Over the past decade, oncology has moved steadily toward a simple idea that is surprisingly hard to execute well: if we want to understand treatment toxicity, we have to listen to patients directly, not just interpret their experience through clinician notes.

The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was created for exactly this purpose. It gives patients a structured way to report symptomatic toxicities such as nausea, diarrhea, neuropathy, or fatigue, using standardized questions that can be analyzed alongside clinician CTCAE grading.

In September 2025, an analysis of 327 oncology trials listed on ClinicalTrials.gov took a closer look at how PRO-CTCAE is actually being used. The picture that emerges is clear: adoption is increasing, particularly in early-phase interventional studies, and gastrointestinal symptoms are among the most commonly assessed patient-reported toxicities.

Below is a high-level look at what that means for researchers, sponsors, and care teams.

What PRO-CTCAE Brings to the Table

Traditional CTCAE grading is assigned by clinicians, based on chart review, lab values, and direct patient encounters. It is essential for safety oversight and regulatory reporting, but it has known limitations:

• Symptoms may be under-reported if they are not explicitly elicited or documented.

• Nuances in severity (for example, “bothersome but manageable” versus “disabling”) can be lost in translation.

• Visit-based encounters may miss fluctuations between appointments.

PRO-CTCAE addresses this gap by asking patients directly about:

• Frequency (how often a symptom occurs)

• Severity (how bad it is)

• Interference (how much it disrupts daily life)

When combined thoughtfully with clinician-assigned CTCAE grades, it gives a more complete view of treatment burden and tolerability.

What the September 2025 Snapshot Shows

Growing adoption across oncology trials

The review of 327 oncology trials using PRO-CTCAE on ClinicalTrials.gov shows a clear upward trend in adoption over time. While PRO-CTCAE is still far from universal, it is moving from niche usage to something closer to standard practice in many research programs.

This growth is particularly visible in trials that:

• Are evaluating novel agents with complex toxicity profiles

• Aim to differentiate treatments not only by efficacy but by tolerability and quality of life

• Need more granular data to support dose optimization and real-world use

Concentration in phase II interventional studies

Most of the identified trials using PRO-CTCAE were phase II interventional studies.

That makes intuitive sense:

• Phase I trials are often primarily focused on safety and dose-finding with relatively small cohorts.

• Phase II is where questions of tolerability, patient experience, and early comparative signals start to matter more.

• By phase III, protocols may already be locked down, and adding new PRO instruments late can be challenging.

In phase II, there is enough structure to systematically collect PRO-CTCAE data, but still enough flexibility to refine how it is used.

Gastrointestinal symptoms dominate the symptom set

Among the trials reviewed, gastrointestinal (GI) symptoms were among the most commonly assessed via PRO-CTCAE. This is not surprising in oncology, where many regimens are associated with:

• nausea and vomiting

• diarrhea or constipation

• appetite changes

• abdominal discomfort

These toxicities are highly symptomatic, often fluctuate over time, and significantly affect quality of life. They are also areas where patients’ day-to-day experience may diverge from what is visible in clinic visits or lab results, which makes PRO-CTCAE especially valuable.

How Trials Are Using PRO-CTCAE Today

As a complementary lens, not a replacement

The analysis of ongoing studies on ClinicalTrials.gov shows a consistent pattern: PRO-CTCAE is typically used as a secondary endpoint, not as a replacement for clinician CTCAE grading.

Many active oncology trials now:

• Use clinician CTCAE for traditional safety reporting and regulatory requirements.

• Add PRO-CTCAE to capture patient-reported symptomatic toxicity as a parallel, structured data stream.

This complementary approach acknowledges that:

• Clinicians provide a critical, standardized safety assessment.

• Patients provide irreplaceable information about how treatment actually feels.

Spread across tumor types and trial phases

The ongoing trials incorporating both CTCAE and PRO-CTCAE span a range of cancers and designs. Examples include:

• Phase I/II neuroendocrine cancer studies, exploring tolerability of novel combinations and targeted agents.

• Breast cancer trials, where long treatment courses and chronic toxicity profiles make patient-reported symptoms particularly important.

• Leukemia trials, where fluctuating symptom burden, supportive care, and treatment intensity can be better understood through patient input.

In these studies, PRO-CTCAE often plays a role in:

• Characterizing tolerability profiles beyond standard lab and imaging data.

• Informing dose modification rules, especially where symptoms drive dose reductions.

• Enriching benefit–risk discussions, both internally and with regulators and patients.

Why This Trend Matters

For sponsors and investigators

Growing use of PRO-CTCAE reflects a broader shift in how trials are designed and evaluated:

• Regulators and payers are increasingly attentive to patient experience, not just survival curves.

• Competing therapies with similar efficacy are often differentiated by tolerability and quality-of-life impact.

• More granular toxicity data can support labeling, shared decision-making, and real-world adoption.

Incorporating PRO-CTCAE thoughtfully can strengthen the totality of evidence without displacing established safety workflows.

For research sites and clinical teams

Sites involved in trials that use PRO-CTCAE will need:

• Clear processes for educating patients on how and when to complete PRO-CTCAE items.

• Reliable workflows for collecting, monitoring, and acting on patient-reported toxicities when thresholds are met.

• Practical integration into existing safety review and AE documentation routines.

Handled well, PRO-CTCAE becomes a tool that enhances patient communication rather than adding noise or unmanageable workload.

For patients

For patients, the rise of PRO-CTCAE represents a quiet but important shift:

• Their experience is not only heard in clinic, it is captured systematically.

• Symptoms that may not trigger immediate dose changes still count as part of the overall treatment story.

• Over time, better PRO data can help future patients and clinicians make more informed choices about therapies.

Key Takeaways from the 327-Trial Review

From this September 2025 analysis of oncology trials on ClinicalTrials.gov, a few concise conclusions emerge:

1. Use of PRO-CTCAE is rising, particularly in phase II interventional oncology studies.

2. Gastrointestinal symptoms are among the most commonly assessed patient-reported toxicities.

3. Most trials use PRO-CTCAE as a secondary endpoint, paired with clinician CTCAE grading rather than replacing it.

4. Active trials across multiple tumor types, including neuroendocrine cancer, breast cancer, and leukemia, are already using integrated CTCAE and PRO-CTCAE reporting to evaluate tolerability.

The direction is clear: oncology trials are moving toward a more complete picture of toxicity, one that combines clinician expertise with the patient’s own voice. How each organization implements PRO-CTCAE will vary, but the underlying trend is now well under way.