5-Aminolevulinic acid (5-ALA) induces tumor-selective accumulation of protoporphyrin IX (PpIX), enabling fluorescence-guided visualization of malignant tissue. In urologic oncology, the most established application is photodynamic diagnosis (PDD) during transurethral resection of non-muscle-invasive bladder cancer, in which fluorescence can identify occult carcinoma in situ and additional papillary lesions; however, specificity may decline in the presence of inflammation, recent instrumentation, or intravesical therapy. Renal applications are emerging: oral 5-ALA before partial nephrectomy can highlight some renal tumors, but fluorescence is often heterogeneous, can overlap with normal parenchyma, and is affected by histologic subtype, necrosis, blood attenuation, and device-dependent optics. Evidence in upper tract urothelial carcinoma and prostate cancer remains preliminary, with small cohorts and practical challenges in endoscopic or robotic workflows, alongside systemic adverse events such as hypotension and photosensitivity. This review synthesizes clinical and preclinical studies of 5-ALA-based fluorescence guidance across bladder, kidney, upper tract, and prostate malignancies, focusing on where the technology is ready for practice versus where it remains investigational. We discuss common pitfalls in interpretation and implementation and outline future directions, including quantitative fluorescence and spectroscopy, standardized dosing and imaging protocols, and prospective multicenter trials linking fluorescence guidance to residual disease, recurrence, margin status, and patient-centered outcomes.
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Precision oncology in urology increasingly depends on integrating heterogeneous data, including multiparametric imaging, histopathology, genomics, and clinical variables. Multimodal artificial intelligence (AI) offers a unified framework to manage this complexity, supporting refined risk stratification, personalized treatment decisions, and informed patient counseling. This narrative review examines applications of multimodal AI in prostate, bladder, and kidney cancers. Beyond listing individual tools, we emphasize how synergistic data fusion enhances the validation of diagnostic and prognostic performance. Clinical advances include more accurate tumor delineation on multiparametric MRI and predictive modeling of functional outcomes after surgery, underscoring the translational potential of these systems. However, major barriers hinder clinical adoption. Prospective validation remains scarce, data harmonization across institutions are limited, and the opaque nature of many algorithms fuels skepticism among clinicians. These factors collectively restrict the integration of multimodal AI into routine clinical practice. Closing this gap requires standardized data curation, development of interpretable and transparent models, and the design of collaborative human-AI workflows. Ultimately, successful translation will depend not only on technical progress but also on redefining trust and expertise in urologic oncology, ensuring that algorithmic insights are meaningfully aligned with bedside decision-making.
Urological cancers exhibit significant sex differences in incidence, treatment response, and prognosis, with males generally showing higher morbidity and mortality. This review systematically summarizes the underlying molecular and clinical mechanisms of these disparities, focusing on sex hormones, chromosome biology, tumor immune microenvironment, and microbiota. Sex hormones modulate key tumor processes including proliferation, apoptosis, non-apoptotic cell death, and DNA repair. Genetic factors such as X chromosome inactivation escape genes and Y chromosome loss also contribute to sex-biased cancer susceptibility. Furthermore, sex-specific differences in the urinary system and gut microbiota influence local immunity and inflammation, thereby affecting tumor progression and therapeutic response. Lifestyle and environmental factors, including smoking, alcohol consumption, and occupational exposures, further exacerbate these disparities. Clinically, sex differences impact the efficacy of immunotherapy and targeted therapies, underscoring the need for sex-informed treatment strategies. Integrating sex as a biological variable in research, clinical practice, and public health policies is essential for advancing precision oncology in urologic cancers.
