By Melane Sampson
Castle Biosciences (NASDAQ: CSTL) is helping clinicians move beyond traditional pathology using gene expression profiling to reveal the underlying biology of a patient’s tumor, enabling more personalized treatment and disease management decisions.
The company’s proprietary molecular tests provide prognostic and diagnostic information that complements conventional clinical and pathological assessment, helping physicians better evaluate a patient’s risk of disease progression, recurrence, and metastasis while tailoring surveillance and treatment strategies accordingly.
“We believe that every patient’s journey is unique, which is why our focus is on delivering testing that goes beyond traditional diagnostic methods with advanced precision and personalized approaches that can help improve patient outcomes,” Matthew Goldberg, MD, senior vice president of medical at Castle, says in an interview with BioTuesdays.
Rather than relying solely on how a tumor appears under the microscope, Dr. Goldberg explains that Castle’s gene expression profiling (GEP) technology measures RNA expression across selected genes associated with tumor behavior, including growth, invasion, and metastasis. The resulting molecular profile provides additional insight into the biological aggressiveness of an individual patient’s cancer, information that can be incorporated alongside traditional clinicopathologic factors to guide treatment decisions.
“Because diseases are biologically complex, developing accurate testing products requires scientific rigor, robust clinical protocols, advanced machine learning expertise, proprietary algorithms, and the dedication of a highly skilled team,” Dr. Goldberg contends.
He adds that once a test is successfully developed and validated, Castle continues generating clinical evidence that supports integration into routine patient care.
The company currently markets six proprietary laboratory-developed tests, including four prognostic assays—DecisionDx-Melanoma for cutaneous melanoma, DecisionDx-SCC for cutaneous squamous cell carcinoma, DecisionDx-UM for uveal melanoma, and TissueCypher for Barrett’s esophagus. It also currently markets MyPath Melanoma, a diagnostic test designed to help classify challenging melanocytic lesions and AdvanceAD-Tx, a therapy selection test designed to guide systemic treatment decision-making in patients with moderate-to-severe atopic dermatitis.
Castle’s tests are supported by multiple peer-reviewed publications demonstrating analytical performance, clinical validity, and clinical utility. According to Dr. Goldberg, numerous studies have also shown that physicians modify patient management after incorporating test results into their decision-making.
“Among Castle’s portfolio, DecisionDx-Melanoma was the first prognostic test for patients with melanoma and is the only gene expression profile test for melanoma shown to be associated with improved survival,” he notes.
Dr. Goldberg points out that the test addresses an important clinical challenge. Although most patients with melanoma present with stage I or stage II disease and are considered relatively low risk, each stage encompasses patients with markedly different tumor biology. As a result, traditional staging alone can underestimate the risk carried by patients whose cancers appear clinically early but possess aggressive molecular characteristics.
“The majority of patients diagnosed with melanoma fortunately present with localized disease that can be completely removed surgically,” Dr. Goldberg says. “However, not all patients carry the same underlying risk.”
He outlines that DecisionDx-Melanoma analyzes the expression profile of 31 genes from a patient’s primary melanoma tumor and integrates that result with established clinicopathologic risk factors through proprietary algorithms, producing two individualized estimates: the risk of recurrence and the likelihood that melanoma has spread to nearby lymph nodes.
Those personalized assessments help physicians answer two critical questions early in the patient’s care: whether a sentinel lymph node biopsy is warranted for staging and how intensively the patient should be monitored.
“High-quality melanoma care is fundamentally risk-aligned,” Dr. Goldberg says. “Patients with higher risk may benefit from more intensive surveillance and multidisciplinary management, while those with lower risk may safely avoid unnecessary procedures and follow-up.”
He adds that the test also supports shared decision-making by giving patients a clearer understanding of their individual prognosis rather than relying solely on population-based staging categories.
“Importantly, DecisionDx-Melanoma is intended to complement—not replace—existing staging systems by adding independent biological information that improves risk stratification beyond conventional clinical and pathological features,” Dr. Goldberg clarifies.
Clinical evidence supporting DecisionDx-Melanoma continues to expand. In one of the largest, real-world evaluations of GEP in melanoma, Castle collaborated with the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program to link testing and outcomes data from more than 4,500 clinically tested patients.
