Surgical outcomes of cytoreductive nephrectomy in patients receiving systemic immunotherapy for advanced renal cell carcinoma.

PURPOSE: The use of systemic immune checkpoint blockade before surgery is increasing in patients with metastatic renal cell carcinoma, however, the safety and feasibility of performing consolidative cytoreductive nephrectomy after the administration of systemic therapy are not well described. PATIENTS AND METHODS: A retrospective review of patients undergoing nephrectomy was performed using our prospectively maintained institutional database. Patients who received preoperative systemic immunotherapy were identified, and the risk of postoperative complications were compared to those who underwent surgery without upfront systemic treatment. Perioperative characteristics and surgical complications within 90 days following surgery were recorded. RESULTS: Overall, we identified 220 patients who underwent cytoreductive nephrectomy from April 2015 to December 2022, of which 46 patients (21%) received systemic therapy before undergoing surgery. Unadjusted rates of surgical complications included 20% (n = 35) in patients who did not receive upfront systemic therapy and 20% (n = 9) in those who received upfront systemic immunotherapy. In our propensity score analysis, there was no statistically significant association between receipt of upfront immunotherapy and 90-day surgical complications [odds ratio (OR): 1.82, 95% confidence interval (CI): 0.59-5.14; P = 0.3]. This model, however, demonstrated an association between receipt of upfront immunotherapy and an increased odds of requiring a blood transfusion [OR: 4.53, 95% CI: 1.83-11.7; P = 0.001]. CONCLUSION: In our cohort, there was no significant difference in surgical complications among patients who received systemic therapy before surgery compared to those who did not receive upfront systemic therapy. Cytoreductive nephrectomy is safe and with low rates of complications following the use of systemic therapy.

Follicular lymphoma presenting as a seminal vesicle mass: Diagnostic path from prostate MRI to 18F-FDG PET/CT.

A 73-year-old man with biopsy-proven Gleason 3+3 prostate cancer presented with a new mass centered in the seminal vesicles with invasion of the base of the prostate on surveillance prostate MRI. Targeted biopsy showed atypical lymphoid proliferation, suspicious for lymphoma. The patient was referred to the nuclear medicine department for [18F]fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT). Multisite 18F-FDG-avid lymphadenopathy observed, as well as FDG uptake in the new mass. Core biopsy from dominant mesenteric mass revealed follicular lymphoma.

Institutional trends and safety profile of same-day discharge for robot-assisted laparoscopic radical prostatectomy: A retrospective analysis.

PURPOSE: To report the trends, predictors, and patient outcomes of same-day discharge (SDD) versus non-SDD for robot-assisted laparoscopic radical prostatectomy (RALP). MATERIALS AND METHODS: We queried our centralized data warehouse to identify men with prostate cancer who underwent RALP between January 2020 and May 2022. Patient demographics and clinical characteristics were compared between SDD and non-SDD. Then, we examined the utilization of SDD in a univariable logistic regression. Then, we fitted a logistic regression model to identify the predictors of SDD. To examine the safety profile of SDD, an inverse probability of treatment weighting (IPTW) adjusted logistic regression was fitted to examine the effect of SDD on 30-day postoperative complications and readmissions. RESULTS: Overall, 1,153 patients underwent RALP, of which 224 (19.4%) were SDD. The proportion of SDD increased from 4.4% in the fourth quarter of 2020 to 45% in the second quarter of 2022 (p < 0.01). The predictors of SDD were the facility where the surgery was performed (OR: 1.57; 95%CI [1.08-2.28]; p = 0.02) and whether a high-volume surgeon performed it (OR: 1.96; 95%CI [1.09-3.54]; p = 0.03). After IPTW, SDD compared to non-SDD was not associated with a difference in complications (OR: 1.07; 95%CI [0.38-2.95]; p = 0.90) or readmissions (OR: 1.22; 95%CI [0.40-3.74]; p = 0.72). CONCLUSION: In our health system, the use of SDD is safe and currently composes of half of our RALP volume. With the advent of the hospital-at-home services, we anticipate that almost all our RALP cases will be SDD.