The management of urothelial carcinoma (UC) is undergoing a paradigm shift from static anatomical staging to molecularly guided dynamic approaches that integrate time as a critical therapeutic variable. This evolution is driven by liquid biopsies, particularly circulating tumor DNA, which allow real-time tumor interrogation. We conducted this expert review to synthesize landmark evidence, enabling technologies, and implementation challenges in dynamic precision oncology for UC. In this non-systematic narrative review, we searched PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library for articles published between January 2015 and February 2026. Studies were selected based on their relevance to dynamic precision oncology, clinical actionability, and translational implementation, prioritizing landmark randomized controlled trials providing level 1-2 evidence, large prospective cohorts, and key translational studies. Enfortumab vedotin plus pembrolizumab established the new first-line standard for metastatic UC, achieving a median overall survival of 33.8 months versus 15.9 months (hazard ratio [HR] 0.51, 95% confidence interval 0.43-0.61). Circulating tumor DNA demonstrates robust prognostic value for molecular residual disease (MRD) detection (Level 2a evidence), stratifying recurrence risk with hazard ratios of approximately 4.5. Critically, the IMvigor011 trial has now provided Level 1b evidence that ctDNA-guided adjuvant atezolizumab improves both disease-free survival (DFS) (HR 0.64, p = 0.0047) and OS (HR 0.59, p = 0.0131) in ctDNA(+) patients, while validating treatment de-escalation in ctDNA(-) patients (1-year DFS 95%). Erdafitinib in patients harboring FGFR2/3 alterations (HR 0.64) confirms the value of genomic profiling. Major limitations include the inherent selection bias of this non-systematic approach, substantial platform heterogeneity, and lack of standardization. In conclusion, dynamic precision oncology has transformed UC management, with the IMvigor011 trial establishing ctDNA-guided MRD status as the first phase 3-validated predictive biomarker framework for adjuvant therapy selection in a solid tumor. Implementation requires adherence to established standardization frameworks, cross-platform and cross-agent validations, and tiered implementation strategies to ensure equitable access across diverse resource settings.
Compared with cancers of other organs, precursor lesions of renal cell neoplasms are rarely discussed. However, there are specific scenarios where cysts or microscopic solid lesions are thought to precede tumor formation. In 2024, the International Society of Urological Pathology (ISUP) held a consensus meeting on precursor lesions of urologic neoplasms in Florence, Italy. This report details the findings of Working Group 3-Precursor Lesions of the Kidney. Papillary adenoma is likely the best-established precursor lesion in the kidney, thought to be an incipient form of papillary renal cell carcinoma (RCC) with shared morphology, immunohistochemistry, and genetics. Likewise, in patients with VHL disease, the kidney often contains multiple small nodules of clear cells and/or cysts lined by one or more layers of clear cells, likely representing early tumor or precursor lesions. Interestingly, a precursor counterpart for clear cell RCC in the sporadic setting is not well established. In other scenarios, cysts are considered potential precursors of neoplasia, such as those in acquired cystic kidney disease (ACKD) and possibly in some hereditary renal tumor syndromes. The consensus panel proposes the following terms "cyst with epithelial proliferation" for tufted/hyperplastic/cribriform cyst lining in ACKD without solid tumor, and "papillary hyperplasia" for tufting of cyst lining in autosomal dominant polycystic kidney. Terms such as "tumorlet," "microtumor," or "incipient tumor" are acceptable for incidental unencapsulated microscopic lesions in hereditary syndrome patients. There is insufficient evidence for the diagnosis of "tubular dysplasia" as a precursor to RCC at the present time.
Observational studies have suggested potential associations between myocardial infarction (MI) and cancer risk, but the causal nature of these relationships remains unclear due to confounding factors and reverse causation. We aimed to investigate the bidirectional causal relationships between MI and urinary system cancers using genetic instruments. We conducted a two-sample Mendelian randomization (MR) analysis using summary statistics from large-scale genome-wide association studies. Genetic variants associated with MI were used as instrumental variables (n = 19 SNPs for prostate cancer [PCa] and malignant neoplasm of kidney [MRN], n = 6 SNPs for bladder cancer, n = 21 SNPs for bladder cancer [BCa] validation). We examined the causal effects of MI on PCa, BCa, and MRN risk, as well as reverse causation. Multiple MR methods were employed, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode approaches. Both discovery and validation datasets were analyzed to ensure robustness. Forward MR analysis revealed no significant causal effect of MI on urinary system cancer risk across all examined malignancies. For PCa, the odds ratios (ORs) ranged from 0.964 to 1.007 across different methods and datasets (all p > 0.05). Similarly, MI showed no causal association with BCa risk (OR = 1.000, 95% CI: 0.999-1.002 in discovery cohort; OR = 1.000, 95% CI: 1.000-1.001 in validation cohort) or MRN risk (OR = 0.989-1.060 across methods in discovery cohort). Reverse MR analysis demonstrated no significant causal effects of PCa or kidney malignancy on MI risk, with ORs ranging from 0.250 to 1.200 (all p > 0.05). Sensitivity analyses confirmed the absence of pleiotropy and heterogeneity. Our genetic evidence does not support causal relationships between MI and urinary system cancers in either direction. The observed associations in epidemiological studies may be attributed to shared risk factors, treatment effects, or residual confounding rather than direct causal mechanisms. These findings have important implications for cancer surveillance strategies in MI patients and understanding cardio-oncology interactions.
