Diagnosis

The PRIME study is a prospective, multicenter, within-patient, noninferiority trial of biopsy-naive men from 22 centers (12 countries) with clinical suspicion of prostate cancer [1] . Of 555 men recruited, 490 were included for primary outcome analysis. It demonstrated that biparametric MRI (bpMRI) is noninferior to multiparametric MRI (mpMRI) for the detection of clinically significant prostate cancer. This conclusion is based on several key findings. The first one is the nearly identical detection rates for significant cancer. The detection rates for clinically significant cancer (Gleason Grade Group ≥ 2) were almost identical, at 29.2% for bpMRI compared to 29.6% for mpMRI. A key concern that a shorter scan might lead to more uncertainty and thus more biopsies was not borne out by the evidence. The study found that bpMRI did not lead to an increase in biopsy recommendations, with the proportion of patients indicated for biopsy being very similar: 55.7% for bpMRI versus 57.1% for mpMRI. The PRIME study also showed similar specificity and test performance between both procedures. The diagnostic performance of both techniques was comparable. There was no major difference in specificity (61.6% for bpMRI vs. 60.1% for mpMRI), indicating a similar rate of false positive results. Sensitivity was also very similar (98.0% for bpMRI vs. 99.3% for mpMRI). These results suggest that the abbreviated bpMRI could become the new standard of care for diagnosing prostate cancer ( Table 1 ). However, these findings are accompanied by important limitations regarding the conditions required to achieve them, including high-quality imaging and radiologist expertise. The results were obtained because the study ensured very high-quality scans. Participating sites had their imaging protocols optimized before the trial began, and a central quality control confirmed that 99% of scans were of adequate diagnostic quality. The study’s conclusions reflect practice in centers with highly experienced radiologists and biopsy operators. The authors caution that for bpMRI to be implemented widely and successfully, structured training programs and quality control initiatives would be necessary to ensure diagnostic accuracy is maintained across more diverse practice settings.

The OPTIMUM trial was an international, multicenter, randomized noninferiority study comparing microultrasonography-guided biopsy (microUS) to MRI/conventional ultrasound fusion-guided biopsy for detecting clinically significant prostate cancer in biopsy-naive men [2] . A total of 802 men were randomized and 678 underwent biopsy. The primary outcome – detection of Gleason Grade Group ≥ 2 cancers – was achieved in 46% of microUS cases and 43% of MRI cases, confirming noninferiority (difference 3.52%, 95% CI –3.95% to 10.92%). No significant differences were found in the detection of insignificant cancer (Grade Group 1) or in complication rates. Importantly, microUS allowed real-time targeting without registration error, using the PRI-MUS score. The findings suggest microUS may offer a viable alternative to MRI-based targeting, especially in low-resource or MRI-inaccessible settings. However, results depend on adequate operator training, and further validation is needed.

The TRANSLATE study aimed to compare prostate biopsies performed under local anesthesia via the transperineal (TP) versus transrectal (TR) approach for the detection of clinically significant prostate cancer (csPCa) and the safety of the procedure [3] . It was a multicenter randomized trial conducted across 10 centers in the UK. A total of 1126 patients suspected of having prostate cancer were included and randomly assigned to two groups: 562 patients in the TP group and 564 patients in the TR group. Patients were selected after undergoing an MRI, and the procedure involved taking an average of 4 targeted biopsies and 12 systematic biopsies. The primary endpoint was the detection rate of ISUP grade ≥ 2 prostate cancer. Secondary endpoints assessed infection rates, complications, post-biopsy pain, and patient satisfaction. The detection of clinically significant prostate cancer was higher in the TP group (60%) compared to the TR group (54%), with a statistically significant difference. Antibiotic use was 100% in the TR group and 10% in the TP group ( Table 2 ). Following TP versus TR biopsies, severe infections and hospitalizations were less frequent (2 cases vs. 9 cases), while post-procedure pain and discomfort were more common (38 vs. 27%), and the biopsy duration was longer (28 minutes vs. 22 minutes), though none of these differences were statistically significant. Patient satisfaction was comparable between the two groups. Limitations of the study included a high refusal rate after randomization, a predominantly white patient population (93% of cases), and a lack of stratification of results based on MRI PIRADS scores and lesion location. All data from the 4 randomised trials are summarized in Table 3 .