Prognostic Factors for Survival in Patients Undergoing Surveillance After Cytoreductive Nephrectomy.

PURPOSE: The clinical course of patients being placed on surveillance in a cohort of systemic therapy-naïve patients who undergo cytoreductive nephrectomy is not well documented. Thus, we evaluated the clinical course of patients placed on surveillance following cytoreductive nephrectomy and identified predictors of survival. MATERIALS AND METHODS: In this large single-institution study, we retrospectively analyzed metastatic renal cell carcinoma patients who underwent cytoreductive nephrectomy followed by surveillance. Predictors of survival were evaluated using the Kaplan-Meier method with a log-rank test. Patients were risk stratified based on IMDC (International mRCC Database Consortium) and number of metastatic sites (Rini score), with IMDC score ≤1 and ≤2 metastatic organ sites considered favorable risk. Primary end point was systemic therapy-free survival. Secondary end points included intervention-free survival, cancer-specific survival, and overall survival. RESULTS: Median systemic therapy-free survival was 23.6 months (95% CI: 15.1-40.6), intervention-free survival was 11.8 months (95% CI: 8.0-18.4), cancer-specific survival was 54.2 months (95% CI: 46.2-71.4), and overall survival 52.4 months (95% CI: 40.3-66.8). Favorable-risk patients compared to unfavorable-risk patients had longer systemic therapy-free survival (50.6 vs 11.1 months, P < .01), survival (25.2 vs 7.3, P < .01), and cancer-specific survival (71.4 vs 46.2 months, P = .02). CONCLUSIONS: Using risk stratification based on IMDC and number of metastatic sites, surveillance in favorable-risk patients can be utilized for a period without the initiation of systemic therapy. This approach can delay patients' exposure to the side effects of systemic therapy.

Advances in Imaging-Based Biomarkers in Renal Cell Carcinoma: A Critical Analysis of the Current Literature.

Cross-sectional imaging is the standard diagnostic tool to determine underlying biology in renal masses, which is crucial for subsequent treatment. Currently, standard CT imaging is limited in its ability to differentiate benign from malignant disease. Therefore, various modalities have been investigated to identify imaging-based parameters to improve the noninvasive diagnosis of renal masses and renal cell carcinoma (RCC) subtypes. MRI was reported to predict grading of RCC and to identify RCC subtypes, and has been shown in a small cohort to predict the response to targeted therapy. Dynamic imaging is promising for the staging and diagnosis of RCC. PET/CT radiotracers, such as 18F-fluorodeoxyglucose (FDG), 124I-cG250, radiolabeled prostate-specific membrane antigen (PSMA), and 11C-acetate, have been reported to improve the identification of histology, grading, detection of metastasis, and assessment of response to systemic therapy, and to predict oncological outcomes. Moreover, 99Tc-sestamibi and SPECT scans have shown promising results in distinguishing low-grade RCC from benign lesions. Radiomics has been used to further characterize renal masses based on semantic and textural analyses. In preliminary studies, integrated machine learning algorithms using radiomics proved to be more accurate in distinguishing benign from malignant renal masses compared to radiologists' interpretations. Radiomics and radiogenomics are used to complement risk classification models to predict oncological outcomes. Imaging-based biomarkers hold strong potential in RCC, but require standardization and external validation before integration into clinical routines.

The Natural History of Renal-Cell Carcinoma with Sarcomatoid Differentiation, a Stage-by-Stage Analysis.

