Transcriptomic Profiling of Primary Prostate Cancers and Nonlocalized Disease on Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography: A Multicenter Retrospective Study.

PURPOSE: To characterize the relationship between Decipher genomic classifier scores and prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-based metastatic spread. MATERIALS AND METHODS: We identified patients from four institutions who underwent PSMA PET/CT scans pretreatment for primary staging or postradical prostatectomy (RP) for suspected recurrence and had Decipher transcriptomic data available from biopsy or RP specimens. PSMA PET/CT-based patterns of spread were classified as localized (miT + N0M0) or nonlocalized (miN1M0 or miM1a-c). We calculated the association between Decipher scores and the risk of nonlocalized disease on PSMA PET/CT using multivariable logistic regression for pretreatment patients and multivariable Cox regression for post-RP patients. We also compared select transcriptomic signatures between patients with localized and nonlocalized diseases. RESULTS: Five hundred eighty-six patients were included (pretreatment: n = 329; post-RP: n = 257). Higher Decipher scores were associated with nonlocalized disease on PSMA PET/CT both pretreatment (odds ratio, 1.18 [95% CI, 1.03 to 1.36] per 0.1 increase in Decipher score, P = .02) and post-RP (hazard ratio, 1.15 [95% CI, 1.05 to 1.27] per 0.1 increase in Decipher score, P = .003). In the pretreatment setting, nonlocalized disease was associated with higher rates of TP53 mutations and lower rates of PAM50 luminal A subtype compared with localized disease. In the post-RP setting, overexpression of signatures related to metabolism, DNA repair, and androgen receptor signaling were associated with higher rates of nonlocalized disease. CONCLUSION: Higher Decipher scores were associated with nonlocalized disease identified on PSMA PET/CT both pretreatment and post-RP. There were several transcriptomic differences between localized and nonlocalized diseases in both settings.

Off-clamp robotic partial nephrectomy is a safe and effective approach for patients with T1b or greater renal tumors.

Robotic partial nephrectomy (RPN) is a gold standard treatment for focal kidney tumors. Off-clamp RPN avoids prolonged ischemia times. We sought to evaluate the safety and efficacy of off-clamp RPN in patients with renal tumors > 4 centimeters (cm). From 2007 to 2021, we examined patients who underwent RPN for cT1b-T2N0M0 renal tumors. Preoperative, intraoperative, and postoperative outcomes were examined for patients who underwent on or off-clamp RPN. Patients with cT1b tumors (4-7 cm) who underwent either approach were retrospectively propensity-matched based on renal function and tumor size. Of 225 patients, on-clamp RPN was employed in 147 patients, while 78 patients underwent an off-clamp approach. Preoperative estimated glomerular filtration rate (eGFR) was significantly lower in the off-clamp group (p = 0.026). Mean nephrometry scores and mean tumor sizes were similar between cohorts. Average estimated blood loss (EBL) and operative times were similar. Major complication risk was 4.4% lower in the off-clamp group. Blood transfusion rate was 5.6% lower in the off-clamp group. Patients in the off-clamp cohort experienced a < 2% higher risk of positive margins. Postoperative eGFR was more favorable for off-clamp RPN following surgery at 1 year. The propensity-matched analysis demonstrated similar intraoperative outcomes. Blood transfusion rate was significantly lower at 1.5% for patients who underwent off-clamp RPN (p = 0.03). Risk of a major complication was 6.1% lower in the off-clamp RPN cohort, while postoperative eGFR and positive margin rates were similar between off and on-clamp groups. A non-inferior approach for patients with cT1b-T2N0M0 and moderately complex localized renal masses is off-clamp RPN.

Prostate-Specific Membrane Antigen-Targeted Imaging and Its Correlation with HOXB13 Expression.

