated with a worse relapse-free survival (RFS; hazard ratio [HR] 1.72; p = 0.0092). A pooled analysis for the two trials (pinteraction = 0.056) revealed that docetaxel-based chemotherapy improved failure-free survival for patients with ERG-positive cancer (HR 0.58; p = 0.03), but not patients with ERG-negative cancer (HR 1.08; p = 0.72). In the ERG-positive subgroup in GETUG 12 (high-risk localized PC), median RFS was 7.79 yr with androgen deprivation therapy (ADT) alone, and was not reached with ADT + docetaxel. In the ERG-negative subgroup, median progression-free survival (mPFS) was 7.79 yr with ADT alone versus 7.08 yr with ADT + docetaxel. In the ERG-positive subgroup in GETUG 15 (metastatic HSPC), mPFS was 10.7 mo with ADT alone versus 18.8 mo with ADT + docetaxel. In the ERG-negative subgroup, mPFS was 10.6 mo with ADT alone versus 13.2 mo with ADT + docetaxel. Conclusions and clinical implications Ki67 may serve as a prognostic factor in HSPC, while ERG expression appears to predict a response to docetaxel in both high-risk localized and metastatic HSPC. Patient summary We assessed factors that could predict outcomes after docetaxel chemotherapy in patients with advanced prostate cancer. We found that expression of a protein called ERG can predict a good response to docetaxel in these patients.

661 Background: Most patients following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) face a poor prognosis. Combination of chemotherapy and immunotherapy in neoadjuvant setting have demonstrated survival improvement in several tumors. Additional systemic therapy in a neoadjuvant setting may prolong survival for UTUC patients, especially those after RNU who are ineligible to receive nephrotoxic chemotherapy. Methods: Phase 2 clinical trial (NCT04617756) was conducted in 10 French centers. Eligible patients had non metastatic, high-grade disease on ureteroscopic tumor biopsy or on urine cytology and infiltrative aspect of renal pelvis/ureteral wall on CT imaging. Subjects received a combination of: Durvalumab/Gemcitabine/Cisplatin (cohort 1) or Carboplatin (cohort 2) every 3 weeks for a total of 4 cycles based on glomerular filtration rate, prior to RNU. The primary objective was to assess the pathological complete response (ypT0) rate (pCR) of each combination. Results: A total of 50 patients were enrolledbetween 2021 and 2023 (31 in cohort 1 and 19 in cohort 2). Median age was 66 years old (range 38-79), 58% were males. 90% of patients (44) received 4 cycles of treatment, 3 patients 3 cycles and 2 patients received 2 cycles. Five patients switched for carboplatin during chemotherapy. We observed in cohort 1 : 20/31 (65%) patients with non infiltrative residual tumor; In cohort 2 : 9/19 (42%) patients (table). Secondary endpoint was safety, no immunotherapy-mediated AE was observed, 2 patients had Grade 3 neutropenia, 1 grade 4, 1 patient had grade 3 thrombopenia and 1 grade 3 anemia. Conclusions: Combination of durvalumab with platin-based chemotherapy, especially cisplatin, showed promising activity in UTUC, with the occurrence of complete responses and a high rate of non-infiltrative residual tumor. Safety profile was secure without increasing surgical risk. A randomized Phase 3 controlled study comparing neoadjuvant chemotherapy with chemotherapy combined with immunotherapy in patients with high-risk localized UTUC (iNDUCT-3) will open soon to validate these encouraging results. Clinical trial information: NCT04617756 . Pathological response rate. ypT0 ypTIS /ypTa ypT1 ypT2 ypT3 ypT4 Missing data Withdrawal surgery Total Cis-Gem Durva 4 (13%) 5 (16%) 11 (36%) 1 (3%) 6 (19%) 1 (3%) 1 2 31 Carbo-Gem Durva 1 (5%) 6 (32%) 1 (5%) 3 (16%) 5 (26%) 1 (5%) 1 1 19