	Localised PCa management

A post hoc analysis of the randomized controlled trial comparing standard versus extended lymph node dissection during radical prostatectomy has been published, focusing on metastasis-free survival [4] . This was a single-center randomized trial comparing standard ilio-obturator lymph node dissection to extended dissection (external iliac, internal iliac, and obturator) during radical prostatectomy, with the primary objective of estimating survival outcomes. A total of 1432 patients were included, with 698 patients in the ilio-obturator dissection arm and 734 patients in the extended dissection arm. The characteristics of the two groups were comparable. There was no significant difference in biochemical recurrence-free survival between the two groups (HR = 1.05; 95% CI: 0.97–1.13; p = 0.3). However, there was a benefit favoring extended dissection for metastasis-free survival, regardless of metastasis location (HR = 0.82; 95% CI: 0.71–0.93; p = 0.003), and for distant metastasis-free survival (HR = 0.75; 95% CI: 0.64–0.88; P < 0.001). To explain these findings, the authors suggest conducting further studies to explore biological mechanisms and the impact of the anatomical location of involved lymph nodes. With these results, this study renews interest in extended lymph node dissection during radical prostatectomy for patients with prostate cancer at risk of biochemical recurrence, as defined by the MSKCC nomogram (no change in previous recommendation Table).

The PACE-B trial compared two irradiation regimens – 78 Gy in 39 fractions or 62 Gy in 20 fractions versus 36.25 Gy in 5 fractions using stereotactic radiotherapy (SBRT) – in 874 patients [5] . Over a median follow-up of 6 years, no significant difference was observed in biochemical and/or clinical control. The trial concluded that the two regimens were noninferior, with similar toxicity profiles between the groups. These findings align with previous findings from non-randomized prospective data, which validated ultra-hypofractionated radiotherapy as a therapeutic option for patients with low-risk or favorable intermediate-risk prostate cancer. This approach is contingent on rigorous control of patient positioning and dosimetry. Together with the HYPO-RT-PC study, this makes SBRT a convenient and cost-effective option, as it significantly reduces treatment time from weeks to just 1–2 weeks, without compromising efficacy or safety for low- to intermediate-risk patients.

The HIFI trial is a prospective, non-randomized, nationwide study comparing high-intensity focused ultrasound (HIFU) to radical prostatectomy (RP) for treating low- to intermediate-risk localized prostate cancer [6] . HIFU treatment should treat at least 70% of the whole gland in one or two sessions. Whole-gland and sub-total HIFU were performed in 80% and 20% of cases, respectively. The protocol included in the HIFU group patients with localized, low- to intermediate risk PCa, classified as clinical stage T1–2 NxM0, with a Prostate Specific Antigen (PSA) dosage < 15 ng/mL, Gleason score ≤ 3 + 4 (Grade group 1 or 2), not eligible for active surveillance (AS) and having a maximum of 4 invaded sextants out of 6 on biopsies performed following multiparametric MRI (mpMRI). HIFU was restricted to patients over 69 years old with a > 5-year life expectancy whereas no minimal age limit was affected to RP patients. Conducted in 46 French centers (2015–2019), it included 3328 patients (1967 HIFU; 1361 RP). The primary endpoint – 30-month salvage therapy-free survival (STFS) – was 90% for HIFU vs. 86% for RP, demonstrating noninferiority of HIFU (HR = 0.71, P = 0.008). HIFU patients, who were older (median age 74.7 vs. 65.1 years), experienced less deterioration in urinary continence (29% vs. 44%) and erectile function (IIEF-5 score difference: –3.0) compared to RP. Serious adverse events were comparable (2.7% HIFU vs. 2.1% RP), though urinary retention was more common after HIFU (10%). No prostate cancer-specific deaths or distant metastases were reported. The study highlights the good short-term oncological and functional outcomes, though results are limited by lack of randomization and age differences between groups. Future research should focus on a broader age limit at inclusion, longer follow-up and focal therapies. The main limitation of this HIFI trial remains the mid-term follow-up, precluding from drawing any firm conclusion regarding the long-term oncologic efficacy. A longer follow-up beyond the primary endpoint timepoint is awaited as all included patients are still monitored.

