Boeri L, Dinkelman-Smit M, Jensen CFS
… +3 more, Minhas S, Salonia A, European Association of Urology Guidelines Panel on Sexual and Reproductive Health
There is some evidence suggesting potential benefits of varicocelectomy in men with nonobstructive azoospermia (NOA), but it is not of sufficient quality to support a strong recommendation for this procedure. There is a...There is some evidence suggesting potential benefits of varicocelectomy in men with nonobstructive azoospermia (NOA), but it is not of sufficient quality to support a strong recommendation for this procedure. There is a possible benefit of surgical correction of clinically detectable varicocele in NOA patients without known genetic abnormalities and with a partner with no evidence of diminished ovarian reserve. Patient counseling should highlight the variability of the outcome data and the limited strength of the evidence available.
BACKGROUND AND OBJECTIVE: Biochemical recurrence (BCR) after radical prostatectomy (RP) is a heterogeneous disease state in prostate cancer with multiple treatment options. Improved risk stratification could enable more...BACKGROUND AND OBJECTIVE: Biochemical recurrence (BCR) after radical prostatectomy (RP) is a heterogeneous disease state in prostate cancer with multiple treatment options. Improved risk stratification could enable more personalized decision-making. We developed and validated a digital pathology-based multimodal artificial intelligence (MMAI) model to predict outcomes in post-RP BCR patients undergoing salvage therapy. METHODS: An MMAI model was trained to predict distant metastasis (DM) using prostate histopathology image features and clinical variables (pathologic grade group, pathologic T stage, prostate-specific antigen level before salvage radiotherapy [SRT], age, and surgical margin). The locked model was validated in 533 patients from NRG/RTOG 9601 and 0534 treated with SRT ± hormone therapy (HT), using Cox regression and time-dependent area under the receiver operating characteristic curve. KEY FINDINGS AND LIMITATIONS: With a median follow-up of 9.3 yrs, MMAI score was significantly associated with DM (subdistribution hazard ratio = 2.17 per standard deviation [95% confidence interval 1.65-2.85]; p < 0.001) and remained independently prognostic after adjusting for clinical variables and treatment. The 10-yr time-dependent area under the receiver operating characteristic curve for MMAI was 0.74 compared with 0.68 for a clinical nomogram. Binary risk categorization demonstrated higher 10-yr DM incidence in the MMAI high-risk (25%) than in the low-risk (8.8%) group. The absolute reduction in 10-yr DM incidence with HT plus SRT versus SRT alone was 21% in the high-risk group versus 2.5% in the low-risk group. Limitations include the use of archived trial cohorts. CONCLUSIONS AND CLINICAL IMPLICATIONS: The post-RP MMAI model provides individualized risk estimates after SRT ± HT and may support shared decision-making about salvage treatment. External and prospective validation are ongoing.
BACKGROUND AND OBJECTIVE: Bladder cancer is the most common tumor of the urinary tract and the ninth most common cancer worldwide. Our objective was to describe and interpret current geographic variations in bladder canc...BACKGROUND AND OBJECTIVE: Bladder cancer is the most common tumor of the urinary tract and the ninth most common cancer worldwide. Our objective was to describe and interpret current geographic variations in bladder cancer incidence and mortality rates using updated national estimates and recorded data from population-based cancer registries alongside national vital statistics. METHODS: The bladder cancer incidence and mortality for 185 countries by sex were obtained from GLOBOCAN (International Agency for Research on Cancer) for the year 2022. Recorded incidence and mortality data were retrieved from national or subnational population-based cancer registries included in the Cancer Incidence in Five Continents series and the World Health Organization database, respectively. Corresponding age-standardized rates (ASRs) per 100000 person-years were calculated using direct standardization (world standard), and temporal trends of ASRs by calendar period and sex are presented by country, with the direction and magnitude of recent trends quantified using the estimated annual percentage change (EAPC). KEY FINDINGS AND LIMITATIONS: In 2022, an estimated 614298 new cases of bladder cancer and 220596 deaths occurred worldwide, with approximately 75% of the burden observed in males. Urothelial and squamous cell carcinomas were the predominant histological subtypes across all regions. Incidence and mortality rates varied substantially across regions and countries, with the highest rates reported in Europe, particularly in southern (ASR: 28.7) and northern (20.4) regions, and elevated rates