BACKGROUND: Sarcomatoid differentiation in patients diagnosed with renal cell carcinoma (sRCC) imply aggressive behavior and often metastatic disease at the time of diagnosis. We aim to examine the overall survival (OS) in patients with sRCC using the National Cancer Database (NCDB). MATERIALS AND METHODS: We identified patients diagnosed with sRCC between 2010-2015. We employed Kaplan-Meier curves and multivariable Cox proportional hazards regression models to examine the impact of several potential risk factors on OS in patients diagnosed with sRCC. RESULTS: In total, 8582 patients with renal cancer were found to have sarcomatoid differentiation, with 4105 patients (47.8%) being diagnosed with AJCC stage IV disease. The median OS was 17.2 months (IQR 5.4, 68.7 months). Compared to patients who did not undergo surgery, OS was significantly longer in patients undergoing partial or total nephrectomy across all stages. This result remained consistent on multivariable Cox proportional hazards regression adjusting for patient and tumor characteristics (Surgery: Hazard ratio 0.54, 95%Confidence interval 0.43 - 0.68, P < .001). CONCLUSION: In our cohort sRCC was found to have an unfavorable median OS, which was mainly caused by the high number of cases diagnosed with late-stage disease. Additionally, surgery was associated with favorable OS across all stages. This study supports the notion that surgical therapy, even in the setting of cytoreductive surgery, provides a survival benefit in patients with sRCC.

Current and Future Biomarkers in the Management of Renal Cell Carcinoma.

Renal cell carcinoma biomarkers include serum, urine, liquid, and tissue biomarkers. There is currently an ongoing search for predictive biomarkers in the detection, recurrence, and treatment of renal cell carcinoma. Emerging signatures in the transcriptomic and translational biomarker space seem promising, although additional work is needed to validate candidates in a larger and more generalizable patient population.

Neurocognitive impairment associated with traditional and novel androgen receptor signaling inhibitors ± androgen deprivation therapy: a pharmacovigilance study.

BACKGROUND: Conflicting evidence exists regarding whether hormone therapy for prostate cancer is associated with neurotoxicity. Thus, we aim to characterize the association between different types of hormone therapy and neurocognitive impairment in a real-world pharmacovigilance database. METHODS: We queried VigiBase, the World Health Organization's international pharmacovigilance database, for reports of neurocognitive impairment among men who took hormone therapy from 1968 to 2021. We performed disproportionality analysis comparing rates of neurocognitive impairment with different types of hormone therapy versus other VigiBase drugs. Traditional hormonal therapy was defined as androgen deprivation therapy (ADT: gonadotropin-releasing-hormone agonists or antagonists) or first-generation androgen receptor (AR) antagonists. Novel AR signaling inhibitors (ARSIs) were defined as ARSIs with or without ADT. Differences were assessed using reporting odds ratio (ROR) with 95% confidence intervals (CI) and Empirical Bayes Estimator (EBE) values ≥1.0 signifying statistical significance. RESULTS: Odds of neurocognitive impairment were significantly elevated with traditional hormone therapy (ROR 1.47, 95% CI 1.34-1.62, EBE = 1.35) and novel ARSIs (ROR 2.40, 95% CI 2.28-2.54, EBE = 2.26). Odds of neurocognitive impairment were significantly elevated with enzalutamide (ROR 2.89, 95% CI 2.73-3.05, EBE = 2.70) and numerically increased with apalutamide (ROR 3.31, 95% CI 1.57-7.00, EBE = 0.98), but were decreased with abiraterone (ROR 0.68, 95% CI 0.55-0.84, EBE = 0.57). CONCLUSIONS: This study demonstrates elevated odds of neurocognitive impairment with hormone therapy in a real-world data set. Neurotoxicity risk was higher with novel ARSIs than traditional agents, and higher with enzalutamide than abiraterone. Due to limitations inherent to disproportionality analysis (measuring associations, not risk) and incomplete data prohibiting the ability to control for factors such as age or use of secondary drugs (e.g., concurrent use of novel ARSIs with ADT), results are exploratory in nature. The amalgamation of these and other conflicting data may contribute to clinical decision-making for men with prostate cancer eligible for treatment with these therapies, especially those with significant neurologic comorbidities.

