TPS4591 Background: ABACUS and PURE-01 trials demonstrated the activity of single agent atezolizumab and pembrolizumab respectively as neoadjuvant therapy for muscle invasive urothelial carcinoma (MIUC). However, downstaging to non-muscle invasive disease was noted in only 50 percent of patients. Resistance to programmed death (PD)- 1/L-1 antibodies is likely to include factors such as impaired dendritic cell maturation/function, infiltration of T-Regs and myeloid derived suppressor cells, impaired T-cell priming and T-cell trafficking in tumors. Cabozantinib is a tyrosine kinase inhibitor which targets MET, AXL, MER, Tyro3 and VEGFR2. Cabozantinib has a unique immunomodulatory profile and has demonstrated clinical activity as monotherapy and in combination with PD-1/L1 antibodies in various solid tumors including UC, renal cell cancer, castrate- resistant prostate cancer, and non-small cell lung cancer. We hypothesize that the combination of cabozantinib and atezolizumab as neoadjuvant therapy for MIUC would improve rates of pathologic downstaging compared to single-agent checkpoint inhibitors. Methods: ABATE(NCT04289779) is an open-label, single arm, multi-center study to assess the efficacy and safety of cabozantinib with atezolizumab as neoadjuvant therapy for cT2-T4aN0/xM0 MIUC. An estimated 38 patients will be enrolled and receive cabozantinib 40 mg PO daily with atezolizumab 1200mg every 3 weeks for a total duration of 9 weeks followed by radical cystectomy. Adults (≥18 years) with resectable UC who are either cisplatin-ineligible or decline cisplatin are eligible. Patients are required to have an ECOG PS of 0-2 and provide tumor tissue for PD-L1 analysis. UC should be predominant component (≥ 50%). Previous systemic anticancer therapies for MIUC are not permitted. CT/MRI will be performed before investigational therapy and cystectomy. Primary endpoint is pathologic response rate defined as the absence of residual muscle-invasive cancer in the surgical specimen ( < pT2). Secondary endpoints are safety and toxicity, pathologic complete response rate and event-free survival. Exploratory end points include patient-reported outcomes and outcome associations with biomarkers. Accrual began May 2020. Clinical trial information: NCT04289779.
Introduction: New techniques in robot-assisted radical prostatectomy (RARP) have evolved as urologists strive to improve patient outcomes. Building on the foundations of the retzius-sparing and lateral approaches to prostatectomy, with the goal of improving our functional outcomes, we developed the functional anatomy sparing technique for prostatectomy (FAST-P).1,2 Materials and Methods: The FAST-P was developed and performed by a single surgeon (K.J.). Data were collected through retrospective chart review on consecutive patients who underwent the procedure from May through September 2017. Patients were not offered this approach if there was a large anterior lesion on MRI, because of preservation of the dorsal venous complex and anterior pubovesical structures. Demographic and operative details were collected, as were results from the validated Leakage Index (LI) and Sexual Health Inventory for Men questionnaires at 6 weeks follow-up. A cohort of consecutive patients who underwent a traditional RARP by the same surgeon was provided as a control. In our traditional RARP, anterior reconstruction includes urethral suspension and approximation of anterior bladder to cut edge of endopelvic fascia. Results: Fifty patients underwent FAST-P. Twenty-five patients underwent traditional RARP. Complete data at 6-week follow-up were available for 45/50 FAST-P patients and all of the traditional approach patients. There was no statistically significant difference in age, BMI, or operative time between the two groups. In the FAST-P series, surgical pathology grade was Gleason Grade 3 + 3 (4), 3 + 4 (34), 4 + 3 (11), or 4 + 5 (1). Stage was pT2 (44), pT3a (4), or pT3b (2). Six weeks postoperatively, 40 of 45 (89%) patients who underwent FAST-P and 16 of 25 (64%) traditional RARP patients were continent as measured by LI and pad usage (p = 0.026). There was no difference in rate of postoperative complication between the two groups. Conclusions: This initial series of FAST-P demonstrates the technique is feasible and reproducible. Although many of these cases are early in the learning curve, the FAST-P functional outcomes are promising, with high rates of early return to continence and a significant improvement on our historical outcomes. Longer follow-up and additional study are warranted based on these encouraging results. No competing financial interests exist. Runtime of video: 8 mins This technique was previously presented by the authors at the American Urological Association annual meeting, May 2018, in San Francisco, CA.
