A Comparison of Percutaneous Ablation Therapy to Partial Nephrectomy for cT1a Renal Cancers: Results from the Canadian Kidney Cancer Information System.

PURPOSE: Percutaneous ablation therapy (AT) and partial nephrectomy (PN) are successful management strategies for T1a renal cancer. Our objective was to compare AT to PN with respect to recurrence-free survival (RFS) and overall survival (OS). MATERIALS AND METHODS: Patients post-PN or -AT for cT1aN0M0 renal cancer from 2011 to 2021 were identified from the national Canadian Kidney Cancer information system. Inverse probability of treatment weighting (IPTW) using propensity score (PS) was used. The primary outcomes, RFS and OS, were compared using Kaplan-Meier log-rank test analyses and Cox proportional hazard regression models. RESULTS: A total of 275 patients underwent AT and 2,001 underwent PN, with a median followup of 2.0 years (IQR 0.6-4.1). Covariates were well balanced between the AT and PN cohorts following PS matching. Two-year RFS following IPTW PS analysis for patients undergoing AT and PN was 88.1% and 97.4% (p <0.0001), respectively, while 2-year OS was 97.4% and 99.0% (p=0.7), respectively. Five-year RFS following IPTW PS analysis for patients undergoing AT and PN was 86.0% and 95.1%, respectively (p=0.003), while 5-year OS was 94.2% and 95.1%, respectively (p=0.9). Following IPTW PS analysis, treatment modality (PN vs AT) was a predictor of disease recurrence (HR 0.36, p=0.003) but not for OS (HR 0.96, p=0.9). CONCLUSIONS: With short followup, PN offers better RFS than AT, although no significant difference in OS was detected following PS adjustments. Both modalities can be offered to appropriately selected patients while we await prospective randomized data.

Late Recurrences Following Radical Cystectomy Have Distinct Prognostic and Management Considerations.

PURPOSE: Disease recurrence after radical cystectomy generally occurs within 2 years and has a poor prognosis. Less well defined are the outcomes in patients who experience a late recurrence (more than 3 years after radical cystectomy). We report our institutional experience with late recurrences and describe the relationships between time to recurrence, management strategies and survival. MATERIALS AND METHODS: The study cohort comprised 2,315 patients who underwent radical cystectomy for urothelial carcinoma at our center between 2000 and 2014, of whom 617 had a recurrence. Median followup for survivors was 2.6 years after recurrence (IQR 0.95-4.5). For the study we considered disease recurrence as recurrences outside the urinary tract. We compared baseline characteristics and post-recurrence management between those with recurrence 3 or less and more than 3 years after radical cystectomy. RESULTS: A total of 58 patients with late recurrence had significantly lower consensus T stage and lower frequency of nodal involvement. The average 1-year bladder cancer death rate from the time of recurrence declined from 66% to 50% to 33% for patients with recurrence times of 6 months, 2 years, and 5 years after radical cystectomy, respectively. For patients who survived at least 1 year after recurrence, the estimated survival at 5 years after recurrence was 45% for those with late recurrence and 21% for patients who had an early recurrence. Local consolidative therapy (metastasectomy or radiation) was more common in patients with late recurrence (19% vs 3.6%, p <0.0001). Cancer specific survival in early recurring cases was significantly worse than in late recurring cases in the subset receiving local consolidation (p=0.02). CONCLUSIONS: The prolonged lifespan of patients experiencing a late recurrence after radical cystectomy can be leveraged to individualize management. There is strong rationale for investigating the role of metastasectomy in the management of late recurrences.

Utility of Routine Preoperative 18F-Fluorodeoxyglucose Positron Emission Tomography/Computerized Tomography in Identifying Pathological Lymph Node Metastases at Radical Cystectomy.