Homeobox 13 (HOXB13) is an oncogenic transcription factor that directly regulates expression of folate hydrolase 1, which encodes prostate-specific membrane antigen (PSMA). HOXB13 is expressed in primary and metastatic prostate cancers (PCs) and promotes androgen-independent PC growth. Since HOXB13 promotes resistance to androgen receptor (AR)-targeted therapies and regulates the expression of folate hydrolase 1, we investigated whether SUVs on PSMA PET would correlate with HOXB13 expression. Methods: We analyzed 2 independent PC patient cohorts who underwent PSMA PET/CT for initial staging or for biochemical recurrence. In the discovery cohort, we examined the relationship between HOXB13, PSMA, and AR messenger RNA (mRNA) expression in prostate biopsy specimens from 179 patients who underwent PSMA PET/CT with 18F-piflufolastat. In the validation cohort, we confirmed the relationship between HOXB13, PSMA, and AR by comparing protein expression in prostatectomy and lymph node (LN) sections from 19 patients enrolled in 18F-rhPSMA-7.3 PET clinical trials. Correlation and association analyses were also used to confirm the relationship between the markers, LN positivity, and PSMA PET SUVs. Results: We observed a significant correlation between PSMA and HOXB13 mRNA (P < 0.01). The association between HOXB13 and 18F-piflufolastat SUVs was also significant (SUVmax, P = 0.0005; SUVpeak, P = 0.0006). Likewise, the PSMA SUVmax was significantly associated with the expression of HOXB13 protein in the 18F-rhPSMA-7.3 PET cohort (P = 0.008). Treatment-naïve patients with LN metastases demonstrated elevated HOXB13 and PSMA levels in their tumors as well as higher PSMA tracer uptake and low AR expression. Conclusion: Our findings demonstrate that HOXB13 correlates with PSMA expression and PSMA PET SUVs at the mRNA and protein levels. Our study suggests that the PSMA PET findings may reflect oncogenic HOXB13 transcriptional activity in PC, thus potentially serving as an imaging biomarker for more aggressive disease.

A Hybrid Approach to Hood-Sparing Robotic Prostatectomy to Maximize Functional Outcomes and Maintain Early Oncologic Efficacy.

Background: We detail our approach and experience with a hybrid version of the endopelvic hood-sparing (HS) robot-assisted radical prostatectomy (RARP) using the da Vinci robotic platform. Materials and Methods: We retrospectively reviewed the records of 200 patients who underwent RARP by a single surgeon. Patients were propensity-matched into three cohorts depending on biopsy and prostatectomy Gleason Grade Groups: traditional retropubic (RP) (n = 80), retzius-sparing (RS) (n = 40), and HS (n = 80). Patient characteristics and oncologic and functional outcomes were examined. Zero pads per day defined return of continence. Erections suitable for penetrative intercourse with/without medications defined return of sexual function. Results: Patient characteristics were similar between cohorts excluding prostate-specific antigen levels (p = 0.014), which were significantly lower in the RS cohort (7.1 ± 5.3 ng/mL) compared with RP (9.2 ± 9.3 ng/mL) and HS (8.8 ± 8.9 ng/mL). Clinically significant positive margin rates were significantly higher (p = 0.046) in the RS cohort (32.5%) compared with RP (17.5%) and HS (13.9%). Biochemical recurrence and metastasis rates were similar between all cohorts. Median time to continence was significantly lower for RS and HS-RARP (p < 0.001) compared with RP-RARP at 1.3, 1.6, and 5.4 months, respectively. Median time to return of sexual function was significantly lower for RS and HS-RARP (p < 0.001) compared with RP-RARP at 4.0, 7.7, and 15.1 months, respectively. Conclusions: Our hybrid HS-RARP approach provides functional outcomes similar to RS-RARP with the early oncologic control of traditional RP-RARP.

Comparing Bladder Neck Contracture Rate Between Robotic Intracorporeal and Extracorporeal Neobladder Construction.

