Andrew T. Lenis

Background: Urothelial cancer typically affects older adults, yet early-onset urothelial cancer (age 45 years and younger) cases are rising and remain poorly characterized. We hypothesized that early-onset urothelial cancer exhibits distinct clinical and genomic features that reflect a different biological etiology from standard-onset urothelial cancer. Methods: We compared clinical, pathologic, and genomic characteristics of patients with early-onset urothelial cancer vs standard-onset urothelial cancer evaluated at Memorial Sloan Kettering Cancer Center from 2000 through 2024. Clinical data included 9221 patients, with tumor and germline genomic profiling by Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay in 2753 patients. Results: Early-onset urothelial cancer accounted for 335 of 9221 (3.6%) patients. Early-onset urothelial cancer patients were more likely never-smokers (43% vs 26%, P < .001), female (30% vs 25%, P = .034), and of Asian race (7.4% vs 3.1%, P < .001). Early-onset urothelial cancer tumors were more often low-grade (41% vs 23%, P < .001) and of pure nonurothelial histology (4.0% vs 1.7%, P = .003). Early-onset urothelial cancer showed marked enrichment for HRAS mutations, independent of histologic subtype, and HRAS-mutated tumors had reduced APOBEC-associated mutation signatures. Germline pathogenic variants were detected in 21.0% of early-onset vs 17.2% of standard-onset urothelial cancer patients (P = .43), driven mostly by mismatch repair and MUTYH gene alterations. Rare cases of somatic mosaicism in HRAS and ERCC2 were observed in patients with very early-onset disease. Conclusions: Early-onset urothelial cancer represents a biologically distinct subset characterized by HRAS-driven oncogenesis, reduced APOBEC mutagenesis, frequent germline variants, and, rarely, somatic mosaicism. These findings suggest developmental or genetic mechanisms underlying early-onset urothelial cancer and supporting age- and biology-informed approaches to risk assessment, genetic counseling, and targeted therapy development.

Purpose of Review To review the landscape of bladder preservation management and active surveillance for those who achieve clinical complete response to neoadjuvant chemotherapy. Recent Findings Multiple cohorts of patients with clinical complete response report overall survival rates over 80% multiple years after treatment without cystectomy. Most recently, prospective clinical trials have been pursuing clinical complete response as a valid primary endpoint. Recent advances in immunotherapy and molecular biomarkers present new horizons in expanding the potential patient population as well as accuracy in prediction of pathologic complete response. Summary While neoadjuvant chemotherapy followed by radical cystectomy is the standard of care for muscle-invasive bladder cancer, interest in active surveillance is growing as evidenced by the increasing number of studies. Accumulating evidence and new prospective data suggest this could be a plausible option in the future. These cohorts remain highly selected, thus generalizability is still under investigation.

We conducted a retrospective analysis of the impact of indocyanine green (ICG) on perioperative outcomes in partial nephrectomy. The utility of ICG in partial nephrectomy remains unclear. We performed a retrospective cohort study of all patients at a single institution who underwent laparoscopic or robotic partial nephrectomy in 2014–2019. Some surgeons used ICG while others did not. Outcomes of interest were estimated blood loss, positive surgical margins, ischemia time, and postoperative kidney function. We used multivariate regression to assess ICG use and outcomes. We identified 150 patients meeting inclusion criteria. The majority of cases (58%) used ICG. Patients who did and did not receive ICG were similar in age, sex, and histologic subtype. Median estimated blood loss was 100 mL (IQR 50–200), 9% had a positive surgical margin, and median ischemia time was 21 min (IQR 16–26). Of those with renal function follow-up, 17% had increased chronic kidney disease stage and mean percent creatinine change was + 4.7 ± 14.9%. On multivariate analysis, ICG use was associated with change in CKD stage (OR 9.9, 95% CI 1.0–93.9, p = 0.05). It was not associated with positive surgical margin status (OR 1.20, 95% CI 0.38–3.85, p = 0.755), percent change creatinine (beta 5.18, 95% CI -1.87–12.23, p = 0.155), ischemia time (beta 0.86, 95% CI − 1.38–3.09, p = 0.45), or EBL (beta − 0.13, 95% CI − 0.53–0.28, p = 0.53). We observed a difference in CKD change according to ICG in partial nephrectomy, but not other perioperative outcomes. ICG may have impacted surgical decision-making in unmeasured ways but did not significantly affect perioperative outcomes.

Supplemental Table 2 from Microsatellite Instability, Tumor Mutational Burden, and Response to Immune Checkpoint Blockade in Patients with Prostate Cancer

Supplemental Table 3 from Microsatellite Instability, Tumor Mutational Burden, and Response to Immune Checkpoint Blockade in Patients with Prostate Cancer