Faculty Bibliography

Purpose: High quality data regarding long-term clinical and patient-reported outcomes (PROs) of genital gender-affirming surgery (GGAS) are lacking, and transgender and non-binary (TGNB) community voices have not historically been included in research development. These factors limit the utility of current research for guiding patients, clinicians, payers, and other GGAS stakeholders in decision-making. The Transgender and Non-Binary Surgery (TRANS) Registry has been developed to meet the needs of GGAS stakeholders and address limitations of traditional GGAS research. Methods: Development of the TRANS Registry occurred over several developmental phases beginning in May 2019 to present. Stakeholder engagement was performed throughout these phases, including: determination of key clinical outcomes and PROs, creation and implementation of data collection tools within the electronic health record (EHR), and development of centralized registry infrastructure. Results: The TRANS Registry is a prospective observational registry of individuals seeking vaginoplasty and vulvoplasty. The EHR-enabled infrastructure allows patients and clinicians to contribute longitudinal outcomes data to the TRANS Registry. We describe our community engaged approach to designing the TRANS Registry, including lessons learned, challenges, and future directions. Conclusions: The TRANS Registry is the first multicenter initiative to prospectively track the health of individuals seeking vaginoplasty and vulvoplasty using EHR-enabled methods, engaging TGNB community members and clinicians as partners in the process. This process may be used as a model for registry development in other emerging fields where high-quality longitudinal outcomes data are needed.

Sexual and gender minority (SGM) communities face stigma and discrimination that impact all aspects of health. To better understand and improve their urologic health outcomes, we must study SGM patients as a distinct population and pursue research on outcomes identified as priorities to SGM communities. Patient-centered outcomes research (PCOR) is a methodology which is increasingly familiar to urologists and is crucial to adequately addressing SGM health in future urological research. We review existing literature focused on urologic outcomes of SGM populations and highlight specific PCOR initiatives built on SGM community engagement.

BACKGROUND:Following gender-affirming penile inversion vaginoplasty or vulvoplasty, patients may seek vulvar revision procedures for a variety of common aesthetic and functional concerns. These indications for revision and accompanying techniques are not well-described in the literature. METHODS:Patients who underwent vulvar revision surgery at the authors' institution were identified, and patient demographics, surgical indications, operative details, and complications were described. Common complaints requiring external genital revision were sorted into four categories: clitoral, labial, introital, and urethral. RESULTS:Thirty-five patients with a history of vaginoplasty underwent vulvar revision between May of 2017 and December of 2019. The mean age at surgical correction was 38.9 years. Ten patients (28.6 percent) had undergone prior secondary procedures (range, 1 to 3). Mean follow-up after revision surgery was 10.7 ± 8.7 months (range, 0 to 30.6 months). The majority of patients underwent concurrent revisions in multiple "categories". Labial aesthetic concerns were most common (n = 27, 77.1 percent), followed by clitoral (n = 20, 57.1 percent), urologic (n = 17, 48.6 percent), and introital complaints (n = 12, 34.3 percent). Twelve patients (34.3 percent) had canal stenosis requiring concurrent robot-assisted canal revision with peritoneal flaps. Complications included labial abscess (n = 1) and deep vein thrombosis (n = 1). Three patients (8.6 percent) underwent subsequent external genital revisions. Management approaches and surgical techniques for each of these common revision categories are provided. CONCLUSION/CONCLUSIONS:As more individuals seek vaginoplasty and vulvoplasty, surgeons must be prepared to address a range of common aesthetic and functional complaints requiring vulvar revision. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Therapeutic, IV.