Patients with urothelial carcinoma (UC) undergoing systemic therapy face an increased risk of venous thromboembolism (VTE). While the Khorana Risk Score (KRS) is widely applied in oncology to predict VTE, its performance in UC remains uncertain. This study evaluated VTE incidence and clinical predictors in a real-world UC cohort. A retrospective cohort study of 140 patients with bladder or upper-tract UC treated with systemic therapy (2008-2020) was conducted. Clinical and laboratory data, including KRS variables, treatment details, and venous catheter (VC) status, were analyzed. Logistic regression, ROC, and decision curve analyses (DCA) assessed predictive factors and model performance. VTE occurred in 24 patients (17.1%) during a median follow-up of 22.4 months. Among KRS components, only erythropoietin (EPO) use showed a statistically significant association with VTE (OR 4.70; 95% CI: 0.96-22.82, p = 0.049). Independent predictors were regional lymph node (LN) metastases (OR 4.35; 95% CI: 1.63-11.94, p = 0.003) and long-term VC presence (OR 4.78; 95% CI: 1.41-22.64, p = 0.023). No other KRS components or traditional factors were significant. None of the patients on therapeutic anticoagulation developed VTE. A multivariable model including EPO, LN metastases, and VC achieved numerically higher predictive accuracy compared with KRS (AUC 0.73 vs. 0.65) and showed greater net clinical benefit on DCA at 5%-40% thresholds. UC patients on systemic therapy face a high VTE risk not well captured by the KRS. Incorporating EPO use, LN status, and VC presence may improve prediction and support the need for UC-specific risk models to guide thromboprophylaxis.
The European Association of Urology (EAU), American Urological Association (AUA) and National Comprehensive Cancer Network (NCCN) guidelines (GL) represent key international standards for clinical practice. We assessed the adherence to EAU-AUA- NCCN GL in a large real-world multicenter cohort of patients with Upper Tract Urothelial Carcinoma (UTUC), treated with nephroureterectomy. A multicenter retrospective analysis from the ROBUUST (ROBotic surgery for Upper tract Urothelial cancer STudy) registry was performed to assess the region-specific adherence rates to guidelines (GL) for perioperative treatments and their impact on oncological outcomes was evaluated with the Kaplan-Meier method. Out of 2307 patients, excision was the most adopted approach for bladder cuff management world-wide (USA 88.6%, EU 90.5%, Asia 89.8%). Postoperative bladder instillation (intravesical chemotherapy) was implemented in 28.4% of all cases and did not impact bladder recurrence-free survival (log rank P=0.45). Lymphadenectomy (LND) in high-risk disease was underused in both locally advanced (cT3-4: USA 35.8%, EU 46.8%, A 25%) and cN+ stages (USA 41.9%, EU 47.9%, A 43%). LND was not associated with better cancer-specific survival (CSS) across all stages (log rank P≥0.53). Adjuvant chemotherapy (AdCHT) was administered overall in 27.8% of pT2-T4 cases, with a significantly higher adoption in Asia (P=0.03); while in pN+ disease, AdCHT rate was 30.2% and did not convey any advantage in CSS (P=0.58). Retrospective design is the main limitation of the present study. The present contemporary "real world" data suggests poor adherence to current EAU-AUA guidelines for key indicators of quality care such as perioperative bladder instillation of chemotherapy, performance of LND and administration of adjuvant chemotherapy for advanced disease. These findings highlight the need of improving the implementation of these guideline driven treatment strategies.