PURPOSE:Sunitinib is a multikinase inhibitor used to treat metastatic renal cell carcinoma (mRCC), with an inter-individual variability of pharmacokinetics and toxicity. Our goal was to assess associations between the pharmacogenetics, pharmacokinetics and toxicity of sunitinib. METHODS:In this multi-center prospective study, 42 patients with mRCC were included. An NGS panel was used to identify variations in 19 genes involved in sunitinib pharmacokinetics and pharmacodynamics. Residual concentration of sunitinib and N-desethyl-sunitinib were used to estimate a composite AUC at steady-state. RESULTS:Fifty-seven percent of patients had a plasma exposure within the optimal therapeutic range. A higher composite AUC led to significantly greater risk of endocrine toxicity (p = 0.008) and neurologic toxicity (p = 0.024), and to a non-significantly greater risk of cardiovascular toxicity (p = 0.11). A alleles of FGFR2-rs2981582 and VEFGFR2-rs1870377 were associated with a lower risk of cardiovascular toxicity (OR = 0.22 [0.05-0.97], p = 0.04 and OR = 0.17 [0.04- 0.73], p = 0.01 respectively) and with a lower composite AUC (p = 0.02 and p = 0.0002 respectively). CONCLUSION:We demonstrated for the first time, an association between genetics polymorphisms in sunitinib targets and extent of exposure to this molecule as well as their association associated with the risk of cardiovascular toxicity. We described the concentration dependence of neurological and endocrine toxicity. TRIAL REGISTRATION:NCT02404584, registered 26 March 2015.

ABSTRACT Background Immune checkpoint inhibitors (ICIs) improved survival in patients with locally advanced or metastatic urothelial carcinoma (la/mUC). Patient‐reported symptoms in this context were poorly studied. The study aimed to compare symptom severity between patients and clinicians. Methodology The secondary analysis of the AMI clinical trial comparing changes in the gut microbiota in patients with la/mUC treated with pembrolizumab was conducted in nine French centers. Secondary endpoints were expected in this prospective study. Patient‐Reported Outcome‐Common Terminology Criteria for Adverse Events (PRO‐CTCAE) and CTCAE were assessed respectively by patients and clinicians before pembrolizumab initiation, and at each treatment visit until treatment cycle 12. Agreement in severity between clinicians and patients for grade ≥ 3 symptoms was calculated with Cohen's kappa coefficient. The toxicity index was generated for CTCAE and PRO‐CTCAE to assess discordance in a longitudinal manner. The Wilcoxon test was used to compare clinicians' and patients' toxicity index and symptom severity frequencies. Results Thirty‐nine patients were included (M/F sex ratio: 2.5) from December 2020 to March 2022. PRO‐CTCAE baseline completion rate was 77.5%. Cohen's kappa coefficient ranged from −0.017 (95% confidence interval (CI), [−0.039, 0.005]) for numbness/tingling to 0.161 (95% CI, [0.045, 0.276]) for fatigue. The patient self‐rated symptom toxicity index was > 2 for all symptoms compared to ≤ 0.62 (fatigue) when assessed by clinicians in longitudinal reporting of symptom frequency and severity with a p value < 0.001. The three most commonly reported symptoms by patients and clinicians, respectively, were: Fatigue 53.3% versus 23.4%, generalized pain 42.4% versus 16.5%, and insomnia 41.1% versus 9.5%. Symptom frequency reports between clinicians and patients were statistically different (p < 0.009). Conclusions Symptom severity assessment showed discordance between patients and physicians. Clinicians reported fewer symptoms and graded them less severely than patients. PROs should be used to accurately reflect patient experience. Trial Registration ClinicalTrials.gov identifier: NCT04566029

