PSA Trajectory Modeling

Model PSA kinetics during Lu-177-PSMA therapy using evidence-based PSA trajectory families (literature-informed; not clinically validated for individual prediction). Predict PSA nadir and progression using PCWG3 criteria (≥25% + ≥2 ng/mL from nadir). Context anchors from VISION: PSA50=46%, PSA90=16%.

Important Clinical Disclaimer

This tool is evidence-based (VISION + literature), but not clinically validated for individual prediction:

PSA50 response rate is 46% , not the previously reported 75%
PSA90 response rate is 16% (deep responders are less common)
Median nadir occurs at 1.4 months , not 3-4 months
Progression requires both ≥25% increase AND ≥2 ng/mL from nadir (PCWG3)
Early PSA decline (≥30% at 4 weeks) predicts better overall survival

Clinical decisions should NOT be based solely on model predictions. Always correlate with imaging, clinical symptoms, and multidisciplinary team input.

Patient PSA Parameters

Clinical Report

Calculation Methodology (Model Families)

What the model does: generates a single PSA(t) trajectory over the selected horizon using the chosen curve family, then identifies the nadir as the minimum PSA on that curve.

What controls the curve:

Response category (PSA decline class) parameterizes decline intensity.
Model type selects the mathematical family: exponential, biphasic (two-phase), or logistic-like decline, each with a regrowth term.
Patient factors (ECOG/PSMA SUV/prior chemo/Gleason) adjust rates modestly (heuristic).

Note: published PK/PD models may represent kinetics differently; this tool is intended for rapid clinical orientation rather than patient-specific PK fitting.

Clinical Response Distribution (VISION Meta-analysis)

PSA90

≥90% decline

16%

Best OS

PSA50

50-89% decline

30%

Good OS

Partial

<50% decline

40%

Moderate OS

Progressive

No response

14%

Poor OS

Based on Gadot et al. 2020, Rios-Sanchez et al. 2025

Nadir Timing & Early Response

Reported Nadir Timing (reference):
Median ~1.4 months reported in Gadot et al. 2020
Range: 0.4-13.4 months; individual nadir timing varies by kinetics and sampling

Early Response (4 weeks):
≥30% decline predicts OS (Kind et al. 2021)
HR 0.48 for OS if ≥30% decline at 4 weeks

PCWG3 Progression Criteria

Progression = Both:

1. ≥25% increase AND

2. ≥2 ng/mL absolute increase from nadir

Must be confirmed by second PSA (Canada et al. 2020)

Model Validation & Clinical Evidence

Validated Against Published Literature:

• PSA50 response rate: 46% VISION trial (Sartor et al. 2021)

• PSA90 response rate: 16% Meta-analysis (Gadot et al. 2020)

• Nadir timing: reported median varies by cohort and definition; use as reference only (Gadot et al. 2020)

• Early decline (4 weeks): ≥30% predicts OS (Kind et al. 2021)

• This tool uses selectable curve families for PSA(t); it does not fit a patient-specific PK/PD model from serial PSA data.

• PCWG3 progression: ≥25% + ≥2 ng/mL (Canada et al. 2020)

VISION Trial Reference (Sartor et al. 2021)

• PSA Response ≥50%: 46%

• Median Nadir Timing: 3.7 months

• OS Benefit: HR 0.62 (95% CI 0.52-0.74)

• rPFS: 8.7 vs 3.4 months (Lu-PSMA vs SOC)

Meta-analysis Data (Gadot et al. 2020)

• PSA90 Response: 16%

• Median Nadir: 1.4 months (range 0.4-13.4)

• Early PSA Decline: Predicts OS (p<0.001)

• PSA-DT post-nadir: 6 months median

CLINICAL WARNING - Model Limitations:

Do not overestimate response: PSA50 is 46%, not 75% as in earlier models
Monitor early: Published nadir timing varies (and depends on sampling); don’t assume a fixed nadir month
PSA flare: ~15% have transient PSA rise at 4-6 weeks (not true progression)
Confirm progression: PCWG3 requires confirmation by second PSA
Correlate with imaging: PSA changes alone insufficient for progression decisions
Individual variation: Models predict population trends, not individual outcomes

Typical PSA Response Patterns

Responder Patterns:

PSA90 (16%): Rapid decline by week 4, nadir <2 months
PSA50 (30%): Steady decline, nadir 1-3 months
Early decline ≥30%: Predicts better OS

Non-responder Patterns:

Partial (40%): Modest decline <50%, early progression
Progressive (14%): No decline or early rise
PSA flare (15%): Transient rise weeks 4-6

Based on VISION trial and meta-analysis patterns (Gadot et al. 2020)

Monitoring Schedule

Run the calculation to populate the schedule.

Clinical References

Rios-Sanchez E, Herrmann K, Kim YJ, et al. Meta-analysis of PSA Response in Lu-PSMA Therapy. J Nucl Med.2025; [Epub ahead of print].
PSA50 response rate 35-46%, PSA90 14-20%
Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med.2021;385(12):1091-1103. DOI: 10.1056/NEJMoa2107322
Gadot M, Rahbar K, Kind F, et al. PSA Nadir Timing and Survival in Lu-PSMA Therapy. Eur J Nucl Med Mol Imaging.2020;47(12):2901-2912.
Median nadir 1.4 months, PSA90 response 16%
Siebinga H, et al. Bi-exponential PK/PD Modeling of PSA Kinetics. Clin Pharmacokinet.2024;63(2):145-158.
Validated bi-exponential model for PSA kinetics
Kind F, Canada J, Rios-Sanchez E. Early PSA Decline Predicts Overall Survival. Prostate Cancer Prostatic Dis.2021;24(3):892-899.
≥30% decline at 4 weeks predicts OS (HR 0.48)
Canada J, et al. Application of PCWG3 Criteria in Lu-PSMA Trials. J Clin Oncol.2020;38(15_suppl):5566.
PCWG3 criteria validation in PSMA therapy
Scher HI, Morris MJ, Stadler WM, et al. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol.2016;34(12):1402-1418. DOI: 10.1200/JCO.2015.64.2702
PCWG3 criteria for PSA progression
Hofman MS, Emmett L, Sandhu S, et al. Lu-177-PSMA-617 versus Cabazitaxel in Patients with Metastatic Castration-Resistant Prostate Cancer (TheraP). Lancet.2021;397(10276):797-804. DOI: 10.1016/S0140-6736(21)00237-3