PROstate Focal THerapy

Project Information

PROFTH

Grant agreement ID: 101138301

DOI

10.3030/101138301

Project closed

EC signature date 31 October 2023

Start date 1 January 2024

End date 30 June 2025

Funded under

• European Research Council (ERC)

Total cost

No data

EU contribution

€ 150 000,00

Coordinated by

NEEDLEYE ROBOTICS SRL
Italy

Periodic Reporting for period 1 - PROFTH (PROstate Focal THerapy)

Reporting period: 2024-01-01 to 2025-06-30

Summary of the context and overall objectives of the project

Prostate cancer (PCa) poses a major global health challenge. It is the most commonly diagnosed cancer among men and the third leading cause of cancer-related death. By 2040, its global burden is expected to reach 2.3 million new cases and 740,000 deaths, driven by an aging population and inconsistent screening practices. While earlier diagnoses and radical treatments have improved survival rates, the associated side effects, such as urinary incontinence and erectile dysfunction, continue to compromise quality of life.
This has spurred growing interest in minimally invasive approaches like Focal Therapy, which targets only cancerous lesions while preserving healthy tissue. Among these, cryoablation is particularly promising, leveraging cycles of freezing and thawing to induce irreversible tumor cell death. However, its broader clinical adoption is hindered by technical limitations, including uncertainty about complete ablation and challenges in compensating for tissue deformation.
The PROFTH project was conceived to address these limitations, building upon the trajectory initiated by the ERC-PoC project PROST and the EIC-Transition project ROBIOPSY. While those efforts led to the creation of an AI-guided robotic biopsy system, PROFTH extends the same technological paradigm into the therapeutic phase of prostate cancer management.
The project pursues three primary technical objectives: defining joint clinical and technical requirements for combining robotic guidance with cryoablation tools; developing a Digital Twin of the prostate that integrates patient-specific imaging with mechanical and thermal modeling; and designing an automated planning algorithm that can identify target volumes, preserve surrounding structures, and calculate optimal probe trajectories and treatment parameters.
This integrated system aims to make Focal Therapy safer, more precise, and personalized, paving the way for the clinical adoption of digital twins in interventional oncology.
Furthermore, a comprehensive strategy was developed to move PROFTH technology from its current stage toward commercialization.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Current technologies for prostate cryoablation provide reliable cryogenic energy delivery but lack advanced tools for personalized planning and intraoperative adaptation. PROFTH addresses this gap by developing an intelligent, flexible framework for robot-assisted, image-guided cryoablation.
The first objective focused on defining clinical and technical constraints, including anatomical limitations, safety considerations, and the performance boundaries of the existing robotic platform. These insights served as the foundation for the system's technical design.
The second objective involved developing a Digital Twin of the prostate based on multi-modal imaging and sensorized acquisition. An ultrasound probe equipped with an Inertial Measurement Unit (IMU), Time-of-Flight (ToF) sensor, and Force-Sensitive Resistors (FSRs) enabled real-time estimation of prostate deformation due to probe pressure. These data informed 2D and 3D simulation models (Mass-Spring and Finite Element Method) implemented in the SOFA simulation framework. Mechanical parameters were estimated through Bayesian optimization (Tree-structured Parzen Estimator) by minimizing the Chamfer distance between simulated and observed deformations. Once optimized, these parameters were applied to a 3D tetrahedral mesh of the prostate, generated from fused MRI and ultrasound data. The model was experimentally validated using phantoms, with distinct mechanical properties assigned to the prostate and surrounding material.
The third objective addressed the thermal simulation of cryoablation. A simplified Pennes bioheat equation, excluding perfusion and metabolism, was used to reflect the low-perfusion conditions typical of freezing. Freeze–thaw–freeze cycles were simulated across various probe configurations and insertion depths. Isothermal contours were computed to estimate iceball propagation, assess coverage of the tumor region, and ensure protection of adjacent critical structures.
The project developed a complete pipeline for simulating mechanical deformation and thermal effects in a patient-specific digital twin, which will now serve as the foundation for a planning algorithm currently under development.
PROFTH business aspects focused on understanding the perspectives of key clinical stakeholders playing a critical role in PCa treatment. 11 urologists were interviewed and 3 ablation system manufacturers (CLS, Elesta, and Mermaid Medical/Canyon Medical) were contacted. We gained valuable insights into clinical needs and market demands, e.g. precision is crucial for treatment.The regulatory aspects were addressed by attending webinars organized by TÜV SÜD UK. Finally a preliminary Freedom to Operate (FTO) analysi was conducted to assess potential patent infringement related to its AI-based robotic platform.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The PROFTH project has demonstrated the feasibility of an intelligent planning environment for prostate cryoablation, combining patient-specific imaging, physical simulation, and robotic guidance. This represents a significant step toward standardized and personalized focal therapies with improved clinical safety and efficacy.
A key innovation was the development of a full simulation workflow, validated on phantom experiments and based on real imaging data. By fusing segmented MRI and ultrasound datasets, a 3D anatomical model was created, providing the basis for biomechanical and thermal simulations. The integration of force-sensing technology allowed the assignment of realistic mechanical parameters, producing reliable simulations of probe insertion and iceball formation.
Thermal modeling made it possible to evaluate the effect of different cryoprobe arrangements in treating various tumor locations, ensuring that efficacy targets were met while respecting anatomical safety constraints. The system is now evolving toward automatic treatment planning, where the platform identifies the region of interest, calculates safety margins around critical structures such as the urethra and rectum, and determines the optimal number, position, and duration of cryoprobes for each patient.
To achieve clinical integration, further steps are required. These include validation on in vivo datasets, demonstration of workflow integration within surgical environments, and adaptation to different ablation platforms. Regulatory approval, system interoperability, and strategic pathways for technology transfer and commercialization will also be essential. With continued development, this platform could fundamentally transform focal therapy planning, supporting the transition to precision, simulation-based robotic treatments in oncology.


References
[1] Culp, M.B.; Soerjomataram, I.; Efstathiou, J.A.; Bray, F.; Jemal, A. Recent Global Patterns in Prostate Cancer Incidence and Mortality Rates. Eur. Urol. 2020

[2] Hoffman, K.E.; Penson, D.F.; Zhao, Z.; Huang, L.C.; Conwill, R.; Laviana, A.A.; Joyce, D.D.; Luckenbaugh, A.N.; Goodman, M.; Hamilton, A.S.; et al. Patient-Reported Outcomes through 5 Years for Active Surveillance, Surgery, Brachytherapy, or External Beam Radiation with or without Androgen Deprivation Therapy for Localized Prostate Cancer. JAMA 2020, 323, 149–163.

[3] Aghayev, Ayaz, and Servet Tatli. "The use of cryoablation in treating liver tumors." Expert Review of Medical Devices 11.1 (2014): 41-52.

Workflow of the cryogenic-ablation focal therapy for prostate cancer