Immune checkpoint inhibitor monotherapy is associated with less cardiac toxicity than combination therapy.

BACKGROUND: Treatment options for many cancers include immune checkpoint inhibitor (ICI) monotherapy and combination therapy with impressive clinical benefit across cancers. We sought to define the comparative cardiac risks of ICI combination and monotherapy. METHODS: We used VigiBase, the World Health Organization pharmacovigilance database, to identify cardiac ADRs (cADRs), such as carditis, heart failure, arrhythmia, myocardial infarction, and valvular dysfunction, related to ICI therapy. To explore possible relationships, we used the reporting odds ratio (ROR) as a proxy of relative risk. A lower bound of a 95% confidence interval of ROR &gt; 1 reflects a disproportionality signal that more ADRs are observed than expected due to chance. RESULTS: We found 2278 cADR for ICI monotherapy and 353 for ICI combination therapy. Combination therapy was associated with significantly higher odds of carditis (ROR 6.9, 95% CI: 5.6-8.3) versus ICI monotherapy (ROR 5.0, 95% CI: 4.6-5.4). Carditis in ICI combination therapy was fatal in 23.4% of reported ADRs, compared to 15.8% for ICI monotherapy (P = 0.058). CONCLUSIONS: Using validated pharmacovigilance methodology, we found increased odds of carditis for all ICI therapies, with the highest odds for combination therapy. Given the substantial risk of severe ADR and death, clinicians should consider these findings when prescribing checkpoint inhibitors.

Surgical Complications Requiring Intervention in Open versus Minimally Invasive Radical Prostatectomy.

INTRODUCTION: Injuries to surrounding structures during radical prostatectomy (RP) are rare but serious complications. However, it remains unknown if injuries to intestines, rectum, or vascular structures occur at different rates depending on the surgical approach. METHODS: We compared the frequency of these outcomes in open RP (ORP) and minimally invasive RP (MIS-RP) using the national American College of Surgeons National Surgical Quality Improvement Program database (2012-2017). Along with important metrics of clinical and surgical outcomes, patients were identified as undergoing surgical repair of small or large bowel, vascular structures, or hernias based on Current Procedural Terminology codes. RESULTS: In our propensity matched analysis, a total of 13,044 patients were captured. Bowel injury occurred more frequently in ORP than in MIS-RP (0.89 vs. 0.26%, p < 0.01). By intestinal segment, rectal and large bowel injuries were more common in ORP than MIS-RP (0.41 vs. 0.11% and 0.31 vs. 0.05%, both p < 0.01). However, there was no statistically significant difference between the groups for small bowel injury (0.17 vs. 0.11%, p = 0.39). Vascular injury was more common in MIS-RP (0.18 vs. 0.08%, p = 0.08). Hernias requiring repair were only identified in the MIS-RP group (0.12%). CONCLUSION: When considering surgical approach, rectal and large bowel injuries were more common in ORP, while vascular injuries and hernia repair were more common in MIS-RP. Our findings can be used in counseling patients and identifying risk factors and strategies to reduce these complications.

Cardiovascular toxicities associated with abiraterone compared to enzalutamide-A pharmacovigilance study.

