Braden Millan

Background: Biochemical recurrence (BCR) following radical prostatectomy (RP) occurs in 20%–40% of patients with localized prostate cancer. Neoadjuvant PROSTVAC has been shown to enhance T‐cell infiltration into the tumor immune microenvironment, but whether these immunologic changes translate into improved long‐term oncologic outcomes remains unknown. Patients and Methods: This secondary analysis evaluated 26 patients from a Phase II neoadjuvant PROSTVAC trial who underwent RP. Patients received recombinant vaccinia‐PSA‐TRICOM priming followed by three fowlpox‐PSA‐TRICOM boosts before surgery. Tumor immune responses (CD4 + /CD8 + T‐cell infiltration) and peripheral antigen‐specific T‐cell responses to PSA, MUC‐1, and brachyury were previously assessed. Primary outcomes included BCR‐free survival (BCR‐FS) and metastatic progression at extended follow‐up. Results: From May 2014 to June 2017, 26 patients were enrolled, received neoadjuvant PROSTVAC, and subsequently underwent RP. Eighteen (69.2%) patients had NCCN® unfavorable‐intermediate, high, or very high‐risk disease at baseline. At a median follow‐up of 8.9 years (range 7.0–10.1), BCR occurred in six patients (23.1%), and none developed metastatic disease. Comparing pre‐ and post‐PROSTVAC peripheral antigen‐specific T‐cell responses, patients with PSA‐specific immune responses had 100% 8‐year BCR‐FS, compared with 70.0% in nonresponders ( p = 0.247). Those with any tumor‐associated antigen response demonstrated 85.7% versus 66.7% 8‐year BCR‐FS ( p = 0.149). Patients with CD4+ or CD8 + T‐cell responses at the tumor site or invasive margin had 86.2% versus 58.9% 8‐year BCR‐FS ( p = 0.257). Conclusion: Neoadjuvant PROSTVAC may have oncologic activity in localized prostate cancer, as we observed a longer BCR‐FS in immune responders and no metastatic progression in a small cohort. Further investigation of the biological mechanism by which therapeutic immunotherapy may establish durable antitumor immunity in localized prostate cancer is warranted.

Hereditary kidney cancer syndromes predispose patients to multifocal, bilateral and/or recurrent renal tumors, requiring repeated interventions over a lifetime. Despite nephron-sparing surgery being the preferred management strategy, some patients ultimately require completion nephrectomy—radical nephrectomy following prior ipsilateral partial nephrectomy—when tumor burden, declining renal function, surgical complications, or pre-transplant indications necessitate definitive kidney removal. Data on outcomes in this population remain limited. We evaluated a prospectively maintained cohort of 58 patients who underwent completion nephrectomy at the National Institutes of Health between 2000 and 2024, following at least one prior ipsilateral partial nephrectomy. Perioperative complication rates and renal functional change were the primary outcomes of interest. Von Hippel–Lindau disease was the most common hereditary diagnosis (62.1%). Open surgery was performed in 56.9% of cases. Overall complications occurred in 43.1% of patients, with 24.1% experiencing a Clavien–Dindo grade ≥ 3 event; perioperative mortality was 6.9%. The median preoperative estimated glomerular filtration rate was 72 mL/min/1.73 m², declining to 50 mL/min/1.73 m² at the first postoperative clinic visit. Completion nephrectomy in hereditary kidney cancer syndrome patients is associated with substantial perioperative morbidity, mortality, and expected renal functional decline. These findings inform patient counseling and surgical decision-making in this high-risk population.

