Dataset Information

Eligibility and Radiologic Assessment in Adjuvant Clinical Trials in Bladder Cancer.

ABSTRACT:

Objective

To harmonize eligibility criteria and radiographic disease assessments in clinical trials of adjuvant therapy for muscle-invasive bladder cancer (MIBC).

Methods

National experts in bladder cancer clinical trial research, including medical and urologic oncologists, radiologists, biostatisticians, and patient advocates, convened at a public workshop on November 28, 2017, to discuss eligibility, radiographic entry criteria, and assessment of disease recurrence in adjuvant clinical trials in patients with MIBC.

Results

The key workshop conclusions for adjuvant MIBC clinical trials included the following points: (1) patients with urothelial carcinoma with divergent histologic differentiation should be allowed to enroll; (2) neoadjuvant chemotherapy is defined as at least 3 cycles of neoadjuvant cisplatin-based combination chemotherapy; (3) patients with muscle-invasive, upper-tract urothelial carcinoma should be included in adjuvant trials of MIBC; (4) patients with severe renal insufficiency can enroll into trials using agents that are not renally excreted; (5) patients with microscopic surgical margins can be included; (6) patients should undergo a standard bilateral lymph node dissection prior to enrollment; (7) computed tomographic (CT) imaging should be performed within 4 weeks prior to enrollment. For patients with renal insufficiency who cannot undergo CT imaging with contrast, noncontrast chest CT and magnetic resonance imaging of the abdomen and pelvis with gadolinium should be done; (8) biopsy of indeterminate lesions to evaluate for malignant disease should be done when feasible; (9) a uniform approach to evaluate indeterminate radiographic lesions when biopsy is not feasible should be included in any trial design; (10) a uniform approach to determining the date of recurrence is important in interpreting adjuvant trial results; and (11) new high-grade, upper-tract primary tumors and new MIBC tumors should be considered recurrence events.

Conclusions and relevance

A uniform approach to eligibility criteria, definitions of no evidence of disease, and definitions of disease recurrence may lead to more consistent interpretations of adjuvant trial results in MIBC.

SUBMITTER: Apolo AB

PROVIDER: S-EPMC8211913 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundBreast cancer (BC) is the most common cancer type in women. The purpose of this study was to assess the eligibility criteria in recent clinical trials in BC, especially those that can limit the enrollment of older patients as well as those with comorbidities and poor performance status.MethodsData on clinical trials in BC were extracted from ClinicalTrials.gov. Co-primary outcomes were proportions of trials with different types of the eligibility criteria. Associations between trial characteristics and the presence of certain types of these criteria (binary variable) were determined with univariate and multivariate logistic regression.ResultsOur analysis included 522 trials of systemic anticancer treatments started between 2020 and 2022. Upper age limits, strict exclusion criteria pertaining to comorbidities, and those referring to inadequate performance status of the patient were used in 204 (39%), 404 (77%), and 360 (69%) trials, respectively. Overall, 493 trials (94%) had at least one of these criteria. The odds of the presence of each type of the exclusion criteria were significantly associated with investigational site location and trial phase. We also showed that the odds of the upper age limits and the exclusion criteria involving the performance status were significantly higher in the cohort of recent trials compared with cohort of 309 trials started between 2010 and 2012 (39% vs 19% and 69% vs 46%, respectively; p < 0.001 for univariate and multivariate analysis in both comparisons). The proportion of trials with strict exclusion criteria was comparable between the two cohorts (p > 0.05). Only three of recent trials (1%) enrolled solely patients aged 65 or 70 and older.ConclusionsMany recent clinical trials in BC exclude large groups of patients, especially older adults, individuals with different comorbidities, and those with poor performance status. Careful modification of some of the eligibility criteria in these trials should be considered to allow investigators to assess the benefits and harms of investigational treatments in participants with characteristics typically encountered in clinical practice.

Project description:Although adjuvant chemotherapy (ACH) is widely used in clinical practice for the management of muscle-invasive bladder cancer (MIBC), a consensus has yet to be established on which ACH regimen is the most effective for improving postoperative survival. In this study, we aimed to systematically assess the optimal ACH regimen for improving survival outcomes in patients treated with radical cystectomy (RC) for MIBC. A comprehensive literature search was conducted in the PubMed, Embase, and the Cochrane Library databases for all articles published until December 2016 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The study end-points were progression-free survival (PFS) and overall survival (OS). A direct pairwise meta-analysis was conducted by pooling the studies that compared RC with ACH and RC alone, and the results are presented as a pooled hazard ratio (HR) with a 95% confidence interval (CI). A Bayesian network meta-analysis was adopted for indirect comparisons among various ACH regimens, and the outcomes are presented as HRs with 95% credible intervals (CrI). The eleven randomized controlled trials ultimately selected for the current analysis comprised of 1,546 patients with 49 to 327 subjects per study. Based on the pairwise meta-analysis, the use of ACH showed significantly better PFS (HR, 0.64; 95% CI, 0.49-0.85) and OS (HR, 0.79; 95% CI, 0.68-0.92) than RC alone. In the network meta-analysis, the gemcitabine/cisplatin/paclitaxel (GCP) combination was the only ACH regimen associated with significant improvement in both the PFS (HR, 0.38; 95% CrI, 0.25-0.58) and OS (HR, 0.38; 95% CrI 0.22-0.65). ACH following RC for MIBC may therefore contribute to improved PFS and OS. In particular, the GCP combination may be the optimal ACH regimen for improving postoperative survival outcomes. Additional well-designed, large scale, prospective, randomized trials are still required to establish the optimal ACH regimen in MIBC patients.

Project description:Loss of ovarian function is a recognized adverse effect of chemotherapy for breast cancer, and of great importance to patients. Little is known about the ovarian toxicity of newer cancer treatments. This study examined whether breast cancer clinical trials include assessment of the impact of trial interventions on ovarian function. Eligible trials were phase 3 (neo)adjuvant trials of pharmacologic treatments for breast cancer recruiting between June 2008-October 2019, which included premenopausal women. MEDLINE, EMBASE, Clinicaltrials.gov, EudraCT were searched. Data were extracted from trial publications, protocols, databases, and a survey sent to all trial chairs. Tests of statistical significance were two-sided. PROSPERO registration CRD42019134551. Of 2,354 records identified, 141 trials were eligible. Investigational treatments included chemotherapy (36.9%), HER2-targeted (24.8%), endocrine (12.8%), immunotherapy (7.8%), CDK4/6-inhibitors (5.0%), PARP-inhibitors (2.8%). Ovarian function was a pre-specified endpoint in 13 (9.2%) trials. Forty-five (31.9%) trials collected ovarian function data, but only 33 (23.4%) collected post-trial-intervention data. Common post-intervention data collected included menstruation (15.6%), pregnancy (13.5%), estradiol (9.9%) and follicle-stimulating hormone levels (8.5%). Only four (2.8%) trials collected post-intervention anti-mullerian hormone levels and three (2.1%) trials collected antral follicle count. Of 22 trials investigating immunotherapy, CDK4/6-inhibitors or PARP-inhibitors, none specified ovarian function as an endpoint, but four (18.2%) collected post-intervention ovarian function data. The impact of pharmacologic interventions on ovarian function is infrequently assessed in phase 3 breast cancer (neo)adjuvant trials that include premenopausal women. Trialists should consider inclusion of ovarian function endpoints when designing clinical trials, given its importance for informed decision-making.