PURPOSE: We determined the diagnostic performance of 18F-FDG (fluorodeoxyglucose) positron emission tomography/computerized tomography for detecting nodal metastases in patients with muscle invasive urothelial bladder cancer before radical cystectomy. MATERIALS AND METHODS: Preoperative 18F-FDG positron emission tomography/computerized tomography scans (208) were retrospectively reviewed. Scans were routinely performed in 185 patients with muscle invasive urothelial bladder cancer between August 2012 and February 2017, all of whom underwent radical cystectomy and pelvic lymph node dissection. Analyses were stratified by clinical node involvement and chemotherapy status. The diagnostic performance of 18F-FDG positron emission tomography/computerized tomography was assessed according to sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: Lymph node metastases at time of pelvic lymph node dissection were present in 21.8% of those without suspicious nodes on computerized tomography (clinically node negative) and 52.6% of those with suspicious nodes on computerized tomography (clinically node positive). Median metastatic focus size was 5 mm. In clinically node negative cases 18F-FDG positron emission tomography/computerized tomography rarely detected nodal metastases (sensitivity 7% to 23%). In clinically node positive cases negative 18F-FDG positron emission tomography/computerized tomography was useful in ruling out lymph node metastases (sensitivity 92% to 100%). This study was limited by its mixed population and focus on pelvic nodal metastases only. CONCLUSIONS: 18F-FDG positron emission tomography/computerized tomography appears to be most useful for better characterization of enlarged nodes identified by computerized tomography. Routine preoperative 18F-FDG positron emission tomography/computerized tomography has limited utility in clinically node negative cases.

Trends in Management and Outcomes among Patients with Urothelial Carcinoma Undergoing Radical Cystectomy from 1995 to 2015: The Memorial Sloan Kettering Experience.

PURPOSE: We evaluated trends in oncologic characteristics and outcomes as well as perioperative management among patients undergoing radical cystectomy at Memorial Sloan Kettering from 1995 to 2015. MATERIALS AND METHODS: We retrospectively reviewed our institutional database to analyze changes in disease recurrence probability, cancer specific and all cause mortality, incidence of muscle invasive bladder cancer, use of perioperative chemotherapy, rate of positive soft tissue surgical margins and lymph node yield. RESULTS: In 2,740 patients with nonmetastatic urothelial carcinoma undergoing radical cystectomy from 1995 to 2015 the 5-year probability of disease recurrence decreased from a peak of 42% in 1997 to 34% in 2013 (p=0.045), while the 5-year probability of cancer specific mortality likewise declined from 36% in 1997 to 24% in 2013 (p=0.009). The incidence of nonmuscle invasive disease before radical cystectomy did not change, comprising 30% to 35% of patients across the study period. Use of neoadjuvant chemotherapy rose significantly as 57% of patients with muscle invasive bladder cancer from 2010 to 2015 received it. We observed a corresponding rise in complete pathological response (pT0) at radical cystectomy, as well as decreasing positive soft tissue surgical margins (10% to 2.5%) and rising lymph node yield (7 to 24) from 1995 to 2015. CONCLUSIONS: During a 21-year period outcomes after radical cystectomy at our institution improved significantly, as the probability of recurrence and cancer specific mortality decreased. Increasing use of neoadjuvant chemotherapy, rising pT0 rates, decreased positive soft tissue surgical margins and increasing lymph node yields likely contributed, suggesting that optimized surgical and perioperative care led to improved cancer outcomes in patients undergoing radical cystectomy.

Clinical Usefulness of Total Length of Gleason Pattern 4 on Biopsy in Men with Grade Group 2 Prostate Cancer.

PURPOSE: To our knowledge the ideal methodology of quantifying secondary Gleason pattern 4 in men with Grade Group 2/Gleason score 3 + 4 = 7 on biopsy remains unknown. We compared various methods of Gleason pattern 4 quantification and evaluated associations with adverse pathology findings at radical prostatectomy. MATERIALS AND METHODS: A total of 457 men with Grade Group 2 prostate cancer on biopsy subsequently underwent radical prostatectomy at our institution. Only patients with 12 or more reviewed cores were included in analysis. We evaluated 3 methods of quantifying Gleason pattern 4, including the maximum percent of Gleason pattern 4 in any single core, the overall percent of Gleason pattern 4 (Gleason pattern 4 mm/total cancer mm) and the total length of Gleason pattern 4 in mm across all cores. Adverse pathology features at radical prostatectomy were defined as Gleason score 4 + 3 = 7 or greater (Grade Group 3 or greater), and any extraprostatic extension, seminal vesical invasion and/or lymph node metastasis. A training/test set approach and multivariable logistic regression were used to determine whether Gleason pattern 4 quantification methods could aid in predicting adverse pathology. RESULTS: On multivariable analysis all Gleason pattern 4 quantification methods were significantly associated with an increased risk of adverse pathology (p <0.0001) and an increased AUC beyond the base model. The largest AUC increase was 0.044 for the total length of Gleason pattern 4 (AUC 0.728, 95% CI 0.663-0.793). Decision curve analysis demonstrated an increased clinical net benefit with the addition of Gleason pattern 4 quantification to the base model. The total length of Gleason pattern 4 clearly provided the largest net benefit. CONCLUSIONS: Our findings support the inclusion of Gleason pattern 4 quantification in the pathology reports and risk prediction models of patients with Grade Group 2/Gleason score 3 + 4 = 7 prostate cancer. The total length of Gleason pattern 4 across all cores provided the strongest benefit to predict adverse pathology features.

