Accurate clinical staging of bladder cancer aids in optimizing the process of clinical decision-making, thereby tailoring the effective treatment and management of patients. While several radiomics approaches have been developed to facilitate the process of clinical diagnosis and staging of bladder cancer using grayscale computed tomography (CT) scans, the performances of these models have been low, with little validation and no clear consensus on specific imaging signatures. We propose a hybrid framework comprising pre-trained deep neural networks for feature extraction, in combination with statistical machine learning techniques for classification, which is capable of performing the following classification tasks: (1) bladder cancer tissue vs. normal tissue, (2) muscle-invasive bladder cancer (MIBC) vs. non-muscle-invasive bladder cancer (NMIBC), and (3) post-treatment changes (PTC) vs. MIBC.

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.

Introduction The systemic therapies available to patients with metastatic prostate cancer (mPC) have improved dramatically over the past decade. Anecdotal experience suggests that the increased available lines of therapy have changed the profile of mPC to include a higher prevalence of visceral metastases. Materials and Methods A retrospective review of 472 patients with prostate cancer who died in 2009 and in 2016 was performed. Patients with metastatic disease who had imaging within six months of death were included. A total of 164 patients were eligible for analysis. Results Overall rates of visceral and distant metastases, including the lung, liver, adrenal, brain, renal, spleen, and thyroid, were higher in patients who died in 2016 as compared to those who died in 2009 (40.0% and 26.1%, respectively, p-value = 0.07). Forty-four percent of patients who died in 2016 used five or more lines of systemic treatments compared to 26.1% of patients in 2009. Conclusion The emergence of new systemic therapies for mPC is changing the natural history of the disease. Visceral metastases are being seen with increasing frequency than in the past. This observation is important for clinicians who are monitoring patients with prostate cancer to maintain a high suspicion for visceral disease.

Small cell bladder cancer (SCBC) is a rare and aggressive disease, often treated with platinum/etoposide-based chemotherapy. Key molecular drivers include the inactivation of onco-suppressor genes (TP53, RB1) and amplifications in proto-oncogenes (MYC). We report a patient with SCBC who achieved an objective and prolonged response to lurbinectedin, which has been approved for metastatic small cell lung cancer, after developing disease progression on cisplatin/etoposide and nivolumab/ipilimumab. A genomic analysis of a metastatic biopsy prior to lurbinectedin initiation revealed a TP53 mutation and amplification of the cell cycle regulators E2F3 and MYCL. A repeat biopsy following the development of lurbinectedin resistance showed a new actionable ERBB2 alteration without significant change in the tumor mutation burden (six mutations/Mb). The present report suggests that lurbinectedin may be active and should be further explored in SCBC harboring TP53 mutations and amplifications in E2F3 and MYC family complexes.

Following lung cancer, prostate cancer is the leading cause of cancer death in men. High-risk localized tumor burden or metastatic disease often progresses, refractory to initial treatment regimens. There is ongoing development of technology to appropriately identify high-risk patients, stage them correctly, and offer appropriate treatments to obtain the best clinical outcomes. Prostate cancer-specific membrane antigen (PSMA) is a transmembrane glutamate carboxypeptidase, which helps regulate folate absorption, and its overexpression is pathologically directly proportional and associated with prostate cancer. Increased PSMA expression is a known independent risk factor for poorer survival, and most metastatic lesions in CRPC are PSMA positive. Over the last decade, several PSMA-based PET radiopharmaceuticals have demonstrated superior sensitivities and specificities compared to traditional imaging methods. These outcomes have been demonstrated by several large clinical trials. As the data emerges, these diagnostics are being integrated into standard of care protocol to facilitate nuanced identification of malignant lesions. PSMA is also being targeted through several therapeutics, including radioligands and immunotherapies such as CAR-T, BiTEs, and ADCs. This review will discuss the landscape of PSMA-based theranostics in the context of prostate cancer.