Robot-assisted radical cystectomy (RARC) has become more accessible to surgeons worldwide, and descriptions of intracorporeal urinary diversion techniques, such as orthotopic neobladder construction, have increased. In this study, we aim to compare the rate of bladder neck contracture (BNC) formation between RARC and two different urinary diversion techniques. We retrospectively reviewed our institutional database for patients with bladder cancer who underwent RARC with intracorporeal neobladder (ICNB) construction (n = 11) or extracorporeal neobladder (ECNB) construction (n = 11) between 2012 and 2020. BNC was defined by the need for an additional surgical procedure (e.g., dilatation, urethrotomy). Patients who underwent RARC with ICNB (n = 11) were compared to patients who underwent RARC with ECNB (n = 11) across patient characteristics and postoperative BNC formation rates. Kaplan-Meier curves were generated for freedom from BNC based on the neobladder approach and compared with the log-rank test. For patients who received an ECNB, 73% (8/11) developed a BNC; in comparison, none of the patients in the ICNB group experienced a BNC. Kaplan-Meier survival analysis demonstrates the ECNB group's median probability of freedom from BNC as 1.3 years, while the ICNB group was free of BNC over the study period (p < 0.001). RARC with ICNB creation demonstrated a significantly reduced BNC rate in contrast to RARC with ECNB construction. Longer-term follow-up is needed to assess the durability of this difference in BNC rates.

Incidental Coronary Arterial Calcification for Cardiovascular Risk Assessment in Men With Prostate Cancer Undergoing PET/CT Imaging.

BACKGROUND: Cardiovascular (CV) disease is common among men with prostate cancer and the leading cause of death in this population. There is a need for CV risk assessment tools that can be easily implemented in the prostate cancer treatment setting. METHODS: Consecutive patients who underwent positron emission tomography/computed tomography (PET/CT) for recurrent prostate cancer at a single institution from 2012 to 2017 were identified retrospectively. Clinical data and coronary calcification on nongated CT imaging were obtained. The primary outcome was major adverse CV event (MACE; myocardial infarction, coronary or peripheral revascularization, stroke, heart failure hospitalization, or all-cause mortality) occurring within 5 years of PET/CT. RESULTS: Among 354 patients included in the study, there were 98 MACE events that occurred in 74 patients (21%). All-cause mortality was the most common MACE event (35%), followed by coronary revascularization/myocardial infarction (26%) and stroke (19%). Coronary calcification was predictive of MACE (HR = 1.9, 95% CI: 1.1-3.4, P = .03) using adjusted Kaplan-Meier analysis. As a comparator, the Framingham risk score was calculated for 198 patients (56%) with complete clinical and laboratory data available. In this subgroup, high baseline Framingham risk (corresponding to 10-year risk of CV disease > 20%) was not predictive of MACE. CONCLUSIONS: MACE was common (21%) in men with recurrent prostate cancer undergoing PET/CT over 5 years of follow-up. Incidental coronary calcification on PET/CT was associated with increased risk of MACE and may have utility as a CV risk predictor that is feasible to implement among all prostate cancer providers.

Prostate-specific membrane antigen-positron emission tomography (PSMA-PET) of prostate cancer: current and emerging applications.

Prostate-specific membrane antigen-positron emission tomography (PSMA-PET) is transforming the management of patients with prostate cancer. In appropriately selected patients, PSMA-PET offers superior sensitivity and specificity compared to conventional imaging (e.g., computed tomography and bone scintigraphy) as well as choline and fluciclovine PET, with the added benefit of consolidating bone and soft tissue evaluation into a single study. Despite being a newly available imaging tool, PSMA-PET has established indications, interpretation guidelines, and reporting criteria, which will be reviewed. The prostate cancer care team, from imaging specialists to those delivering treatment, should have knowledge of physiologic PSMA radiotracer uptake, patterns of disease spread, and the strengths and limitations of PSMA-PET. In this review, current and emerging applications of PSMA-PET, including appropriateness use criteria as well as image interpretation and pitfalls, will be provided with an emphasis on clinical implications.

Symptomatic Benign Prostatic Hyperplasia with Suppressed Epigenetic Regulator HOXB13 Shows a Lower Incidence of Prostate Cancer Development.