The study demonstrated that DecisionDx-Melanoma provided significant prognostic information independent of the American Joint Committee on Cancer’s Eighth Edition staging system. In a matched analysis comparing patients tested with DecisionDx-Melanoma with untested patients who had similar clinicopathologic and demographic profiles, testing was associated with a 29% lower three-year melanoma-specific mortality rate and a 17% lower overall mortality rate.
“We found that the test provides independent prognostic information beyond traditional clinical and pathological factors,” Dr. Goldberg says. “Patients who received DecisionDx-Melanoma as part of their clinical care were associated with significantly improved survival compared with similar patients who were not tested.”
Additional studies suggest that more accurate risk stratification can also improve disease surveillance. Dr. Goldberg highlights a retrospective analysis conducted at three National Cancer Institute-designated cancer centers where physicians used DecisionDx-Melanoma results to guide follow-up imaging for patients with high-risk GEP scores despite negative sentinel lymph node biopsies.
“The study concluded that patients who received routine imaging after high-risk GEP test scores had earlier recurrence diagnoses with lower tumor burden, which was associated with better clinical outcomes,” Dr. Goldberg says.
He emphasizes that compared with patients managed using conventional follow-up alone, recurrence was detected approximately 10 months earlier in tested patients who received routine imaging, tumor burden was substantially lower, and overall survival was improved.
The company also generated prospective evidence supporting the test’s role in guiding sentinel lymph node biopsy (SLNB) decision-making through its multicenter DECIDE study. The study
showed that the DecisionDx-Melanoma test can predict a patient’s likelihood of having a
positive sentinel lymph node (SLN) and also identify low-risk patients who may
consider forgoing the biopsy procedure. Moreover, the study demonstrated a 9.3-fold difference in SLN positivity between the lowest- and highest-risk groups among patients with tumors ranging from T1a with high-risk features through T2a, the population in which SLNB guidance is most clinically relevant. Among these patients who underwent SLNB, the observed SLN positivity rate was 1.8% for those predicted by the test to have less than 5% risk, compared with 16.7% for those predicted to have greater than 10% risk.
Dr. Goldberg underscores that the 1.8% observed SLN positivity rate is clinically important because it falls well below the 5% threshold below which National Comprehensive Cancer Network (NCCN) guidelines recommend forgoing SLNB. These results show that the test’s individualized risk estimates can help inform important SLNB decisions within established NCCN Guideline thresholds. Further, patients identified by the DecisionDx-Melanoma test as having less than a 5% likelihood of SLN positivity experienced excellent outcomes, with nearly 98% remaining recurrence-free at three years.
“The goal is to bring the right intensity of management to the right patient,” Dr. Goldberg says. “By improving risk stratification, clinicians can more closely align surveillance and treatment with a patient’s true biological risk.”
Dr. Goldberg says Castle has also demonstrated the value of GEP in diagnostically challenging melanocytic lesions. Studies show that incorporating Castle’s MyPath Melanoma results can reduce ambiguous diagnoses by more than 40%, while benign test results have been associated with a 72% reduction in re-excisions compared with initial pathology recommendations—potentially sparing patients unnecessary procedures.
“To date, DecisionDx-Melanoma has been ordered for more than 250,000 patients by over 17,000 clinicians and is supported by more than 50 peer-reviewed publications, including prospective studies and meta-analyses,” Dr. Goldberg says. “The test is covered by Medicare and multiple commercial insurers, reflecting growing acceptance of molecular risk stratification as part of routine melanoma care.”
Beyond melanoma, Castle continues expanding its precision diagnostics platform across dermatology, gastroenterology, and ocular oncology through a portfolio designed to address significant unmet needs where improved risk assessment can meaningfully influence patient management.
Looking ahead, Dr. Goldberg says the company remains focused on advancing first- and best-in-class molecular tests supported by robust clinical evidence and real-world validation. As of June 2026, Castle reported cash, cash equivalents, and marketable investment securities totaling approximately $266.8 million, providing financial flexibility to support continued product development and commercial expansion.
“We’re excited about our ability to answer important clinical questions throughout the patient journey,” Dr. Goldberg concludes. “By providing personalized molecular insights, we’re helping clinicians make better-informed decisions while empowering patients with a clearer understanding of their disease.”
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