This study evaluated whether a CE-marked deep-learning-based web platform (PSMA-DLwp) maintains a per-patient detection rate (DR) comparable to that of an experienced nuclear medicine physician (ENMP) for identifying prostate cancer (PCa) foci using [18F]-piflufolastat PET/CT in patients with first biochemical recurrence. Secondary objectives included per-region DR and the correlation of SUVmax and tumor burden assessments between the ENMP and PSMA-DLwp. Methods: A retrospective analysis was conducted using data from the phase III PYTHON study, which compared [18F]-piflufolastat PET/CT to [18F]-fluoromethylcholine PET/CT in patients with first biochemical recurrence of PCa. Both ENMP and PSMA-DLwp independently reviewed [18F]-piflufolastat PET/CT scans. Concordance in DRs, regional analysis, and correlation of semi-quantitative parameters (SUVmax, tumor burden) were assessed. Discordant cases were re-evaluated by the ENMP to assess potential improvements provided by PSMA-DLwp. Results: Out of 192 evaluable scans, per-patient DRs were concordant in 75

Despite several improvements in outcomes, metastatic prostate cancer remains deadly. Alterations in the homologous recombination repair (HRR) pathway are associated with more aggressive disease. Olaparib and rucaparib, two poly-ADP-ribose polymerase (PARP) inhibitors, have received approval from the authorities of several countries for their anti-tumoral effects in patients with metastatic castration-resistant prostate cancers harboring HRR gene alterations, in particular BRCA2 . More recently, it has been hypothesized that new hormonal therapies (NHTs) and PARP inhibitors (PARPi) could have synergistic actions and act independently of HRR deficiency. This review proposes to discuss the advantages and disadvantages of PARPi used as monotherapy or in combination with NHTs and whether there is a need for molecular selection.

Primary objective was to compare the per-patient detection rates (DR) of [18F]DCFPyL versus [18F]fluoromethylcholine positron emission tomography/computed tomography (PET/CT), in patients with first prostate cancer (PCa) biochemical recurrence (BCR). Secondary endpoints included safety and impact on patient management (PM). This was a prospective, open label, cross-over, comparative study with randomized treatment administration of [18F]DCFPyL (investigational medicinal product) or [18F]fluoromethylcholine (comparator). Men with rising prostate-specific antigen (PSA) after initial curative therapy were enrolled. [18F]DCFPyL and [18F]fluoromethylcholine PET/CTs were performed within a maximum time interval of 12 days. DR was defined as the percentage of positive PET/CT scans identified by 3 central imaging readers. PM was assessed by comparing the proposed pre-PET/CT treatment with the local treatment", defined after considering both PET/CTs. A total of 205 patients with first BCR after radical prostatectomy (73

Le cancer de la prostate (CaP) est un problème de santé publique. La stratégie diagnostique du CaP est aujourd’hui codifiée et s’évalue par le toucher rectal, le dosage du PSA et l’IRM multiparamétrique conduisant ou non à la réalisation de biopsies prostatiques. Le bénéfice formel du dépistage organisé du CaP, étudié il y a plus de 10 ans à l'échelle internationale et pour tous les hommes, n’est pas été démontré. Les modalités diagnostiques et thérapeutiques ont cependant évolué depuis les études pivotales. L’apport de l’IRM et des biopsies ciblées, la généralisation de la surveillance active pour les cancers de bon pronostic, l’amélioration des techniques chirurgicales et de la radiothérapie… ont permis de mieux définir les populations à risque de cancer significatif et de renforcer l’intérêt d’une démarche d’évaluation individualisée en réduisant le risque de surtraitement. C’est dans cette optique d’améliorer la couverture et l’accès au dépistage de la population que la Commission Européenne a proposé fin 2022 de promouvoir une nouvelle évaluation du dépistage organisé du CaP, incluant l’IRM. L’absence de tout programme de dépistage est devenue une stratégie préjudiciable et doit évoluer vers une politique de détection précoce adaptée au risque de chaque malade.

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. (c) 2023 Elsevier Masson SAS. All rights reserved.