Introduction: Sotorasib is a first-in-class small molecule that specifically and irreversibly inhibits KRAS^G12C. The phase 1/2 CodeBreaK 100 trial evaluated sotorasib in patients with pretreated advanced non-small cell lung cancer (NSCLC) harboring KRAS p.G12C. In the registrational phase 2 part, sotorasib showed an objective response rate (ORR) of 37.1% and a median progression-free survival (PFS) of 6.8 months. Here, we report on the activity of sotorasib in patients with treated brain metastases (BM).
Method(s): Patients from the phase 1/2 CodeBreaK 100 trial receiving 960mg dose were included. Patients with active untreated BM were excluded. Patients who had BM resected or had received radiation therapy ending >=4 weeks prior to the trial were eligible. Systemic response was assessed by independent central review per RECIST 1.1. The presence of neurologically stable/asymptomatic BM at baseline was determined by investigators. CNS response was retrospectively evaluated by central neuroradiologic review, using the response assessment in neuro-oncology BM (RANO-BM) criteria, in patients with >=1 target CNS lesions (>= 10mm) and/or non-target CNS lesions. For non-target lesions, stable disease (SD) refers to response that is neither complete response (CR) nor progressive disease (PD).
Result(s): 174 patients were included: 40 had stable BM (23.0%) while 134 (77.0%) had no BM at baseline. In the BM group, 65% had received prior radiotherapy, and 20% had received prior brain surgery. Systemic efficacy of sotorasib per RECIST 1.1 is shown in the Table. Per central RANO-BM review, 16 patients had baseline and >=1 on-treatment evaluable scans: 3 had target and 13 had non-target CNS lesions. 9 patients had 1 lesion, 2 had 4 lesions, and 5 had >=5 lesions. Of 13 patients with non-target CNS lesions, 2 had CR, 11 had SD. Of 3 patients with target lesions, 1 had SD, and 2 had PD. Overall, intracranial disease control was achieved in 14 of 16 patients (87.5%) with evaluable BM. Safety in the BM group was consistent with previous reports. [Formula presented]
Conclusion(s): Sotorasib demonstrated systemic durable anticancer activity, with a median PFS and OS of 5.3 and 8.3 months in NSCLC patients with stable BM previously treated with radiation or surgery. Intracranial complete responses were observed, with continued intracranial stabilization observed in the majority of patients with evaluable BM. Additional studies are ongoing to evaluate sotorasib in patients with active untreated BM (NCT04185883). Keywords: brain metastases, KRAS p.G12C, sotorasib (AMG 510)
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Introduction: Sotorasib is a first-in-class small molecule that specifically and irreversibly inhibits KRAS^G12C. In the registrational phase 2 CodeBreaK 100 trial, sotorasib showed an objective response rate (ORR) of 37.1% and a median progression-free survival (PFS) of 6.8 months in patients with KRAS p.G12C-mutated non-small cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy and/or immunotherapy. Response to sotorasib has been observed across co-occurring mutational profiles. Here, we report preliminary data on the genomic profiles and potential determinants of response to sotorasib from an exploratory analysis of this trial.
Method(s): Baseline tissue samples were collected and analyzed for genomic alterations in KEAP1, the upstream RTK pathway, and the downstream PI3K/AKT/mTOR and MAPK pathways. Patients were categorized into the following 3 groups: early progressors (patients with an event of progressive disease and PFS of <3 months), late progressors (patients with an event of progressive disease and PFS of >= 3 months), non-progressors (patients with no event of progressive disease and PFS of >= 3 months).
Result(s): A total of 126 patients were enrolled into the phase 2 trial. 65 patients with available data from baseline tissue samples were categorized per methods: 22 early progressors, 23 late progressors, and 20 non-progressors. 11 of the 65 patients had KEAP1 mutations (7 in the early progressor group, 2 in the late progressor group, and 2 in the non-progressor group). In the early progressor group, we observed mutations in EGFR, FGFR, PDGFR, RET, and MET, which were also identified in other groups. Among the patients with mutations in the MAPK pathway genes, the late progressor group was the most prevalent (43%, n=6), followed by early progressor (29%, n=4) and non-progressor (29%, n=4). Among patients with mutations in genes of the PI3K/AKT/mTOR pathway, late progressor and early progressor groups were the most prevalent (36%, n=9, each), followed by non-progressor group (28%, n=7) (summary Table below). [Formula presented]
Conclusion(s): In this descriptive biomarker analysis of baseline tissue specimens from the phase 2 CodeBreaK 100 trial of sotorasib in KRAS p.G12C-mutated NSCLC, diverse mutation patterns were observed. No unique genomic profiles were identified in patient groups. The presence of KEAP1 mutation was observed across all groups and was more prevalent in early progressors. These findings warrant further investigation of the longitudinal cfDNA dynamics in patients receiving sotorasib. Keywords: biomarkers, sotorasib (AMG 510), KRAS p.G12C NSCLC
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Background Robotic pelvic surgery is increasingly utilized for reconstruction proximal to the genitourinary diaphragm. We describe a combined robotic transabdominal and open transperineal approach for complex anastomotic posterior urethroplasty. Methods We performed a multi-institutional retrospective study of patients who underwent anastomotic posterior urethroplasty by a combined robotic transabdominal and open transperineal approach between 1/2012 and 12/2018. Patient demographics; preoperative, intraoperative, and postoperative clinical data; and complications were reviewed. Urethroplasty success, de novo stress urinary incontinence (SUI), and de novo erectile dysfunction (ED) were evaluated. Results 12 patients were identified with a mean follow-up of 596 (range 73-1618) days. Mean patient age was 65.9 (range 53.4-76.8). Reconstruction required corporal splitting, prostatectomy, and gracilis muscle flap use in 1 (8.3%), 8 (66.7%), and 4 (33.3%) patients, respectively. Postoperative urinary leak, thromboembolic event, and wound abscess occurred in 1 (8.3%), 1 (8.3%), and 2 (16.7%) patients, respectively. Stenosis recurrence occurred in 2 patients (16.7%) at a mean 187.5 (20-355) postoperative days. De novo ED and de novo SUI were reported in 2 (16.7%) and 4 (33.3%) patients, respectively. Nine patients (75.0%) underwent placement of an artificial urinary sphincter at a mean interval of 359.2 (111-1456) days after the index procedure with no subsequent erosion. Conclusions Complex posterior urethroplasty by a combined robotic transabdominal and open transperineal approach is associated with success and complications rates comparable to open techniques and may allow for adjunctive procedures such as prostatectomy. This technique allows for reconstruction of posterior urethral stenoses that would otherwise have been managed conservatively or with urinary diversion.