Pheochromocytoma arising in the settingof adrenal-renal fusion.

Adrenal-renal fusion is an anomaly misclassified as a renal tumor due to the absence of pathognomonic radiographic features. Herein, we report a case of a 61-year-old male who underwent a right radical nephrectomy for a presumed renal malignancy. Pathologic evaluation demonstrated a pheochromocytoma in the context of adrenal-renal fusion. Neoplastic transformation of fused adrenal tissue is rare but not unheard of and is typically adrenal cortical in origin. To our knowledge, this is the first description of a pheochromocytoma originating from an adrenal-renal fusion. The clinical presentation did not raise a high index of suspicion for the ultimate diagnosis rendered.

The impact of robotic surgery access on the management of patients with clinical stage I kidney tumors.

INTRODUCTION: Robotic surgery is used in the treatment of kidney tumors. We aimed to determine if robotic access was associated with initial choice of management for patients with a clinical stage I kidney mass. METHODS: Patients with a clinical stage I kidney mass were identified from the Canadian Kidney Cancer information system (CKCis) cohort. Sites were classified by year and access to robotic surgery. Associations between robotic access and initial management were determined using logistic regression. Univariable and multivariable analyses were performed, adjusting for tumor size and stage, and presented as relative risks (RR ) or adjusted RR (aRR) and 95% confidence intervals (CI). RESULTS: Overall, 4160 patients were included. Among patients treated with surgery, the proportion of partial nephrectomy compared to radical nephrectomy was significantly higher in robotic sites (77.3% for robotic sites vs. 65.9% for non-robotic sites; RR 1.17, 95% CI 1.12-1.23, p<0.0001; aRR 1.12, 95% CI 1.08-1.17, p<0.0001). Patients receiving partial nephrectomy at sites with robotic access were more likely to receive a minimally invasive approach compared to patients at non-robotic sites (61.4% vs. 50.9%, RR 1.21, 95% CI 1.12-1.30; aRR 1.16, 95% CI 1.08-1.25, p<0.0001). The proportion of patients managed by active surveillance was not significantly different between robotic (405, 16.9%) and non-robotic (258, 14.7%) sites (RR 1.15, 95% CI 0.99-1.32; aRR 0.97, 95% CI 0.84-1.12). CONCLUSIONS: Access to robotic kidney surgery was associated with increased use of partial nephrectomy and minimally invasive partial nephrectomy. Use of active surveillance was similar at robotic and non-robotic institutions. Limitations of this study include lack of data on perioperative complications and cancer recurrence.

Control4Life: A randomized controlled trial protocol examining the feasibility and efficacy of a combined pelvic health rehabilitation and exercise fitness program for individuals undergoing prostatectomy.

BACKGROUND: Urinary incontinence (UI), erectile dysfunction and cardiometabolic conditions are common after prostatectomy for prostate cancer (PCa). Although physical activity could improve overall survival and quality of survivorship, fear of UI can restrict participation in exercise. Individuals with PCa could benefit from therapeutic exercise programming to support continence recovery and cardiometabolic health. AIM: The main objective of this study is to determine the feasibility and the effects of a combined pelvic health rehabilitation and exercise fitness program on UI after prostatectomy. The combined exercise program will be delivered both in-person and virtually. METHODS: This study follows a modified Zelen, two-arm parallel randomized controlled trial design. A total of 106 individuals with PCa will be recruited before prostatectomy surgery. Participants will be randomized between two groups: one receiving usual care and one receiving a combined exercise fitness and intensive pelvic floor muscle training program. Exercise programming will begin 6-8 weeks after prostatectomy and will last 12 weeks. Outcomes include: the 24-h pad test (primary outcome for UI); physical fitness, metabolic indicators, and patient-reported outcomes on erectile function, self-efficacy, severity of cancer symptoms and quality of life. Important timepoints for assessments include before surgery (T0), after surgery (T1), after intervention (T3) and at one-year after surgery (T4). CONCLUSION: This study will inform the feasibility of offering comprehensive exercise programming that has the potential to positively impact urinary continence, erectile function and cardiometabolic health of individuals undergoing prostatectomy for prostate cancer. CLINICALTRIALS REGISTRATION NUMBER: NCT06072911.

