Design and Rationale of the Outcomes Database to Prospectively Assess the Changing Therapy Landscape in Renal Cell Carcinoma Registry: A Multi-institutional, Prospective Study of Patients with Metastatic Renal Cell Carcinoma.

Introduction and hypotheses: The Outcomes Database to prospectivelY aSSEss the changing TherapY landscape in Renal Cell Carcinoma (ODYSSEY RCC) Registry is a large, nationally representative prospective registry of patients with metastatic renal cell carcinoma (mRCC) that aims to provide a real-world picture of longitudinal clinical management and patient experiences that impact clinical outcomes. The primary goal of this study is to understand the cancer management and health-related quality of life in patients with mRCC in routine real-world clinical practice in the USA. Design: This is an observational, phase 4 study with planned enrollment of up to 800 patients aged ≥19 yr with mRCC in the USA. Patients will be identified through electronic health record (EHR) data from the PCORnet network of sites for care received at collaborating sites. A unique aspect of the study is the multiple data sources that will be linked to the EHR data. These include: (1) Medicare claims data, (2) laboratory results, (3) tissue specimens, (4) radiographic images, and (5) patient-reported outcomes, physicians' treatment selection, and discontinuation surveys. Protocol overview: We created a novel data resource that can inform patient care. Investigators have the opportunity to use these to study novel research questions after submitting an ancillary proposal and upon approval of the executive committee. Limitations include the potential for selection bias, residual confounding, and missing information. Summary: The ODYSSEY Registry will provide an advanced data resource that can examine numerous clinical questions related to patient and physician choice, and support methodological research related to omics and artificial intelligence. Patient summary: Cancer medications and treatments are changing rapidly. Collecting data on real-world clinical practice and patient-answered questionnaires will help us better understand cancer management and health-related quality of life while receiving metastatic renal cell carcinoma-specific treatment.

Updated 5-year results for short course abiraterone acetate and LHRH agonist for unfavorable intermediate and favorable high-risk prostate cancer.

Combined androgen deprivation therapy (ADT) and radiotherapy (RT) improves outcomes for intermediate and high-risk prostate cancer. Treatment intensification with abiraterone acetate/prednisone (AAP) provides additional benefit for high-risk disease. We previously reported 3-year outcomes of a single-arm prospective multicenter trial (AbiRT trial) of 33 patients with unfavorable intermediate risk (UIR) and favorable high risk (FHR) prostate cancer undergoing short course, combination therapy with ADT, AAP, and RT. Here we report the final analysis demonstrating a high rate of testosterone recovery (97%) and excellent biochemical progression-free survival (97%) at 5 years. These data support comparative prospective studies of shorter, more potent ADT courses in favorable high-risk prostate cancer.

Evaluation of a Magnetic Compression Anastomosis for Jejunoileal Partial Diversion in Rhesus Macaques.

PURPOSE: Metabolic surgery remains underutilized for treating type 2 diabetes, as less invasive alternative interventions with improved risk profiles are needed. We conducted a pilot study to evaluate the feasibility of a novel magnetic compression device to create a patent limited caliber side-to-side jejunoileal partial diversion in a nonhuman primate model. MATERIALS AND METHODS: Using an established nonhuman primate model of diet-induced insulin resistance, a magnetic compression device was used to create a side-to-side jejunoileal anastomosis. Primary outcomes evaluated feasibility (e.g., device mating and anastomosis patency) and safety (e.g., device-related complications). Secondary outcomes evaluated the device's ability to produce metabolic changes associated with jejunoileal partial diversion (e.g., homeostatic model assessment of insulin resistance [HOMA-IR] and body weight). RESULTS: Device mating, spontaneous detachment, and excretion occurred in all animals (n = 5). There were no device-related adverse events. Upon completion of the study, ex vivo anastomoses were widely patent with healthy mucosa and no evidence of stricture. At 6 weeks post-device placement, HOMA-IR improved to below baseline values (p < 0.05). Total weight also decreased in a linear fashion (R2 = 0.97) with total weight loss at 6 weeks post-device placement of 14.4% (p < 0.05). CONCLUSION: The use of this novel magnetic compression device to create a limited caliber side-to-side jejunoileal anastomosis is safe and likely feasible in a nonhuman primate model. The observed glucoregulatory and metabolic effects of a partial jejunoileal bypass with this device warrant further investigation to validate the long-term glucometabolic impact of this approach.

Pediatric Device Clinical Trials Activity: 1999-2022.

