We discuss evidence supporting the benefit of centralized review of orchiectomy specimens by expert genitourinary pathologists. This approach would ultimately contribute to better patient management and more personalized treatment planning for individual patients.

Immune checkpoint inhibition can result in deep and durable responses in clear-cell renal cell carcinoma (ccRCC), yet no biomarkers currently guide management. While mismatch repair (MMR) deficiency is an established predictive biomarker for immunotherapy response in other malignancies, this has not been evaluated in ccRCC, despite the proximity of MMR gene MLH1 to VHL on chromosome 3p. Through genomic and immunohistochemical analyses across multiple cohorts, we identify somatic MLH1 deficiency as a relatively rare but robust predictor of exceptional immunotherapy response in ccRCC.

There is uncertainty over medium-term cancer outcomes for men who avoid biopsy (Bx) after nonsuspicious magnetic resonance imaging (MRI), and men with a negative Bx after suspicious MRI findings. We report on cancer diagnosis, treatment, and Bx rates for this population over a period of 5 yr.

Nivolumab improved survival in patients with refractory metastatic clear-cell renal cell carcinoma (ccRCC), but no reliable biomarker of activity has been identified. We conducted a real-world phase 2 trial of nivolumab in patients progressing after one or more vascular endothelial growth factor (VEGF) receptor-directed therapies, which included an integrated translational programme. Candidate tissue and circulating biomarkers were assessed using immunoassays and gene expression profiling. Overall, 720 patients were treated, with activity and safety in line with pivotal trial data. Exploration of tissue architecture showed that the presence of tertiary lymphoid structures, CD8+ lymphocytes, and CD163+ macrophage infiltration at the invasive margin were all marginally associated with longer progression-free survival, similarly to PD-1 expression on immune cells. Expression of hypoxia-related marker VEGF on tumour cells was however strongly associated with shorter progression-free and overall survival. Recapitulation of microenvironment composition based on gene expression signatures showed that patients harbouring a high tumour lymphocyte infiltration, concomitantly to low infiltration of neutrophil and non-immune stromal cells, had improved response to nivolumab. Conversely, circulating cytokines related to protumoral inflammation interleukin (IL)-6 and IL-8 were independently associated with shorter progression-free and overall survival. Overall, immune and angiogenic features helped inform outcomes to nivolumab. Circulating factors were best potential predictors for immunotherapy activity in ccRCC.

The impact of germline pathogenic variants (PVs) in cancer predisposition genes on risk of prostate cancer (PCa) remains understudied in large populations of African ancestry. This study aims to characterize the range of genetic risk of PCa and aggressive disease phenotypes in men of African ancestry.

There are barriers to the clinical use of cisplatin-based neoadjuvant regimens in muscle-invasive bladder cancer (MIBC), especially for patients with renal dysfunction, hearing loss, heart diseases, or other severe comorbidities. Favorable efficacy and safety of disitamab vedotin (DV), an antibody-drug conjugate targeting HER2, have recently been demonstrated in urothelial carcinoma. We explored neoadjuvant gemcitabine combined with RC48 in the MIBC setting. Initially, 26 patients with clinical stage T2-4a Nx M0 MIBC and a HER2 immunohistochemical expression score of 2+/3+ were enrolled. The neoadjuvant regime comprised DV (2 mg/kg intravenous infusion, day 1) and gemcitabine (1000 mg/m intravenous infusion, day 2) in a 14-d cycle. Thirteen patients received three cycles, and the other 13 patients received four cycles, in a nonrandomized manner. Subsequently, 22 patients underwent radical cystectomy (RC). Postoperative pathology revealed a pathological complete response (pCR) rate of 59% (13/22) among RC patients, 40% (4/10) of whom had received three cycles and 75% (9/12), four cycles. Intention-to-treat analysis revealed pCR rates of 50% (13/26) overall, 31% (4/13) for the three-cycle group, and 69% (9/13) for the four-cycle group. At median follow-up of 16.9 mo, 25 patients remained event-free. Treatment-related adverse events primarily included aspartate aminotransferase elevation (35%), alanine aminotransferase elevation (38%), a decrease in appetite (23%), alopecia (23%), and sensory neuropathy (23%). Validation of the long-term efficacy of this regimen is required.

We aimed to assess the comparative effectiveness of contemporary systemic treatment options across patients with metastatic hormone-sensitive prostate cancer (mHSPC) across clinically relevant prognostic subgroups (synchronous high [SHV] and low [SLV] volume, and metachronous high [MHV] and low [MLV] volume).

We propose a Sustainable Urology Recommendations (SUR) score for rating the sustainability of recommendations in urology guidelines. Five examples show how the SUR score could be applied to recommendations in the 2025 European Association of Urology guidelines. We call for feedback and partnerships to refine and advance this scoring system as part of the efforts to make daily urology practice more sustainable.