Low-Risk and Very-Low-Risk Prostate Cancer: Is There a Role for Focal Therapy in the Era of Active Surveillance? Yes, the Two Approaches Complement Each Other

Publication
Article
OncologyOncology Vol 28 No 11
Volume 28
Issue 11

Investigators and physicians caring for the spectrum of prostate cancer should have a targeted treatment option available for patients who would benefit by it.

The challenge in prostate cancer (PCa) is to match the aggressiveness of the treatment to that of the cancer. Until recently, all screen-diagnosed localized cancers were considered at least potentially aggressive and in most cases were treated radically. Active surveillance represented a major step forward in acknowledging that some cancers were clinically insignificant and did not pose a threat to the patient’s life. Recently, a third option-focal therapy-has emerged as a potential middle ground between radical treatment and active surveillance.

In managing PCa, the physician’s goal is to characterize the biology of the patient’s cancer, particularly with respect to the risk of progression, and advise the patient accordingly. Multiparametric magnetic resonance imaging (MRI) is a game changer in the context of focal therapy. Multiparametric MRI allows identification of large-volume, higher-grade lesions in men whose biopsy shows low-risk disease only, and equally important, it has a high negative predictive value for the normal areas of the prostate. The evaluation pathway for focal therapy requires detailed imaging assessment, including three-dimensional spatial mapping within the gland. This has not generally been a requirement for whole-gland treatment.

Most Gleason 6 prostate cancers have a slow growth rate and will not require treatment. The increasing use of multiparametric MRI has given rise to a novel clinical scenario: patients with a single index lesion that appears to be clinically significant and yet is confined to a small portion of the prostate.

Two other clinical scenarios are those of Gleason 6 cancers in patients who refuse surveillance and large-volume unilateral Gleason 6 cancers in very young patients (< 55 years). The motivation to treat patients in both these settings is usually the uncertainty about whether the prostate harbors higher-grade cancer. The patient may simply wish to target and eradicate the known cancer while attempting to preserve continence and potency. Of course, some of these considerations can pertain equally to select, very localized Gleason 7 cancers, depending on expected patient longevity and treatment preferences.

The concept of treating the lesion while managing the rest of the prostate with surveillance is compelling. The focal therapy outcome data are limited due to the relatively recent adoption of this approach. However, the data that have been published are impressive. A recent meta-analysis of 2,350 cases reported rates of pad-free continence between 95% and 100%, rates of erectile function between 54% and 100%, and absence of clinically significant cancer between 83% and 100%.[1] This represents a “trifecta rate” of 84%.[2]

A recent conference on focal therapy has issued the following consensus recommendations:

1. Eligible patients are intermediate risk with unifocal and multifocal PCa.

2. MRI-targeted or template-mapping biopsy should be used to plan treatment.

3. Planned treatment margins should be 5 mm from the known tumor.

4. Prostate volume or patient age should not be a primary determinant of eligibility.

5. Foci of indolent cancer can be left untreated during treatment of the dominant index lesion.

6. Histologic outcomes should be defined by targeted biopsy at 1 year.

7. Residual disease in the treated area of ≤ 3 mm of Gleason 3+3 cancer does not require treatment.

8. Focal retreatment rates of ≤ 20% should be considered clinically acceptable.

9. These reasonable recommendations should guide our approach for the foreseeable future.[3]

Given the morbidity of conventional radical treatment, the indolent phenotype of many prostate cancers, the accuracy of multiparametric MRI in excluding significant disease elsewhere in the prostate, and the availability of noninvasive, minimally invasive, and needle-based therapies capable of providing precise focal treatment, it is clear that focal therapy is an approach whose time has come. Investigators and physicians caring for the spectrum of PCa should have a targeted treatment option available for those patients who would benefit by it. We view focal therapy as complementary to surveillance, not in competition with it.

Financial Disclosure:Dr. Polascik is a consultant for and has received research support from Endocare; he is also an investigator on a clinical trial for Angiodynamics. Dr. Klotz has no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.

References:

1. Valerio M, Ahmed HU, Emberton M, et al. The role of focal atherapy in the management of localised prostate cancer: a systematic review. Eur Urol. 2014;66:732-51.

2. Ahmed HU, Hindley RG, Dickinson L, et al. Focal therapy for localised unifocal and multifocal prostate cancer: a prospective development study. Lancet Oncol. 2012;13:622-32.

3. Donaldson IA, Alonzi R, Barratt D, et al. Focal therapy: patients, interventions, and outcomes-a report from a consensus meeting. Eur Urol. 2014 Sep 30. [Epub ahead of print]

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