OBJECTIVES: This study assessed the state of pediatric medical device (PMD) development by comparing PMD clinical trials to pediatric trials evaluating drugs and biologics, from 1999 to 2022. METHODS: The site www.clinicaltrials.gov was used to identify and quantify both PMD clinical trials and pediatric trials for drugs and biologics. Clinical specialty was also assessed. The institutions included were the 7 children's hospitals primarily affiliated with the Food and Drug Administration (FDA) Pediatric Device Consortia (PDC) grant program between 2018 and 2023. For a national comparison, an additional search assessed PMD trials across all US medical institutions. RESULTS: A total of 243 PMD clinical trials were identified at the FDA-PDC institutions on the basis of the year of initiation; the average number of PMD trials initiated per year per institution was 1.5 from 1999 to 2022. However, PMD trials significantly increased during the period 2014 to 2022 compared with 1999 to 2013 (P < .001); the rate of initiation of drug and biologic pediatric trials demonstrated no significant differences between these time periods. A national survey of all institutions initiating PMD trials, and drugs and biologics trials, identified 1885 PMD trials out of a total 12 943. A comparable trend was noted in the national survey with initiation of PMD trials increasing significantly from 2014 to 2022 (P < .001), compared with 1999 to 2013, whereas the rate of initiation of drug and biologic trials during these periods did not demonstrate a significant change. CONCLUSIONS: Although pediatric clinical trial initiation for drugs and biologics remained stable from 1999 to 2022, the rate of new PMD trials significantly increased during the period 2014 to 2022 at FDA-PDC institutions and nationally.

Intensifying Salvage Therapy in Prostate-specific Antigen Recurrent Prostate Cancer After Radical Prostatectomy with Apalutamide, Salvage Radiation, and Docetaxel: The Phase 2 STARTAR Trial.

BACKGROUND AND OBJECTIVE: Androgen deprivation therapy (ADT) with salvage radiation therapy (RT) improves survival for patients with prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP) for prostate cancer (PC), but many patients suffer further relapse. This study aims to determine the benefit of the combination of ADT, apalutamide, salvage RT, and docetaxel for high-risk PSA recurrent PC. METHODS: STARTAR is a multicenter, investigator-initiated phase 2 trial of men with PSA recurrent PC after RP. The key inclusion criteria included M0 by computed tomography/bone scan, Gleason 7 with either T3/positive margin/N1 disease or Gleason 8-10 prostate adenocarcinoma, PSA relapse (0.2-4 ng/ml) <4 yr after RP, and fewer than four positive resected lymph nodes. Patients received ADT with apalutamide for 9 mo, RT starting week 8, and then six cycles of docetaxel. The primary endpoint was 36-mo progression-free survival (PFS) with testosterone recovery and compared against the prior STREAM trial. KEY FINDINGS AND LIMITATIONS: We enrolled 39 men, including those with Gleason 8-10 (46%), pN1 (23%); the median PSA was 0.58 ng/ml. The median follow-up was 37 mo. All patients achieved undetectable PSA nadir. At 24 and 36 mo, PFS rates were 84% and 71%, respectively, which improved significantly over 3-yr 47% historic PFS and 54% enzalutamide/ADT/RT (STREAM) PFS rates (p = 0.004 and p = 0.039, respectively). Common any-grade adverse events included 98% hot flashes, 88% fatigue, 77% alopecia, 53% rash (10% G3), and 5% febrile neutropenia. CONCLUSIONS AND CLINICAL IMPLICATIONS: In this phase 2 trial of ADT, apalutamide, salvage RT, and six cycles of docetaxel for high-risk PSA recurrence, the 3-yr PFS rate improved to 71%, indicating feasible and efficacious treatment intensification, with durable remissions beyond historic data. PATIENT SUMMARY: Prostate cancer recurrence after surgical removal of the tumor occurs often, and current treatment options to limit recurrence after surgery are only partially effective. In this study, we found that the addition of an androgen receptor inhibitor and docetaxel chemotherapy to standard postsurgery radiation therapy and androgen deprivation therapy significantly improved progression-free survival at 3 yr after treatment. These results suggest that intensification of treatment after surgery can provide long-term benefit to a subset of patients with high-risk prostate cancer.

Immune features are associated with response to neoadjuvant chemo-immunotherapy for muscle-invasive bladder cancer.

Neoadjuvant cisplatin-based chemotherapy is standard of care for muscle-invasive bladder cancer (MIBC). Immune checkpoint inhibition (ICI) alone, and ICI in combination with chemotherapy, have demonstrated promising pathologic response (