Our objective was to identify variations in gene expression that could help elucidate the pathways for the development of prostate cancer (PCa) in men with Benign Prostatic Hyperplasia (BPH). We included 98 men with BPH, a positive prostate MRI (Prostate Imaging Reporting and Data System; PIRADS ≥ 4), and a negative biopsy from November 2014 to January 2018. RNA sequencing (RNA-Seq) was performed on tissue cores from the MRI lesion and a geographically distant region (two regions per patient). All patients were followed for at least three years to identify who went on to develop PCa. We compared the gene expressions of those who did not develop PCa ("BPH-only") vs. those who did ("BPH/PCa"). Then, we identified the subset of men with BPH who had the highest American Urological Association (AUA) symptom scores ("symptomatic BPH") and compared their gene expression to the BPH/PCa group. At a median follow-up of 47.5 months, 15 men had developed PCa while 83 did not. We compared gene expressions of 14 men with symptomatic BPH (AUAss ≥ 18) vs. 15 with BPH/PCa. We found two clusters of genes, suggesting the two groups had distinctive molecular features. Differential analysis revealed genes that were upregulated in BPH-only and downregulated in BPH/PCa, and vice versa. Symptomatic BPH men had upregulation of T-cell activation markers (TCR, CD3, ZAP70, IL-2 and IFN-γ and chemokine receptors, CXCL9/10) expression. In contrast, men with BPH/PCa had upregulation of NKX3-1 and HOXB13 transcription factors associated with luminal epithelial progenitors but depleted of immune cells, suggesting a cell-autonomous role in immune evasion. Symptomatic BPH with immune-enriched landscapes may support anti-tumor immunity. RNA sequencing of benign prostate biopsy tissue showing upregulation of NKX3-1 and HOXB13 with the absence of T-cells might help in identifying men at higher risk of future PCa development, which may be useful in determining ongoing PCa screening.

Local Treatment and Treatment-Related Adverse Effects Among Patients With Advanced Prostate Cancer.

Importance: Recent data suggest that local treatment with radical prostatectomy or radiation may improve survival outcomes in men with advanced prostate cancer. However, evidence is lacking on treatment-related adverse effects among men with advanced prostate cancer. Objective: To assess the association of local treatment on treatment-related adverse effects among men diagnosed with advanced prostate cancer. Design, Setting, and Participants: This cohort study assessed men diagnosed with advanced prostate cancer (defined as T4, N1, and/or M1 prostate cancer) between January 1, 1999, and December 31, 2013, with follow-up through December 31, 2021, who were treated at Veterans Health Administration medical centers. Exposure: Local treatment with radical prostatectomy or radiation. Main Outcomes and Measures: Main outcomes were treatment-related adverse effects, including constitutional, gastrointestinal, pain, sexual function, and urinary function conditions, at 3 intervals after initial treatment (≤1 year, >1 to ≤2 years, and >2 to ≤5 years) after initial treatment. Results: This cohort study consisted of 5502 men (mean [SD] age, 68.7 [10.3] years) diagnosed with advanced prostate cancer. Of the cohort, 1705 men (31.0%) received local treatment. There was a high prevalence of adverse conditions in men receiving both local and nonlocal treatment, and these adverse conditions persisted for more than 2 years to 5 years or less after initial treatment. A total of 916 men (75.2%) with initial local treatment and 897 men (67.1%) with initial nonlocal treatment reported the presence of at least 1 adverse condition for more than 2 years to 5 years or less after initial treatment. In the first year, local treatment (vs nonlocal) was associated with adverse gastrointestinal (multivariable-adjusted odds ratio [AOR], 4.08; 95% CI, 3.06-5.45), pain (AOR, 1.57; 95% CI, 1.35-1.83), sexual (AOR, 2.96; 95% CI, 2.42-3.62), and urinary (AOR, 2.25; 95% CI, 1.90-2.66) conditions. Local treatment (without secondary treatment) remained significantly associated with adverse gastrointestinal (AOR, 2.39; 95% CI, 1.52-3.77), sexual (AOR, 3.36; 95% CI, 2.56-4.41), and urinary (AOR, 1.39; 95% CI, 1.09-1.78) conditions at more than 2 years to 5 years or less after treatment. Conclusions and Relevance: In this cohort study of men with advanced prostate cancer, local treatment was associated with persistent treatment-related adverse effects across multiple domains. These results suggest that patients and clinicians should consider the adverse effects of local treatment when making treatment decisions in the setting of advanced prostate cancer.

Malignant priapism: case report and update on management protocols.

