This prospective, multicentre, intra-patient comparator study assessed urinary radioactivity, and patient-level and region-level detection rates (DR) with PSMA-PET radiopharmaceuticals, 18F-piflufolastat (18F-DCFPyL) and 18F-flotufolastat (18F-rhPSMA-7.3) in patients with biochemical recurrence (BCR) of prostate cancer to evaluate the hypothesis that lower urinary radioactivity is observed with 18F-flotufolastat. Patients with low PSA (≤0.5 ng/mL) BCR ≥6 months post-prostatectomy with undetectable PSA post-surgery, scheduled for standard-of-care 18F-piflufolastat PSMA-PET were enrolled. Patients underwent PET/CT 60 minutes post-18F-piflufolastat (9 mCi) administration, and a second PET/CT on the same scanner 1–10 days later, 60 minutes post-18F-flotufolastat (8 mCi) administration. The primary endpoint was the difference in urinary radioactivity (SUVmean) between the radiopharmaceuticals. Secondary endpoints included patient-level and region-level DR for each radiopharmaceutical, assessed by two blinded readers (a third resolved disagreements, allowing majority reads). Fifty-five evaluable patients (mean PSA, 0.28 ng/mL) were enrolled. Median bladder SUVmean was significantly higher with 18F-piflufolastat (29.0; interquartile range, 18.9–40.8) than 18F-flotufolastat (10.9; interquartile range, 6.0–18.5; p < 0.001 [Wilcoxon signed-rank test]). Majority read patient-level DR were 27.3
PURPOSE:We assessed the diagnostic performance of semen RNA-based biomarkers for detecting prostate cancer and differentiating cancer grade groups. MATERIALS AND METHODS:In a multicenter prospective study, semen samples were collected from men before undergoing prostate biopsy. RNA was extracted and sequenced to generate exome-wide gene expression profiles. Differentially expressed genes were selected and used to train a machine-learning classifier designed to detect prostate cancer with ≥ 95% sensitivity. The finalized model was locked and independently evaluated in a validation cohort. Histopathological diagnosis served as the reference standard. Model performance was further analyzed in relation to International Society of Urological Pathology Grade Group classification. RESULTS:Of 301 enrolled participants, 279 samples met quality criteria and were included in model development (training set: n = 199; validation set: n = 80). The median age and PSA level were 62 years and 5.70 ng/mL, respectively. In the validation cohort, the classifier achieved an AUC of 0.90, sensitivity of 92%, and specificity of 69%, with no significant performance difference compared with the training cohort. Importantly, high-risk cancers (International Society of Urological Pathology Grade Group ≥3) were ruled out with a negative predictive value of 96% in validation. CONCLUSIONS:This study demonstrates that noninvasive, high-accuracy prostate cancer tests can be developed using semen samples collected at home. The proposed test could potentially eliminate 60% to 70% of unnecessary biopsies, representing a substantial improvement in prostate cancer testing and risk stratification.
PURPOSE:TAR-200 is a first-in-class intravesical drug-releasing system designed to provide sustained delivery of gemcitabine in the bladder. TAR-200 alone or in combination with cetrelimab (PD-1 inhibitor) could improve outcomes in patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (NMIBC) ineligible for or refusing radical cystectomy. METHODS:In this phase IIb parallel cohort study, patients with BCG-unresponsive carcinoma in situ (CIS) with/without papillary disease received TAR-200 monotherapy (Cohort 2 [C2]), TAR-200 plus cetrelimab (C1), or cetrelimab monotherapy (C3). Patients with BCG-unresponsive high-risk papillary disease-only NMIBC received TAR-200 monotherapy (C4). TAR-200 was dosed through month 24 and cetrelimab through month 18. Primary end points were centrally confirmed overall complete response (CR) rate (C1-3) or disease-free survival (DFS) rate (C4) (ClinicalTrials.gov number: NCT04640623). RESULTS:At data cutoff (March 31, 2025), 53, 85, 28, and 52 patients were treated in C1-4, respectively. In C2, CR rate and median duration of response were 82.4% (95% CI, 72.6 to 89.8) and 25.8 months (95% CI, 8.3 to not estimable), respectively. In C4, 6-, 9-, and 12-month DFS rates were 85.3% (95% CI, 71.6 to 92.7), 81.1% (95% CI, 66.7 to 89.7), and 70.2% (95% CI, 51.6 to 82.8), respectively. In C1 and C3, CR rates were 67.9% (95% CI, 53.7 to 80.1) and 46.4% (95% CI, 27.5 to 66.1), respectively. Rates of grade ≥3 treatment-related adverse events (AEs) were 12.9%, 13.5%, 37.7%, and 7.1% in C2, C4, C1, and C3, respectively, and of serious treatment-related AEs, 5.9%, 5.8%, 15.1%, and 3.6%. No treatment-related deaths occurred. CONCLUSION:TAR-200 monotherapy was well tolerated, with a high CR rate, durable responses, and prolonged DFS in patients with BCG-unresponsive high-risk NMIBC. TAR-200 monotherapy offered a more favorable risk-benefit profile versus TAR-200 plus cetrelimab or cetrelimab alone in BCG-unresponsive CIS.
The gonadotropin-releasing hormone (GnRH) receptor antagonist relugolix is the only oral androgen deprivation therapy (ADT) indicated for advanced prostate cancer (aPC). Combining ADT with androgen receptor signaling inhibitors (ARSIs) has shown improved clinical outcomes. To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of relugolix in combination with ARSIs in patients with aPC. In this 52-week, open-label study, patients received relugolix (120 mg once daily) with abiraterone (1,000 mg once daily) and corticosteroid (Part 1) or relugolix (240 mg once daily) with apalutamide (240 mg once daily) (Part 2). Metastatic castration-sensitive patients were eligible for both parts, whereas castration-resistant patients were eligible for Part 1 if metastatic and Part 2 if non-metastatic. Adverse events and other safety data were evaluated over 52 weeks, while pharmacodynamic and pharmacokinetic (Part 2 only) data were assessed over 12 weeks. Medication adherence to relugolix was measured by pill count. Of 48 patients, 21 completed Part 1 and 20 completed Part 2. Most adverse events were grade 1 or 2, with hypertension (Part 1) and rash (Part 2) being most common. Mean testosterone concentrations remained below castrate level. Median prostate-specific antigen concentration was 0.04 ng/mL at week 12 in both parts. Concentrations of relugolix, apalutamide, and N-desmethyl-apalutamide were stable over 12 weeks similar to previous data. Relugolix adherence rates were > 97
GOAL:To present data from published clinical trials of treatment of patients with prostate cancer with enzalutamide described in plain language and in a dashboard format available at: https://clinical-trials.dimensions.ai/enzalutamide-clinical-review/. RATIONALE:Treatments that are clinically active in advanced prostate cancer may benefit patients as they are treated earlier in the disease. OBJECTIVE:To show how overall survival improves as patients are treated with enzalutamide earlier in the disease.
