Min Yuen Teo

Objectives: To determine the prevalence of programmed death ligand 1 (PD‐L1) expression in penile squamous cell carcinoma (PSCC) and evaluate its associations with clinicopathological features and survival outcomes. Patients and Methods: A systematic review was carried out using PubMed, the Excerpta Medica dataBASE (EMBASE), Scopus, Web of Science and Cochrane. Random‐effects meta‐analysis synthesised prevalence, hazard ratios (HRs) for overall survival (OS) and cancer‐specific survival (CSS), and odds ratios (ORs) for lymph node metastases (LNM) and tumour characteristics. Meta‐regression was caried out for pre‐specified moderators. Results: A total of 16 studies (1634 patients) were included, with median follow‐up of 44 months. The pooled PD‐L1 prevalence was 53% (95% confidence interval [CI] 44–62%) with substantial between‐study heterogeneity. PD‐L1 positivity was associated with worse CSS (HR 1.94, 95% CI 1.54–2.44; P < 0.001) but not OS (HR 1.28, 95% CI 0.89–1.86; P = 0.2). PD‐L1 positivity was associated with higher tumour stage (pathological T stage [pT]1 vs pT2–4, OR 1.67, 95% CI 1.22–2.29, P = 0.001), higher tumour grade (Grade 1 vs Grade 2–3, OR 2.60, 95% CI 1.94–3.5, P < 0.001), and LNM (OR 2.32, 95% CI 1.57–3.42, P < 0.001). Sensitivity testing and meta‐regression did not materially alter pooled effects. Conclusions: Programmed death ligand 1 is associated with adverse clinicopathological features and worse CSS in PSCC. Prospective validation is required to assess its independent prognostic value. Similarly PD‐L1's predictive value for immunotherapy benefit cannot be determined from the current evidence and requires evaluation with treatment‐specific prospective studies.

Plasma cell-free DNA sequencing data

Representativeness of Study Participants

Supplementary Table 3. Summary of Grade 3 to 5 Treatment-emergent Adverse Events

Supplementary Table 1. Representativeness of Study Participants

Supplementary Figure S3. Mutational Profile by Cohort and Treatment Group. Distribution of key genomic alterations among patients with metastatic prostate cancer. (Left) Comparison of alteration frequencies between Cohort A and Cohort B. (Right) Comparison of alteration frequencies between treatment groups receiving Apa alone versus Apa + AAP. The most frequently altered genes included TP53, PTEN, SPOP, FOXA1, and AGO2.

Purpose:To accelerate prostate cancer drug development and identification of promising therapies, we aimed to establish a framework for a multimodal therapy (MMT) approach using intermediate endpoints of efficacy due to treatment.Patients and Methods:In the MetaCURE trial, patients with untreated, high-risk localized (cohort A) or low-volume metastatic (cohort B) disease were randomized 1:1 to apalutamide or apalutamide and abiraterone acetate plus prednisone and androgen deprivation therapy for 10 months. Cohort B also received stereotactic body radiotherapy (RT) at 4 months. All patients underwent a radical prostatectomy (6 months ± postoperative RT at 10 months). The primary endpoint was pathologic complete response (pCR; no residual tumor) or minimal residual disease (MRD; ≤5 mm residual carcinoma), and the secondary endpoint an undetectable PSA following testosterone (T) recovery (T ≥ 150 ng/dL) at 24 months.Results:A pCR or MRD was achieved in 4 [12%; 90% confidence interval (CI), 4%–26%] and 5 (15%; 90% CI, 6%–29%) patients in cohorts A and B, respectively. Undetectable PSA and T-recovery at 24 months occurred in 20 (61%; 95% CI, 42%–77%) patients in cohort A and 13 (39%; 95% CI, 23%–58%) patients in cohort B.Conclusions:MMT for newly diagnosed high-risk localized and low-volume metastatic prostate cancer is feasible, safe, and provides a rapid readout of efficacy. A significant proportion of patients, including those with oligometastatic disease, maintained an undetectable PSA following T-recovery at the 2-year endpoint. These results have informed the design of an adaptive trial using MMT on a continuous basis to prioritize effective approaches for further study.

Supplementary Figure S2. Time to Testosterone Recovery by Cohort and Treatment Assignment. Cumulative probability curves depict time to testosterone recover measured from the end of systemic therapy among participants in Cohort A (red) and Cohort B (blue). Solid lines represent participants treated with ADT + Apa, while dashed lines represent those receiving ADT + Apa + AAP. The number of participants at risk at each time point is shown below the graph.