To evaluate a multicentre series of robot-assisted partial nephrectomy (RAPN) performed for the treatment of large angiomyolipomas (AMLs).Between 2005 and 2016, 40 patients with large or symptomatic AMLs underwent RAPN at five academic centres in the USA. Patient demographics, AML characteristics, operative and postoperative clinical outcomes were recorded and analysed. Surgical outcomes were compared between patients who underwent selective arterial embolisation (SAE) before RAPN and patients who did not undergo pre-RAPN SAE.The median (interquartile range [IQR]) tumour diameter was 7.2 (5-8.5) cm, and the median (IQR) nephrometry score was 9 (7-10). Six patients (15%) had a history of tuberous sclerosis and 11 (28%) had previously undergone SAE. The median (IQR) operative time and warm ischaemia time was 207 (180-231) and 22.5 (16-28) min, respectively. A non-clamping technique was used in eight (20%) patients. The median (IQR) estimated blood loss was 200 (100-245) mL, and four patients (10%) received blood transfusion postoperatively. One intraoperative complication occurred (2.5%), and seven postoperative complications occurred in six patients (15%). During a median (IQR) follow-up of 8 (1-15) months, none of the patients developed AML-related symptoms. The median estimated glomerular filtration rate preservation rate was 95%. There were no differences in operative or perioperative outcomes between patients who underwent SAE before RAPN and those who did not.Robot-assisted partial nephrectomy appears to be a safe primary or secondary (post-SAE) treatment for large AMLs, with a favourable perioperative morbidity profile and excellent functional preservation. Longer follow-up is required to fully evaluate therapeutic efficacy.
A phonon often is described as “a quantum of lattice vibration,” but this description can be difficult to reconcile with the wave functions explored in a typical undergraduate quantum mechanics class. A phonon wave function is similar to the harmonic oscillator wave functions studied in introductory quantum mechanics, except that it is many-dimensional. We suggest a way to visualize the probability density for this very high-dimensional wave function. The resulting pictures are especially clear and intuitive for a coherent state, which is both a good approximation to a sound wave and a discrete analog to laser light. These pictures can also provide a qualitative introduction to quantum field theory.
Introduction: In this study, we aim to characterize diagnosed and undiagnosed comorbid conditions as well as the sufficiency of their management in order to demonstrate the opportunity available to improve the overall health in men presenting with a new prostate cancer diagnosis. Methods: A retrospective chart review was performed on patients presenting with a new prostate cancer diagnosis from January 2020 to March 2022 to determine undiagnosed conditions and adequacy of the management of comorbidities. Results: Of the included patients, 24.9% had prediabetes, 19.3% diabetes mellitus (DM), 68.5% hypertension (HTN), 70.2% hyperlipidemia (HLD), and 43.1% metabolic syndrome. For DM, HTN, and HLD, 10.5%, 18.8%, and 18.8% of patients were screened but inadequately treated, respectively; 5.5%, 13.8%, and 8.3% were not diagnosed; 2.8%, 0, and 5.5% were not screened. The average 10-year ASCVD risk in patients with metabolic syndrome was 25.6% vs 15.1% in those without ( P < .001), and 21.8% vs 15.1% in patients who were incompletely screened for chronic disease compared with those who were screened per guidelines ( P < .001). Conclusion: The study population has high rates of comorbidities, and undermanaged chronic diseases. This significant unmet health care need represents an opportunity for urologists to champion men’s health in new prostate cancer patients.