Summary of changes in the management of low-risk and intermediate-risk PCa are listed in Table 4 .

	Metastasis-directed therapy

The STORM trial, a randomized study, compared stereotactic body radiotherapy (SBRT) to elective nodal radiotherapy (ENRT), both combined with 6 months of ADT, in patients with oligopelvic prostate cancer recurrence, confirmed by PSMA PET in 80% of cases [7] . Results demonstrated a significant benefit for ENRT in terms of biochemical recurrence-free survival and locoregional recurrence-free survival, with a 22% improvement at 3 years for ENRT. Toxicity data revealed similar rectal toxicity (5–6%) in both groups but higher urinary toxicity (22–26%), primarily due to irradiation of the prostatectomy bed.

In the setting of oligometastatic recurrence, the oncological benefit of stereotactic body radiotherapy (SBRT) remains under evaluation pending phase III trials. The RADIOSA study, a randomized phase II trial comparing SBRT alone to SBRT combined with short-term androgen deprivation therapy (ADT), included 102 patients with up to three metastatic lesions [8] . Two-thirds of the patients had lymph node recurrence. After a median follow-up of 31 months, both biochemical progression-free survival (BPFS) and clinical progression-free survival (CPFS) were significantly improved when SBRT was combined with ADT: BPFS hazard ratio (HR) = 0.40 (95% CI: 0.24–0.66); CPFS HR = 0.39 (95% CI: 0.23–0.68). The median BPFS was 12.6 months in the SBRT-alone arm (Arm A) and 26.8 months in the SBRT + ADT arm (Arm B). The median CPFS was 15.1 months in Arm A and 32.8 months in Arm B. Notably, patterns of recurrence differed between the two treatment arms: 15 patients experienced polymetastatic recurrence during follow-up in Arm A, compared to only 6 patients in Arm B. Subgroup analysis confirmed the benefit of combined treatment across various subgroups. Patients with favorable characteristics, such as low PSA levels and a longer interval since initial treatment, might still benefit from SBRT alone.

The phase 2 randomized RAVENS trial evaluates the outcomes of radium-223 plus stereotactic body radiotherapy (SBRT) compared to SBRT alone for oligometastatic prostate cancer [9] . The primary endpoint was composite progression-free survival. From August 2019 to March 2023, 64 patients were randomized. The arms were balanced for key covariates, and 26 patients (87%) completed all 6 planned cycles of radium-223. With a median follow-up of 18.7 months, the median progression-free survival was 11.8 months with SBRT alone versus 10.5 months with SBRT plus radium-223 (stratified HR 1.37, 95% CI 0.78–2.39, P = 0.27). SBRT alone for hormone-sensitive oligometastatic prostate cancer offers progression-free survival benefits, but the emergence of additional bone metastases in most patients remains a challenge. This is the first negative trial indicating that adding radium-223 to metastasis-directed SBRT does not delay disease progression. These results highlight the importance of phase III randomized clinical trials in hormone-sensitive oligometastatic prostate cancer, the need to define appropriate patient selection criteria, and the exploration of biomarkers to personalize treatment approaches ( Table 5 ).