Purpose of Review This review examines the modern role of open partial nephrectomy (OPN), indications for this surgical approach, and outcomes associated with the open technique in the era of robotic surgery. Recent Findings Robotic-assisted partial nephrectomy (RAPN) now predominates for small renal masses and is increasingly applied to larger and more complex masses. Across multiple comparative series and meta-analyses, RAPN offers equivalent oncologic control and functional preservation compared to OPN, while demonstrating reduced perioperative morbidity. Nonetheless, OPN remains valuable for tumors in hostile or re-operative fields, certain hereditary syndromes, solitary kidneys when cold ischemia is preferred, and settings without reliable robotic access. Declining open case exposure during training raises concerns about maintaining surgical competency. Summary OPN remains an important option when use of the approach provides improved surgical exposure, ischemia management, intra-operative safety, or feasibility of nephron sparing. A pragmatic, surgeon-experience–based approach that prioritizes oncologic control, parenchymal preservation, and patient safety best serves individualized care.

Introduction: Neoadjuvant intense androgen deprivation therapy (ADT) with androgen receptor signaling inhibitors (ARSIs) has shown pathologic complete responses (pCR) in prostate cancer (PCa), but long‐term survival outcomes remain unclear. This study evaluates the durability of response following neoadjuvant ADT plus enzalutamide before robot‐assisted radical prostatectomy (RARP) and lymph node dissection. Methods: We conducted a secondary analysis of an open‐label feasibility trial enrolling men with NCCN intermediate‐, high‐, very high‐risk localized and regional PCa treated with 6 months of neoadjuvant ADT and enzalutamide. Factors associated with biochemical recurrence (BCR) and metastases were evaluated using appropriate univariable statistical tests, and BCR‐, metastasis‐free survival (MFS), and cancer‐specific survival (CSS) were estimated using the Kaplan‐Meier method. Results: Of 39 patients enrolled, 36 patients completed all study interventions. Eighteen (66.7%) patients had NCCN very high‐risk disease or clinical regional lymph nodes on imaging. Four patients (11.1%) achieved pCR, although two (5.6%) developed BCR. One patient (2.8%) had M1 and three (8.3%) had N1 disease on final pathology, and all four developed metastases. Eleven (30.6%) patients received salvage therapy, with all but one receiving ADT with radiation. Factors associated with BCR included biopsy ISUP grade and positive surgical margins, while NCCN risk group, biopsy ISUP grade, perineural invasion, and pathological stage were associated with metastases ( p < 0.05). Median follow‐up was 7.3 (95% CI 6.3–8.3) years, and the 5‐year BCR‐free survival, MFS, and CSS were 64.1%, 84.6%, and 94.3%, respectively. Conclusions: Neoadjuvant enzalutamide and ADT was associated with favorable long‐term oncologic outcomes, supporting continued investigation in localized PCa.

Looking back at 2024, the authors highlight the top five clinical advances in bladder cancer (urothelial carcinoma), from: (1) novel drug‐delivery mechanisms in intravesical therapy for nonmuscle‐invasive bladder cancer and muscle‐invasive bladder cancer (MIBC); (2) immune checkpoint inhibition (ICI) as adjuvant and (3) perioperative therapy in MIBC; (4) circulating tumor DNA as a biomarker in MIBC; to (5) a new standard of care in first‐line metastatic urothelial carcinoma. TAR‐200 is a new intravesical drug‐delivery system that enables controlled release of gemcitabine but may be used with other anticancer drugs to treat nonmuscle‐invasive bladder cancer and MIBC. Two phase 3 studies of adjuvant ICI (nivolumab and pembrolizumab) have both reported a doubling of disease‐free survival in patients with high‐risk MIBC receiving therapy. Perioperative durvalumab, including neoadjuvant therapy plus gemcitabine and cisplatin before radical cystectomy followed by adjuvant durvalumab, demonstrated an improvement in event‐free survival and overall survival for patients with MIBC. Circulating tumor DNA is a promising biomarker to select patients with MIBC for adjuvant ICI therapy. Finally, the combination of enfortumab vedotin, an antibody–drug conjugate, plus pembrolizumab doubled overall survival compared with standard gemcitabine plus platinum in patients with metastatic urothelial carcinoma and has been implemented in treatment guidelines in the United States, Europe, and Asia as the new standard of care in this setting, transforming the treatment landscape for bladder cancer.