Context The contribution of [18F]F-fluorocholine (FCH)-positron emission tomography (PET)/computed tomography (CT) in normocalcemic primary hyperparathyroidism (nPHPT) remains unknown. Objective To evaluate the sensitivity and specificity of FCH-PET/CT in a cohort of osteoporotic patients with nPHPT and discordant or negative [99mTc]Tc-sestamibi scintigraphy and ultrasonography who all underwent parathyroidectomy (PTX). Design Longitudinal retrospective cohort study in patients referred for osteoporosis with mild biological primary hyperparathyroidism. Setting Tertiary referral center with expertise in bone metabolism and surgical management of hyperparathyroidism. Patients Among 109 patients with PHPT analyzed, 3 groups were individualized according to total serum calcium (tCa) and ionized calcium (iCa): 32 patients with hypercalcemia (HtCa group), 39 patients with normal tCa and elevated iCa (NtCa group), and 38 patients with both normal tCa and iCa (NiCa). All patients had biochemical follow-up confirming or not the success of PTX. Main outcome measures To evaluate the performance of FCH-PET/CT in terms of sensitivity and specificity, and to compare with first-line imaging procedures in the setting of nPHPT. Results The sensitivity of FCH-PET/CT was 67% in the hypercalcemic group, 48% in the NtCa group (P = .05 vs HtCa), and 33% in the NiCa group (P = .004 vs HtCa). Specificity ranged from 97% to 99%. FCH-PET/CT was positive in 64.3% of patients with negative conventional imaging, with biochemical resolution after PTX in 77.8% of patients. Triple negative imaging was observed in 20 patients, with PHPT resolution in 85% of these patients. Conclusion This study highlights the contribution of FCH-PET/CT in a well-phenotyped cohort of normocalcemic patients with discordant or negative findings in [99mTc]Tc-sestamibi scintigraphy and ultrasonography. However, negative imaging in nPHPT does not rule out the possibility of surgical cure by an experienced surgeon.

In the original publication [...].

PURPOSE:Primary objective was to compare the per-patient detection rates (DR) of [18F]DCFPyL versus [18F]fluoromethylcholine positron emission tomography/computed tomography (PET/CT), in patients with first prostate cancer (PCa) biochemical recurrence (BCR). Secondary endpoints included safety and impact on patient management (PM). METHODS:This was a prospective, open label, cross-over, comparative study with randomized treatment administration of [18F]DCFPyL (investigational medicinal product) or [18F]fluoromethylcholine (comparator). Men with rising prostate-specific antigen (PSA) after initial curative therapy were enrolled. [18F]DCFPyL and [18F]fluoromethylcholine PET/CTs were performed within a maximum time interval of 12 days. DR was defined as the percentage of positive PET/CT scans identified by 3 central imaging readers. PM was assessed by comparing the proposed pre-PET/CT treatment with the local treatment", defined after considering both PET/CTs. RESULTS:A total of 205 patients with first BCR after radical prostatectomy (73%; median PSA = 0.46 ng/ml [CI 0.16;27.0]) or radiation therapy (27%; median PSA = 4.23 ng/ml [CI 1.4;98.6]) underwent [18F]DCFPyL- and/or [18F]fluoromethylcholine -PET/CTs, between July and December 2020, at 22 European sites. 201 patients completed the study. The per-patient DR was significantly higher for [18F]DCFPyL- compared to [18F]fluoromethylcholine -PET/CTs (58% (117/201 patients) vs. 40% (81/201 patients), p < 0.0001). DR increased with higher PSA values for both tracers (PSA ≤ 0.5 ng/ml: 26/74 (35%) vs. 22/74 (30%); PSA 0.5 to ≤ 1.0 ng/ml: 17/31 (55%) vs. 10/31 (32%); PSA 1.01 to < 2.0 ng/ml: 13/19 (68%) vs. 6/19 (32%);PSA > 2.0: 50/57 (88%) vs. 39/57 (68%) for [18F]DCFPyL- and [18F]fluoromethylcholine -PET/CT, respectively). [18F]DCFPyL PET/CT had an impact on PM in 44% (90/204) of patients versus 29% (58/202) for [18F]fluoromethylcholine. Overall, no drug-related nor serious adverse events were observed. CONCLUSIONS:The primary endpoint of this study was achieved, confirming a significantly higher detection rate for [18F]DCFPyL compared to [18F]fluoromethylcholine, in men with first BCR of PCa, across a wide PSA range. [18F]DCFPyL was safe and well tolerated.

