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FOCAL THERAPY Defining Candidates for Partial Gland Prostate Ablation: A Critical Challenge for Focal Therapy

By: Ardalan E. Ahmad, MD, Rady Faculty of Health Sciences, The University of Manitoba, Winnipeg, Canada; Chi-Hang Yee, MD, The Chinese University of Hong Kong; James S. Wysock, MD, NYU Langone Health, NYU Grossman School of Medicine, New York, New York; John F. Ward, MD, The University of Texas MD Anderson Cancer Center, Houston | Posted on: 09 Jun 2023

Improvement in prostate cancer (PCa) localization through multiparametric MRI (mpMRI) coupled with targeted biopsy has spurred interest in applying similar principles to address magnetic resonance (MR)-visible lesions via partial gland ablation.1-4 Although ongoing work from the centers of excellence provides encouraging short- and intermediate-term oncological outcomes for partial gland ablation strategies, clear recommendations on the ideal selection criteria for focal therapy (FT) remain undefined.5

FT is not recommended for PCa treatment by major guidelines6,7; therefore, patient selection, ablation approach, and surveillance following FT currently is based on several international multidisciplinary consensus statements.8-14

Working from the improvements provided by mpMRI and targeted biopsy, identification of MR-visible/biopsy concordant disease offers the initial rationale for a FT candidate. In essence, disease that can be reliably targeted represents exactly that, a viable target. From there, the ideal candidate selection becomes more challenging. Disease grade, anatomical location, and tumor volume all remain important factors. The increasing emergence of novel modalities for tissue ablation, each with varying treatment constraints, further complicates candidate selection.15 Given these varied disease and treatment factors and drawing from existing consensus reports, the initial guidance on candidate selection can be summarized (see Table).

Table. Focal Therapy: Patient Selection Summary

Lesion characterization
  • mpMRI is the standard diagnostic tool for FT patient selection.
    • Ideal candidate harbors a visible unifocal lesion on mpMRI.
    • Ideally the lesion is localized to the prostate gland without invasion of seminal vesicles, bladder neck, or extraprostatic extension.
  • Presence of prostate cancer (GG 2-3) of MR-visible lesion should be confirmed by targeted biopsy.
Treatment volume and treatment margin
  • An adequate margin (about 1 cm) should be considered when planning treatment of MR-visible lesion.
  • Prostate volume is not considered a limiting factor for selecting patients for FT.
    • Tumor location should be considered when planning for FT.
    • Limitations of FT modality/energy in treating the target lesion should be considered when planning for FT.
Disease characteristics
  • FT can be considered in National Comprehensive Cancer Network intermediate-risk disease.
    • GG2 (GS 3 + 4) or GG3 (GS 4 + 3)
    • PSA <20 ng/dL
    • ≤ cT2c
Patients’ characteristics
  • Life expectancy considerations are similar to those stated by major guidelines for whole-gland treatments.
  • Erectile dysfunction does not exclude a patient from FT.
Abbreviations: FT, focal therapy; GG, grade group; GS, Gleason score; mpMRI, multiparametric magnetic resonance imaging; MR, magnetic resonance.

1. Can You See the Tumor? Clearly Identified Target—MR Visible and Biopsy Proven

It is generally agreed upon that patient selection should be based on MRI and targeted biopsy techniques to provide histological confirmation of MR-visible, biopsy concordant disease. Imaging findings suspicious for seminal vesicle invasion, bladder neck invasion, or extraprostatic disease are similarly outside of the bounds of ideal targets for current ablation techniques.16,17 Although multifocal, MR-visible tumors may offer multiple targets amenable to treatment, bilateral ablation erodes the advantages of FT without conferring the same degree of oncological control associated with whole-gland therapy.

