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Anatomically versus biologically unifocal prostate cancer: a pathological evaluation in the context of focal therapy.

ABSTRACT: OBJECTIVES:Since tumor focality in prostate cancer continues to be considered a major limitation for focal prostate therapy, in this study we attempted to compare the pathological features and the proportion of patients with anatomically unifocal versus biologically unifocal tumors (i.e. multifocal prostate cancer in which the secondary nonindex elements are small, low grade and clinically insignificant) who were suitable for focal therapy. METHODS:Ninety-five consecutive whole mount laparoscopic radical prostatectomy samples underwent pathological assessment (from January 2007 to November 2009). Tumor focality, laterality, Gleason score and volume of individual foci, total tumor volume, pathological stage and surgical margin status were assessed. The index lesion was defined as the largest by volume. Patients suitable for focal ablation were defined as having tumors that were unifocal, organ confined, with a Gleason score (GS) up to 7 prostate cancer, or multifocal, organ confined, GS up to 7 prostate cancer, with one large index lesion and the remaining foci demonstrating features of clinically insignificant disease (total tumor volume of all secondary foci ?0.5 cm(3) with GS ? 6). RESULTS:Patients with biologically unifocal cancer had significantly lower total tumor volume (3.26 versus 7.28 cm(3); p < 0.001), index lesion volume (2.9 versus 7.16 cm(3); p < 0.001), rates of seminal vesicle invasion (4% versus 34%; p < 0.001), rates of positive surgical margins (22.4% versus 52.1%; p < 0.001) and rates of 4+3 GS tumors (10.2% versus 29.1%; p = 0.018). The proportion of patients suitable for focal therapy was higher in the biologically unifocal versus anatomically unifocal cancer group, although without reaching statistical significance (65.3% versus 45.8%; p = 0.11). CONCLUSIONS:Patients with biologically unifocal tumors have better pathological outcome than those with anatomically unifocal disease. At present the assumption that multifocality should a priori exclude patients from any organ-preserving prostate cancer treatment is only theoretical and needs to be validated by future clinical trials since there are a large proportion of patients with multifocal disease apparently suitable for focal prostate therapy.

SUBMITTER: Karavitakis M

PROVIDER: S-EPMC3398599 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Anatomically versus biologically unifocal prostate cancer: a pathological evaluation in the context of focal therapy.

Karavitakis Markos M Ahmed Hashim U HU Abel Paul D PD Hazell Steven S Winkler Mathias H MH

Therapeutic advances in urology 20120801 4

<h4>Objectives</h4>Since tumor focality in prostate cancer continues to be considered a major limitation for focal prostate therapy, in this study we attempted to compare the pathological features and the proportion of patients with anatomically unifocal versus biologically unifocal tumors (i.e. multifocal prostate cancer in which the secondary nonindex elements are small, low grade and clinically insignificant) who were suitable for focal therapy.<h4>Methods</h4>Ninety-five consecutive whole mo ...[more]

PMID: 22852025

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Project description: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.

Project description:Focal therapy is being offered as a viable alternative for men with localised prostate cancer (PCa), but it is unclear which men may be suitable.To determine the proportion of men with localised PCa who are potentially suitable for focal therapy.Our institutional transperineal template prostate-mapping (TTPM) biopsy registry of 377 men from 2006 to 2010 identified 291 consecutive men with no prior treatment.TTPM biopsies using a 5-mm sampling frame.Suitability for focal therapy required the cancer to be (1) unifocal, (2) unilateral, (3) bilateral/bifocal with at least one neurovascular bundle avoided, or (4) bilateral/multifocal with one dominant index lesion and secondary lesions with Gleason ?3 + 3 and cancer core involvement ?3 mm. Binary logistic regression modelling was used to determine variables predictive for focal therapy suitability.The median age was 61 yr, and the median prostate-specific antigen was 6.8 ng/ml. The median total was 29 cores, with a median of 8 positive cores. Of 239 of 291 men with cancer, 29% (70 men), 60% (144 men), and 8% (20 men) had low-, intermediate-, and high-risk PCa, respectively. Ninety-two percent (220 men) were suitable for one form of focal therapy: hemiablation (22%, 53 men), unifocal ablation (31%, 73 men), bilateral/bifocal ablation (14%, 33 men), and index lesion ablation (26%, 61 men). Binary logistic regression modelling incorporating transrectal biopsy parameters showed no statistically significant predictive variable. When incorporating TTPM parameters, only T stage was a significant negative predictor for suitability (p=0.001) (odds ratio: 0.001 [95% confidence interval, 0.000-0.048]). Limitations of the study include potential selection bias caused by tertiary referral practise and lack of long-term results on focal therapy efficacy.Focal therapy requires an accurate tool to localise individual cancer lesions. When such a test, TTPM biopsy, was applied to men with low- and intermediate-risk PCa, most of the men were suitable for a tissue preservation strategy.

Project description:Diffusion-weighted magnetic resonance imaging (dMRI) enables the microstructural characterization and reconstruction of white matter pathways in vivo non-invasively. However, dMRI only provides information on the orientation of potential fibers but not on their anatomical plausibility. To that end, recent methodological advances facilitate the effective use of anatomical priors in the process of fiber reconstruction, thus improving the accuracy of the results. Here, we investigated the potential of anatomically constrained tracking (ACT), a modular addition to the tractography software package MRtrix3, to accurately reconstruct the optic radiation, a commonly affected pathway in multiple sclerosis (MS). Diffusion MRI data were acquired from 28 MS patients and 22 age- and sex-matched healthy controls. For each participant, the optic radiation was segmented based on the fiber reconstruction obtained using ACT. When implementing ACT in MS, it proved essential to incorporate lesion maps to avoid incorrect reconstructions due to tissue-type misclassifications in lesional areas. The ACT-based results were compared with those obtained using two commonly used probabilistic fiber tracking procedures, based on FSL (FMRIB Software Library) and MRtrix3 without ACT. All three procedures enabled a reliable localization of the optic radiation in both MS patients and controls. However, for FSL and MRtrix3 without ACT it was necessary to place an additional waypoint halfway between the lateral geniculate nucleus and the primary visual cortex to filter out anatomically implausible tracks. In the case of ACT, the results with and without an additional waypoint were virtually identical, presumably because the employed anatomical constraints already prevented the occurrence of the most implausible tracks. Irrespective of the employed tractography procedure, increased diffusivity and decreased anisotropy were found in the optic radiation of the MS patients compared to the controls.

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Anatomically versus biologically unifocal prostate cancer: a pathological evaluation in the context of focal therapy.

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Anatomically versus biologically unifocal prostate cancer: a pathological evaluation in the context of focal therapy.

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