OBJECTIVES/OBJECTIVE:To present the technique and early outcomes of salvage neovaginal reconstruction using robotic dissection and peritoneal flap mobilization. METHODS:Twenty-four patients underwent robotic peritoneal flap revision vaginoplasty from 2017-2020. A canal is dissected between the bladder and rectum towards the stenosed vaginal cavity, which is incised and widened. Peritoneal flaps from the posterior bladder and pararectal fossa are advanced and sutured to edges of the stenosed cavity. Proximal peritoneal flap edges are approximated to form the neovaginal apex. Patient demographics, comorbidities, surgical indications, and operative details are described. Outcome measures include postoperative neovaginal dimensions and complications. RESULTS:Mean age at revision was 39 years (range 27-58). All patients had previously undergone PIV, with revision surgery occurring at a median 35.3 months (range 6-252) after primary vaginoplasty. Surgical indications included short or stenotic vagina or absent canal. Average procedure length was 5 hours. At mean follow up of 410 days (range 179-683), vaginal depth and width were 13.6 cm (range 10.9-14.5) and 3.6 cm (range 2.9-3.8), respectively. There were no immediate or intraoperative complications related to peritoneal flap harvest. No patient had rectal injury. One patient had post-operative canal bleeding requiring return to the operating room for hemostasis. CONCLUSIONS:Robotic peritoneal flap vaginoplasty is a safe, novel approach to canal revision after primary PIV with minimal donor site morbidity.