	Recurrence

The EMBARK trial, a three-arm randomised phase III trial, evaluated patients considered with a high-risk biochemical recurrence (BCR): PSA-DT of ≤ 9 months and PSA ≥ nadir +2 ng/mL after radiotherapy or ≥ 1 ng/mL after prostatectomy ± postoperative radiotherapy [10] . Patients were randomised on a 1:1:1 scheme to receive either enzalutamide plus leuprolide (combined arm), placebo plus leuprolide, or enzalutamide in monotherapy. A total of 1068 patients were randomised. With a median follow-up of 60.7 months, the 5-year metastasis-free survival was 87.3% (95% CI: 83.0–90.6) in the combination arm, 71.4% (95% CI: 65.7–76.3) in the leuprolide + placebo arm, and 80.0% (95% CI: 75.0–84.1) in the enzalutamide monotherapy arm. The combination of leuprolide and enzalutamide was superior to leuprolide + placebo in terms of metastasis-free survival (HR: 0.42; 95% CI: 0.30–0.61; P < 0.001). Enzalutamide monotherapy was also superior to leuprolide + placebo (HR: 0.63; 95% CI: 0.46–0.87; P = 0.005). Secondary data showed that enzalutamide combined or alone preserved health-related quality of life [11] . Post hoc analysis has also demonstrated a better sexual activity profile of patients undergoing enzalutamide monotherapy alone [12] . Based on these results, enzalumatide combined or not with ADT is a recommended treatment in the case of high-risk BCR defined according to EMBARK criteria, non-metastatic on conventional imaging, and in the absence of feasible salvage local treatment ( Table 5 ).

	Metastatic hormone-sensitive PCa (mHSPC)

Summary of changes in the management of mHSPC are listed in Table 6 .

The results of the PEACE-1 trial, with double randomisation to systemic treatment (ADT versus ADT + Abiraterone) as well as prostate irradiation, showed that radiotherapy improves progression-free radiological and castration resistance-free survival without any benefit in terms of overall survival. On the basis of these data and the pooled analysis of PEACE 1, STAMPEDE and HORRAD, prostate irradiation may be considered as an effective and low-toxicity option in the synchronous low-volume metastatic population treated with the current standard of double hormonal therapy [13, 14] . Overall, radiation therapy of the primary in patients with high-volume disease may decrease the need for subsequent pelvic treatment, as based on PEACE 1, STAMPEDE and HORRAD studies.

The ARANOTE study is a phase 3, randomized, double-blind, placebo-controlled trial that evaluated darolutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic hormone-sensitive prostate cancer (mHSPC) [15] . In this trial, darolutamide demonstrated a significant benefit in radiographic progression-free survival (rPFS), reducing the risk of radiographic progression by 46%, with a favorable safety profile (Grade 3 or 4 adverse events: 30.8% vs. 30.3%, respectively). This benefit was observed regardless of disease volume (high vs. low) or disease history (synchronous vs. metachronous). While a positive trend in overall survival (OS) was observed, the difference was not statistically significant (HR, 0.81 [95% CI, 0.59 to 1.12]). The ARANOTE study confirms the value of ADT intensification with an ARPI in mHSPC, positioning darolutamide as an additional option for doublet intensification. The choice of doublet therapy and patient counseling should consider the methodological limitations, which currently do not allow for a definitive conclusion on overall survival benefit with darolutamide.

Changes have been implemented in Fig. 1 .

