Elsevier

The Lancet Oncology

Volume 13, Issue 6, June 2012, Pages 622-632
The Lancet Oncology

Articles
Focal therapy for localised unifocal and multifocal prostate cancer: a prospective development study

https://doi.org/10.1016/S1470-2045(12)70121-3Get rights and content

Summary

Background

Radical whole-gland therapy can lead to significant genitourinary and rectal side-effects for men with localised prostate cancer. We report on whether selective focal ablation of unifocal and multifocal cancer lesions can reduce this treatment burden.

Methods

Men aged 45–80 years were eligible for this prospective development study if they had low-risk to high-risk localised prostate cancer (prostate specific antigen [PSA] ≤15 ng/mL, Gleason score ≤4 + 3, stage ≤T2), with no previous androgen deprivation or treatment for prostate cancer, and who could safely undergo multiparametric MRI and have a general anaesthetic. Patients received focal therapy using high-intensity focused ultrasound, delivered to all known cancer lesions, with a margin of normal tissue, identified on multiparametric MRI, template prostate-mapping biopsies, or both. Primary endpoints were adverse events (serious and otherwise) and urinary symptoms and erectile function assessed using patient questionnaires. Analyses were done on a per-protocol basis. This study is registered with ClinicalTrials.gov, number NCT00561314.

Findings

42 men were recruited between June 27, 2007, and June 30, 2010; one man died from an unrelated cause (pneumonia) 3 months after treatment and was excluded from analyses. After treatment, one man was admitted to hospital for acute urinary retention, and another had stricture interventions requiring hospital admission. Nine men (22%, 95% CI 11–38) had self-resolving, mild to moderate, intermittent dysuria (median duration 5·0 days [IQR 2·5–18·5]). Urinary debris occurred in 14 men (34%, 95% CI 20–51), with a median duration of 14·5 days (IQR 6·0–16·5). Urinary tract infection was noted in seven men (17%, 95% CI 7–32). Median overall International Index of Erectile Function-15 (IIEF-15) scores were similar at baseline and at 12 months (p=0·060), as were median IIEF-15 scores for intercourse satisfaction (p=0·454), sexual desire (p=0·644), and overall satisfaction (p=0·257). Significant deteriorations between baseline and 12 months were noted for IIEF-15 erectile (p=0·042) and orgasmic function (p=0·003). Of 35 men with good baseline function, 31 (89%, 95% CI 73–97) had erections sufficient for penetration 12 months after focal therapy. Median UCLA Expanded Prostate Cancer Index Composite (EPIC) urinary incontinence scores were similar at baseline as and 12 months (p=0·045). There was an improvement in lower urinary tract symptoms, assessed by International Prostate Symptom Score (IPSS), between baseline and 12 months (p=0·026), but the IPSS-quality of life score showed no difference between baseline and 12 months (p=0·655). All 38 men with no baseline urinary incontinence were leak-free and pad-free by 9 months. All 40 men pad-free at baseline were pad-free by 3 months and maintained pad-free continence at 12 months. No significant difference was reported in median Trial Outcomes Index scores between baseline and 12 months (p=0·113) but significant improvement was shown in median Functional Assessment of Cancer Therapy (FACT)-Prostate (p=0·045) and median FACT-General scores (p=0·041). No histological evidence of cancer was identified in 30 of 39 men biopsied at 6 months (77%, 95% CI 61–89); 36 (92%, 79–98) were free of clinically significant cancer. After retreatment in four men, 39 of 41 (95%, 95% CI 83–99) had no evidence of disease on multiparametric MRI at 12 months.

Interpretation

Focal therapy of individual prostate cancer lesions, whether multifocal or unifocal, leads to a low rate of genitourinary side-effects and an encouraging rate of early absence of clinically significant prostate cancer.

Funding

Medical Research Council (UK), Pelican Cancer Foundation, and St Peters Trust.

Introduction

The management of localised prostate cancer remains controversial because the systematic over-diagnosis that accompanies the current diagnostic pathway results in over-treatment.1 At present, radical whole-gland surgery or radiotherapy can result in substantial side-effects that are a consequence of damage to surrounding structures. These include urinary incontinence (5–20%), erectile dysfunction (30–70%), and bowel toxicity (5–10%).2, 3 Technological refinements do not seem to have reduced the burden of harm.4, 5

Apart from active surveillance for low-risk disease, few strategies are available to address the burden of treatment-related side-effects in other risk categories. One strategy that has shown promise relates to managing prostate cancer in the same manner as most other solid organ malignancies—by focusing the therapy to the cancer lesion, injury to the bladder, rectum, and neurovascular bundles could be reduced.6, 7

We have previously assessed hemi-ablation of patients with localised unilateral prostate cancer,8 which included treatment of the entire half of the prostate associated with cancer. Regardless of the grade, volume, or location of cancer that affected half of the prostate, the entire side was ablated. This strategy is the most straightforward to undertake, standardise, and train others to do, but is limited because only one in five men have true unilateral disease on template biopsies. Furthermore, hemi-ablation might represent overtreatment since a low-volume, low-grade lesion would be treated in the same manner as a high-volume, high-grade cancer. In this study, we postulated that selective focal ablation of unifocal and multifocal cancer lesions with a margin of normal tissue could reduce genitourinary and rectal side-effects for men with localised prostate cancer.

Section snippets

Study design and patients

We undertook a two-centre, prospective development study, as defined by the IDEAL (Idea, Development, Exploration, Assessment, and Long-term) guidelines for assessing innovation in surgery.9 Men could enter into the study if they had localised prostate cancer on multiparametric MRI and transperineal template-prostate-mapping biopsies.10

We included men with low-risk to high-risk disease (prostate-specific antigen [PSA] ≤15 ng/mL, Gleason score ≤4+3, stage ≤T2), aged 45–80 years with a life

Results

42 men were recruited between June 27, 2007, and June 30, 2010. One man had an unrelated death 3 months after focal therapy. He had baseline retroperitoneal fibrosis, hypertension, and a single kidney. He had an uneventful recovery after HIFU and had no respiratory symptoms immediately before treatment, or at 2 weeks and 6 weeks after treatment during the formal trial visits. The cause was independently verified by local physicians as respiratory failure following pneumonia. As a result, 41 men

Discussion

To our knowledge, our study is the first to assess targeting of individual known cancer areas, with a margin of normal tissue, in men with multifocal as well as unifocal prostate cancer across all cancer-risk categories. Focal therapy of discrete areas of cancer, whether unifocal or multifocal, is feasible, safe, and can be delivered in an ambulatory care setting. Early self-resolving lower urinary-tract symptoms were common. However, the strategy was well tolerated in the genitourinary

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