Focal or Radical Therapy: a Lesion-based Molecular Evaluation in Prostate Cancer (FLAME-PC)

Focal therapy (FT) is a new approach to treating localized prostate cancer. Instead of treating the entire prostate, it targets only the cancerous areas while preserving healthy tissue. This helps reduce side effects like urinary, sexual, and bowel problems.

In a prospective observational expansion of a phase II clinical trial (ProAMFocal), 80% of patients with small, localized prostate cancers treated with FT had no cancer recurrence at one year, and 70% at 3 years after treatment. The investigators studied the genetic makeup of each cancer, and found that certain genetic markers and cancer subtypes were better at predicting recurrence than standard clinical measures.

Based on this, the investigators are launching the FLAME-PC trial. In this study, all patients who qualify for FT will first undergo genetic profiling of their cancer. Patients with favorable profiles (low risk based on genetic markers) will receive FT, while those with high-risk profiles will be advised to undergo standard treatments like prostate removal or radiation.

The investigators current main goal is to test if genetic profiling can help us better select patients for FT. They believe that patients chosen using this method will have low recurrence rates (<10%) compared to those in their previous study (20-30%). FLAME-PC aims to show that personalized treatment based on genetic profiling can improve outcomes for prostate cancer patients, offering effective cancer control with fewer side effects.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Diagnostic test: Molecular Evaluation for Risk of Recurrence after FT

Detailed Description

Prostate cancer is the leading male cancer in the developed world. However, most prostate cancers are indolent, with only a few being aggressive, or clinically significant (csPCa). Standard radical whole-prostate treatments are effective but result in significant urinary, sexual and bowel side effects. Focal Therapy (FT) is a novel strategy where just the area of csPCa is treated, leaving normal prostate tissue intact, reducing damage to surrounding structures, thus minimizing the morbidity of treatment. This strategy is feasible if the csPCa is early and limited to a lesion of small volume.

However, despite detailed imaging and histological sampling, a significant proportion of patients identified today for FT still experience cancer recurrence. The investigators have recorded a 19.1% csPCa recurrence rate 1 year, and 29.3% (cumulative) 3 years after FT in their NMRC-NIG-funded clinical trial (n=80) despite mapping out csPCa tumors in detail using high resolution (3 Tesla) multiparametric magnetic resonance imaging (mpMRI) and extensive biopsies. Interrogating these failures in their NMRC-TA project, they found that csPCa lesions that recurred had greater transcriptomic risk (genomic classifier [GC] score 0.60 vs 0.38, P=0.014), and were more likely to be of a luminal molecular subtype (prostate subtyping classifier luminal proliferative [PSC-LP]). The investigators hypothesize that patients with lesions that are high GC, and are PSC-LP should undergo standard radical therapy rather than FT.

FLAME-PC (Focal therapy or radical therapy: Lesion-based Molecular Evaluation in Prostate Cancer), aims to prospectively validate the stratification of csPCa patients to FT or radical therapy based on their genomic risk and molecular profiles. Patients deemed clinically suitable for FT based on imaging and biopsy, will be offered FT if they additionally have a GC score ≤0.5 or non-PSC-LP subtype, whereas those with a GC score >0.5 and PSC-LP subtype will be offered radical therapy instead.

The investigators Hypothesis is that patients stratified to receive FT in FLAME-PC based on their molecular profiles will have a better cancer outcome than a historical prospective cohort of patients undergoing FT based on clinical criteria only. If proven, this will be transformative as this will be the first evidence for the use of molecular profiling in prostate cancer treatment selection. Additionally, the investigators will gain further insights into the pre-FT molecular profiling (RNA analysis will be supported by and performed in collaboration with industry partner Veracyte, Inc.)

FLAME-PC is the first prospective trial to attempt to stratify early prostate cancer treatment between FT and radical therapy. This will provide the investigators with the opportunity to transform clinical paradigm of primary treatment selection in localized prostate cancer, lead to better patient cancer outcomes with FT, and reduce overall morbidity in patients suffering from prostate cancer.

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kae Jack Tay, MBBS; Phone Number: +65 63214639; Email: tay.kae.jack@singhealth.com.sg

Study Locations

• Singapore
  • Singapore, Singapore
    • Recruiting
    • Singapore General Hospital
    • Contact: Kae Jack Tay, MBBS; Phone Number: +6563214639; Email: tay.kae.jack@singhealth.com.sg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Prostate Adenocarcinoma
• Grade Group 2-4
• MRI lesion size ≤3ml for single lesions ≤1.5ml for 2 lesions
• no gross EPE
• assessed to be completely ablatable with margin with focal therapy.