Visual Abstract The objective of this study was to compare 18F-PSMA-1007 PET/CT and 18F-fluorocholine PET/CT for the localization of prostate cancer (PCa) biochemical recurrence. Methods: This prospective, open-label, randomized, crossover multicenter study included PCa patients with prior definitive therapy and suspected PCa recurrence. All men underwent both 18F-PSMA-1007 PET/CT and 18F-fluorocholine PET/CT (102 received 18F-PSMA-1007 PET/CT first and 88 received 18F-fluorocholine PET/CT first). All images were assessed independently by 3 readers masked to all clinical information using a 3-point qualitative scale (0 = no recurrence, 1 = undetermined, and 2 = recurrence). Patients were monitored for approximately 6 mo. An independent panel with a urologist, radiologist, and nuclear physician reviewed all clinical data, including imaging and response to therapy, but were masked regarding PET/CT information; acting in consensus, they determined a patient-based and region-based composite standard of truth for PCa lesions. The “correct detection rates” for PCa lesions on a patient basis for each radiopharmaceutical were compared for the 3 readers individually and for the “average reader.” Secondary objectives included determining whether PET/CT findings affected diagnostic thinking (impact of a test result on posttest vs. pretest probability of a correct diagnosis), therapeutic decision making (description and quantification of impact of diagnostic information gained with both radiopharmaceuticals on patient management), and adequacy of management changes. Results: A total of 190 patients were included. The primary endpoint was met. The overall correct detection rates were 0.82 for 18F-PSMA-1007 and 0.65 for 18F-fluorocholine (P < 0.0001) when undetermined findings were considered positive for malignancy and 0.77 and 0.57, respectively (P < 0.0001), when undetermined findings were considered negative for malignancy. A change in diagnostic thinking due to PET/CT was reported in 149 patients; 18F-PSMA-1007 contributed more than 18F-fluorocholine in 93 of these patients. In 122 patients, PET/CT led to an adequate diagnosis that benefited the patient; 18F-PSMA-1007 contributed more than 18F-fluorocholine in 88 of these patients. Conclusion: 18F-PSMA-1007 PET/CT is superior to 18F-fluorocholine PET/CT for the localization of PCa recurrence. Decision making was more beneficial when based on 18F-PSMA-1007 PET/CT results.

Background: A biochemical recurrence (BCR) risk model was created based on pretest prostate specific antigen (PSA) and groupings by restaging prostate specific membrane antigen (PSMA) PET/CT. Methods: A cohort of 1216 BCR patients were analyzed for overall survival (OS) according to the PSA threshold and restaging PSMA PET/CT. A Cox regression analysis of OS was carried out to detect significant clinical characteristics. Results: In the cohort, 271 patients had a pretest PSA of <0.5 ng/mL and 945 patients had higher PSA values. The restaging PSMA PET/CT was positive for 834 patients and negative for 369. Of 1203 patients, 133 (11%) died, including 19 of the 369 (5%) patients without positive sites on the restaging PSMA PET/CT, 82 of the 711 (12%) with 1–5 positive sites, and 32 of the 123 (26%) with >5 positive sites. In the Cox regression analysis, four variables significantly predicted OS: treatment center, International Society of Urologic Pathology (ISUP) grade, pretest PSA threshold, and the grouping of positive sites on the restaging PSMA PET/CT. Conclusions: The pretest PSA and PSMA PET/CT were important for the OS of the BCR patients. The findings argue for the new BCR risk model and serve as framework for ongoing trials.

The aim of this study was to systematically review the current evidence regarding the oncological and functional outcomes of salvage radical prostatectomy (sRP) for recurrent prostate cancer. A systematic review was conducted throughout September 2022 using the PubMed, Science Direct, Scopus, and Embase databases. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. A total of 55 studies (3836 patients) met our eligibility criteria. The vast majority of men included had radiation therapy (including brachytherapy) as their first-line treatment (n = 3240, 84%). Other first-line treatments included HIFU (n = 338, 9%), electroporation (n = 59, 2%), proton beam therapy (n = 54, 1.5%), cryotherapy (n = 34, 1%), focal vascular targeted photodynamic therapy (n = 22, 0.6%), and transurethral ultrasound ablation (n = 19, 0.5%). Median preoperative PSA, at the time of recurrence, ranged from 1.5 to 14.4 ng/mL. The surgical approach was open in 2300 (60%) cases, robotic in 1465 (38%) cases, and laparoscopic in 71 (2%) cases. Since 2019, there has been a clear increase in robotic versus conventional surgery (1245 versus 525 cases, respectively). The median operative time and blood loss ranged from 80 to 297 min and 75 to 914 mL, respectively. Concomitant lymph node dissection was performed in 2587 cases (79%). The overall complication rate was 34%, with a majority of Clavien grade I or II complications. Clavien ≥ 3 complications ranged from 0 to 64%. Positive surgical margins were noted in 792 cases (32%). The median follow-up ranged from 4.6 to 94 months. Biochemical recurrence after sRP ranged from 8% to 51.5% at 12 months, from 0% to 66% at 22 months, and from 48% to 59% at 60 months. The specific and overall survival rates ranged from 13.4 to 98% and 62 to 100% at 5 years, respectively. Urinary continence was maintained in 52.1% of cases. sRP demonstrated acceptable oncological outcomes. These results, after sRP, are influenced by several factors, and above all by pre-treatment assessment, including imaging, with the development of mpMRI and metabolic imaging. Our results demonstrated that SRP can be considered a suitable treatment option for selected patients, but the level of evidence remains low.