Background: Malignant priapism, a rare disease with only about 500 reported cases to date, consists of persistent erection secondary to invasion or metastasis of a primary neoplasm. While treatment guidelines for priapism in non-malignant cases have been established, there is currently no guideline for treating malignant priapism. Herein, we describe three cases of malignant priapism and suggest a step-by-step approach for clinical management. Case Description: This study reports three cases of malignant priapism resulting from advanced genitourinary cancers. All patients experienced a sub-acute progression of penile pain and ultimately underwent palliative penectomy, resulting in sustained symptom relief. Conclusions: Treatment of malignant priapism needs to be individualized to the needs of the patient. No matter the primary or secondary nature of the disease, current data suggest that malignant priapism is associated with poor outcomes and emphasis should be put on palliative care. Similar to previous cases, our cases died shortly after the diagnosis of malignant priapism. Conventional procedures such as shunting may not necessarily provide symptom relief in these patients. Although new radiation techniques have shown favorable outcomes, penectomy should be considered the last resort in clinical management. Revisions to the existing management guidelines for priapism are necessary to address its occurrence in malignant contexts.

Does Chemo-Radiotherapy Improve Survival Outcomes vs. Radiotherapy Alone for High-Grade cT1 Urothelial Carcinoma of the Bladder?

BACKGROUND: Non-muscle invasive bladder cancer (non-MIBC) that is high-grade and confined to the lamina propria (HGT1) often has an aggressive clinical course. Currently, there is limited data on the comparative effectiveness of RT vs. CRT for HGT1 non-MIBC. We hypothesized that CRT would be associated with improved overall survival (OS) vs. RT in HGT1 bladder cancer. METHODS: Patients diagnosed with HGT1 non-MIBC, and treated with transurethral resection of bladder tumor followed by either treatment with RT alone or CRT, were identified in the National Cancer Database. Inverse probability of treatment weighting (IPTW) was employed and weight-adjusted multivariable analysis (MVA) using Cox regression modeling was used to compare overall survival (OS) hazard ratios. OS was the primary endpoint, and was estimated using the Kaplan-Meier method and log-rank tests. RESULTS: A total of 259 patients with HGT1 UC were treated with: (i) RT alone (n = 123) or (ii) CRT (n = 136). Propensity-weighted MVA showed that combined modality treatment with CRT was associated with improved OS relative to radiation alone (Hazard Ratio [HR]: 0.62, 95% Confidence Interval (95% CI): 0.44-0.88, P = .007). Four-year OS for the CRT vs. RT alone was 36% and 19%, respectively (log-rank P <.008). CONCLUSION: For patients with HGT1 bladder cancer, concurrent CRT was associated with improved OS compared with radiation alone in a retrospective cohort. These results are hypothesis-generating. The NRG is currently developing a phase II randomized clinical trial comparing CRT to other novel, bladder preservation strategies.

Optimum threshold of the 4Kscore for biopsy in men with negative or indeterminate multiparametric magnetic resonance imaging.

Objective: The study aims to identify the optimal 4Kscore thresholds to determine the need for a prostate biopsy when multiparametric magnetic resonance imaging (MRI) (mpMRI) is negative or indeterminate. Materials and methods: We analysed retrospective data from men in eight different institutions who underwent an mpMRI, 4Kscore and prostate biopsy for evaluation of prostate cancer. We selected men with a negative (PIRADS ≤2) or indeterminate (PIRADS 3) mpMRI. 4Kscore values were categorized into ranges of 1-7, 8-19, 20-32 and greater than 32. We evaluated the proportion of men with grade group 2 or higher (GG2+) cancer in groups defined by PIRADS and 4Kscore. We also evaluated the number of biopsies avoided and GG2+ cancer missed in each group reported depend on 4Kscore cutoff points. Results: Among 1111 men who had an mpMRI, 4Kscore and biopsy, 625 of them had PIRADS ≤3 on mpMRI: 374 negative (PIRADS ≤2) and 251 indeterminate (PIRADS 3). In men with a negative mpMRI, we found a 4Kscore cut-point of 33 resulted in an increased risk of GG2+ cancer on biopsy. In patients with an equivocal lesion on mpMRI, men with a 4Kscore cutoff ≥8 had a greater risk of GG2+ cancer on biopsy. Decision curve analysis supported the proposed cut-points in each mpMRI group. Conclusions: In men with negative and indeterminate mpMRI, we found the best 4Kscore threshold to determine the need for biopsy to be 33 and 8 respectively. Future prospective studies in independent populations are needed to confirm these findings.

