Oncology & Hematology Insight Report

Overall Survival in Oncology: When Should Surrogate Endpoints Count?

A peer-level look at how oncology and hematology clinicians weigh overall survival against PFS/EFS, MRD and ctDNA, quality of life, toxicity, reimbursement, and the evidence needed to trust accelerated approvals.

Audience: Oncology & Hematology Clinicians

Countries: 6

Completion Rate: 70.8%

SGID: 8945208

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-Hero findings

0 %
view a regulator-approved drug with a robust PFS/EFS gain but no OS benefit as moderately acceptable, prescribing it while explaining that longer total lifespan has not been confirmed.
say OS is necessary in late-stage or relapsed disease, while surrogate endpoints should replace it in selected early, adjuvant, or certain settings.
0 %
identify hematologic malignancies as the setting most ready for negative MRD/ctDNA to serve as a standalone approval endpoint.
0 %
say symptom palliation, preserved function, and daily quality of life most often drive the final late-line shared decision.
0 %
say mandatory real-world evidence tracking alongside confirmatory trials would most improve confidence in accelerated approvals.
0 %

– Quick Read — Key Findings

01 // OS benchmark
40.4%

Make OS setting-specific

The largest group keeps OS central in late-stage or relapsed disease but supports earlier surrogate endpoints in selected settings.

02 // Benefit-risk
59.6%

Modest OS gains trigger patient selection

Most would offer a higher-toxicity regimen primarily to younger, fit patients who prioritize maximum survival.

03 // MRD/ctDNA
46.2%

Hematologic malignancies look most ready

Clinicians place the strongest standalone-endpoint confidence in diseases such as myeloma, leukemia, and lymphoma.

04 // De-escalation
46.2%

MRD changes intensity before it stops therapy

The most common response to persistent MRD negativity is dose or frequency reduction, not complete cessation.

05 // Late-line decisions
40.4%

Function and symptom control can lead

In advanced disease discussions, palliation, performance status, and daily QoL outrank OS as the single largest decision driver.

06 // Accelerated approval
43.1%

RWE is the preferred confidence-builder

When OS takes years to mature, what should count as enough evidence?

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The backstory

The endpoint debate is now about context, not OS versus everything else

Overall survival remains one of the clearest measures of benefit in oncology, but modern treatment sequences, crossover, long post-progression survival, molecular response, and patient-reported outcomes make the endpoint hierarchy less uniform across disease settings.

 

The MDForLives survey asks oncology and hematology clinicians where they still need mature OS, where surrogates such as PFS or EFS are credible, when molecular response can support earlier decisions, and how much quality of life, toxicity, reimbursement, and confirmatory evidence shape what happens after a positive trial. External regulatory context is moving the same way: FDA Project Endpoint examines the complementary roles of early and late endpoints, and recent FDA guidance covers core patient-reported outcomes (2024), ctDNA in early-stage solid tumors (2024), assessing OS when it is not the primary endpoint (2025 draft), and MRD and complete response as accelerated-approval endpoints in multiple myeloma (January 2026 draft).

MDForLives interpretation: The emerging question is not whether OS still matters. It is how oncologists decide when an earlier endpoint is mature enough, clinically meaningful enough, and supported enough to act on before OS can answer every uncertainty.
Finding 1

Most clinicians keep OS, but not as a universal endpoint

40.4% say OS remains necessary in late-stage or relapsed settings, while surrogate endpoints should replace it in early, adjuvant, or selected settings.

 

The distribution is balanced around one idea: OS still matters, but its role should depend on the disease setting. Fifteen clinicians (28.8%) would keep OS mandatory for all definitive Phase 3 approvals, another 15 (28.8%) would demote it to secondary when PFS/EFS and QoL gains are convincing, and only one (1.9%) considers OS broadly obsolete, leaving the largest group using a setting-specific hierarchy rather than a single rule. Read against Finding 5, where 55.8% accept a robust PFS/EFS gain without proven OS, the pattern is consistent: clinicians will act on surrogates but want the endpoint matched to the setting, turning interpretation into a case-by-case judgment about when waiting for mature survival is worth it.

What this could mean for oncologists: Trial interpretation may increasingly start with the disease trajectory and treatment setting. In a long-survival or curative-intent setting, waiting for mature OS can take years; in aggressive relapsed disease, OS may remain the most consequential anchor.
Finding 2

A significant OS gain is not automatically a prescribing signal

59.6% would offer a higher-toxicity regimen with a modest OS benefit primarily to younger, fit patients who prioritize maximum survival.

For most respondents, a modest survival extension depends on who receives it and what toxicity they can carry: 31 of 52 clinicians make patient fitness and preference the main filter, 28.8% would routinely recommend any significant OS extension if toxicity stays manageable, and 9.6% favor the milder standard of care unless the patient asks for the aggressive option. The deeper signal is that a significant OS result is necessary but not sufficient, with fitness and tolerability as a second gate, so uptake of a modest-benefit, higher-toxicity regimen is likely to concentrate in younger, fitter patients rather than spread across all who are eligible.

Finding 3

Molecular response is most approval-ready in blood cancers

46.2% identify hematologic malignancies as the disease setting most ready for negative MRD/ctDNA status to serve as a standalone approval endpoint.

Nearly half choose hematologic diseases such as multiple myeloma, leukemia, and lymphoma, while 25.0% (13) choose early-stage curative solid tumors, 15.4% (8) late-stage or metastatic solid tumors, and 13.5% (7) say the evidence is not mature in any setting. The pattern mirrors the uneven maturity of molecular-response endpoints rather than blanket enthusiasm for ctDNA: grouped together, the three solid-tumor answers outweigh the hematologic vote, so this reads less as a green light for ctDNA than a judgment that only hematologic malignancies are close today, and solid-tumor programs should plan for a higher validation bar before molecular response can stand alone.