825 Background: Pembrolizumab (Pb) is a treatment (trt) for advanced urothelial carcinoma (aUC). In this study, we analyzed the fecal metaproteome of aUC patients (pts) to investigate the differences in the taxonomic and functional composition of the gut microbiome in responders (R) vs non-responders (NR) to pembrolizumab monotherapy as second-line trt. Methods: We designed a prospective multicenter study in France. Stool samples were collected before and nine weeks after the start of Pb, with a maximum follow-up of 36 weeks. Trt efficacy was evaluated using the Response Evaluation Criteria in Solid Tumors v1.1. Proteins were extracted from each sample and analyzed using high-resolution tandem mass spectrometry combined with liquid reverse phase chromatography. Raw data were interpreted without a priori assumptions. The R package Metacoder was used to analyze taxonomic diversity, while the mixOmics package was used to perform partial least squares discriminant analysis (sPLSDA) to reveal microbiota changes between R and NR pts. A Benjamini-Hochberg (BH)-corrected Wilcoxon test identified microbial functions with different frequencies in R and NR pts. A multivariate logistic regression analysis with Bonferroni correction was conducted to create a response-prediction classifier based on clinical variables and identified relevant microbial genera. The significance threshold was set at 5%. Results: From 2019 to 2022, 53 samples were taken from 34 different pts. Of these, 3 (8.8%) pts with complete response, 5 (14.7%) with partial response and 2 (5.9%) with stable disease were classified as R. Four (11.8%) deceased pts before response evaluation were excluded from the analysis. NR corresponded to disease progression in 20 pts (58.8%). No dysbiosis was detected. There were no statistically significant differences in alpha diversity over time or between R and NR. Beta diversity index showed microbiome stability at individual level during follow-up. sPLSDA at the genus level pooling all samples (before and after trt) showed a distinctive separation between R and NR (p ≤ 0.05). Of the genera contributing most to this separation, 4 genera were identified using logistic regression: Anaerostipes, Sutterella, Escherichia, Evtepia (adj. p ≤ 0.05). Functional composition analysis identified 31 signaling pathways that differ between R and NR. These signaling pathways were clustered highlighting 7 functions that differed between R and NR when modulated by Pb. Host function analysis identified the “response to external biotic stimuli” signaling pathway significantly associated to R (BH adj p-value ≤0.05). Conclusions: The composition of the gut microbiome and metabolic functions differed between R and NR pts with aUC under Pb. The genera Anaerostipes , Sutterella, Escherichia and Evtepia could be biomarkers for the efficacy of pembrolizumab. Clinical trial information: NCT03584659 .

To assess the feasibility of a remission consultation with on-going personalized care for patients treated for localized breast cancer entering a monitoring phase, while collecting quality of life data for one year. The primary objective was to evaluate the rate of acceptance of the remission consultation and, in the group who accepted, evaluate the change in quality of life using the EORTC QLQ-C30 over time. The secondary objectives were to evaluate change over time of the patient’s perception of body image via the BIS score, change over time in psychological distress score on a visual analog scale, time until return to work, and to describe the characteristics of patients according to the management methods chosen. Patients in remission from non-metastatic breast cancer were invited to a one-hour consultation interview to assess psychological condition and identify personalized supportive care needs. Various psychological follow-up options were offered depending on patient needs (e.g., anxiety or depression; fear of recurrence; or difficulty reconnecting with family, friends or at work). Patients were followed up at 3, 6 and 12 months after the remission consultation. Of the 69 patients included, 50 (72

INTRODUCTION:FGFR3 alterations are observed in 10% to 15% of patients with advanced urothelial carcinoma (UC). We aimed to clarify the prognostic and predictive value of FGFR3 alterations in patients receiving first-line platinum-based chemotherapy (PBC) for advanced urothelial carcinoma. PATIENTS AND METHODS:We conducted a multicenter retrospective cohort study including patients with histologically confirmed UC treated in first line with PBC, with or without immune-checkpoint inhibitors (ICIs) administered as maintenance or second line. Only patients with known FGFR3 status on baseline tumor tissue, locally assessed were included. Progression-free survival (PFS) was the primary endpoint. Secondary endpoints included overall survival (OS), objective response rates (ORR), and PFS with ICIs, stratified by FGFR3 status. RESULTS:Between 2016 and 2022, 191 pts were included, of whom 58 (30.4%) had FGFR3-altered tumors (FGFR3^alt). Baseline characteristics were well balanced. ICIs were administered to 34% of patients. After a median follow-up of 32 months, median PFS under PBC was 6.6 months in FGFR3^alt and 7.5 in FGFR3 wild type subgroups (HR = 1.27; P = .15) respectively. Median OS was 22.1 versus 20.8 months (HR = 0.91; P = .658), and ORR in 133 pts were similar across subgroups (70.7% vs. 69.2% respectively). In multivariate analysis, FGFR3 status was not associated with survival. CONCLUSIONS:FGFR3 status did not significantly impact response to PBC in first-line treatment or ICIs. These findings underscore that the presence of an FGFR3 alteration does not guide the choice of platinum-based treatment, and the need for prospective biomarker-driven trials to identify best treatment sequences in advanced UC.

