Plus Therapeutics wins major reimbursement milestone as Humana approves CNSide cerebrospinal fluid assay

Plus Therapeutics, Inc. (NASDAQ: PSTV) has strengthened its commercial position in the central nervous system oncology space after securing national coverage from Humana Inc. for the company’s CNSide cerebrospinal fluid assay. The agreement, which took effect on October 29, 2025, extends reimbursable access to approximately 16 million additional members, raising the test’s total coverage pool to an estimated 67 million people. For a company that has been working to advance both diagnostics and radiotherapeutics for complex CNS malignancies, the addition of a major national payer marks a defining moment that materially improves adoption prospects and reinforces the clinical relevance of tumor-cell enumeration in metastatic CNS cancer care.

The company highlighted that Humana’s evaluation process considered real-world evidence demonstrating how CNSide can support oncologists in identifying tumor cells in cerebrospinal fluid with reported sensitivity and specificity above 90 percent. Because leptomeningeal metastases remain difficult to diagnose and monitor due to subtle clinical presentation and limitations in MRI and cytology, the ability to generate quantitative tumor-cell data has been gaining attention among specialists. Plus Therapeutics reported that clinicians have already performed more than 11,000 CNSide tests since 2020, and its use at more than 120 U.S. cancer centers played a meaningful role in validating payer confidence. This combination of clinical data and demonstrated utilization contributed to Humana’s decision to recognize the assay’s potential to improve care management for patients with metastatic central nervous system disease.

As the company described, reimbursement expansion represents not only a validation milestone but also a structural improvement in access. Broader coverage directly reduces financial barriers that have historically slowed adoption of novel diagnostic technologies, especially those that sit between oncology, neurology, and advanced pathology workflows. With Humana’s national policy in place, oncologists treating patients with suspected or confirmed leptomeningeal metastases may incorporate the test more routinely as part of longitudinal monitoring. This enhanced access supports clinical decision-making by providing timely insights into disease activity, therapeutic response, and potential recurrence patterns, all of which are critical for patients facing aggressive metastatic progression.

How expanding national reimbursement may influence early adoption trends for a cerebrospinal fluid assay used in metastatic CNS cancer

The increased reimbursement footprint deepens the foundation for more widespread clinical adoption. Specialists in neuro-oncology have repeatedly stressed the need for tools that can capture dynamic changes in disease activity, and tumor-cell enumeration has emerged as a promising approach because it offers quantitative data rather than subjective assessments. For clinicians accustomed to relying on MRI findings that can lag behind biological changes, or CSF cytology that may miss early metastatic spread, CNSide provides a more consistent and actionable dataset. The addition of Humana’s coverage therefore positions more patients to undergo testing at regular intervals, which may lead to earlier interventions and finer-tuned treatment adjustments.

From an operational perspective, the expanded coverage may also encourage cancer centers to integrate the assay more deeply into their workflows. Reimbursement stability often accelerates test ordering, improves approval predictability, and reduces administrative friction—factors that can significantly influence clinical behavior. Plus Therapeutics has emphasized its aim to build a more standardized diagnostic ecosystem around CNSide, and payer alignment helps reduce uncertainty for providers who previously weighed cost-effectiveness concerns before incorporating novel assays into routine practice. Over time, these changes can foster broader institutional protocols for metastatic CNS monitoring and strengthen the position of CSF-based diagnostics within multidisciplinary tumor boards.

Why a national payer agreement may shape the competitive dynamics around emerging diagnostics for CNS metastases

The CNS metastasis diagnostics market is still in an early growth phase, with several companies developing novel approaches but few possessing widespread payer support. Coverage decisions often establish competitive baselines, and Humana’s approval serves as a differentiating factor for Plus Therapeutics at a time when the industry is increasingly focused on commercialization pathways. Real-world evidence demonstrating CNSide’s influence on treatment decisions was a distinct advantage in payer negotiations, reinforcing the assay’s relevance in day-to-day oncology care rather than positioning it solely as a specialized research tool.

This coverage decision also aligns with broader shifts in payer strategy. As healthcare systems confront rising oncology costs, payers are demonstrating growing interest in diagnostics that help guide targeted therapy selection, prevent unnecessary interventions, and provide more accurate assessments of treatment progression. CNSide’s quantitative results address exactly these needs by providing clinicians with an objective metric for disease activity, reducing ambiguity in cases where traditional diagnostic methods fall short. If adoption expands at major academic centers and community oncology networks, this could accelerate additional coverage decisions from other insurers and raise competitive barriers for diagnostics still navigating early validation phases.

How investors may interpret the reimbursement expansion given Plus Therapeutics’ stock performance and clinical-stage profile

Plus Therapeutics’ share price remains in the sub-$1 range, consistent with its status as a clinical-stage company operating in capital-intensive oncology segments. Investor sentiment toward companies at this stage typically depends on the strength of their scientific foundation, commercial strategy, and near-term catalysts. While diagnostics revenue is not expected to transform the company’s financial profile in the immediate term, Humana’s coverage decision signals commercial traction that investors often treat as an early form of validation. This type of milestone reduces perceived reimbursement risk and demonstrates that a major payer has assessed both clinical and economic value.

The company continues to face the challenges inherent to small-cap biotech development, including the need for capital to advance its radiotherapeutic pipeline for glioblastoma and leptomeningeal metastases. However, the diagnostics business provides a complementary avenue for building credibility while offering an incremental revenue channel that softens reliance on longer-timeline therapeutic milestones. Investors will likely monitor how frequently CNSide is ordered under Humana coverage, whether test volumes rise at a pace consistent with coverage expansion, and how payer mix evolves as additional insurers update their policies. Sustained volume growth could materially influence sentiment by illustrating that the diagnostics unit is not only gaining coverage but also converting coverage into meaningful clinical adoption.

What expanded payer momentum could mean for future iterations of CSF-based cancer diagnostics and integrated CNS disease management

The national coverage agreement places Plus Therapeutics in a position to help shape the future of CSF-based diagnostic innovation. As utilization increases and more real-world evidence accumulates, the company could explore enhancements such as deeper phenotypic characterization, integration of additional biomarkers, or AI-driven pattern recognition tools that refine predictive and prognostic capabilities. Payers increasingly value diagnostics that improve monitoring accuracy and reduce avoidable interventions, creating opportunities for companies that can link advanced analytics with clear clinical outcomes.

For providers, improved access may encourage broader adoption of serial testing, enabling oncologists to generate time-based tumor-cell profiles that reveal treatment sensitivity, resistance trends, or early signs of relapse. This longitudinal view aligns with modern oncology’s shift toward personalized and adaptive care. As CNS-focused cancer centers evaluate the clinical value of frequent monitoring, the presence of stable national reimbursement lowers barriers to experimenting with new diagnostic algorithms and incorporating them into multidisciplinary management pathways.

For patients, Humana’s decision represents a meaningful expansion of access to high-value diagnostic information at a critical point in the cancer journey. Leptomeningeal metastases are among the most challenging complications of metastatic disease, and the ability to track disease activity with greater accuracy can influence treatment choices and potentially improve quality of life. As more payers follow suit, the standard of care for metastatic CNS involvement may shift toward more proactive, data-driven monitoring, with CNSide serving as a central component of that evolution.