PDE4D7 Expression Risk Stratification for Prostate Cancer

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Solution Overview

Problem

Current methods for diagnosing and treating prostate cancer often result in over-diagnosis and unnecessary treatments, leading to significant side effects and high costs, with a need for more accurate pre-surgical predictions of tumor aggressiveness to optimize patient care.

Innovation Solution

A method for risk stratification in prostate cancer using the expression level of PDE4D7, normalized against reference genes, to determine a prognostic risk score, which guides therapy selection between active surveillance and intervention, incorporating a diagnostic kit and computer program for computing risk scores.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional diagnostic methods (PSA, DRE, TRUS) are used to detect prostate cancer, then the detection coverage is high, but the false positive rate increases leading to over-diagnosis of benign conditions

Engineering Contradiction:
Improvedetection accuracyVSAvoiddiagnostic precision
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent changes the diagnostic parameter from traditional clinical markers (PSA levels, physical exam findings) to molecular gene expression profiles. By measuring the expression levels of specific genes (PDE4D7, PDE4D5, PDE4D1, PDE4D2) and calculating a PDE-Index, the method achieves more precise differentiation between benign and malignant conditions, reducing false positives while maintaining high detection coverage.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If active intervention (surgery, radiation) is applied to all detected cases, then treatment completeness is improved, but patient quality of life deteriorates due to side effects

Engineering Contradiction:
Improvetreatment completenessVSAvoidtreatment side effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by providing personalized treatment recommendations based on individual patient risk stratification. Instead of uniform treatment for all detected cases, the PDE-Index divides patients into risk groups (very low, low, intermediate, high, very high) with corresponding tailored management strategies. This ensures aggressive treatment only for those who need it while allowing conservative management for low-risk patients, maintaining treatment completeness for malignant cases while minimizing harm to benign cases.

Inventive Principle:
Principle #3Local quality

3Object-affected harmful factors

If active surveillance is used for low-risk patients, then quality of life is improved and costs are reduced, but the risk of disease progression must be accurately predicted

Engineering Contradiction:
Improvepatient quality of lifeVSAvoidprogression prediction accuracy
Core Design Contradiction:
Object-affected harmful factorsVSMeasurement precision

Solution Approach 1:

The patent implements feedback by using the PDE-Index as a dynamic risk assessment tool that can be measured at different time points. The gene expression profile provides continuous feedback on disease status, allowing clinicians to monitor patients under active surveillance and switch to active intervention when the PDE-Index indicates progression to higher risk categories. This feedback mechanism ensures safe active surveillance with accurate progression prediction.

Inventive Principle:
Principle #23Feedback

4Measurement precision

If extensive lymph node dissection is performed during prostatectomy, then metastasis detection is improved, but surgical complexity and complication rates increase

Engineering Contradiction:
Improvemetastasis detection accuracyVSAvoidsurgical procedure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by determining the PDE-Index and risk stratification before surgery. This pre-surgical molecular assessment provides advance information about the likelihood of lymph node metastasis, allowing the surgical team to plan the appropriate extent of lymph node dissection in advance. High-risk patients can undergo extensive dissection with full preparation, while low-risk patients can avoid unnecessary extensive surgery, reducing operational complexity without compromising metastasis detection for those who need it.

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentEP3548631B1Risk scores based on human phosphodiesterase 4d variant 7 expression
Publication Date: 2021.08.25 KONINKLIJKE PHILIPS NV
  • EP3548631B1 patent drawingFigure 1
  • EP3548631B1 patent drawingFigure 2
  • EP3548631B1 patent drawingFigure 3

AI summary

Methods are described for stratifying patient risk for patients with prostate cancer and for providing a treatment recommendation to a patient based on a phosphodiesterase 4D variant 7 (PDE4D7) risk score. A diagnostic kit and a computer program product for the analysis and determination of the PDE4D7 risk score are also described.