Exclusion Criteria:

• Grade Group 5 cancer
• gross EPE
• multifocal (>2) clinically significant prostate cancer
• unablatable location (very apical, basal tumors, or otherwise determined by procedurist).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Focal Therapy, Low Transcriptomic Risk Cohort; Low Transcriptomic Risk for recurrence after FT: Decipher GC Score <0.5; OR GC 0.5-0.85 and non PSC-LP subtype	Diagnostic test: Molecular Evaluation for Risk of Recurrence after FT; Low Risk - Decipher GC <0.5, OR GC 0.5-0.85 and non-PSC-LP subtype High Risk - Decipher GC 0.5-0.85 and PSC-LP subtype, OR GC>0.85; Other Names: Decipher GC score; Transcriptomic Signature
Experimental: Radical Therapy, High Transcriptomic Risk Cohort; High Transcriptomic Risk for recurrence after FT: Decipher GC 0.5-0.85 and PSC-LP subtype, or GC >0.85	Diagnostic test: Molecular Evaluation for Risk of Recurrence after FT; Low Risk - Decipher GC <0.5, OR GC 0.5-0.85 and non-PSC-LP subtype High Risk - Decipher GC 0.5-0.85 and PSC-LP subtype, OR GC>0.85; Other Names: Decipher GC score; Transcriptomic Signature
No Intervention: Focal Therapy, Unselected for Transcriptomic Risk of Recurrence (Historical); From ProAMFocal (NCT06491056): Focal Therapy performed on all comers (no molecular evaluation) based on clinical criteria only (PSA ≤15 ng/ml, GG2-4, MRI lesion size ≤3ml for single and ≤1.5ml for two lesions, no gross EPE, determined to be completely ablatable).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year Post-Focal Therapy (FT) clinically significant cancer recurrence	Recurrence of clinically significant prostate cancer infield or outfield at 12-month MRI and biopsy after focal therapy	12 months after FT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1 year Post-Focal Therapy Infield clinically significant cancer recurrence	Recurrence of clinically significant cancer (≥GG2) within the treated area at 12 months MRI and biopsy	12 months after FT
1 year Post-Focal Therapy Outfield clinically significant cancer recurrence	Recurrence of clinically significant cancer (≥GG2) outside the treated area at 12 months MRI and biopsy	12 months after FT
Failure-free survival	salvage treatment, metastatic cancer, systemic treatment, or transition to watchful waiting.	Over 20 years following enrolment
Metastatic Cancer Free Survival	Free from metastatic cancer on imaging, and/or PSA ≥50 ng/ml	Over 20 years following enrolment
Cancer-specific Survival	Death from Prostate Cancer	Over 20 years following enrolment
Overall Survival	Death from any cause	Over 20 years following enrolment

Collaborators and Investigators

• Sponsor: Singapore General Hospital
• Collaborators: Veracyte, Inc.
• Investigators: Principal Investigator: Kae Jack Tay, MBBS, Singapore General Hospital

Publications and helpful links

General Publications

• Tay KJ, Hong BH, Ong EHW, Tan KM, Pacho GC, Wong SJ, Tan YG, Law YM, Ngo NT, Tan PH, Yuen JSP, Ho HSS, Chen K, Peng J, Foo CWT, Sam XX, Tuan JKL, Kanesvaran R, Gupta RT, Rozen S, Polascik TJ, Liu Y, Proudfoot J, Davicioni E, Khor LY, Chua MLK. Transcriptomic predictors of prostate cancer recurrence following focal cryotherapy: a pooled analysis of phase II trial and prospective cohort data. J Natl Cancer Cent. 2025 May 29;5(5):515-523. doi: 10.1016/j.jncc.2025.04.002. eCollection 2025 Oct.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2048

Study Registration Dates

• First Submitted: November 20, 2025
• First Submitted That Met QC Criteria: December 1, 2025
• First Posted (Estimated): December 15, 2025

Study Record Updates

• Last Update Posted (Actual): January 8, 2026
• Last Update Submitted That Met QC Criteria: January 6, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: biomarker; cryotherapy; irreversible electroporation; hifu; focal therapy; decipher
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 2025-1018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized IPD is available to bona fide investigators who wish to collaborate
• IPD Sharing Time Frame: 7 years from end of study
• IPD Sharing Access Criteria: via the principle investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No