Background Prostate cancer (PCa) patients are at increased fracture risk due to the need for androgen deprivation therapy (ADT) and progressive bone metastases. Previous meta-analyses of randomised controlled trials suggest that androgen receptor pathway inhibitors (ARPIs) increase fracture risk. Objective We assessed the impact of abiraterone-based treatment intensification on fracture-related hospitalisation (FRH) within the STAMPEDE trial platform. Design, setting and participants We performed a secondary analysis of two STAMPEDE trials in patients with high-risk non-metastatic (M0) or metastatic (M1) disease. Interventions Patients were allocated to either standard of care (SOC) or SOC plus abiraterone with prednisolone (AAP) or, in a later comparison, SOC+AAP with enzalutamide (Enza). Outcome measurements and statistical analysis A prespecified coding framework within Hospital Episode Statistics (HES) identified FRHs. Flexible parametric competing-risk models estimated 5-year cumulative incidence of FRH and sub-distribution hazard ratios (SDHR), with death as a competing risk. Outcome measurements and statistical analysis Between Nov 2011 and Mar 2016, 3893 patients were randomised to the STAMPEDE AAP±Enza trials. Linked HES data were available for 3102 patients in England. In M1 disease, 5-year FRH incidence was significantly lower with SOC + AAP than SOC alone (22% vs 30%; SDHR 0.77, 95%CI 0.59-0.99; p = 0.04) and with SOC + AAP + Enza than SOC alone (28% vs 38%; SDHR 0.69, 95%CI 0.54-0.88; p = 0.002). No significant difference was observed in M0 patients. Limitations include potential under-estimation of total fracture burden by exclusion of non-hospitalised fractures, lack of baseline assessment of fracture risk including bone mineral density, and longitudinal use of bone-protective therapy. Conclusions Abiraterone-based treatment intensification did not increase FRH compared to SOC alone. In M1 disease, abiraterone reduced rather than augmented fracture risk, most plausibly reflecting improved metastatic bone disease control.
Confirmatory prostate-specific antigen measurement reclassifies many younger men below the biopsy threshold, offering a simple, low-cost way to reduce magnetic resonance imaging and biopsy. For most, reclassification means deferral rather than exclusion, and follow-up remains insufficient to rule out missed clinically significant cancers."
In ARANOTE (NCT04736199), darolutamide plus androgen-deprivation therapy (ADT) significantly reduced the risk of radiologic progression or death versus placebo plus ADT in patients with metastatic hormone-sensitive prostate cancer, with favorable safety. Here, we report on post hoc outcomes by disease volume/risk. Randomized patients received darolutamide plus ADT or placebo plus ADT (2:1). High-volume (HV) and high-risk (HR) disease were defined by the CHAARTED and LATITUDE criteria, respectively. End points included radiologic progression-free survival (primary; rPFS), time to initiation of subsequent systemic anticancer therapy, time to metastatic castration-resistant prostate cancer, time to prostate-specific antigen (PSA) progression, time to pain progression, PSA <0.2 ng/ml rates, overall survival, and safety. Of 669 patients, 472 had HV disease, 197 had low-volume (LV) disease, 400 had HR disease, and 269 had low-risk (LR) disease; baseline characteristics were generally balanced. Darolutamide consistently reduced the rPFS (HV: 40% [hazard ratio, 0.60; 95% confidence interval, 0.44 to 0.80]; LV: 70% [0.30; 0.15 to 0.60]; HR: 39% [0.61; 0.44 to 0.86]; LR: 60% [0.40; 0.25 to 0.62]), with similar trends for all secondary end points versus placebo. Treatment-emergent adverse events were similar between treatment arms across all subgroups. Darolutamide was well tolerated, and outcomes were improved versus placebo, regardless of disease volume/risk. Prior presentation: Presented at the American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, San Francisco, CA, February 13-15, 2025. Clinical trial registration: NCT04736199 (EudraCT 2020-003093-48).
We report the results of a prospective trial aimed at describing the feasibility and accuracy of prostate-specific membrane antigen (PSMA) radio-guided surgery (RGS) during robot-assisted radical prostatectomy (RARP) with extended pelvic lymph node dissection (ePLND) in patients with prostate cancer (PCa). This was a phase 2 study (NCT04832958) that enrolled 82 patients with localized PCa and a lymph node invasion (LNI) risk >5%. All patients underwent preoperative PSMA positron emission tomography (PET). [99mTc]Tc-PSMA-I&S was administered intravenously the day before surgery, followed by single-photon emission computed tomography/computed tomography. Side effects, perioperative outcomes, and the performance characteristics of PSMA-RGS for LNI detection were measured. A total of 62 patients completed all study procedures and were included in the final analyses. Median blood loss and length of stay were 50 ml and 4 d, respectively. No adverse events after tracer administration or intraoperative complications were recorded. Four patients experienced a Clavien-Dindo grade 3 complication within 30 d. Overall, PSMA-RGS identified two additional patients with high-risk PCa and pathologically node-positive (pN1) disease compared with preoperative PSMA PET, exhibiting a lower positive predictive value (PPV) and a similar negative predictive value (NPV) in the per-patient analysis (PPV: 50% vs 70%; NPV: 83% vs 83%). The PPV and NPV at per-region analysis in patients with molecular imaging node-positive (miN1) disease were higher for PSMA-RGS than for PSMA PET (PPV: 55% vs 42%; NPV: 85% vs 81%). In conclusion, PSMA-RGS identifies additional patients with pN1 disease missed by preoperative PSMA-PET among men with high-risk PCa, and extends the ePLND template in patients with miN1 disease, in whom PSMA PET underestimates the nodal burden. However, its NPV is suboptimal for avoiding ePLND in patients with PCa who have a LNI risk >5% and negative PSMA-RGS findings during RARP.
As renal tumor classification continues to evolve and new hereditary entities emerge, accurate recognition of hereditary renal neoplasms is increasingly important. Advances in precision genomics, genetic testing, and international registries will improve early detection, risk stratification, and precision management.
