Screened But Unproven

I read with interest the paper by Cheng et al¹ on cardiac troponin screening with immune checkpoint inhibitors (ICIs). The study addresses an important concern; however, I have several critiques.

First, the single-center retrospective design lacked a control group not undergoing troponin surveillance. This absence of a comparator limits causal inference regarding the benefit of troponin screening. Any association between routine troponin monitoring and improved outcomes cannot be conclusively attributed to the screening itself without a comparison. Evidence from prospective or randomized studies evaluating cardiac monitoring in ICI patients remains absent,² making it premature to assume troponin surveillance alters clinical outcomes.

Second, the analysis did not adequately adjust for confounders (cancer type, ICI regimen, or pre-existing cardiac risk factors). Combination therapy carries higher myocarditis risk than monotherapy.² Without adjustment for these variables, outcome differences may reflect baseline risk rather than the effect of troponin screening.³

Third, only 6 patients (≈1.4% of 428) were diagnosed with ICI-associated myocarditis.¹ This small number of events limits statistical power and makes subgroup analyses unstable. Given the rarity of ICI myocarditis (0.1%-1% in large studies),² the study was underpowered to detect meaningful outcome differences.

Fourth, the generalizability of the troponin screening protocol is unclear. The investigators describe systematic surveillance with a specialized triage algorithm and 24/7 cardio-oncology support,¹ a resource-intensive model not likely feasible at most centers. Notably, 145 of 709 eligible patients could not undergo the protocol, because they were receiving care at outside clinics lacking this infrastructure.¹ Although guidelines suggest troponin monitoring during early ICI cycles,⁴ these recommendations rely on expert opinion rather than trial evidence, and many institutions cannot replicate real-time triage.

Finally, the investigators highlight the 100% negative predictive value (NPV) of troponin screening.¹ Yet in a low-prevalence setting such as ICI myocarditis, a high NPV is expected and potentially misleading: most patients will test negative regardless.² This reflects rarity more than clinical utility. Moreover, the positive predictive value of troponin elevations is likely low, with many false positives. Overreliance on NPV risks overstating the usefulness of routine troponin testing.

In summary, Cheng et al¹ provide insights into troponin monitoring in ICI patients, but the limitations weaken their conclusions. The claim that surveillance “facilitates early intervention” should be cautious; only prospective studies can clarify its true value, and for now, a risk-stratified approach is most appropriate.