Background and objective: High-intensity focused ultrasound (HIFU) has emerged as an interesting ablative alternative to radical prostatectomy (RP) and radiation therapy (RT) for localized prostate cancer (PC). However, no prospective comparative data have been published for HIFU. Methods: We performed a prospective nonrandomized nationwide trial in 46 centers in France comparing RP versus HIFU. The main inclusion criterion was low-to intermediate-risk PC. The primary endpoint was salvage therapy-free survival (STFS). Secondary endpoints were metastasis-free survival, PC-specific survival, overall survival, and functional outcomes. Key findings and limitations: From 2015 to 2019, 3328 patients were included (1967 HIFU and 1361 RP). Median age was 74.7 versus 65.1 yr (p < 0.001) and median PSA was 7.1 versus 6.9 ng/ml (p = 0.5) in the HIFU and RP groups, respectively. Intermediate-risk PC was diagnosed in 61% of patients in the HIFU group and 64% in the RP group (p = 0.10). The 30-mo STFS was not inferior in the HIFU group (hazard ratio 0.71, 95% confidence interval 0.52-0.97; p = 0.008). Some 10% of patients experienced urinary retention after HIFU. Grade >IIIa complications occurred in 54/1967 cases in the HIFU group and 29/1361 cases in the RP group (p = 0.3). In the HIFU group, fewer patients experienced a deterioration in 12-mo urinary continence (29% vs 44%) and the decrease in median International Index of Erectile Function-5 score was lower (difference 7 vs 13) in comparison to RP. Internal Prostate Symptom Scores and quality-of-life scores were comparable in the two groups. The main limitations are the lack of randomization and the age difference between the groups. Conclusions and clinical implications: This large prospective trial demonstrates that whole-gland or subtotal HIFU provides comparable medium-term STFS outcomes to RP. Urinary continence and erectile function were less impaired after HIFU. These results should be interpreted with caution owing to the lack of randomization and the age difference between the groups. Future research should consider longer follow-up and evaluate focal treatments. (c) 2024 European Association of Urology. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Background and objective: The CABASTY study showed that more frequent administration of a lower dose of cabazitaxel (CBZ) reduced toxicity in older men with metastatic castration-resistant prostate cancer (mCRPC), without compromising efficacy. Here, we investigated the impact of a biweekly CBZ schedule on patient-reported pain and health-related quality of life (HRQoL). Methods: We randomized 196 patients from 25 centers (1:1, stratified by age and G8 score) to the biweekly CBZ16 (CBZ 16 mg/m2) experimental arm or the triweekly CBZ25 (CBZ 25 mg/m2) control arm (CABASTY study, NCT02961257). We assessed pain using the Numeric Pain Rating Scale and HRQoL using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. Key findings and limitations: A total of 141 patients were available for a pain and 160 for an HRQoL analysis. Median time to pain progression (stratified hazard ratio [HR]: 1.7, confidence interval [CI]: 0.67-4.22, p = 0.3) and median time to first opiate use (stratified HR: 1.05, CI: 0.44-2.55, p = 0.9) did not differ between arms. We did not see a significant difference in median time to deterioration of FACT-P total score between treatments (stratified HR: 0.88, CI: 0.47-1.7, p = 0.7). Interestingly, the time to onset of several adverse events was significantly longer in the biweekly CBZ16 group. Conclusions and clinical implications: HRQoL did not significantly differ between the biweekly CBZ16 and the standard schedule. Additionally, onset of some adverse events was delayed. These results may increase health care providers' confidence in using CBZ in older patients with mCRPC who are denied chemotherapy. Patient summary: Androgen receptor pathway inhibitors are often preferred to taxane chemotherapy as a treatment of second or subsequent line in older metastatic castration-resistant prostate cancer patients due to more frequent treatment-related toxicities. Here, we showed that quality of life and pain did not differ significantly with an adapted schedule of cabazitaxel (CBZ), compared with the standard regimen. This CBZ schedule could increase eligibility of older patients for chemotherapy. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