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.

Previous reports have shown an association between vasectomy and prostate cancer (PCa). However, there exist significant discrepancies between studies and systematic reviews due to a lack of strong causal association and residual confounding factors such as prostate-specific antigen (PSA) screening.To assess the association between vasectomy and PCa, in both unadjusted and PSA screen-adjusted studies.We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses. The PubMed, Scopus, and Web of Science databases were searched in January 2022 for studies that analyzed the association between vasectomy and PCa.A total of 37 studies including 16 931 805 patients met our inclusion criteria. A pooled analysis from all studies showed a significant association between vasectomy and any-grade PCa (odds ratio [OR] 1.23; 95% confidence interval [CI], 1.10-1.37; p < 0.001; I2 = 96%), localized PCa (OR 1.08; 95% CI, 1.06-1.11; p < 0.00001; I2 = 31%), or advanced PCa (OR 1.07; 95% CI, 1.02-1.13; p = 0.006; I2 = 0%). The association with PCa remained significant when the analyses were restricted to studies with a low risk of bias (OR 1.06; 95% CI, 1.02-1.10; p = 0.02; I2 = 48%) or cohort studies (OR 1.09; 95% CI, 1.04-1.13; p < 0.0001; I2 = 64%). Among studies adjusted for PSA screening, the association with localized PCa (OR 1.06; 95% CI, 1.03-1.09; p < 0.001; I2 = 0%) remained significant. Conversely, vasectomy was no longer associated with localized high-grade (p = 0.19), advanced (p = 0.22), and lethal (p = 0.42) PCa.Our meta-analysis found an association between vasectomy and any, mainly localized, PCa. However, the effect estimates of the association were increasingly close to null when examining studies of robust design and high quality. On exploratory analyses including studies, which adjusted for PSA screening, the association for aggressive and/or advanced PCa diminished.In this study, we found an association between vasectomy and the risk of developing localized prostate cancer without being able to determine whether the procedure leads to a higher prostate cancer incidence.

The aim was to evaluate the prognostic role of sub-categories of ISUP 4 prostate cancer (PCa) on final pathology, and assess the tumor architecture prognostic role for predicting biochemical recurrence (BCR) after radical prostatectomy. From a prospectively-maintained database, we included 370 individuals with ISUP 4 on final pathology. The main outcomes were to evaluate the relationship between different ISUP patterns within the group 4 with pathological and oncological outcomes. Binary logistic regression and Kaplan–Meier estimator were used to evaluate the role of the different categories (3 + 5, 4 + 4, 5 + 3) and tumor architecture (intraductal and/or cribriform) on pathological and oncological outcomes. Among the 370 individuals with ISUP considered for the study, 9, 85 and 6

Despite recent improvements in survival, metastatic castration-resistant prostate cancers (mCRPCs) remain lethal. Alterations in genes involved in the homologous recombination repair (HRR) pathway are associated with poor prognosis. Poly-ADP-ribose polymerase (PARP) inhibitors (PARPis) have demonstrated anti-tumoral effects by synthetic lethality in patients with mCRPCs harboring HRR gene alterations, in particular BRCA2. While both olaparib and rucaparib have obtained government approvals for use, the selection of eligible patients as well as the prescription of these treatments within the clinical urology community are challenging. This review proposes a brief review of the rationale and outcomes of PARPi treatment, then a pragmatic vision of PARPi use in terms of prescription and the selection of patients based on molecular screening, which can involve potential genetic counseling in the case of associated germinal alterations.