2. Can You Treat the Tumor? Target Amenable to Ablation Approach

The confluent destruction of the index lesion is the tantamount goal of FT. Although this assessment involves multiple factors, a critical consideration is the necessary treatment margin. Multiple studies have demonstrated that MRI underestimates the exact tumor volume by anywhere from 3-12.5 mm, predominantly in the cephalad-caudad dimension (depending on lesion size).18 Therefore, an adequate safety margin should be included when considering FT.19 Although a standard treatment margin is not realistic given the complex 3-dimensional nature of tumors, pragmatically, planning a treatment margin of about 1 cm allows the assessment of treatment feasibility. Careful scrutiny of the impact of total treatment volume with margin on such surrounding structures as the rectum, neurovascular bundle, rhabdosphincter, and urethra not only aids in proper candidate selection but also provides guidance on the likelihood of success for the given ablation energy being considered.8-14 Certain modalities may be better suited to treat certain anatomical regions. For example, high-intensity–focused ultrasound may better achieve confluent tissue ablation when the tumor is located posteriorly, whereas needle-based, transperineal energies (eg, cryoablation or irreversible electroporation) may be more amenable for anterior tumors.17

3. Should You Treat the Tumor? Targetable Disease Is Appropriate for Improved Oncological Control

Ultimately, the most important factor when considering FT is the histopathology and disease risk. For men with low-risk, grade group (GG) 1, active surveillance is endorsed by all national and international guidelines as the treatment of choice. Patients who harbor intermediate-risk PCa now pose the greatest treatment conundrum because tests to differentiate those destined to progress from those who harbor disease that can still be observed for long periods are not available. With growing confidence in FT techniques and promising medium-term follow-up, consensus is coalescing around patients with pattern 4 disease, but not pattern 5 disease, as the ideal histological candidates for FT (ie, intermediate-risk PCa based on National Comprehensive Cancer Network risk stratification [GG2 or 3]). Because our ability to sample the prostate through target-directed biopsy has improved, detection of intermediate-risk PCa has increased, yet we do not know whether this will affect cancer-specific outcomes or result in a new group of men overtreated for their PCa.

4. Should This Patient Choose FT? Patient Characteristics Amenable to FT Strategy

Patient education before embarking on a pathway of focal therapy is critical. The education need includes an understanding of the therapeutic goals (clinically significant cancer elimination, functional preservation); how it will be measured (repeat imaging +/− prostate biopsy, functional outcome questionnaires); and an agreement that ongoing surveillance is crucial. Patients on active surveillance for low-risk disease have demonstrated poor compliance in some studies.20 For FT, a follow-up strategy that lessens patient noncompliance is critical. The follow-up also should not be more burdensome than the disease potential. Anxiety and treatment regret, unmanaged in patients undergoing FT, may result in unnecessary whole-gland salvage treatments. It is important to set accurate expectations regarding sexual function and the reported initial decline and then recovery over a 3-6–month period. Although some men may retain wet ejaculation, this is difficult to predict.21 In addition, consideration of prostate volume, baseline lower urinary tract symptoms, and risk of post-ablation urinary retention also should be considered, and patients be counseled accordingly. Although preservation of sexual function is one of the key advantages of choosing FT, its relative superiority in preservation of urinary continence compared with whole-gland treatments makes FT a worthwhile option, even for patients with baseline erectile dysfunction.

In summary, FT success ultimately relies on accurate disease localization followed by confluent tissue ablation of the target volume (visible disease+margin) with minimal treatment effect to surrounding normal tissue. Although further work is needed to identify the ideal candidates for this treatment paradigm, given current understanding and the limitations of MRI, biopsy, and available FT modalities, FT candidate selection is limited to MR-visible, biopsy concordant, intermediate-risk (GG2, GG3) PCa. While serving as an initial starting point for candidate selection, the limitations surrounding multifocality of PCa, the index lesion hypothesis, accurate tumor mapping and disease volume, lack of clear follow-up parameters, and paucity of rigorous long-term data pose important challenges in the safe oncological application of this treatment strategy. In the end, patients should understand that they may be sacrificing some local oncological treatment efficiency to receive the document functional benefits of FT.

The field of FT is evolving rapidly, with multiple ongoing trials focusing on the role of prostate-specific membrane antigen positron emission tomography/MRI and genomic markers, which will further our understanding to better identify patients who are candidates for FT.

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