Robotic platforms automatically record intraoperative telemetry, but body mass index (BMI) effects on these micrometrics are unclear. This study aimed to evaluate BMI-telemetry associations overall and by procedure, focusing on robot-assisted radical prostatectomy (RARP) and robot-assisted partial nephrectomy (RAPN). A retrospective consecutive single-surgeon cohort of 100 robot-assisted urologic procedures performed between April 2, 2024 and December 22, 2025 was analyzed. BMI was calculated for all participants. The primary outcome was console time, while secondary outcomes included instrument active time and camera installation rate. The associations were evaluated using the Spearman correlation and prespecified procedure-stratified models (log-linear regression for time outcomes and negative binomial regression with log [console time] offset for rate outcomes). The cohort included RARP (n = 43), RAPN (n = 36), and other procedures (n = 21). BMI and console time were available for 97 cases. BMI correlated with console time overall (r = 0.272; P = 0.007) and in RARP (r = 0.487; P = 0.001; n = 40), but not in RAPN (r = 0.09; P = 0.6; n = 36). In the adjusted RARP models (age and extended pelvic lymph node dissection), each 5 kg/m² increment in BMI was associated with a 16.8% longer console time (95% CI, 4-31.2; P = 0.009), a 17.7% longer instrument active time (95% CI, 4-33.2; P = 0.01), and a higher camera installation rate (incidence rate ratio, 1.36 per +5 kg/m2; 95% CI, 1.07-1.72; P = 0.01). Quantile regression suggested a larger effect in prolonged RARP cases (75th percentile, +45 min per +5 kg/m2; P <⁠0.001). Higher BMI was associated with longer surgeon-controlled times and increased camera management burden in RARP but not in RAPN. Telemetry may support BMI-adapted scheduling and workflow optimization.
Pembrolizumab has shown manageable safety and modest antitumor activity when used as a single agent in participants with metastatic castration-resistant prostate cancer (mCRPC). Preclinical evidence suggests that lenvatinib, a vascular endothelial growth factor-targeted agent, inhibits angiogenesis and cell migration in prostate cancer. Safety and efficacy of pembrolizumab plus lenvatinib in participants with docetaxel-pretreated mCRPC were evaluated in cohort E of the phase 1b/2 KEYNOTE-365 study. Eligible adults with confirmed mCRPC, Eastern Cooperative Oncology Group performance status (ECOG PS) scores of 0 or 1, and prior docetaxel treatment for mCRPC received pembrolizumab 200 mg intravenously every 3 wk, for ≤35 cycles, plus oral lenvatinib 20 mg daily, continuously from day 1 of cycle 1, unless specific discontinuation criteria were met. Primary endpoints were prostate-specific antigen (PSA) response rate; objective response rate (ORR), per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST) v1.1, by blinded independent central review; and safety. A total of 39 participants received treatment, with a median follow-up of 9.7 mo (interquartile range, 8.5-11.3). Confirmed PSA response rate was 34% (95% confidence interval [CI], 20-51). ORR for participants with RECIST-measurable disease was 36% (95% CI, 18-57). Treatment-related adverse events (AEs) of any grade occurred in 92% of participants and grade 3-5 treatment-related AEs occurred in 62% of participants. Two participants died of non-treatment-related AEs (acute kidney injury and unspecified death). Clinical trial registry: NCT02861573.
TAPUR is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations. Results of two cohorts of patients with urothelial (UC) or ovarian/fallopian tube cancer (OC/FTC) with ERBB2/3 alterations treated with pertuzumab plus trastuzumab (P + T) are reported. Eligible patients had advanced cancer, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with ERBB2/3 alterations, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration. Simon's two-stage design is based on a null DC rate of 15% versus 35% (power = 0.85; α = .10). Secondary end points included OR, progression-free survival (PFS), overall survival (OS), duration of response, duration of SD, and safety. Patients with UC (n = 28) or OC/FTC (n = 25) with ERBB2/3 alterations were enrolled from March 2017 to June 2023. In the UC cohort, the DC and OR rates were 37% (90% CI, 24 to 100) and 25% (95% CI, 11 to 45), respectively. The null hypothesis of 15% DC rate was rejected (P = .005). In the OC/FTC cancer cohort, the DC and OR rates were 23% (90% CI, 9 to 100) and 8% (95% CI, 1 to 26), respectively. The null hypothesis of 15% DC rate was not rejected (P = .35). Six patients had at least one grade 3-5 adverse event (AE) or serious AE at least possibly related to treatment. The combination of P + T met prespecified criteria to declare a signal of activity in patients with UC with ERBB2/3 alterations, but not in patients with OC/FTC.