were also seen in North America (18.0), Northern Africa (16.3), and Western Asia (15.2). Despite lower age-standardized rates, Eastern Asia reported the highest absolute numbers due to its large population. Temporal trends indicate a stabilizing or declining incidence in many high-income countries. Mortality rates have overall declined across many populations, for example, in Australia (EAPC in male: -2.6; female: -2.3), the Netherlands (male: 2.9; female: -1.6), and the USA (male: -1.3; female: -1.0). Interpretation of bladder cancer incidence patterns and trends requires caution given possible variations in cancer registration practice, notably as to whether noninvasive tumors are included in reporting. CONCLUSIONS AND CLINICAL IMPLICATIONS: Bladder cancer continues to pose a significant global health challenge, with marked geographic and sex-based disparities in the incidence and mortality. While encouraging declines in rates are observed in many high-income countries, the burden remains substantial in these regions and rates are rising in some settings. Tobacco smoking remains the predominant risk factor, with historical and current prevalence patterns aligned closely with disease trends. However, in Northern Africa, schistosomiasis contributes to an elevated incidence and a distinct histological profile. Interpretation of these patterns is complex given the potential variations in registration practice, with respect to reporting of noninvasive tumors.
Carlsson SV, Krilaviciute A, Al-Monajjed R
… +12 more, Seibold P, Kuczyk M, Gschwend JE, Debus J, Antoch G, Schimmöller L, Schlemmer HP, Kristiansen G, Kaaks R, Becker N, Albers P, PROBASE Study Group
Using Germany as a case example, a comparison between organized mammography screening and contemporary, risk-adapted screening for prostate cancer suggests that prostate-specific antigen-based early detection with incorp...Using Germany as a case example, a comparison between organized mammography screening and contemporary, risk-adapted screening for prostate cancer suggests that prostate-specific antigen-based early detection with incorporation of magnetic resonance imaging and active surveillance can achieve benefits comparable to those of mammography while addressing previous concerns about overdiagnosis and overtreatment. Findings from the PROBASE trial support the potential of such an approach to provide a favorable balance between benefit and harm when initiated at younger ages.
We describe the rationale for using quantification of Gleason pattern 4 rather than the proportion of Gleason patterns for risk stratification in prostate cancer, as proposed by the ProQuant Group. We outline research th...We describe the rationale for using quantification of Gleason pattern 4 rather than the proportion of Gleason patterns for risk stratification in prostate cancer, as proposed by the ProQuant Group. We outline research that will be conducted to assess this strategy, and invite individuals interested in collaboration to join the group.
Prostate-specific membrane antigen (PSMA)-targeted theranostic agents have transformed prostate cancer (PC) management, but their performance is limited by variable PSMA expression and off-target uptake. We investigates...Prostate-specific membrane antigen (PSMA)-targeted theranostic agents have transformed prostate cancer (PC) management, but their performance is limited by variable PSMA expression and off-target uptake. We investigates the first-in-human positron emission tomography (PET) imaging of prostatic acid phosphatase (ACP3), a novel and highly specific PC target, using the radioligand [Ga]Ga-OncoACP3-DOTA. We analyzed and matched [Ga]Ga-OncoACP3-DOTA and [F]PSMA-1007 PET scans in a cohort of 25 patients with PC. We compared the biodistribution and tumor uptake of the two tracers using the Wilcoxon rank-sum test and compared their performance. Superiority was defined as >10% more lesions detected or >50% higher lesional maximum standardized uptake value (SUV). [Ga]Ga-OncoACP3-DOTA showed low background uptake, including in the salivary glands and kidneys, with a significant difference from the high [F]PSMA-1007 uptake in these organs (p < 0.002). Overall, SUV in localized or metastatic PC did not significantly differ between the two tracers. Better [Ga]Ga-OncoACP3-DOTA performance was observed in 11/25 matched scan pairs, and better [F]PSMA-1007 performance in eight of 25 pairs. [Ga]Ga-OncoACP3-DOTA changed therapeutic management in three of six patients with biochemical recurrence, and in two of 12 patients with known metastases. Although the retrospective comparison is potentially biased, the intense and reliable tumor uptake and the low off-target activity of OncoACP3-DOTA provide a strong rationale for future exploration in trials on PET imaging and radioligand therapy with β- and α-particle emitters.
