CONTEXT: Earlier evidence syntheses reached uncertain conclusions about the effect of prostate-specific antigen (PSA)-based screening on prostate cancer (PCa)-specific mortality (PCSM). Extended follow-up from major tria...CONTEXT: Earlier evidence syntheses reached uncertain conclusions about the effect of prostate-specific antigen (PSA)-based screening on prostate cancer (PCa)-specific mortality (PCSM). Extended follow-up from major trials has provided an opportunity to re-evaluate the evidence. OBJECTIVE: To estimate the effect of PSA-based screening versus no screening or usual care on PCSM in individuals engaging in screening. EVIDENCE ACQUISITION: We systematically searched PubMed, MEDLINE, EMBASE, and CENTRAL through October 2025 for randomized controlled trials (RCTs) comparing PSA-based screening with no screening or usual care among adults with prostates. The primary outcome was PCSM at the longest available follow-up. Secondary outcomes were PCSM beyond 12 yr and PCSM closest to 10 yr of follow-up. Risk of bias was assessed using the Risk Of Bias instrument for Use in SysTematic reviews-for RCTs (ROBUST-RCT). Incidence rate ratios were pooled using fixed-effect models. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. EVIDENCE SYNTHESIS: We included 5 RCTs analyzing 721,607 participants aged 45-80 yr of age with 11-23 yr of follow-up. PSA-based screening, with a high certainty in the evidence, demonstrated a reduced risk of PCSM at the longest follow-up (p < 0.001). Secondary analyses suggested greater relative PCSM reduction with longer follow-up. The overall effect was observed despite limitations including differing screening protocols and control-arm contamination, which likely underestimated benefit. CONCLUSIONS: With 11-23 yr of follow-up, high-certainty evidence demonstrates that PSA-based PCa screening is associated with reduced PCSM among individuals who engage in screening-a finding that contrasts with earlier evidence syntheses. This finding does not in itself justify population-based screening or imply that every well-informed individual would elect to undergo screening. This PCSM benefit should be weighed against known harms and consider emerging approaches under study that may mitigate these harms.
BACKGROUND AND OBJECTIVE: The European Association of Urology (EAU) produces an annual guidelines document based on the most recent evidence for the diagnosis, treatment, and follow-up of testicular cancer (TC). To summa...BACKGROUND AND OBJECTIVE: The European Association of Urology (EAU) produces an annual guidelines document based on the most recent evidence for the diagnosis, treatment, and follow-up of testicular cancer (TC). To summarize the 2026 version of the EAU Guidelines on TC and highlight the main changes compared to the previous version. METHODS: A multidisciplinary team of clinicians with specific expertise in the disease (urologists, medical oncologists, radiation oncologists, and pathologists) reviewed the results of a comprehensive appraisal of the published literature on the topic since the last Guidelines update paper in 2023. KEY FINDINGS AND LIMITATIONS: Recommendations based on the highest available level of evidence are presented across TC stages, histologies and prognostic categories regarding diagnosis, primary management, detection and treatment of relapse and survivorship care. Areas of lack of strong recommendation consensus are highlighted. CONCLUSIONS AND CLINICAL IMPLICATIONS: The 2026 version of the EAU Guidelines on TC collates the highest available scientific evidence to standardize the management of patients with TC.