Why the disease setting matters: FDA has long addressed MRD as a biomarker in hematologic malignancies, and its January 2026 draft guidance specifically discusses MRD and complete response as primary endpoints for accelerated approval in multiple myeloma. In solid tumors, ctDNA is moving forward too, but assay harmonization, prognostic versus predictive meaning, and validation against clinical outcomes remain central.
Finding 4

QoL matters, but differently in regulation and at the bedside

50.0% would give validated PRO/QoL improvements secondary regulatory weight only when they are accompanied by statistically significant PFS/EFS gains.

The regulatory view is cautious: 26 of 52 clinicians place PRO/QoL behind a conventional efficacy signal such as PFS/EFS, 30.8% would give a meaningful, durable QoL improvement weight equal to OS, 13.5% see it mainly as supportive labeling and counseling evidence, and only 5.8% assign it minimal weight. The bedside points the other way, symptom palliation, preserved performance, and daily QoL are the largest single driver of late-line shared decisions at 40.4%, ahead of expected OS at 32.7% and PFS/EFS at 25.0%.

Finding 5

PFS/EFS without OS is usually acceptable, but the evidence problem persists

55.8% view a robust PFS/EFS extension without an OS benefit as moderately acceptable and would prescribe while explaining that total lifespan has not been shown to improve.

Twenty-nine clinicians take the middle position, using the drug but separating more time without progression from longer total survival, while 30.8% (16) consider the PFS/EFS gain fully meaningful on its own and only seven combined call it questionable or unacceptable. Access can still interrupt that acceptance: for surrogate-approved therapies, 42.3% see reimbursement or prior-authorization hurdles occasionally and 26.9% frequently, and 43.1%, the largest group, want mandatory real-world evidence tracking alongside confirmatory trials. Combined, 86.6% place PFS/EFS in acceptable territory, so surrogate-based decisions are mainstream, but the majority at moderately acceptable plus the 43.1% demand for RWE tracking shows acceptance is conditional, shifting the evidence burden downstream to confirmation and monitoring rather than ending at approval.

Closing Perspective

The debate is not OS versus surrogates, but matching evidence to the question

Across the survey, clinicians are not ready to abandon overall survival; they are building a more conditional evidence hierarchy. OS remains especially important where the decision is about irreversible mortality and mature survival can be measured meaningfully, while surrogate endpoints gain credibility when waiting for OS is slow, confounded, or poorly matched to the disease setting.

 

That hierarchy shifts once the result reaches the clinic. A modest OS gain may be offered selectively as toxicity and fitness change its value, persistent MRD negativity may support de-escalation before full cessation, a PFS/EFS benefit can justify prescribing while still requiring an explicit conversation that lifespan has not been proven, and in late-line care symptom relief, function, and daily quality of life can matter more to the patient than the endpoint that carried the trial.

// at a glance
Total Survey Records
72
Countries Covered
6
Specialty
Oncologists
Published Date
16 August 2026
Completion Rate
70.8%
Survey ID
8945208
// browse categories

Endocrinology, Diabetes & Metabolism

7

Oncology & Hematology

7

Hospital Administration

6

Primary Care & Family Medicine

6

Dermatology

6

Ophthalmology

6

Gastroenterology & Hepatology

6

Dentistry & Oral Health

5

Surgery & Procedural Care

5

Pharmacy

5

Pediatrics

5

Neurology

5

Nurses, NPs & Physician Assistants

4

Cardiology

4

Radiology & Imaging

3

Laboratory & Diagnostics

3

Optometry & Optical Care

3

Diabetes, Weight & Metabolic Health

3

Cancer Care

1

Skin & Aesthetic Care

1

Social Work & Patient Support

1

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People also ask

Frequently asked questions

Direct answers to common questions around this topic.

Is overall survival still the gold-standard endpoint in oncology trials?

Overall survival remains one of the most direct and important measures of clinical benefit because it measures how long patients live. However, oncology trials may also use validated earlier endpoints such as progression-free survival, event-free survival, response, disease-free survival, MRD, or other measures when the disease setting and evidence support them. FDA guidance increasingly addresses how OS should be assessed even when it is not the primary endpoint.

 

A surrogate endpoint is a laboratory, imaging, response, or other measure expected to predict clinical benefit but that is not itself a direct measure of how a patient feels, functions, or survives. In oncology, examples can include response rate, PFS, DFS, EFS, or molecular-response measures, depending on the disease and regulatory context.

 

PFS or EFS may be appropriate when they are clinically meaningful, reliably measured, and suitable for the disease setting, especially when waiting for mature OS would take many years or be confounded by subsequent treatment. Whether they can support approval depends on the endpoint, effect size, trial design, disease context, and the totality of evidence.

 

Potentially, but not universally. FDA has guidance on MRD in hematologic malignancies and ctDNA in early-stage solid-tumor drug development. A January 2026 draft guidance specifically addresses MRD and complete response as primary endpoints to support accelerated approval in multiple myeloma. Assay performance, disease setting, and validation remain critical.

 

Patient-reported outcomes can capture symptoms, physical function, treatment burden, and health-related quality of life directly from patients. FDA issued final guidance in 2024 on a core set of PROs for cancer trials. Their regulatory weight depends on how they are measured, the trial design, and how they fit with efficacy and safety evidence.

 

FDA accelerated approval can allow earlier access to a treatment for a serious condition based on a surrogate endpoint that is reasonably likely to predict clinical benefit. Confirmatory studies are required to verify that benefit, and an indication can be withdrawn if the expected benefit is not confirmed.

 

Direct answers to the questions healthcare professionals are most likely to ask about these findings.

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