Evaluating relugolix for the treatment of prostate cancer in real-world settings of care: the OPTYX study protocol.

OPTYX is a multi-center, prospective, observational study designed to further understand the actual experience of patients with advanced prostate cancer treated with relugolix (ORGOVYX®), an oral androgen deprivation therapy (ADT), by collecting clinical and patient-reported outcomes from routine care settings. The study aims to enroll 1000 consented patients with advanced prostate cancer from community, academic and government operated clinical practices across the USA. At planned timepoints, real-world data analysis on treatment patterns, adherence and safety as well as health outcomes and health-related quality-of-life (HRQOL) after treatment discontinuation will be published in scientific peer-reviewed journals and presented at relevant conferences. This study will provide real-world data for practitioners and researchers in their understanding of the safety and effectiveness of relugolix. Clinical Trial Registration: NCT05467176 (ClinicalTrials.gov).

What is this summary about? This is a protocol summary for a research study named OPTYX. Who can participate in this research? Men 18 or older with advanced prostate cancer initiating treatment with relugolix, an oral androgen deprivation therapy (ADT), at the time of enrollment or within the 1 month before enrollment (remaining on treatment at enrollment) and are willing and able to complete patient assessments during the study. What institutions are performing this research? Community practices, academic institutions and Veterans Health Administration facilities across the USA. What are the research assessments to obtain the results? Data will be collected from the routine medical visits twice yearly including patient demographics, medical history (co-morbidities and cardiac risk factors), prostate cancer history and treatments and test results (routine lab testosterone, PSA levels and imaging). Relugolix response and all serious adverse events (SAEs) and any nonserious adverse events (AE) leading to relugolix treatment discontinuation will be assessed. Patients will be asked to respond to evaluations about their health-related quality of life and adherence to relugolix treatment. How long would the study last? Up to 5 years from enrollment date and/or up to 2 years after relugolix discontinuation. Follow-up will end with consent withdrawal, loss to follow-up, death, or study termination, whichever comes first. What do the results of the study mean? Real-world understanding of the experience and clinical outcomes in patients with advanced prostate cancer in routine clinical care and their clinical trajectory following cessation of relugolix therapy.

Understanding and Improving 18F-Fluciclovine PET/CT Reports: A Guide for Physicians Treating Patients with Biochemical Recurrence of Prostate Cancer.

The positron emission tomography (PET) tracer 18F-fluciclovine has seen increasing use to localize disease in men with biochemical recurrence of prostate cancer, i.e., elevated prostate-specific antigen (PSA) levels post-treatment. 18F-Fluciclovine PET/computed tomography (CT) imaging reports now play central roles in many physician-patient discussions. However, because no standardized grading system or templates yet exist for 18F-fluciclovine image assessment, reports vary in format, comprehensiveness, and terminology and may be challenging to fully understand. To better utilize these documents, referring physicians should be aware of six key features of 18F-fluciclovine PET/CT. First, 18F-fluciclovine is a radiolabeled synthetic amino acid targeting the amino acid transporters ASCT2 and LAT1, which are ubiquitous throughout the body, but overexpressed in prostate cancer. Second, 18F-fluciclovine image interpretation is predominantly visual/qualitative: radiotracer uptake in suspicious lesions is compared with uptake in bone marrow or blood pool. Location of 18F-fluciclovine-avid lesions relative to typical recurrence sites and findings elsewhere in the patient are considered when evaluating lesions' probability of malignancy, as is visibility on maximum intensity projection images when assessing bone lesions. Third, 18F-fluciclovine PET/CT detection rates increase as PSA levels rise. Fourth, detection rates may differ among centers, possibly due to equipment and reader experience. Fifth, since no diagnostic test is 100% accurate, scan data should not be used in isolation. Lastly, 18F-fluciclovine PET/CT findings frequently induce changes in disease management plans. In the prospective multicenter LOCATE and FALCON studies, scans altered management plans in 59% (126/213) and 64% (66/104) of patients, respectively; 78% (98/126) and 65% (43/66) of changes, respectively, involved modality switches. Referring physicians and imagers should collaborate to improve scan reports. Referrers should clearly convey critical information, including prescan PSA levels, and open clinical questions. Imagers should produce reports that read like consultations, avoid leaving open questions, and if needed, provide thoughts on next diagnostic steps.

Robot-assisted radical cystectomy in women: technique and initial experience.

