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.

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.

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.

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.

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.

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.

Validation of preoperative variables and stratification of patients to help predict benefit of cytoreductive nephrectomy in the targeted therapy ERA

ABSTRACT Objectives To further elucidate which patients with metastatic renal cell carcinoma (mRCC) may benefit from cytoreductive nephrectomy (CN) before targeted therapy (TT), and to assess the overall survival of patients undergoing CN and TT versus TT alone. Materials and Methods We identified 88 patients who underwent CN at our institution prior to planned TT and 35 patients who received TT without undergoing CN. Preoperative risk factors described in the literature were assessed in our patient population (serum albumin, liver metastasis, symptomatic metastasis, clinical ≥T3 disease, retroperitoneal and supradiaphragmatic lymphadenopathy). Patients were stratified by number of pretreatment risk factors and overall survival (OS) was compared. Results TT patients had significantly more risk factors compared to CN patients (3.06 vs. 2.11, p<0.01). Patients who received TT alone had median OS of 5.8 months. All but one patient receiving TT alone had two or more risk factors. A comparison of the CN and TT groups was performed by constructing Kaplan-Meier curves. There was no significant difference in median OS for those patients with exactly two risk factors (447 vs. 389 days, p=0.24), and those with three or more risk factors (184 vs. 155 days, p=0.87). Conclusions Using previously described pretreatment risk factors we found that patients with two or more risk factors derived no significant survival advantage from CN in the TT era. These risk factors should be incorporated in the assessment of patients for CN.