Jani AB, Dhere VR, Goyal S
… +18 more, Schreibmann E, Patel PR, Hershatter B, Shelton JW, Hanasoge S, Sebastian NT, Patel SA, Halkar R, Cooper S, Fielder B, Abiodun-Ojo OA, Lawal I, Mushtaq A, Master VA, Joshi SS, Kucuk O, Bilen MA, Schuster DM
BACKGROUND AND OBJECTIVE: In EMPIRE-1, [F]-fluciclovine positron emission tomography (PET) imaging to guide salvage radiotherapy (RT) for prostate cancer recurrence after prostatectomy resulted in an improvement in event...BACKGROUND AND OBJECTIVE: In EMPIRE-1, [F]-fluciclovine positron emission tomography (PET) imaging to guide salvage radiotherapy (RT) for prostate cancer recurrence after prostatectomy resulted in an improvement in event-free survival (EFS) over conventional imaging alone. The aim of EMPIRE-2 was to explore the impact of RT dose escalation to sites of uptake on PET in comparison to EMPIRE-1. METHODS: EMPIRE-2 was a randomized trial of [F]-fluciclovine versus [Ga]-PSMA-11 in a cohort of men with biochemical progression after prostatectomy and negative conventional imaging findings. After stratification, patients were randomized to RT guided by [F]-fluciclovine PET (arm 1) or [Ga]-PSMA-11 PET (arm 2). PET findings were used for treatment decisions and for RT dose escalation (≤76.0 Gy to the prostate bed and ≤56.0 Gy to the pelvis). The primary endpoint was 2-yr EFS in comparison to the [F]-fluciclovine RT arm in EMPIRE-1. The secondary endpoint was a planned EFS comparison for [F]-fluciclovine versus [Ga]-PSMA-11 in EMPIRE-2. KEY FINDINGS AND LIMITATIONS: In the cohort of 140 patients, 59 randomized to arm 1 patients and 60 randomized to arm 2 completed RT. Median follow-up was 2.6 yr (interquartile range 1.8-4.0). The 2-yr EFS rates were 87% for the overall EMPIRE-2 cohort versus 80% for the EMPIRE-1 comparison cohort (difference 7.7%, 95% confidence interval [CI] 4.7-12%; p = 0.01). After propensity score weighting, the corresponding 2-yr EFS rates were 84% versus 73% (difference 11%, 95% CI 3.6-24%; p = 0.01). The 2-yr EFS rates in the EMPIRE-2 study arms were 87% for [F]-fluciclovine versus 88% for [Ga]-PSMA-11 (difference 0.7%, 95% CI 0.3-1.3%; p > 0.9). CONCLUSIONS AND CLINICAL IMPLICATIONS: Use of either [F]-fluciclovine or [Ga]-PSMA-11 imaging to guide RT dose escalation to sites of PET uptake in the prostate bed and/or pelvis was associated with an improvement in EFS in comparison to a prior trial without dose escalation.