Fluorine-18 Prostate-Specific Membrane Antigen-1007 PET/CT vs Multiparametric MRI for Locoregional Staging of Prostate Cancer.

Importance: Prostate-specific membrane antigen (PSMA) demonstrates overexpression in prostate cancer and correlates with tumor aggressiveness. PSMA positron emission tomography (PET) is superior to conventional imaging for the metastatic staging of prostate cancer per current research but studies of second-generation PSMA PET radioligands for locoregional staging are limited. Objective: To determine the accuracy of fluorine-18 PSMA-1007 PET/computed tomography (18F-PSMA-1007 PET/CT) compared to multiparametric magnetic resonance imaging (MRI) in the primary locoregional staging of intermediate-risk and high-risk prostate cancers. Design, Setting, and Participants: The Next Generation Trial was a phase 2 prospective validating paired cohort study assessing the accuracy of 18F-PSMA-1007 PET/CT and MRI for locoregional staging of prostate cancer, with results of histopathologic examination as the reference standard comparator. Radiologists, nuclear medicine physicians, and pathologists were blinded to preoperative clinical, pathology, and imaging data. Patients underwent all imaging studies and radical prostatectomies at 2 tertiary care hospitals in Alberta, Canada. Eligible participants included men with intermediate-risk or high-risk prostate cancer who consented to radical prostatectomy. Participants who underwent radical prostatectomy were included in the final analysis. Patients were recruited between March 2022 and June 2023, and data analysis occurred between July 2023 and December 2023. Exposures: All participants underwent both 18F-PSMA-1007 PET/CT and MRI within 2 weeks of one another and before radical prostatectomy. Main Outcomes and Measures: The primary outcome was the correct identification of the prostate cancer tumor stage by each imaging test. The secondary outcomes were correct identification of the dominant nodule, laterality, extracapsular extension, and seminal vesical invasion. Results: Of 150 eligible men with prostate cancer, 134 patients ultimately underwent radical prostatectomy (mean [SD] age at prostatectomy, 62.0 [5.7] years). PSMA PET was superior to MRI for the accurate identification of the final pathological tumor stage (61 [45%] vs 38 [28%]; P = .003). PSMA PET was also superior to MRI for the correct identification of the dominant nodule (126 [94%] vs 112 [83%]; P = .01), laterality (86 [64%] vs 60 [44%]; P = .001), and extracapsular extension (100 [75%] vs 84 [63%]; P = .01), but not for seminal vesicle invasion (122 [91%] vs 115 [85%]; P = .07). Conclusions and Relevance: In this phase 2 prospective validating paired cohort study, 18F-PSMA-1007 PET/CT was superior to MRI for the locoregional staging of prostate cancer. These findings support PSMA PET in the preoperative workflow of intermediate-risk and high-risk tumors.

Comparison of patients with renal cell carcinoma in adjuvant therapy trials to a real-world population.

PURPOSE: To compare characteristics and outcomes of patients included versus those not in adjuvant therapy trials post complete resection of renal cell carcinoma (RCC). METHODS: Adult patients following complete resection for clear cell RCC between January 1, 2011, and March 31, 2021, were included. Patients had intermediate high, high risk nonmetastatic disease (modified UCLA Integrated Staging System) or fully resected metastatic (M1) disease as per the inclusion criteria of adjuvant studies. Demographic, clinical, and outcomes between trial and nontrial patients were compared. RESULTS: Of 1,459 eligible patients, 63 (4.3%) participated in an adjuvant trial. Disease characteristics were similar between groups. Trial patients were younger (mean age 58.1 vs. 63.6 years; P < 0.0001) and had lower Charlson Comorbidity Index scores (mean 4.2 vs. 4.9; P = 0.009). Unadjusted disease-free survival (DFS) at 5 years for trial patients was 48.6% and 39.2% for nontrial patients (HR 0.71, 0.48-1.05, P = 0.08). Median DFS was higher for trial patients in comparison to nontrial patients (4.4 years, IQR 1.7- not reached; vs. 3.0 years, IQR 0.8-8.6; P = 0.08). Cancer specific survival (CSS) at 5 years for trial patients was 85.2% in comparison to 78.6% for nontrial patients (HR 0.45, 0.22-0.92, P = 0.03). Unadjusted estimated overall survival (OS) at 5 years was 80.8% for trial patients and 74.8% (HR 0.42, 0.18-0.94; P = 0.04) for nontrial patients. CONCLUSIONS: Patients in adjuvant trials were younger and healthier with longer CSS and OS in comparison to those not included in adjuvant trials. These findings may have implications when we generalize trial results to real world patients.

