Ablation of Low-Risk Prostate Cancer: Both Sides of the Story

The current management of grade group (GG) 1 prostate cancer is often active surveillance (AS) but can also include whole gland therapy such as radical prostatectomy, ablation, or radiation. Patients may elect radical treatment because of several factors: fear of under treatment, patient anxiety, and the possibility of disease progression and losing the “window of cure.” Since GG1 disease is still being treated based on the aforementioned reasons, focal therapy (FT) should also be included in the treatment algorithm as a way of reducing the risk of morbidity compared with other whole gland treatment modalities. When compared with radiation and surgery, FT has a lower complication rate with no significant changes in I-PSS or SHIM at 12 months post-treatment.¹ With new FT treatment options, updated platforms and protocols, the treatment of prostate cancer by FT is steadily rising.² Currently, the rationale for FT in localized prostate cancer is being justified in intermediate-risk disease, but FT in low-risk disease has not been established. Expert opinion from the 2020 Focal Therapy Consensus Meeting does specify that this is a feasible treatment, however, long-term outcomes and a randomized controlled trial are lacking.³ These two-point counter-point review articles look into this.

There are certain clinical scenarios wherein FT may be preferable to other treatment modalities, and other situations wherein it should not be considered. In these reviews by Berends et al. and Sugano and colleagues, each presents the case for the ubiquitous treatment of patients with GG1 with FT and AS for GG1 disease, respectively.^4,5

Berends et al. advocate for FT in patients enrolled in AS with GG1 disease. This avoids future overtreatment by whole gland therapy, prevents progression, prolongs survival, and preserves patient's quality of life.⁴ In contrast, Sugano and colleagues explain that there is no need to advocate for focal therapy in the GG1 cohort since historically GG1 has not progressed to metastatic disease.⁵ Therefore, even though the harms of FT are minimal, there are no benefits with regard to improvement in overall or cancer-specific survival.

To help decide whether FT should be considered for low-risk disease, herein we balance the pros and cons of either option.

PRO: While remaining on AS, patients must be aware of the risk of upgrading in ∼30% of GG1 patients on whole-mount pathology analysis.⁵ However, the risk of clinically significant prostate cancer progression will be lowered by the treatment of these GG1 lesions. In decreasing the future risk of clinically significant disease with early treatment, FT helps mitigate complications from invasive therapy such as erectile dysfunction, urinary incontinence, and operative morbidity/mortality while preserving quality of life and potentially deferring definitive therapy indefinitely.⁴ This is especially useful in young patients who desire to avoid invasive treatment in the future. There is also a psychosocial aspect when treating low-risk disease with focal therapy, as patients will have relief of anxiety because of no longer “living with a malignancy” and minimizing their routine surveillance with biopsies and the risks associated with repeat biopsy.⁴ Therefore, FT is an option in a specific subset of low-risk disease patients who wish to enroll in “super-active surveillance” and avoid the side effects of surgery or radiation.⁶

CON: Although these lesions are currently classified as cancerous areas within the prostate, most have minimal risk of progression to clinically significant disease. Therefore, if the majority of GG1 lesions are not destined to progress to higher grade disease, then most patients would be overtreated by FT. Thus, we may see over time that those patients treated with FT may have recurrent lesions that will ultimately progress. As a result, retreatment of most lesions over time is found to be feasible and occasionally required.^4,7 Although comparatively FT is low risk for procedural morbidity compared with other interventions, it is not harm free. In certain cases, risks of erectile dysfunction are reported up to 38%, urinary retention or incontinence 27%, and hematuria have been reported.⁷

The goal in treating prostate cancer is to avoid overtreatment and associated treatment effects, prolong survival, and prevent disease progression. It is imperative that we continue to improve the classification of patients undergoing AS and or definitive treatment and avoid observing cancer that may progress. For patients who are eligible for FT, enrollment in a clinical trial should be strongly considered. If FT is a feasible option, then adherence to strict guidelines is crucial. There is no “one size fits all” treatment in low-risk prostate cancer, as age, grade, ethnicity, family history, prostate-specific antigen (PSA), density, amount of disease on imaging, visible lesions on MRI, and tissue diagnosis are all factors taken into consideration before intervention. We must take into account specific individual patient needs and more personalized treatment algorithms especially for patients in this particular risk category. We know that prostate cancer is a multifocal disease process and understanding the propensity of each lesion to progress will help determine the efficacy of treating individual lesions with FT.

Abbreviations Used

AS

active surveillance

FT

focal therapy

GG

grade group

I-PSS

international prostate symptom score

MRI

magnetic resonance imaging

PSA

prostate-specific antigen

SHIM

sexual health inventory for men