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.

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.

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).

Anonymized IPD is available to bona fide investigators who wish to collaborate

7 years from end of study

via the principle investigator