Routine Postoperative Hemoglobin Assessment Poorly PredictsTransfusion Requirement among Patients Undergoing Minimally Invasive Radical Prostatectomy.

INTRODUCTION: An advantage of minimally invasive radical prostatectomy over open surgery is decreased blood loss. At our institution hemoglobin is routinely checked 4 and 14 hours postoperatively. We assessed the relevance of this practice in a contemporary cohort undergoing minimally invasive radical prostatectomy. METHODS: We retrospectively reviewed data from patients undergoing laparoscopic or robotic radical prostatectomy at our institution between January 2010 and September 2018. We identified 3,631 patients with preoperative and postoperative hemoglobin values, and assessed the role of routine hemoglobin assessment in determining need for transfusion within 30 days. Medicare reimbursement rates for 2019 were used for cost analysis. RESULTS: Of 3,631 patients in our cohort 44 (1.2%) required transfusion. At 4 hours following surgery the median hemoglobin decrease was 8.0% (IQR 4.8 to 11.4) for patients who did not receive transfusion and 12.5% (9.5 to 19.2) for those who received transfusion. At 14 hours the median decrease was 14.2% (IQR 10.0 to 18.4) vs 33.1% (22.6 to 38.6). Routine hemoglobin assessment had no role in the decision to transfuse in 18 patients (41%). No patient was transfused based on 4-hour values alone. Omitting 1 hemoglobin assessment could have resulted in institutional savings of $37,000 during this period. CONCLUSIONS: As transfusion following minimally invasive radical prostatectomy is rare, scheduled postoperative hemoglobin assessments in the absence of symptoms are unnecessary to recognize bleeding events. The largest hemoglobin difference between men who did vs did not receive transfusion was seen at 14 hours postoperatively. Thus, this single hemoglobin evaluation is sufficient.

Contemporary Management of Hemorrhage After Minimally Invasive Radical Prostatectomy.

OBJECTIVE: To describe contemporary management and outcomes of patients experiencing postoperative hemorrhage after minimally invasive radical prostatectomy. MATERIALS AND METHODS: We retrospectively analyzed data from patients who underwent minimally invasive radical prostatectomy at our institution between January 2010 and January 2017. Clinically significant hemorrhage was defined as a decrease in hemoglobin of ≥30% or 4 g/dL from preoperative to 4 or 14 hours postoperative measurement, receiving a blood transfusion within 30 days, or undergoing a secondary procedure to control bleeding. Patients were analyzed in 3 groups: (1) serially monitored only, (2) received a blood transfusion, and (3) underwent a secondary procedure. Outcomes included imaging studies performed, length of stay, emergency room visits, hospital readmissions, complication rates, and functional outcomes. RESULTS: Of 3749 men, 4% (151/3749) had clinically significant hemorrhage, 1.6% (60/3749) received a transfusion; 0.32% (12/3749) underwent a secondary procedure to control bleeding. In a 30-day composite outcome, increased healthcare utilization (emergency room visit, readmission, or Grade ≥3 complications), was seen in 25% of the serial monitoring group, 65% of the transfusion group, and 100% in the secondary procedure group. This rate in 3598 men without hemorrhage was 12.5%. One-year erectile function was poorest in men who underwent a secondary procedure. Urinary functional outcomes were similar in the 3 groups. CONCLUSION: Most patients experiencing clinically significant hemorrhage will stabilize without transfusion, and a very small fraction require secondary intervention. Patients experiencing milder bleeding events utilized additional healthcare resources at approximately twice the rate of those who did not, warranting appropriate counseling and postoperative monitoring.