IntroductionLes évolutions thérapeutiques actuelles du cancer de la prostate (CaP) tendent à personnaliser de plus en plus la stratégie de traitement, notamment en fonction de la génomique tumorale. Récemment, les inhibiteurs de la poly ADP-ribose polymérase (PARPi) ont montré leur efficacité au stade de la résistance à la castration métastatique, en cas d’altération des gènes de réparation de l’ADN dans le tissu tumoral.Matériel et méthodesUne revue narrative a été effectuée sur les données récentes de la littérature depuis 2000. Un consensus entre les membres du Comité a été obtenu afin de faire la synthèse des données actuelles, avec un focus particulier sur les considérations pratiques de l’indication et de la mise en place des circuits d’analyse moléculaire concernant les gènes de réparation de l’ADN, à visée théranostique.RésultatsLa mise en place d’un réseau efficient d’analyse moléculaire repose sur l’organisation pluridisciplinaire des différents acteurs et la coordination de ressources nécessaires. Son but est la recherche en routine des mutations somatiques (dans le tissu tumoral) des gènes BRCA1/2 chez des patients pouvant bénéficier d’un PARPi. Les indications actuelles sont les CaP métastatiques résistants à la castration BRCA1 ou 2 mutés, après échec d’une hormonothérapie de nouvelle génération, mais celles-ci seront probablement élargies aux stades plus précoces dans un avenir proche. La demande d’analyse moléculaire doit être décidée en RCP, en privilégiant le tissu archivé de moins de 10 ans. En cas d’impossibilité ou d’échec de la procédure, des biopsies sur le primitif ou les métastases, voire une analyse de l’ADN tumoral circulant, peuvent être nécessaires. Toute demande de test génétique sur tissu tumoral doit être accompagnée d’une information du patient sur les conséquences familiales éventuelles en cas de mutation germinale associée.ConclusionCette mise au point permet de guider la mise en place pratique des circuits d’analyse moléculaire, pour la recherche des altérations des gènes de réparation de l’ADN, afin de guider la prise en charge thérapeutique des patients atteints de CaP avancé.

The diagnosis of prostate cancer (PCa) still relies on the performance of both targeted (TB) and systematic biopsies (SB). Micro-ultrasound (mUS)-guided biopsies demonstrated a high sensitivity in detecting clinically significant prostate cancer (csPCa), which could be comparable to that of magnetic resonance imaging (MRI)-TB, but their added value has not been compared to SB yet. We conducted a systematic review and meta-analysis, based on Medline, EMBASE, Scopus, and Web of Science, in accordance with PRISMA guidelines, to compare mUS-guided biopsies to SB. Based on the literature search of 2957 articles, 15 met the inclusion criteria (2967 patients). Most patients underwent mUS-guided biopsies, followed by MRI-TB and SB. Respectively 5 (n = 670) and 4 (n = 467) studies, providing raw data on SB, were included in a random-effect meta-analysis of the detection rate of csPCa, i.e. Gleason Grade Group (GGG) ≥ 2 or non-csPCa (GGG = 1). Overall, PCa was detected in 56–71

An individual patient meta-analysis followed 1216 patients with PSA-only recurrence (biochemical recurrence, BCR) restaged with [68Ga]Ga-PSMA-11 PET/CT before the salvage treatment for median 3.5 years and analyzed the overall survival (OS). A new risk model included a good risk group with a prescan PSA < 0.5 ng/mL (26%), an intermediate risk group with a prescan PSA > 0.5 ng/mL and a PSMA PET/CT with 1 to 5 positive sites (65%), and a poor risk group with a prescan PSA > 0.5 ng/mL and a PSA PET/CT with > 5 positive sites (9%) (p < 0.0001, log rank test). The poor risk group had a five-year OS > 60%. Adding a BCR risk score by the European Association of Urology did not significantly improve the prediction of OS (p = 0.64). In conclusion, the restaging PSMA PET/CT markedly predicted the 5-year OS. The new risk model for patients with PSA-only relapse requires a restaging PSMA PET/CT for patients with a prescan PSA > 0.5 ng/mL and has a potential use in new trials aiming to improve the outcome for patients with PSA-only recurrence who have polysites prostate cancer detected on PSMA PET/CT.