The majority of kidney cancers are detected incidentally and typically diagnosed at a localized stage, however, the development of regional or distant disease occurs in one-third of patients. Over 90% of kidney tumors are renal cell carcinomas, of which, clear cell is the most predominate histologic subtype. Von Hippel Lindau (VHL) gene alterations result in the overexpression of growth factors that are central to the pathogenesis of clear cell carcinoma. The therapeutic strategies have revolved around this tumor suppressor gene and have led to the approval of tyrosine kinase inhibitors (TKI) targeting the vascular endothelial growth factor (VEGF) axis. The treatment paradigm shifted with the introduction of immune checkpoint inhibitors (ICI) and programed death-1 (PD-1) inhibition, leading to durable response rates and improved survival. Combinations of TKI and/or ICIs have become the standard of care for advanced clear cell renal cell carcinoma (ccRCC), changing the outlook for patients, with several new and promising therapeutic targets under development.

The majority of patients with castrate-resistant prostate cancer will have metastatic disease at the time of diagnosis. Investigative efforts on new therapeutics for this patient population have improved with the development of androgen signaling inhibitors, such as abiraterone and enzalutamide, and PARP inhibitors, such as rucaparib and olaparib, to accompany the previously FDA-approved docetaxel, cabazitaxel, sipuleucel-T, and Radium 223. However, new therapeutic strategies are necessary to prolong survival as progression after these agents is inevitable. CDK4/6 inhibitors have advanced the field of estrogen receptor positive breast cancer treatment and are being investigated in prostate cancer given the role of androgen receptor signaling effects on the cell cycle. Response to CDK4/6 inhibitors may be predicted by the tumors’ genomic profile and may provide insight into combinatory therapy with CDK4/6 inhibitors in order to delay resistance or provide synergistic effects. Here, we review the use of CDK4/6 inhibitors in prostate cancer and potential combinations based on known resistance mechanisms to CDK4/6 inhibitors, prostate cancer regulatory pathways, and prostate-cancer-specific genomic alterations.

Enfortumab vedotin plus pembrolizumab has emerged as a new standard of care for previously untreated patients with advanced urothelial carcinoma following the EV-302 trial. However, data on its efficacy and safety in routine clinical practice remain limited. Herein, we evaluated real-world clinical outcomes for patients with advanced urothelial carcinoma receiving the combination as first-line or subsequent-line therapy. This retrospective cohort study included adults (≥18 years) with histologically confirmed bladder or upper tract urothelial carcinoma (other histologic type variants were also included), who initiated treatment with enfortumab vedotin-pembrolizumab therapy between May 2020 and December 2024 at the Mayo Clinic. Patients initiating therapy after December 2024 or with incomplete data were excluded. Patients were stratified by line of therapy: Cohort A included patients who received enfortumab vedotin-pembrolizumab as first-line therapy, and Cohort B included patients who received it as subsequent-line therapy. The primary endpoint was to estimate median progression-free survival in cohort A and cohort B. A total of 183 patients with advanced urothelial carcinoma treated with the enfortumab vedotin-pembrolizumab combination were included. The median age at treatment initiation was 71.9 years (IQR, 64.7-77.4). Most patients were male (71.0%) and white (90.7%). The median progression-free survival was 12.9 months (95% CI, 9.5-NE) in Cohort A and 9.3 months (95% CI, 6.3-NE) in Cohort B. This difference was not statistically significant (HR, 1.30; 95% CI, 0.83-2.04; P = .246). Treatment-related adverse events of any grade were reported in 93.4% of patients, with 30.6% experiencing Grade ≥3 AEs. In this real-world cohort, enfortumab vedotin-pembrolizumab combination demonstrated meaningful clinical activity and manageable toxicity in both first-line and subsequent-line settings, consistent with results from the EV-302 trial.

Given the prevalence of breast cancer and the mortality associated with metastatic disease, it is imperative for physicians to not only be aware of common sites but also of rare metastatic destinations such as the bladder. A postmenopausal woman with a medical history of stage 2 invasive ductal carcinoma, oestrogen receptor/progesterone receptor positive and human epidermal growth factor receptor 2 negative, in remission for 9 years, presented to her primary care physician with concerns of increased urinary urgency, frequency and incontinence. The patient underwent cystoscopy with biopsy of an area of granulation tissue. Biopsy revealed adenocarcinoma consistent with breast primary. The common sites of metastases from breast cancer are lung, bone and liver. This case is unique where breast cancer was found to metastasise to the bladder. It is important for physicians to consider further investigation when a breast cancer survivor develops urinary symptoms even without haematuria.