Sherry AD, To V, D'souza C
… +22 more, Kiany S, Thio N, Liu S, Sun X, Castle B, Macdonald S, Choi H, Seo A, Hara K, Pryor D, Azad A, Tran B, Au L, Spain L, Ludmir EB, Jonasch E, Tannir NM, Msaouel P, Neeson P, Haymaker C, Tang C, Siva S
Radiotherapy-based metastasis-directed therapy (MDT) has emerged as a treatment strategy for oligometastatic clear cell renal cell carcinoma (ccRCC). However, optimal integration of MDT with immune checkpoint inhibition...Radiotherapy-based metastasis-directed therapy (MDT) has emerged as a treatment strategy for oligometastatic clear cell renal cell carcinoma (ccRCC). However, optimal integration of MDT with immune checkpoint inhibition (ICI) is unclear, especially in light of the M1 no evidence of disease subgroup analysis of KEYNOTE-564. We undertook an exploratory cohort study of two previously reported trials evaluating either MDT+ICI (NCT02855203) or MDT (NCT03575611) for oligometastatic ccRCC. The objective was primarily to compare RECIST-defined progression-free survival (PFS) and secondarily to compare peripheral immune populations. Among the 150 patients included in the analysis (MDT+ICI: 30; MDT: 120), the MDT+ICI cohort had more metastases (median 3 vs 1) and was slightly younger (median 62 vs 66) than MDT. After a median follow-up time of 34 mo, there was evidence for longer PFS after MDT+ICI vs MDT that did not reach statistical significance (hazard ratio, 0.57; 95% confidence interval: 0.32-1.02; p = 0.058). Interaction testing demonstrated greater PFS benefit with MDT+ICI among patients with previous receipt of systemic therapy. Immediate systemic induction of activated CD8 T cells (ICOS) was more common after MDT+ICI, as were decreases in less functional CD8 T cell subsets. Taken together, this study provides evidence that adding maintenance ICI to MDT improves clinical outcomes for patients with oligometastatic ccRCC. MDT+ICI-evoked immunomodulatory signals are promising and support the observed superiority in clinical outcomes. The A Randomized Trial of Maintenance Systemic Therapy After Radiation for Oligometastatic Renal Cell Carcinoma (ASTROs) trial (NCT06004336) has been initiated to test the hypotheses generated by the present study.
CONTEXT AND OBJECTIVE: The 2026 European Association of Urology and American Society of Clinical Oncology (EAU-ASCO) guideline update reflects significant developments in the diagnosis and management of penile cancer. Th...CONTEXT AND OBJECTIVE: The 2026 European Association of Urology and American Society of Clinical Oncology (EAU-ASCO) guideline update reflects significant developments in the diagnosis and management of penile cancer. This review summarises the key changes and contrasts them with previous recommendations, with particular focus on staging, treatment, quality of life and emerging personalised approaches. EVIDENCE ACQUISITION: The summary is based on a critical appraisal of the full 2026 guideline and its underpinning systematic reviews, with comparison to earlier versions. Recommendations were informed by structured literature assessment and expert panel consensus, incorporating evaluation of benefits and harms, evidence uncertainty and patient values. EVIDENCE SYNTHESIS: Major updates include refined pathological risk stratification, routine ultrasound (US)-guided nodal assessment, and broader guidance on organ-preserving surgery. There is support for selective genomic testing and clearer, restructured algorithms are introduced, including newly developed flow diagrams for nodal management, alongside an expanded evidence base for systemic therapy. Greater emphasis is placed on survivorship, centralisation of care and rationalisation of follow-up. However, many recommendations remain informed by retrospective data and expert consensus, reflecting the rarity of the disease and limited prospective evidence. CONCLUSIONS: The updated guideline promotes more nuanced selection of organ-preserving strategies, earlier detection of regional lymphatic disease, and holistic palliative care, while reinforcing the central role of shared decision-making. PATIENT SUMMARY: The new guidance for penile cancer aims to improve care, personalise treatment and better address quality of life, while acknowledging that further research is still needed.
Recurrence after nephrectomy in high-risk localized renal cell carcinoma is common, but the genomic and transcriptomic differences between primary and recurrent tumors are not well understood. In the IMmotion010 trial, p...Recurrence after nephrectomy in high-risk localized renal cell carcinoma is common, but the genomic and transcriptomic differences between primary and recurrent tumors are not well understood. In the IMmotion010 trial, patients were randomized to receive adjuvant atezolizumab versus placebo. Tumor tissue was collected at pre-treatment baseline (n = 754) and subsequently at the time of recurrence (n = 80). We performed matched transcriptomic (n = 80) and genomic (n = 52) analyses on primary versus recurrent samples. Using previously described transcriptomic classifications, resected primary tumors had a higher proportion of angiogenic and small nucleolar RNA transcriptomic signatures and lower proportion of T-effector/proliferative and stromal/proliferative signatures compared with published metastatic cohorts. Sites of recurrence exhibited upregulation of signatures related to cell proliferation, fatty acid synthesis, and stromal biology, including matrix and fibroblasts. Comparing treatment arms, tumors that recurred in placebo-treated patients demonstrated increased B cell and macrophage signatures, while tumors that recurred despite adjuvant atezolizumab showed downregulation of major histocompatibility complex (MHC)-I. Although requiring further clinical validation, the latter finding may substantiate scientifically a potential rationale for transitioning to vascular endothelial growth factor (VEGF)-inhibition after adjuvant checkpoint inhibition.