Nadir Concept
title: “Nadir Concept” type: descriptor category: recist/descriptor tags: [recist, nadir, progressive-disease, partial-response] sources:
- file: “recist_eisenhauer_2009.pdf” page: “233”
- file: “recist_schwartz_2016.pdf” page: “133” date_created: 2025-04-15 date_modified: 2025-04-15 confidence: high anki_deck: “Radiology::RECIST” weak_area: false
Definition
The nadir is the smallest sum of diameters recorded at any timepoint during the study. It is the reference point against which Progressive Disease (PD) and continuing Partial Response (PR) are calculated.
Nadir vs. Baseline — Two Different References
| Assessment | Reference Point | Threshold |
|---|---|---|
| PR (Partial Response) | Baseline sum | ≥30% decrease |
| PD (Progressive Disease) | Nadir sum | ≥20% increase AND ≥5mm absolute |
| CR (Complete Response) | Baseline sum | All lesions = 0mm |
| SD (Stable Disease) | Nadir sum | Neither PR nor PD |
Two Different References
PR is calculated against BASELINE (the starting sum). PD is calculated against NADIR (the smallest sum seen so far). These are almost always different values.
Why Nadir Exists
The nadir concept exists to prevent false PD from transient fluctuations around the threshold:
- Measurement variability between readers and timepoints is approximately ±5% and ±1–2mm
- Without the nadir concept, a lesion shrinking 30% (PR) then bouncing back 1–2mm from that PR would immediately become PD
- The nadir is the “best confirmed response so far” — PD can only be declared when disease clearly grows beyond that best point
Practical Example
Baseline sum: 100mm
Week 8 sum: 55mm → PR (55/100 = 45% decrease, ≥30% = PR vs. baseline)
Week 16 sum: 62mm → SD (62/55 = 13% increase, <20% = SD vs. nadir)
Week 24 sum: 40mm → PR (40/100 = 60% decrease ≥30%, also below nadir)
Week 32 sum: 72mm → PD? (72/40 = 80% increase, ≥20% = yes; 72-40 = 32mm ≥5mm = yes → PD)
At week 32, nadir = 40mm (week 24). The 80% increase from 40mm and 32mm absolute increase both meet PD criteria → PD.
The 20% Threshold — Why It Exists
The 20% threshold for PD was chosen because:
- It is approximately 4 times the measurement variability (±5%)
- A 20% increase is unlikely to occur by chance alone
- It corresponds to approximately 30% change in the perpendicular diameter (the old WHO standard)
The 5mm Absolute Threshold — Why It Exists
The 5mm absolute minimum prevents PD calls from tiny lesions:
- A lesion with nadir of 8mm: a 2mm increase = 25% (above 20%) but only 2mm absolute (below 5mm) → NOT PD
- A lesion with nadir of 30mm: a 6mm increase = 20% AND 6mm absolute → PD
- This dual-threshold approach is specifically protective for small target lesions where percentage changes are exaggerated by tiny absolute fluctuations
Continuing PR
Once PR is confirmed, subsequent assessments continue to be reported as “continuing PR” until:
- PD criteria are met (vs. nadir)
- CR is achieved
- The patient progresses
The assessment at week 16 in the example above (sum 62mm) was SD vs. nadir 55mm — the patient remains in continuing PR overall. The 62mm does not re-trigger a new PR calculation against baseline.
Nadir in Clinical Practice
Outside clinical trials, the nadir concept is clinically intuitive:
- “How low did this patient’s tumor go?”
- “Is current imaging showing regrowth beyond that best response?”
- Disease that stays below nadir + 20% + 5mm = continuing response
- Disease that breaks above nadir + 20% + 5mm = progression