Clinical trials test new therapies by selecting specific, measurable outcomes, known as endpoints, to track patients. In oncology, two frequently used endpoints are Progression-Free Survival (PFS) and Event-Free Survival (EFS). Both metrics measure the time a patient lives without a negative health outcome. However, they differ significantly in what they count as a “negative outcome” or “event,” which ultimately influences how treatment success is interpreted.
Defining Progression-Free Survival (PFS)
Progression-Free Survival (PFS) measures the length of time a patient lives during and after treatment without the cancer worsening or the patient dying. This endpoint is widely used in trials for advanced or metastatic cancer because it offers a quick assessment of a drug’s direct impact on tumor growth. The time period begins when a patient is enrolled and ends with the first documented instance of disease progression or death from any cause.
Defining “progression” relies on objective, measurable changes in tumor size or the appearance of new lesions. This is typically determined by standardized radiological assessments, such as computed tomography (CT) or magnetic resonance imaging (MRI) scans. Researchers use internationally recognized rules, like the Response Evaluation Criteria in Solid Tumors (RECIST), to declare progression. Because it includes death from any cause, PFS provides a more robust measure than simply tracking tumor growth alone.
Defining Event-Free Survival (EFS)
Event-Free Survival (EFS) is a broader measure of treatment success compared to PFS, capturing more of the patient’s overall journey. EFS is defined as the time from the start of treatment until the first occurrence of a predefined, negative clinical outcome, known as an “event.” While progression is certainly an event, EFS incorporates a wider spectrum of adverse outcomes that impact the patient’s health and treatment plan.
The events that stop the EFS clock typically include cancer relapse, disease progression, or death from any cause. EFS definitions often account for major complications not directly related to tumor growth, such as the development of a second, unrelated cancer. EFS is frequently employed in studies where patients are treated with the intent to cure, such as in neoadjuvant or adjuvant settings, providing a comprehensive picture of long-term therapeutic benefit and treatment failure.
The Key Distinction: Criteria for Measurement
The fundamental difference between the two endpoints lies in the types of clinical setbacks that qualify as an “event.” Progression-Free Survival is narrowly focused on the tumor’s status, defined by quantifiable changes in tumor volume. For instance, according to RECIST criteria used in solid tumors, an increase in the sum of diameters of target lesions by at least 20% is required to meet the definition of progression, thus ending the PFS period.
Event-Free Survival, however, encompasses a much wider range of negative clinical occurrences that reflect a failure of the overall treatment strategy, even if the tumor size remains stable. In trials for hematologic malignancies like acute myeloid leukemia, an EFS event might be defined as the failure to achieve a complete remission after induction therapy. EFS definitions can also include non-tumor-related adverse occurrences, such as a severe adverse event that necessitates discontinuing the study treatment. This makes EFS a better reflection of the tolerability and feasibility of a complex treatment regimen, capturing the entire clinical experience rather than just the anti-cancer effect.
Why Researchers Choose One Over the Other
The choice between PFS and EFS is determined by the specific research question, the stage of the disease, and the type of treatment under investigation. Progression-Free Survival is the preferred endpoint when the goal is to demonstrate the anti-tumor activity of a new drug in patients with measurable disease. Since progression can be detected earlier than a difference in overall survival, PFS allows clinical trials to be completed more quickly and with fewer patients, accelerating the development of new treatments.
Conversely, researchers select Event-Free Survival when testing a complex treatment strategy, often involving multiple steps like chemotherapy followed by surgery. EFS is common in the neoadjuvant setting, where treatment is given before surgery, as it captures failures like the inability to proceed with the planned surgery due to disease progression or toxicity. EFS accounts for a greater number of potential pitfalls along the patient’s therapeutic journey, providing a comprehensive measure of long-term success.