An atlas of healthy and injured cell states and niches in the human kidney.

Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles and interactions within tissue neighbourhoods1. Here we applied multiple single-cell and single-nucleus assays (>400,000 nuclei or cells) and spatial imaging technologies to a broad spectrum of healthy reference kidneys (45 donors) and diseased kidneys (48 patients). This has provided a high-resolution cellular atlas of 51 main cell types, which include rare and previously undescribed cell populations. The multi-omic approach provides detailed transcriptomic profiles, regulatory factors and spatial localizations spanning the entire kidney. We also define 28 cellular states across nephron segments and interstitium that were altered in kidney injury, encompassing cycling, adaptive (successful or maladaptive repair), transitioning and degenerative states. Molecular signatures permitted the localization of these states within injury neighbourhoods using spatial transcriptomics, while large-scale 3D imaging analysis (around 1.2 million neighbourhoods) provided corresponding linkages to active immune responses. These analyses defined biological pathways that are relevant to injury time-course and niches, including signatures underlying epithelial repair that predicted maladaptive states associated with a decline in kidney function. This integrated multimodal spatial cell atlas of healthy and diseased human kidneys represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.

Financial burden of men with localized prostate cancer: a process paper.

Background: Many individuals undergoing cancer treatment experience substantial financial hardship, often referred to as financial toxicity (FT). Those undergoing prostate cancer treatment may experience FT and its impact can exacerbate disparate health outcomes. Localized prostate cancer treatment options include: radiation, surgery, and/or active surveillance. Quality of life tradeoffs and costs differ between treatment options. In this project, our aim was to quantify direct healthcare costs to support patients and clinicians as they discuss prostate cancer treatment options. We provide the transparent steps to estimate healthcare costs associated with treatment for localized prostate cancer among the privately insured population using a large claims dataset. Methods: To quantify the costs associated with their prostate cancer treatment, we used data from the Truven Health Analytics MarketScan Commercial Claims and Encounters, including MarketScan Medicaid, and peer reviewed literature. Strategies to estimate costs included: (1) identifying the problem, (2) engaging a multidisciplinary team, (3) reviewing the literature and identifying the database, (4) identifying outcomes, (5) defining the cohort, and (6) designing the analytic plan. The costs consist of patient, clinician, and system/facility costs, at 1-year, 3-years, and 5-years following diagnosis. Results: We outline our specific strategies to estimate costs, including: defining complex research questions, defining the study population, defining initial prostate cancer treatment, linking facility and provider level related costs, and developing a shared understanding of definitions on our research team. Discussion and next steps: Analyses are underway. We plan to include these costs in a prostate cancer patient decision aid alongside other clinical tradeoffs.

Renal Mass Imaging with MRI Clear Cell Likelihood Score: A User's Guide.

Small solid renal masses (SRMs) are frequently detected at imaging. Nearly 20% are benign, making careful evaluation with MRI an important consideration before deciding on management. Clear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma subtype with potentially aggressive behavior. Thus, confident identification of ccRCC imaging features is a critical task for the radiologist. Imaging features distinguishing ccRCC from other benign and malignant renal masses are based on major features (T2 signal intensity, corticomedullary phase enhancement, and the presence of microscopic fat) and ancillary features (segmental enhancement inversion, arterial-to-delayed enhancement ratio, and diffusion restriction). The clear cell likelihood score (ccLS) system was recently devised to provide a standardized framework for categorizing SRMs, offering a Likert score of the likelihood of ccRCC ranging from 1 (very unlikely) to 5 (very likely). Alternative diagnoses based on imaging appearance are also suggested by the algorithm. Furthermore, the ccLS system aims to stratify which patients may or may not benefit from biopsy. The authors use case examples to guide the reader through the evaluation of major and ancillary MRI features of the ccLS algorithm for assigning a likelihood score to an SRM. The authors also discuss patient selection, imaging parameters, pitfalls, and areas for future development. The goal is for radiologists to be better equipped to guide management and improve shared decision making between the patient and treating physician. © RSNA, 2023 Quiz questions for this article are available in the supplemental material. See the invited commentary by Pedrosa in this issue.