PURPOSE After radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), prognosis is poor for high-risk patients. This study evaluated safety and efficacy of neoadjuvant chemotherapy (cisplatin or carboplatin + gemcitabine) in combination with durvalumab in these patients. PATIENTS AND METHODS This phase II trial (ClinicalTrials.gov identifier: NCT04617756 ) included patients with nonmetastatic, high-grade UTUC, on the basis of the ureteroscopic biopsy or urine cytology, and/or infiltrative aspect of the renal pelvis/ureteral wall by computed tomography imaging. Before RNU, patients received durvalumab plus gemcitabine/cisplatin (cohort 1) or durvalumab plus gemcitabine/carboplatin (cohort 2) once every 3 weeks for a total of four cycles (cohort choice on the basis of the glomerular filtration rate). The primary objective was the pathologic complete response (ypT0) rate in each cohort. RESULTS Fifty patients were enrolled between 2021 and 2024 (31 in cohort 1; 19 in cohort 2). Median age was 68 years (range, 38-79), and 59% were men. Forty-five patients received four cycles of treatment, three patients three cycles, and one patient two cycles. Five patients switched to carboplatin during treatment. At surgery (N = 45 patients), rates of pT0 were 13% (4/29) in cohort 1 and 5% (1/19) in cohort 2. Fifty percent (15/29) of patients were pTa/pT1 in cohort 1, and 42% (8/19) in cohort 2. No severe immunotherapy-mediated toxicity was observed. Four patients had chemotherapy-related grade 3 neutropenia, one grade 4; one patient had grade 3 thrombopenia, one grade 4; and four patients had grade 3 anemia. CONCLUSION Although our negative study did not meet its primary end point in either cohort, the combination of durvalumab and platin-based chemotherapy, especially cisplatin, showed promising results in terms of downstaging. The safety profile was good and the surgical risk was not increased.

Background Colorectal cancer (CRC) is the third most common cancer type and one of the leading causes of cancer-related death worldwide. The treatment of advanced metastatic CRC relies on classical chemotherapy combinations (5-fluorouracil, oxaliplatin or irinotecan). However, their use is limited by the emergence of resistance mechanisms, including to oxaliplatin. In this context, we recently showed that the combination of oxaliplatin and ataxia telangiectasia and Rad3-related protein inhibition (VE-822) is synergistic and may have a potential therapeutic effect in metastatic CRC management.Methods In this study, we investigated the role of the VE-822+oxaliplatin (Vox) combination on the immune response and its potential synergy with an anti-programmed-cell Death receptor-1 (PD-1) antibody. We used cell lines and organoids from metastatic CRC to investigate in vitro Vox efficacy and orthotopic syngeneic mouse models of metastatic CRC to assess the efficacy of Vox+anti-PD-1 antibody and identify the involved immune cells.Results The Vox+anti-PD-1 antibody combination completely cured tumor-bearing mice and protected them from a rechallenge. Vox was associated with a reduction of tumor-infiltrated neutrophils, CD206+ macrophages and regulatory T cells. Vox also induced a deep depletion of blood neutrophils. The increased bone marrow granulopoiesis failed to compensate for the Vox-mediated mature neutrophil depletion. Neutrophil depletion using a mouse recombinant anti-Ly6G antibody partially mimicked the Vox effect on the tumor microenvironment, but to a lower extent compared with the Vox+anti-PD-1 antibody combination. Vox, but not neutrophil depletion, led to the emergence of an Ly6C+ PD-1+ CD8+ T-cell population in the blood and spleen of tumor-harboring mice. These cells were proliferating, and expressed IFN-γ, CD62L, CXCR3 and Eomes. Moreover, the proportion of tumor antigen-specific T cells and of CD122+ BCL6+ T cells, which shared phenotypic characteristics with stem-like CD8+ T cells, was increased in treated mice.Conclusions Our work strongly suggests that the Vox+anti-PD-1 antibody combination might significantly improve survival in patients with metastatic and treatment-refractory CRC by acting both on cancer cells and CD8+ T cells.