Chemotherapy with gemcitabine and cisplatin remains the cornerstone of treatment for advanced urothelial carcinoma (UC), yet response rates vary significantly among patients. Predicting treatment response is crucial to avoid unnecessary toxicity and optimize therapeutic strategies. This study aims to develop a deep learning model leveraging RNA sequencing data to predict chemotherapy response in UC patients. We developed a deep learning model using RNA sequencing gene expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus to predict chemotherapy (gemcitabine and cisplatin) response in UC patients. The model was externally validated using an independent cohort from the Pusan National University Yangsan Hospital. Model interpretation was performed through gene ontology and survival analyses using predictions from TCGA samples not included in the training set. The deep learning model demonstrated excellent predictive performance, achieving 94.7% accuracy in the training dataset and 90.0% accuracy in external validation. Gene ontology analysis revealed four key functional clusters associated with chemotherapy response: DNA damage response, cell cycle regulation, kinesins/microtubule dynamics, and mitotic cytokinesis. Notably, the model showed significant prognostic value in early-stage, with predicted responders displaying markedly better survival outcomes (p=0.019). Our transcriptome-based deep learning approach offers a promising computational strategy for predicting chemotherapy response in urothelial carcinoma. By integrating high-dimensional RNA-seq data and advanced machine learning techniques, we provide a potential decision-support tool for personalized treatment planning.
Kidney cancer (KC) is a significant global health concern. This study comprehensively assesses its burden in China versus global trends to inform strategic responses. Using Global Burden of Disease (GBD) 2021 data (1990-2021), we examined KC incidence, prevalence, mortality, and disability-adjusted life years (DALYs) globally and in China. We calculated age-standardized rates (ASIR, ASMR, ASPR, and DALY rate), estimated annual percentage changes (AAPC), and male-to-female ratios, stratified by age, sex, region, and sociodemographic index (SDI). Bayesian Age-Period-Cohort modeling projected trends to 2041. From 1990 to 2021, Chinese male ASIR rose from 2.3 to 4.8 per 100,000 (AAPC 2.83%), while female ASIR increased more modestly. Chinese male ASPR more than doubled. Globally, ASIR increased modestly with persistent gender disparity. Mortality declined globally but increased among Chinese males. DALY rates decreased globally but rose in Chinese males. In 2021, the global burden reached 387,829 new cases and 161,195 deaths. Projections to 2041 indicate a continued ASIR rise in Chinese males alongside a global ASMR decline. The rapid growth of China's kidney cancer burden, coupled with nondeclining mortality, underscores an urgent need for tailored strategies. Health policies should prioritize equitable access to timely diagnosis and guideline-concordant treatment, expand standardized multidisciplinary care, and strengthen prevention targeting modifiable risk factors to ensure that earlier detection translates into improved survival.
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This study aimed to explore the effect of prostate-specific membrane antigen (PSMA) positron emission tomography and computed tomography (PET/CT) on clinical TNM (cTNM) staging assessment and treatment decision-making in prostate cancer,providing real-world evidence for its clinical application in China. We retrospectively analyzed the clinical data of 125 prostate cancer patients who underwent PSMA PET/CT at Chongqing University Cancer Hospital from January 2019 to June 2022. The results were compared with traditional imaging methods (bone scan, CT, MRI) in the overlapping subset of patients with both examinations to assess changes in TNM staging and treatment plans. After PSMA PET/CT, TNM staging changed in 48 patients (38.40%), particularly in the primary prostate cancer and pre-radical surgery groups regarding regional lymph node detection (P = 0.007, P = 0.040). CTNM staging was revised in 36 patients (28.80%), most significantly in the post-radical surgery and mCRPC groups (47.06% and 55.88%, respectively; P = 0.036, P = 0.000). Changes in treatment plans did not reach statistical significance for newly diagnosis of Prostate and pre-radical surgery group (P = 0.222,P= 0.151). PSMA PET/CT significantly impacts cTNM staging assessment and treatment decisions in prostate cancer, offering precise evaluation and auxiliary diagnosis.
This systematic review aimed to identify robust clinicopathologic predictors of overall (OS), cancer-specific (CSS), and recurrence-free survival (RFS) following radical cystectomy (RC) from published prediction models. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) recommendations were followed, and the study was registered in PROSPERO (CRD42024509410). MEDLINE (Ovid) and Embase (Elsevier) were searched from inception to January 2024 for studies developing or validating multivariable prediction models in patients undergoing RC for non-metastatic bladder cancer. Data were extracted following the CHARMS checklist, and risk of bias was assessed using the PROBAST (Prediction model Risk Of Bias Assessment) tool. Pooled hazard ratios (HRs) were estimated with DerSimonian-Laird random-effects models. Seventy-seven studies involving survival models met the inclusion criteria: 36 for OS, 44 for CSS, and 26 for RFS. For OS, adverse predictors included advanced age (HR 1.03, 95% confidence interval [CI] 1.02-1.04), gender (female) (HR 1.08, 95% CI 1.01-1.14), higher pathologic T stage, lymph node involvement (HR 1.91, 95% CI 1.70-2.14), lymphovascular invasion (LVI) (HR 1.49, 95% CI 1.40-1.58), positive surgical margins (HR 1.74, 95% CI 1.46-2.06), and concomitant carcinoma in situ (HR 1.09, 95% CI 1.03-1.16). Neoadjuvant (HR 0.66, 95% CI 0.47-0.93) and adjuvant chemotherapy (HR 0.74, 95% CI 0.71-0.76) and compliance with pentafecta criteria (HR 0.49, 95% CI 0.30-0.79) were associated with improved OS. CSS displayed similar prognostic patterns, with additional associations for lymph node density, hydronephrosis, sarcopenia, and elevated neutrophil-lymphocyte ratio. This meta-analysis identified consistent clinicopathologic predictors of adverse oncological outcomes after RC for bladder cancer. Systematic assessment of these variables allows more accurate postoperative prognostic stratification and supports clinical decision-making regarding adjuvant treatment selection, surveillance intensification, and patient counseling.