BACKGROUND AND PURPOSE: Robot-assisted radical cystectomy (RARC) is a new management option for the treatment of bladder cancer. This study evaluates an initial experience with RARC with ileal conduit diversion in women. PATIENTS AND METHODS: Twenty patients underwent RARC with ileal conduit urinary diversion, including four women, and our surgical technique is described here. A retrospective chart review was performed to evaluate clinical stage, tumor grade, operative times, estimated blood loss (EBL), pathologic stage, lymph node pathology, and complications. RESULTS: Mean patient age was 69.5 years, median operative time was 350 minutes, and median EBL was 300 mL. Median length of stay was 5 days, with the two most recent patients leaving by postoperative day 3. The median number of lymph nodes removed was 12, with one patient revealing node-positive disease. Surgical margins were negative for disease in all patients. No patients required blood transfusion or had major complications. CONCLUSION: RARC is a new technique available for the treatment of high-risk or invasive bladder cancer in women. This surgery provides decreased morbidity while maintaining the oncologic goals of traditional radical cystectomy.

EGF and HB-EGF modulate inward potassium current in human bladder urothelial cells from normal and interstitial cystitis patients.

Interstitial cystitis (IC) is an idiopathic condition characterized by bladder hyperalgesia. Studies have shown cytokine and purinergic signaling abnormalities in cultured bladder urothelial cells (BUC) from IC patients. We performed single-cell electrophysiological studies in both normal and IC BUC. A strongly inward rectifying potassium current with conductance of the Kir2.1 channel was identified in normal BUC. This current was significantly reduced in IC BUC. Kir2.1 protein and mRNA were detected in both IC and normal BUC. Epidermal growth factor (EGF) caused a dose-dependent decrease in the inward potassium current in normal BUC. EGF is secreted in higher amounts by IC BUC and is known to decrease Kir2.1 conductance by phosphorylation of Kir2.1. Genistein, a nonspecific phosphorylation inhibitor, increased the inward potassium current in IC BUC and blocked the effect of EGF on normal BUC. Treatment of IC BUC with heparin-binding epidermal growth factor-like growth factor (HB-EGF), previously shown to be secreted in lower amounts by IC BUC, significantly increased inward potassium current. These data show that the inward potassium current in BUC can be modulated by EGF and HB-EGF. Changes in BUC membrane potassium conductance caused by altered levels of EGF and HB-EGF may therefore play a role in the pathophysiology of IC.

Variants of the exstrophy complex: a single institution experience.

PURPOSE: Variants of the bladder/cloacal exstrophy complex are rare. Different presentations and subsequent management and outcome are discussed. MATERIALS AND METHODS: We performed a retrospective review of our database of more than 815 patients with the exstrophy complex. Patients with variants of classic epispadias or bladder or cloacal exstrophy were identified. Anatomical presentation, surgical management, type of continence procedures and final outcome were evaluated. RESULTS: Of the 25 patients with variants 13 were treated primarily at our institution and 12 were referred. Time until primary bladder closure ranged from 1 day to 4 years. Followup after continence procedure ranged from 1 month to 39 years. Seven of the 25 patients are awaiting a continence procedure. Six patients are dry without a continence procedure, of whom 4 have superior vesical fistulas. A total of 11 patients underwent bladder neck reconstruction (BNR), of whom 3 are dry, 2 are dry during the day but are wet at night, 1 had a failed procedure and 5 are dry after continent diversion (CD). One additional patient underwent CD initially and is dry. Referred cases of epispadias with bladder prolapse were not recognized at birth and had delayed closure. Impaired bladder growth or failed BNR required CD in 4 patients, and 2 are awaiting a continence procedure. Skin covered and duplicate exstrophy had comparable outcomes to the classic presentations. Duplicated organs were used for reconstructive procedures. Of the 6 patients with cloacal variant 2 are continent of stool and 2 await a Pena procedure. One of these patients has an ileal stoma and 1 has a colostomy. CONCLUSIONS: The initial presentation of exstrophy variants can be confusing, often delaying initial treatment. Superior vesical fistulas permit continence without BNR due to an intact urinary sphincter. Variants such as epispadias with bladder prolapse and duplicate or skin covered exstrophy should be closed at birth with standardized techniques to promote bladder growth for later BNR. These cases are faced with the same long-term problems as the classic presentation. Cloacal variants can present with intact anal innervation, allowing a later Pena procedure.