An open-label phase III study from the STAMPEDE platform investigated the effect of the antidiabetic drug metformin in mHSPC patients starting androgen deprivation therapy (ADT) [16] . Metformin is well-tolerated, inexpensive, carries no risk of hypoglycemia, and has a scientific hypothesis of inhibiting the mTOR pathway, thereby reducing tumor proliferation. Its antimetabolic role also makes it an interesting option to counteract the effects of hormone therapy. The multi-arm STAMPEDE platform is a phase III trial that enrolled patients with metastatic or high-risk/locally advanced prostate cancer on conventional imaging. The Metformin arm is the first phase III trial to assess the overall survival benefit of adding metformin (starting around day 7) to standard-of-care androgen suppression (ADT ± ARPI ± docetaxel ± primary radiotherapy) in non-diabetic mHSPC patients, with a median metformin treatment duration of 39 months. Patients were recruited between 2016 and 2023 across 112 centers in England and Switzerland, including 1874 mHSPC patients (94% de novo metastatic, 44% high-volume), randomized into two arms. In 82% of cases, SOC included ADT + docetaxel, while only 3% included an ARPI (abiraterone acetate, enzalutamide, or apalutamide). Median overall survival (OS) was 61.8 months in the SOC arm (IQR 29.7–NR) and 67.4 months in the SOC + metformin arm (IQR 32.5–NR), with no significant difference (HR 0.91, 95% CI 0.80–1.03, p = 0.15). No significant difference was observed in prostate cancer-specific survival (HR 0.97, 95% CI 0.85–1.12, P = 0.7). Treatment tolerance was similar between the two groups (52% Grade 3 adverse events in SOC vs. 57% in SOC + metformin), though diarrhea was more frequent in the metformin arm (86 vs. 67%, with only 5 vs. 3% Grade 3). However, metformin appeared to provide a potential oncological effect (improved overall survival and progression-free survival) only in the high-tumor-volume subgroup (44% of the population, pre-stratified but underpowered; HR 0.79, 95% CI 0.67–0.94, P = 0.0072). This effect may be mediated, in part, by reducing mortality from non-prostate cancer causes (including cardiovascular and metabolic causes) through mitochondrial complex inhibition. Metformin significantly reduced metabolic side effects of androgen suppression: weight gain (2 kg vs. 4.4 kg in SOC, P < 0.0001), waist circumference ( P = 0.038), and improved lipid and glucose profiles (no effect on BMI). This study positions metformin as a valuable complement to prevent metabolic and cardiovascular complications in patients starting long-term androgen suppression, particularly those with cardiovascular risk factors. It remains to be seen – and confirmed – whether these results also apply to the current mHSPC population, who are more commonly treated with doublet therapy (ADT + ARPI).

The phase III AMPLITUDE trial ( NCT04497844 ) enrolled 696 patients with metastatic castration-sensitive prostate cancer (mHSPC) harboring homologous recombination repair (HRR) gene alterations [17] . Patients were randomized to receive either the niraparib plus abiraterone acetate and prednisone (NIRA + AAP) combination or placebo plus abiraterone acetate and prednisone. The primary objective was to evaluate the efficacy and safety of the niraparib + abiraterone acetate combination in mHSPC patients with a BRCA1 or BRCA2 mutation or other preselected HRR gene alterations: BRIP1 , CDK12 , CHEK2 , FANCA , PALB2 , RAD51B , and RAD54L . The combination treatment significantly improved radiographic progression-free survival (rPFS) and delayed symptomatic progression. For rPFS, the median was not reached in the experimental arm, compared to 29.5 months in the control arm (HR 0.63; 95% CI: 0.49–0.80; P = 0.0001). A benefit was also observed in symptomatic progression, with an HR of 0.50 in the overall population and 0.44 in BRCA1/2 patients. The risk of symptomatic progression was reduced by 56% in the BRCA subgroup, and by 50% reduction in the overall study population (ITT group). Overall survival (OS), a secondary endpoint, was assessed at an interim stage in AMPLITUDE, with 193 deaths out of the 389 required for the final analysis. A favorable trend was observed in the NIRA + AAP arm (HR 0.79; 95% CI: 0.59–1.04; P = 0.10), though it did not reach statistical significance. Final analysis and publication are needed for more conclusive results. The effect of treatment in patients with non-BRCA1/2 alterations remains difficult to interpret. Exploratory analyses by gene revealed heterogeneous responses: some alterations were associated with clinical benefit, while others showed no demonstrated benefit. Grade 3 or 4 adverse events were more frequent in the NIRA + AAP arm (75.2 vs. 58.9%), primarily anemia (29.1 vs. 4.6%) and hypertension (26.5 vs. 18.4%). The discontinuation rate due to toxicity remained moderate (11.0 vs. 6.9%), and no unexpected safety signals were observed. AMPLITUDE is the first trial to evaluate a PARPi/ARPI combination in mHSPC patients selected based on their genetic profile. This approach justifies a shift in clinical practice by promoting early genomic testing and PARP targeting in mHRR patients since the mHSPC setting.

