Citations

Key Points Genetic testing in CKD showed diagnostic and clinical utility in the year following reporting of test results. Genetic testing was helpful for or changed management in 86% of patients with a positive finding and 42% with a negative finding. Clinical utility was seen across 12 clinical cohorts, including CKD of unknown etiology and hypertension or diabetes-related nephropathy. Background CKD is a significant public health burden, affecting >800 million people worldwide with significant cost to the health care system. CKD is a disease process with substantial genetic and phenotypic heterogeneity that can obscure a definitive diagnosis, resulting in suboptimal management. Recent guidelines support greater adoption of genetic testing in CKD. We assessed the diagnostic and clinical utility in the year following broad-panel CKD genetic testing. Methods The Renasight Clinical Application, Review, and Evaluation (RenaCARE) study (NCT05846113) was a single-arm, interventional, prospective, multicenter study evaluating the utility of genetic testing with a 385-gene panel on the diagnosis and management of CKD. Clinical history was collected before testing, and nephrologists responded to questionnaires at both 1 month and 1 year after testing. The impact of genetic testing on CKD diagnosis and management were assessed in active study patients at the 1-year time point. Results In a cohort of 1388 CKD patients with 13 pretest clinical categories of CKD, 335 (24%) patients had a positive genetic finding; 1174 had a questionnaire completed at 1 year and were included in the analysis. Genetic testing was reported helpful for clinical management and/or led to a change in management in 86% of patients with a positive test finding and 42% of patients with a negative test finding. In addition, genetic testing resulted in a change in the physician estimation of the 5-year prognosis for 55% of patients with a positive test finding and 18% of those with a negative test finding. Conclusions Supporting the previous results of the RenaCARE study at 1 month, this report demonstrated that genetic testing was helpful in the clinical management and estimated prognosis of patients with CKD. Clinical Trial registry name and registration number: ClinicalTrials.gov, NCT05846113.

Objective: In this study, we evaluate the utility of ctDNA analysis in a large cohort of patients for whom ctDNA testing was ordered commercially with real-world application. Summary Background Data: Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for assessing post-surgical molecular residual disease (MRD) and response to treatment. Methods: A real-world data analysis was performed using commercial ctDNA testing (SignateraTM) from patients (N=795, n=5,971 plasma samples) with stage I-III colon cancer treated at multiple US institutions. The association of ctDNA detection within the MRD window, during surveillance, and the impact of ACT was correlated with patient outcomes. Results: ctDNA-positive patients during the MRD window and surveillance showed significantly shorter DFS compared to ctDNA-negative patients (hazard ratio (HR): 9.85, P<0.0001; HR: 26.91, P<0.0001). Multivariate analysis of the MRD window revealed ctDNA-positivity as the most significant factor associated with inferior DFS (adjHR: 7.7, P<0.001). MRD-positive patients who received ACT showed improved DFS compared to patients observed post-surgery (adjHR: 6.1, FDR adj P=0.0007). No ACT benefit was observed in MRD-negative patients (adj HR: 1.20, FDR adj P=0.768). On evaluating ctDNA dynamics from MRD to surveillance, patients who remained ctDNA-positive or converted from negative to positive showed a significantly inferior DFS (HR: 34.40, P<0.0001; HR: 13.65, P<0.0001) compared to persistently ctDNA-negative patients. Conclusions: Postsurgical ctDNA detection is prognostic of relapse and potentially predictive of ACT benefit in patients with resectable colon cancer, which may enable personalized surveillance, intervention, and/or trial options, ultimately improving patient outcomes.

Background: MRI-guided transurethral ultrasound ablation (TULSA) is under investigation for whole-gland ablation of low- and intermediate-risk prostate cancer. The ideal method for post-TULSA bladder drainage through postoperative suprapubic tube (SPT) vs indwelling urethral catheter (UC) has not been established. The objective of this study was to evaluate urinary outcomes after whole-gland TULSA, comparing postoperative SPT with UC. Materials and Methods: Two-institution retrospective analysis of whole-gland TULSA for men with grade group 1 and 2 prostate cancer. One institution placed SPT at the time of TULSA with clamp trials (day 10) and removal once voiding. The second placed UC until void trial (day 7). Outcomes included the International Prostate Symptom Score (IPSS), urinary bother score, catheter reinsertion, stricture, clean intermittent catheterization (CIC), and incontinence. Results: Forty-five patients (median age 67) were analyzed. The UC cohort ( N = 26) was older ( p = 0.007) than the SPT cohort ( N = 19) but with similar baseline prostate volumes, IPSS, and urinary bother scores. Patients receiving UC had fewer days with catheter ( p = 0.013). Although UC patients suffered more lower urinary tract symptoms at 1-month post-TULSA, there was no significant difference between IPSS scores at baseline and 6 months after surgery regardless of urinary management strategy, although the UC group noted significantly decreased urinary bother. Rates of infection were similar between groups. Six strictures were observed overall, with more in the SPT group, although the difference was not significant (4/19 [21.1%] SPT; 2/26 [7.7%] UC). At 6 months, incontinence rates were low and similar between groups (2/19 [10.5%] SPT; 4/26 [15.4%] UC) and only one patient (UC) required CIC. Conclusions: Our overall findings suggest that SPT and UC are both acceptable options for postoperative bladder drainage after whole-gland TULSA, with statistically similar rates of urinary complications but a slightly different side effect profile.