BACKGROUND AND OBJECTIVE: Prostate-specific antigen (PSA)-based screening for prostate cancer (PCa) has limited accuracy, and it is linked to overdiagnosis. The PROSA trial aimed to evaluate whether a contrast-free bipar...BACKGROUND AND OBJECTIVE: Prostate-specific antigen (PSA)-based screening for prostate cancer (PCa) has limited accuracy, and it is linked to overdiagnosis. The PROSA trial aimed to evaluate whether a contrast-free biparametric magnetic resonance imaging (bpMRI)-first screening strategy improves the detection of clinically significant PCa (csPCa) as the primary outcome. The secondary outcomes included overall PCa detection, benefit-harm metrics, and cost effectiveness from a health care payer perspective. METHODS: This single-center, randomized controlled trial enrolled 816 asymptomatic men aged 49-69 yr (≥40 yr with a PCa family history). Participants were randomized into two arms: arm A underwent bpMRI regardless of the PSA levels; arm B received bpMRI only if PSA ≥3 ng/ml (or 2.5 ng/ml with a family history). Men with Prostate Imaging Reporting and Data System score ≥3 were directed to a targeted biopsy. Imaging and pathology assessors were blinded; csPCa is defined as International Society of Urological Pathology grade group ≥2. The primary outcomes included csPCa detection, benefit-harm metrics, and cost effectiveness from a health care payer perspective. KEY FINDINGS AND LIMITATIONS: Among 759 randomized men, biopsy and csPCa detection rates were higher in arm A (10.8% and 4.6%, respectively) than in arm B (5.2% and 1.8%, respectively), with a relative risk of 2.6 (95% confidence interval 1.1-6.1; p = 0.05) for the csPCa detection rate. Benefit-harm metrics favored the MRI-first strategy, showing higher grade selectivity (1.89 vs 1.75), biopsy efficiency (0.74 vs 0.54), and biopsy avoidance (23.1 vs 11.9). No serious adverse event was recorded. The MRI-first strategy yielded an incremental cost-effectiveness ratio of €2201.75 per csPCa case detected. Limitations include single-round design and short follow-up. CONCLUSIONS AND CLINICAL IMPLICATIONS: In this randomized screening trial, a contrast-free MRI-first pathway improved csPCa detection, enhanced benefit-harm metrics, and showed favorable cost effectiveness.
BACKGROUND AND OBJECTIVE: Robot-assisted bladder augmentation in children is rarely utilized across Europe. Performing this procedure robotically with an ileal loop "W" configuration is innovative. We analyzed the prelim...BACKGROUND AND OBJECTIVE: Robot-assisted bladder augmentation in children is rarely utilized across Europe. Performing this procedure robotically with an ileal loop "W" configuration is innovative. We analyzed the preliminary results of our experience in robotic-assisted laparoscopic W-shaped ileocystoplasty (RALAWI) in children. METHODS AND SURGICAL PROCEDURE: A prospective bicentric study included all patients who had RALAWI (2020-2024). The procedures were performed using the DaVinci Xi robot. The statistical analysis was descriptive (median [range]) and comparative. Thirteen patients were included (age 9.5 [5-16] yr, weight 31 [19-99] kg), and followed up for 15.5 (12-50) mo. Etiologies included the following: neuropathic bladder (nine cases), bladder exstrophy (two cases), rhabdomyosarcoma (one case), and bilateral ectopic ureters (one case). KEY FINDINGS AND LIMITATIONS: All procedures were performed intra-abdominally without conversion. The median operative time and length of stay were 670 (450-930) min and 12 (6-30) d, respectively. The associated procedures were extraserosal appendicovesicostomy (APV; eight cases), bladder neck reconstruction (six cases), bladder neck closure (one case), and bilateral ureteral reimplantation (two cases). Six patients had multiple abdominal surgeries previously. Four patients had complications at <30 d: urinary anastomotic leakage (N = 2, IIIB according to Clavien-Dindo), abscess (N = 1, IIIA), and ventriculoperitoneal shunt dysfunction (N = 1, IIIB). Five patients had nine complications at >30 d: stoma leakage (three cases, IIIB), bladder stone (one case, IIIB), difficult catheterization (two cases, IIIB), and ileocystoplasty perforation (one case, IIIB, and one case, IVA). None had APV stenosis. Postoperative bladder capacity was significantly higher (170 vs 350 ml; p < 0.01). All patients achieved continence. CONCLUSIONS AND CLINICAL IMPLICATIONS: To our knowledge, this is the first report of robot-assisted ileocystoplasty in children with a W-shape reconfiguration. It is feasible even after multiple surgeries, offering potential benefits for patients with fragile abdominal wall. The technique requires further refinements to reduce operative time and early postoperative complications.
Androgen deprivation therapy (ADT) causes hot flushes that can disrupt an individual's quality of life. NK3R antagonists provide rapid, sustained, and nonhormonal relief of hot flushes in women, but an approved treatment...Androgen deprivation therapy (ADT) causes hot flushes that can disrupt an individual's quality of life. NK3R antagonists provide rapid, sustained, and nonhormonal relief of hot flushes in women, but an approved treatment is lacking for men. Pragmatic trials are needed to generate evidence to support approval of these agents for the ADT setting.