BACKGROUND: Androgen deprivation therapy (ADT) is standard-of-care for advanced prostate cancer. Studies have generally found increased cardiovascular risks associated with ADT, but the comparative risk of newer agents is under-characterized. We defined the cardiac risks of abiraterone and enzalutamide, using gonadotropic releasing hormone (GnRH) agonists to establish baseline ADT risk. METHODS: We used VigiBase, the World Health Organization pharmacovigilance database, to identify cardiac adverse drug reactions (ADRs) in a cohort taking GnRH agonists, abiraterone, or enzalutamide therapy for prostate cancer, comparing them to all other patients. To examine the relationship, we used an empirical Bayes estimator to screen for significance, then calculated the reporting odds ratio (ROR), a surrogate measure of association. A lower bound of a 95% confidence interval (CI) of ROR > 1 reflects a disproportionality signal that more ADRs are observed than expected due to chance. FINDINGS: We identified 2,433 cardiac ADRs, with higher odds for abiraterone compared to all other VigiBase drugs for overall cardiac events (ROR 1•59, 95% CI 1•48-1•71), myocardial infarction (1•35, 1•16-1•58), arrythmia (2•04, 1•82-2•30), and heart failure (3•02, 2•60-3•51), but found no signal for enzalutamide. Patients on GnRH agonists also had increased risk of cardiac events (ROR 1•21, 95% CI 1•12-1•30), myocardial infarction (1•80, 1•61-2•03) and heart failure (2•06, 1•76-2•41). INTERPRETATION: We found higher reported odds of cardiac events for abiraterone but not enzalutamide. Our data may suggest that patients with significant cardiac comorbidities may be better-suited for therapy with enzalutamide over abiraterone. FUNDING: None.

Lessons from Pharmacovigilance: Pulmonary Immune-Related Adverse Events After Immune Checkpoint Inhibitor Therapy.

PURPOSE: To characterize pulmonary toxicities associated with the use of novel immune checkpoint inhibitors METHODS: Adverse event reports from immune checkpoint inhibitors targeting PD-1/L1 and CTLA-4 were captured from the W.H.O pharmacovigilance database (VigiBase) up until Dec. 31st 2019 and were analyzed to evaluate for measures of association between the use of immune checkpoint inhibitors and pulmonary toxicities. Disproportionality analysis using both frequentist and Bayesian approaches were used to detect signals between pulmonary immune-related adverse events and the use of these agents. RESULTS: A total of 9202 adverse pulmonary immune checkpoint inhibitor-related events were captured up until 2019. Adverse pulmonary events were compromised of 1305 airway, 18 alveolar, 5491 interstitial, 898 pleural, 560 vascular and 939 non-specific pulmonary events. We found a common association between all immune checkpoint inhibitors studied and pneumonitis, interstitial lung disease, pulmonary embolism and respiratory failure. We also noted other associations between immune checkpoint inhibitors, however not as uniformly across agents. Most of these immune-related adverse drug reactions were noted to be severe and accounted for a significant source of mortality in the reported cases. CONCLUSION: Immune checkpoint inhibitors are associated with a spectrum of inflammatory pulmonary toxicities. The breadth of pulmonary complications and prevalence may be underappreciated with the use of these agents.

Temporal Trends in the Incidence of Testicular Cancer in the United States over the Past Four Decades.

Testicular cancer is the most commonly diagnosed solid-organ neoplasm among young men, with variable incidence across racial groups. Testicular cancer incidence has increased since the 1970s, most notably among white men. Such trends in testicular cancer remain poorly understood. We investigated age-adjusted incidence rates of testicular cancer from 1975 to 2015 using Surveillance, Epidemiology and End Results data to further understand the nature of the temporal trends and potential drivers of disease. Across this time period, white men had the highest incidence and the largest increase in rate; however, we also note more recent increases in the incidence of testicular cancer across all racial groups being examined. PATIENT SUMMARY: We analyzed the rate of testicular cancer in the United States between 1975 and 2015. In that time, white patients had the highest rate and increase in rate of testicular cancer, but non-white patients also had increasing rates of disease.

Recovery from minimally invasive vs. open surgery in kidney cancer patients: Opioid use and workplace absenteeism.