Single-port vs multi-port robot-assisted renal surgery: analysis of perioperative outcomes for excision of high and low complexity renal masses.

There is emerging but limited data assessing single-port (SP) robot-assisted surgery as an alternative to multi-port (MP) platforms. We compared perioperative outcomes between SP and MP robot-assisted approaches for excision of high and low complexity renal masses. Retrospective chart review was performed for patients undergoing robot-assisted partial or radical nephrectomy using the SP surgical system (n = 23) at our institution between November 2019 and November 2021. Renal masses were categorized as high complexity (7+) or low complexity (4-6) using the R.E.N.A.L. nephrometry scoring system. Adjusting for baseline characteristics, patients were matched using a prospectively maintained MP database in a 2:1 (MP:SP) ratio. For high complexity tumors (n = 12), SP surgery was associated with a significantly longer operative time compared to MP (248.4 vs 188.1 min, p = 0.02) but a significantly shorter length of stay (1.9 vs 2.8 days, p = 0.02). For low complexity tumors (n = 11), operative time (177.7 vs 161.4 min, p = 0.53), estimated blood loss (69.6.0 vs 142.0 mL, p = 0.62), and length of stay (1.6 vs 1.8 days, p = 0.528) were comparable between SP and MP approaches. Increasing nephrometry score was associated with a greater relative increase in operative time for SP compared to MP renal surgery (p = 0.07) using best of fit linear modeling. SP robot-assisted partial and radical nephrectomy is safe and feasible for low complexity renal masses. For high complexity renal masses, the SP system is associated with a significantly longer operative time compared to the MP technique. Careful consideration should be given when selecting patients for SP robot-assisted kidney surgery.

Association between Presurgical Weight Status and Urinary and Sexual Function in Prostate Cancer Patients Treated by Radical Prostatectomy: A Prospective Cohort Study.

OBJECTIVE: To prospectively examine the influence of weight status on urinary and sexual function in clinically localized prostate cancer patients treated by radical prostatectomy (RP). METHODS: The Prostatectomy, Incontinence and Erectile dysfunction study recruited patients at 2 US institutions between 2011 and 2014. At baseline, height and weight were measured, and urinary and sexual function were collected by the modified Expanded Prostate Cancer Index Composite-50. This index was repeated at the 5-week, 6-month, and 12-month postsurgical assessments and compared to baseline using linear generalized estimating equations. Logistic equations were used to evaluate the likelihood of functional recovery at the 6- and 12-month assessments. RESULT: Presurgery, nonobese patients (68.8% of 407 patients) had similar urinary function as those with obesity (P = .217), but better sexual function (P = .006). One year after surgery, 50.5% and 28.9% patients had recovered to baseline levels for urinary and sexual function, respectively. Recovery was not, however, uniform by obesity. Compared to those with obesity, nonobese patients had better urinary function at the 6- (P < .001) and 12-month postsurgical assessments (P = .011) and were more likely to recover their function by the 6-month assessment (OR = 2.55, 95% CI = 1.36-4.76). For sexual function, nonobese patients had better function at the 6- (P = .028) and 12-month (P = .051) assessments, but a similar likelihood of recovery 1-year postsurgery. CONCLUSION: Nonobese prostate cancer patients had better and likely earlier recovery in urinary function postsurgery, and better sexual function both pre- and postsurgery. These findings support the potential for tailored presurgical counseling about RP side-effects and prehabilitation to improve these side-effects.

Urine cell-free DNA multi-omics to detect MRD and predict survival in bladder cancer patients.