Bone Metastases (BM) are associated with a poor prognosis in metastatic clear-cell renal cell carcinoma (mccRCC). In the immune checkpoint inhibitor (IO) era, evidence for and use of bone-protective agents (BPAs) is limited. We investigated oncologic outcomes in mccRCC patients with BM at diagnosis and the use of BPA in a contemporary real-world cohort. We identified patients with mccRCC treated between 2011 and 2023. Adjusted Kaplan-Meier estimates were used to estimate time to treatment failure (TTF) and overall survival (OS), and cohort comparisons were performed using Cox proportional hazards model. Of 2482 patients with mccRCC, 956 (38.5%) had BM at diagnosis, and 210 (22.0%) received a BPA. First-line tyrosine kinase inhibitor (TKI) containing regimen use was higher in BM + patients (79.3% vs. 74.9%). First-line median TTF was similar (9.4 vs. 8.7 mos); however, median OS was longer in BM- vs. BM + patients: 54.2 vs. 35.0 mos (HR, 1.32; P < .0001), irrespective of first-line therapy. BPA omission in BM + only patients resulted in a non-statistically significant shorter TTF (8.3 vs. 10.4 mos; HR, 0.91) and OS (34.3 vs. 38.5 mos; HR, 1.00). Receipt of first-line IO/IO (HR, 0.69; 0.60-0.81) and IO + TKI (HR, 0.61; 0.54-0.74) compared to monotherapy TKI resulted in a significantly longer OS in all patients, though not in BM + only patients. BM remain a poor prognostic factor in mccRCC in this contemporary cohort. Despite more use in BM + patients, BPAs were not associated with improved TTF or OS, though their potential impact on skeletal-related events is not captured in the current study.
The indications for robotic surgery in urology continue to expand with the evolution of surgical techniques and technologies. The feasibility of combined robotic/laparoscopic surgery for the treatment of synchronous upper and lower urinary tract malignancies has been previously described. However, to our knowledge, this is the first reported series of robotic-assisted simple prostatectomy (RASP) and robotic/laparoscopic nephrectomies performed in a single operative session. Case 1 involves an 80-year-old non-Hispanic White man of European descent with a history of low-risk prostate cancer who presented with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), and renal cell carcinoma (RCC). Robotic-assisted partial nephrectomy (RAPN) and RASP were performed sequentially, with modified port placements that allowed reuse of several trocar sites. Case 2 involves a 75-year-old North African man with a history of bilateral polycystic kidneys and stage IV chronic kidney disease who presented with LUTS due to BPH and unilateral RCC. This patient underwent RASP and conventional laparoscopic radical nephrectomy (LRN) in a single operative session. The total operative time was 221 min for Case 1 (94 min for RAPN and 77 min for RASP) and 255 min for Case 2 (104 min for LRN and 95 min for RASP). The estimated blood loss was 100 ml and 80 ml, respectively, with no transfusions required. Case 1 was discharged on post-operative day (POD) 1. Subsequent follow-up demonstrated alleviation of LUTS and no evidence of cancer recurrence. Case 2 was discharged on POD 3, with ongoing oncological surveillance. These cases demonstrate that combined RAPN or LRN with RASP can be performed safely even in patients with significant comorbidities. The success of these cases can be attributed to meticulous preoperative planning and involvement of a multidisciplinary care team. When feasible, combined surgery may offer benefits such as decreased risks associated with anesthesia and shorter hospitalizations.