	Metastatic castration-resistant PCa (mCRPC)

Summary of changes in the management of mHSPC are listed in Table 7 .

In pts with mCRPC, two phase II studies (ARTO and GROUQ-PCS9) randomised the addition of stereotactic radiotherapy to ARPI [18, 19] . Both studies showed that SBRT significantly improved progression-free survival and even radiographic progression-free survival in the GROUQ-PCS9 study.

Three randomized phase 3 trials, all positive on their primary endpoint, have investigated new treatment used either alone or in combination with ARPI, in chemonaïve patients mCRPC. There is no direct comparison between these 3 trials.

The randomized industry-sponsored phase 3 PSMAfore compared 6 cycles of ¹⁷⁷ LuPSMA-617 given every 6 weeks, to an ARPI switch in patients with mCRPC and positive PSMA PET, for whom chemotherapy may be delayed [20, 21] . Unlike VISION trial, a combination with an ARPI was not allowed in the experimental arm. The primary endpoint was rPFS assessed on standard imaging, OS was a secondary endpoint. A significant improvement in rPFS (HR = 0.49; 95% CI 0.39–0.61) was reported at the interim analysis, favoring ¹⁷⁷ LuPSMA-617. With 60.3% of patients who crossed over from the standard to the experimental arm at radiographic progression, OS was not significantly improved (HR = 0.91; 95% CI 0.72–1.14; P = 0.2) on final analysis. Main treatment related adverse events, mostly grade 1–2, were xerostomia, fatigue, nausea and anemia. In this open label trial, PRO showed a longer time to worsening in HRQoL and pain in patients treated with ¹⁷⁷ LuPSMA [22] . Thus, in patients with mCRPC progressing under a first ARPI, with positive PSMA PET, not deemed to receive an immediate chemotherapy, ¹⁷⁷ LuPSMA-617 is an alternative treatment option.

TALAPRO-2 is an industry-sponsored phase 3 randomizing enzalutamide + talazoparib vs. enzalutamide + placebo in no or mildly symptomatic patients with mCRPC not treated with chemotherapy in castration resistance [23, 24] . Among 3 phase 3 trials comparing ARPI + PARPI vs. ARPI + placebo in this setting (MAGNITUDE, PROpel), TALAPRO-2 is the only one to show a significant OS improvement favoring enzalutamide + talazoparib in the ITT final analysis (i.e., regardless HRR status). The absolute benefit in OS was 8.8 months. While toxicity was comparable between all comers and patients with HRR alterations, 45% grade 3 anemia were reported, mostly in the first 4 months and in part depending on baseline hemoglobin. Dose adjustments and adaptated supportive care reduced the rate of permanent discontinuation of talazoparib to 8% for anemia [25] . In this double-blind study, HRQoL was not worsened with the combination [26, 27] . While positive regardless of HRR status, these results should not advocate against BRCA and ideally HRR testing for these patients. Beyond the poor prognosis information and potential genetic counselling that may derive from the testing, HR OS is ranging from 0.5 (95% CI 0.32–0.78; P = 0.0017), 0.73 (95% CI 0.52–1.02; P = 0.066) to 0.8 (95% CI 0.66–0.96; P = 0.016), for patients with BRCA alterations, HRR alterations and whole population, respectively. Besides, OS benefit is no longer significant if patients with HRR alterations or unknown are withdrawn (HR = 0.88; 95% CI 0.71–1.08; P = 0.22). This highlights that efficacy of this combination is mainly driven by these alterations. Finally, in this trial only 5% of patients were previously treated with an ARPI, which is difficult to implement to our current clinical practice. Hence, the benefit/risk ratio of such a combination should be frankly discussed with the patient, including different parameters such as comorbidities, expected toxicity, HRR status and previous exposure to an ARPI prior castration resistance. Patients must be closely followed, including a blood test every 2 weeks within the first 4 months.

