The FDA has granted Breakthrough Device designation to the DCISionRT test developed by PreludeDx, a significant step forward in personalized risk assessment for women diagnosed with ductal carcinoma in situ (DCIS), also known as stage 0 breast cancer. This designation aims to expedite the development and review of innovative devices that show promise in improving the treatment or diagnosis of life-threatening conditions.
DCISionRT is designed to predict the benefit of radiation therapy (RT) following breast-conserving surgery (BCS) and to provide a 10-year risk assessment for breast cancer recurrence. The test analyzes seven protein biomarkers and four clinical factors, using a non-linear algorithm to generate a DecisionScore that categorizes a patient's risk as low, elevated, or residual. This score helps oncologists determine which patients are most likely to benefit from RT, potentially reducing both under- and over-treatment.
Clinical Utility Demonstrated in PREDICT Study
The clinical utility of DCISionRT was highlighted in the prospective, multi-center PREDICT study (NCT03448926), which enrolled 2,496 patients between February 2018 and January 2022. Findings from 2,007 eligible women across 63 centers in the United States, who were offered the DCISionRT test as part of their standard of care, were reported. The study's primary endpoint was the percentage of patients in whom DCISionRT testing led to a change in radiotherapy recommendation.
The results of the PREDICT study demonstrated that DCISionRT test results led to changes in pre-test to post-test radiotherapy recommendations in 38% of patients. Notably, there was a 20% net reduction in the number of patients recommended for radiotherapy post-test (51%) compared to pre-test (71%; P < .001). Furthermore, the test influenced treatment decisions, with 41% of patients initially recommended for radiotherapy having their recommendation changed to no radiotherapy post-test, and 31% of those not initially recommended for radiotherapy subsequently being recommended for it based on DCISionRT results.
Impact on Treatment Decisions
The DecisionScore generated by DCISionRT was found to be the strongest predictor of post-test radiotherapy recommendation compared to traditional clinicopathologic factors, including tumor grade and size. Specifically, the rates of post-test radiotherapy recommendations increased with increasing DecisionScore: 29% for DecisionScore < 2, 66% for DecisionScore 2-4, and 91% for DecisionScore > 4. The odds ratio for DecisionScore > 3 vs ≤ 3 was 22.2 (95% CI, 16.3-30.7), underscoring the test's significant impact on treatment planning.
Identifying Risk in HER2-Positive DCIS
Another study demonstrated the utility of DCISionRT in identifying increased risk of in-breast recurrence in patients with HER2-positive DCIS. Among 178 patients with HER2-positive DCIS who underwent BCS with chemotherapy, 63% were identified as having residual risk subtype disease by the DCISionRT test. Patients with the residual risk subtype had a significantly higher total in-breast recurrence risk compared to other subtypes (HR, 8.3; 95% CI, 1.1-50.0; P = .01).
Management Perspective
Dan Forche, president and CEO of PreludeDx, emphasized the importance of DCISionRT in addressing the unmet need for DCIS patients by providing answers to critical questions regarding the necessity and benefit of radiation therapy. He stated, "DCISionRT helps patients and their physicians to make a better and more informed treatment decision." Forche also expressed the company's commitment to working closely with the FDA and providing access to advanced precision diagnostics in breast cancer care.
With over 60,000 women newly diagnosed with DCIS each year in the United States, DCISionRT represents a significant advancement in personalized breast cancer care, offering the potential to refine treatment strategies and improve patient outcomes.