Circulating tumor DNA (ctDNA) sensitivity remains subpar for molecular residual disease (MRD) detection in bladder cancer patients. To remedy this problem, we focused on the biofluid most proximal to the disease, urine, and analyzed urine tumor DNA in 74 localized bladder cancer patients. We integrated ultra-low-pass whole genome sequencing (ULP-WGS) with urine cancer personalized profiling by deep sequencing (uCAPP-Seq) to achieve sensitive MRD detection and predict overall survival. Variant allele frequency, inferred tumor mutational burden, and copy number-derived tumor fraction levels in urine cell-free DNA (cfDNA) significantly predicted pathologic complete response status, far better than plasma ctDNA was able to. A random forest model incorporating these urine cfDNA-derived factors with leave-one-out cross-validation was 87% sensitive for predicting residual disease in reference to gold-standard surgical pathology. Both progression-free survival (HR = 3.00, p = 0.01) and overall survival (HR = 4.81, p = 0.009) were dramatically worse by Kaplan-Meier analysis for patients predicted by the model to have MRD, which was corroborated by Cox regression analysis. Additional survival analyses performed on muscle-invasive, neoadjuvant chemotherapy, and held-out validation subgroups corroborated these findings. In summary, we profiled urine samples from 74 patients with localized bladder cancer and used urine cfDNA multi-omics to detect MRD sensitively and predict survival accurately.

Definitive treatment and risk of death among men diagnosed with metastatic prostate cancer at the Veterans Health Administration.

PURPOSE: To assess the potential survival benefit associated with receipt of definitive treatment (radical prostatectomy or radiation), compared to non-definitive treatment (hormonal therapy or chemotherapy) among men with metastatic prostate cancer. METHODS: A cohort of men diagnosed with metastatic (T4/M1/N1 or T4/M1) prostate cancer from 1999 to 2013 in the Veterans Health Administration were identified and followed to December 28, 2014. All-cause and prostate cancer-specific mortality were evaluated at 10 years for the T4/M1/N1 cohort and 8 years for the T4/M1/ cohort. The association of definitive treatment (radical prostatectomy or radiation), compared to non-definitive (hormonal therapy or chemotherapy) with both all-cause and prostate cancer-specific mortality was assessed using inverse probability of treatment weighted (IPTW) multivariable survival analyses. RESULTS: The cohort included 2919 with T4/M1/N1 disease and 1479 men with T4/M1 disease. Receipt of definitive treatment was associated with a reduced risk of 10-year all-cause (Hazard Ratio (HR): 0.61; 95% Confidence Interval (CI): 0.57-0.65) and prostate cancer-specific mortality (HR: 0.50; 95% CI: 0.46-0.55) among men diagnosed with T4/M1/N1 met-astatic disease. Definitive treatment was similarly associated with a reduced risk of all-cause (HR: 0.84; 95% CI: 0.77-0.91) and prostate cancer-specific (HR: 0.81; 95% CI: 0.73-0.90) mortality among men diagnosed with T4/M1 only metastatic disease. CONCLUSIONS: Definitive treatment may improve survival in men diagnosed with metastatic prostate cancer.

Should men undergo MRI before prostate biopsy - CON.

Prostate magnetic resonance imaging (MRI) is increasingly used prior to biopsy in response to the overdiagnosis and overtreatment of prostate cancer (CaP) associated with prostate-specific antigen (PSA) based screening. However, technical limitations in the conventional diffusion-weighted imaging (DWI) sequences as well as the high degree of radiologist-to-radiologist variability in interpreting prostate MRI result in inadequate accuracy. Specifically, the insufficient negative predictive value (NPV) of prostate MRI (76%-87%) does not allow biopsy to be omitted in the negative MRI setting. Additionally, the variable, and relatively low positive predictive value (PPV) of MRI (27%-44%) provides only an incremental improvement in risk prediction compared to readily available clinical tools such as the Prostate Cancer Prevention Trial risk calculator. This small benefit is likely confined to the minority of patients with positive MRI findings in a typically under-sampled region of the prostate (e.g., anterior lesions), which may be obviated by newer biopsy approaches and tools such as transperineal prostate biopsy and micro-ultrasound technology. With these considerations in mind, pre-biopsy prostate MRI in its current form is unlikely to provide a clinically significant benefit, and should not be considered as routine practice until its accuracy is sufficiently improved.