PEACE-3 is an academic phase 3 trial, comparing enzalutamide + 6 cycles of radium-223 given monthly vs. enzalutamide alone in patients with no or mildly symptomatic mCRPC, with bone but no visceral metastases [28] . Primary endpoint was rPFS (assessed on standard imaging) and OS was one of the secondary endpoints. At the interim analysis rPFS was significantly improved in favor of the experimental arm (HR = 0.69; 95% CI 0.54–0.87; P = 0.0009). With 80% of maturity OS was at that time significantly improved (HR = 0.69; 95% CI 0.52–0.9; P = 0.0031) with roughly 70% of death related to prostate cancer in each arm. Negative results from the randomized phase 3 ERA-223 (abiraterone + radium-223 vs. abiraterone + pb) – early closed due to an excess of symptomatic skeletal events (SSE) and mortality in the experimental arm – led to an amendment in PEACE-3 requiring the use of bone resorptive agent at the inclusion [29] . The incidence of fractures has then decreased in both arms following this amendment, even though no difference was reported in time to first SSE between the 2 arms [30] . The rate of hypertension was more important in this trial compared to other trials using enzalutamide, likely due to a population with more comorbidities. As for TALAPRO-2, only 2.5% of patients were previously treated with ARPI prior castration resistance limiting the implementation of such a combination in current practice. Thus, this combination is an option in patients with no or mildly symptomatic bone mCRPC without visceral metastases, for whom the use of bone resorptive agents is requested.

Disclosure of interest

Guillaume Ploussard: Astellas; IPSEN; FERRING; Astra Zeneca; ACCORD; JANSSEN; BOUCHARA; KOELIS; INTUITIVE. Michael Baboudjian: Pierre Fabre; Coloplast; Accord healthcare; Photocure; Prostalund. Eric Barret: Angiodynamics; Accord healthcare; Bayer; Astellas. Laurent Brureau: Janssen; Bayer; MSD. Gaëlle Fiard: AAA; Astellas; Bayer; BMS; Ipsen; Janssen; MSD; Pierre-Fabre. Gaëlle Fromont: Astra zeneca; Astellas; Bouchara; Recordati. Jonathan Olivier: IPSEN; Janssen; Bayer; Astellas; Accord-Helthcare; Bouchara; Novartis. Charles Dariane: Ipsen; Jansen; Besins; Bayer. Romain Mathieu: AAA; Accord; Astellas; Astra Zeneca; Bayer; Ferring; Ipsen; Intuitive; Janssen; MSD; Pfizer; Viatris. François Rozet: Astellas; Bayer; Ipsen; Janssen; Pfizer; MSD; Viatris. Guilhem Roubaud: AAA; Astellas; Astra-Zeneca; Bayer; Janssen; Ipsen; Novartis; MSD; Pfizer. Raphaele Renard-Penna: Incepto; IPSEN; Janssen; Astellas; Bracco. Paul Sargos: Expert, Consultant; Astellas; Bayer; Janssen; Sanofi; Ipsen; Ferring; Takeda; Recordati; Astra Zeneca. Stéphane Supiot: Astra-Zeneca; BMS; MSD; Astellas; Janssen; Ferring; Bayer; Ipsen; Adacap; Curium. Léa Turpin: Novartis; Curium; Viatris. Morgan Rouprêt: Bayer; Ipsen; Astra zeneca; Pfizer; Janssen; Astellas. Arthur Peyrottes declares that he has no competing interest.