Over the past decade, targeted radionuclide therapy has progressed substantially, especially for the treatment of neuroendocrine tumours. The frequent overexpression of prostate-specific membrane antigen (PSMA) in prostate cancers opened the way for the development of tracers for diagnostic purposes and for therapeutic applications, thereby offering a more precise and personalised approach for the treatment of castration-resistant tumours. 1 Baum RP Kulkarni HR Schuchardt C et al. 177Lu-labeled prostate-specific membrane antigen radioligand therapy of metastatic castration-resistant prostate cancer: safety and efficacy. J Nucl Med. 2016; 57: 1006-1013 Crossref PubMed Google Scholar [177Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): an open-label, multicentre, randomised, phase 2 trialThe addition of [177Lu]Lu-PSMA-617 to enzalutamide improved PSA progression-free survival providing evidence of enhanced anticancer activity in patients with metastatic castration-resistant prostate cancer with risk factors for early progression on enzalutamide and warrants further evaluation of the combination more broadly in metastatic prostate cancer. Full-Text PDF

Introduction Les complications après HIFU en primo-traitement du cancer localisé de la prostate (CaP) sont étudiées à partir de la base de vigilance tenue par l’AFU promotrice de l’étude HIFI (IDRCB : 2013-A01042-43) dans le cadre du Forfait Innovation. Ces résultats sont présentés selon le standard européen exigé par l’Agence nationale des médicaments et produits de santé. Méthodes Les critères d’inclusion dans la cohorte HIFU étaient un cancer de la prostate de risque faible ou intermédiaire favorable (cT1-2 NxM0, PSA<15ng/mL) non éligible à la surveillance active. Selon les recommandations 2013, les patients étaient âgés de plus de 69 ans dans le bras HIFU. Les traitements ont été réalisés en une ou deux séances (Focal One : 90 %, Ablatherm : 10 %).Tous les effets indésirables graves (EIG) ont été enregistrés de façon exhaustive dans la base de vigilance réglementaire de l’AFU au cours du suivi d’au moins 30 mois entre avril 2015 et septembre 2022. Résultats Au total, 1967 patients (âge médian : 74,7 ans) ont été traités de façon consécutive dans 46 centres. 471 EIG sont décrits dont 300 attendus et 171 inattendus. Seuls 2 cas étaient inattendus et attribuables au traitement : il s’agit de 2 endocardites consécutives à des infections urinaires mal contrôlées. L’essentiel des ré-hospitalisations concerne des épisodes rétentionnels (9,8 %) allant de 4 à 30 % selon les équipes. Un resondage a concerné 149 patients. Le taux de Clavien-Dindo>3a est 2,74 %. Les reprises chirurgicales sont des interventions endoscopiques de désobstruction : 41 résections (2,1 %) et 4 urètrotomies. Deux cas de fistules urètro-rectales (1/1000) ont guéri sans séquelle dont un avec une colostomie transitoire. Une deuxième séance d’HIFU (5,5 %) n’a pas entraîné de complications supplémentaires. Aucun décès lié au traitement ou au CaP. Au total, 38 % des centres étaient en courbe d’apprentissage en début d’étude. Conclusion Il s’agit de la plus grande cohorte prospective, en vie réelle, d’HIFU en première intention pour cancer localisé de la prostate. Compte tenu de l’âge élevé des patients, le taux de complications graves est faible. Aucun décès lié au traitement. La prévention du risque rétentionnel, la durée du sondage postopératoire et la gestion des rétentions urinaires avérées mériteraient d’être mieux standardisées.