PURPOSE: Does surgical approach (minimally invasive vs. open) and type (radical vs. partial nephrectomy) affects opioid use and workplace absenteeism. MATERIALS AND METHODS: Retrospective multivariable regression analysis of 2,646 opioid-naïve patients between 18 and 64 undergoing radical or partial nephrectomy via either a minimally invasive vs. open approach for kidney cancer in the United States between 2012 and 2017 drawn from the IBM Watson Health Database was performed. Outcomes included: (1) opioid use in opioid-naïve patients as measured by opioid prescriptions in the post-operative setting at early, intermediate and prolonged time periods and (2) workplace absenteeism after surgery. RESULTS: Patients undergoing minimally invasive surgery had a lower odds of opioid use in the early and intermediate post-operative periods (early: odds ratio [OR], 0.77; 95% confidence interval [CI], 0.62-0.97; p=0.02, intermediate: OR, 0.60; 95% CI, 0.48-0.75; p<0.01), but not in the prolonged setting (prolonged: OR, 1.00; 95% CI, 0.75-1.34; p=0.98) and had earlier return to work (minimally invasive vs. open: -10.53 days; 95% CI, -17.79 to -3.26; p<0.01). Controlling for approach, patient undergoing partial nephrectomy had lower rates of opioid use across all time periods examined and returned to work earlier than patients undergoing radical nephrectomy (partial vs. radical: -14.41 days; 95% CI, -21.22 to -7.60; p<0.01). CONCLUSIONS: Patients undergoing various forms of surgery for kidney cancer had lower rates of peri-operative opioid use, fewer days of workplace absenteeism, but no difference in long-term rates of opioid use in patients undergoing minimally invasive as compared to open surgery.

Minimally invasive cancer surgery is associated with a lower risk of venous thromboembolic events.

BACKGROUND: Venous thromboembolism (VTE) is a significant source of postoperative morbidity and mortality in patients undergoing common oncologic procedures. We sought to estimate the effect of surgical approach on the risk of developing a VTE. METHODS: IBM Watson Health Marketscan Database was used to conduct this retrospective study. In total, 12 938 patients who underwent either a radical prostatectomy, partial colectomy, or hysterectomy via a minimally invasive or open approach. We used a propensity-weighted logistic regression analysis to assess the independent effect of surgical approach on VTE. The primary outcome of interest was the 90-day rate of VTE after surgery. RESULTS: Patients undergoing minimally invasive surgery across all three surgical procedures were noted to have a lower odds of developing a VTE: (radical prostatectomy, odds ratio [OR]: 0.667, 95% confidence interval [CI]: 0.500-0.891; P = .006 |partial colectomy: OR, 0.620, 95% CI: 0.477-0.805; P < .001| hysterectomy: OR, 0.549 95% CI: 0.353-0.854; P = .008). CONCLUSION: We found that a minimally invasive approach was associated with significantly lower odds of VTE compared with undergoing the same open procedure. This study highlights how surgical approach may be an independent risk factor for development of VTE and may elucidate potential risk mitigation strategy.

Trends in Adherence to Thromboprophylaxis Guideline in Patients Undergoing Radical Cystectomy.

OBJECTIVE: To examine the use of in-hospital pharmacologic thromboprophylaxis (PTP) in patients undergoing radical cystectomy between 2004 and 2014 and to assess the risk of venous thromboembolism (VTE) across the study period. MATERIAL AND METHODS: We identified 8322 patients without contraindications to PTP undergoing radical cystectomy in the US using the Premier Healthcare Database. Nonparametric Wilcoxon type test for trend was employed to examine the trend of PTP utilization across the study period. Ensuing, we employed multivariable logistic regression and generalized linear regression models to examine the odds of receiving PTP and the risk of being diagnosed with VTE, respectively. RESULTS: Based on VTE risk-stratification, the majority of patients (87.8%) qualified as "high-risk." Across the study period the use of PTP increased (Odds ratio 1.02, 95% confidence interval (CI) 1.00-1.03, P = .044), but remained underutilized as the maximum percentage of patients receiving in-hospital PTP did not exceed 58.6%. The risk of VTE did not vary across the study period (risk ratio 0.97, 95%CI 0.92-1.02, P = .178). CONCLUSION: Utilization of PTP increased throughout the study period, while the risk of VTE did not change. Future studies are necessary to improve implementation of guideline-driven care, as PTP remained underutilized throughout the study period.