Abstract Context The incidence of localised prostate cancer is increasing worldwide. In light of recent evidence, current, radical, whole-gland treatments for organ-confined disease have being ...questioned with respect to their side effects, cancer control, and cost. Focal therapy may be an effective alternative strategy. Objective To systematically review the existing literature on baseline characteristics of the target population; preoperative evaluation to localise disease; and perioperative, functional, and disease control outcomes following focal therapy. Evidence acquisition Medline (through PubMed), Embase, Web of Science, and Cochrane Review databases were searched from inception to 31 October 2012. In addition, registered but not yet published trials were retrieved. Studies evaluating tissue-preserving therapies in men with biopsy-proven prostate cancer in the primary or salvage setting were included. Evidence synthesis A total of 2350 cases were treated to date across 30 studies. Most studies were retrospective with variable standards of reporting, although there was an increasing number of prospective registered trials. Focal therapy was mainly delivered to men with low and intermediate disease, although some high-risk cases were treated that had known, unilateral, significant cancer. In most of the cases, biopsy findings were correlated to specific preoperative imaging, such as multiparametric magnetic resonance imaging or Doppler ultrasound to determine eligibility. Follow-up varied between 0 and 11.1 yr. In treatment-naïve prostates, pad-free continence ranged from 95% to 100%, erectile function ranged from 54% to 100%, and absence of clinically significant cancer ranged from 83% to 100%. In focal salvage cases for radiotherapy failure, the same outcomes were achieved in 87.2–100%, 29–40%, and 92% of cases, respectively. Biochemical disease-free survival was reported using a number of definitions that were not validated in the focal-therapy setting. Conclusions Our systematic review highlights that, when focal therapy is delivered with intention to treat, the perioperative, functional, and disease control outcomes are encouraging within a short- to medium-term follow-up. Focal therapy is a strategy by which the overtreatment burden of the current prostate cancer pathway could be reduced, but robust comparative effectiveness studies are now required.
Abstract Context Focal therapy of prostate cancer has been proposed as an alternative to whole-gland treatments. Objective To summarize the evidence regarding sources of energy employed in focal ...therapy. Evidence acquisition Embase and Medline (PubMed) were searched from 1996 to October 31, 2015 following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Ongoing trials were selected from electronic registries. The stage of assessment of each source of energy was determined using the Idea, Development, Exploration, Assessment, Long-term study recommendations. Evidence synthesis Thirty-seven articles reporting on 3230 patients undergoing focal therapy were selected. Thirteen reported on high-intensity focused ultrasound, 11 on cryotherapy, three on photodynamic therapy, four on laser interstitial thermotherapy, two on brachytherapy, three on irreversible electroporation, and one on radiofrequency. High-intensity focused ultrasound, cryotherapy, photodynamic therapy, and brachytherapy have been assessed in up to Stage 2b studies. Laser interstitial thermotherapy and irreversible electroporation have been evaluated in up to Stage 2a studies. Radiofrequency has been evaluated in one Stage 1 study. Median follow-up varied between 4 mo and 61 mo, and the median rate of serious adverse events ranged between 0% and 10.6%. Pad-free leak-free continence and potency were obtained in 83.3–100% and 81.5–100%, respectively. In series with intention to treat, the median rate of significant and insignificant disease at control biopsy varied between 0% and 13.4% and 5.1% and 45.9%, respectively. The main limitations were the length of follow-up, the absence of a comparator arm, and study heterogeneity. Conclusions Focal therapy has been evaluated using seven sources of energy in single-arm retrospective and prospective development studies up to Stage 2b. Focal therapy seems to have a minor impact on quality of life and genito-urinary function. Oncological effectiveness is yet to be defined against standard of care. Patient summary Seven sources of energy have been employed to selectively ablate discrete areas of prostate cancer. There is high evidence that focal therapy is safe and has low detrimental impact on continence and potency. The oncological outcome has yet to be evaluated against standard of care.
Abstract Context Cryoablation (CA) is a minimally invasive modality with low complication rates, but its use in urology is relatively recent. Objective To summarize available evidence for CA for ...small renal masses (SRMs) and to assess the selection criteria, complications, and functional and oncologic results based on the latest CA literature. Evidence acquisition A systematic literature search of the Medline, Embase, and Scopus databases was performed in August 2014 using Medical Subject Headings and free-text protocol. The following search terms were included: kidney cryosurgery, renal cryosurgery, kidney cryoablation, renal cryoablation, kidney cryotherapy , and renal cryotherapy. Evidence synthesis Due to the relatively recent mainstream utilization of CA and lack of long-term efficacy data from large prospective or randomized studies, most of the data available on CA are limited to treatment of SRMs in patients who are often older or are poor surgical candidates. The rates of major complications across the CA literature remain relatively low. Studies assessing renal function after CA suggest a degree of functional decline following CA because proper application includes freezing of a tumor margin; however, often this is not clinically significant. Specific oncologic outcomes should be evaluated in patients with biopsy-proven renal cell carcinoma; when SRM series include benign or unbiopsied tumors, the results of these outcomes are skewed. Although earlier series were suggestive of a higher recurrence rate after CA, some studies have challenged this view reporting recurrence rates comparable with extirpative nephron-sparing surgery. Conclusions CA represents an alternative approach to treatment for patients diagnosed with renal neoplasm. There is no consensus within the literature on the best patient selection criteria. Due to higher rates of treatment failure, it is often not offered to patients with minimal comorbidities and good life expectancy. In terms of functional outcomes, CA signifies a modality with minimum impact on renal function; however, well-designed studies precisely assessing this factor are lacking. CA is a minimally invasive modality with suitably low rates of complications, particularly if delivered via the percutaneous route. Patient summary Cryoablation (CA) represents an alternative approach for treating renal neoplasm. Excellent functional outcomes and low rates of complications make CA an ideal minimally invasive modality. Patient selection criteria and oncologic outcomes require further study.
Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that ...incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services.
A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider).
Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing-initial testing of priority genes followed by expanded testing-was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included
and mismatch repair genes, with broader testing, such as
, for clinical trial eligibility.
was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for
carriers, with consideration in
, and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches.
This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.
Abstract Multiparametric magnetic resonance imaging (mpMRI) is increasingly used in staging early prostate cancer (PCa) but remains heavily reader-dependent. We aim to define the incremental utility ...of mpMRI over clinical parameters in determining the pathologic extracapsular extension (pECE) of PCa interpreted in a standard radiologic setting and when further over-read by a specialized reader. We retrospectively reviewed 120 men with clinically localized PCa undergoing mpMRI and radical prostatectomy. We obtained radiologic prediction of pECE from standard radiologic reports (standard read) and by a specialized reader blinded to clinical and pathologic findings (specialized read). We determined the incremental benefit of standard read and specialized read by sequential addition to a baseline clinical parameters-only logistic regression model predicting pECE. The sensitivity and specificity of standard read were 77% and 44%, respectively, whereas those of specialized read were 86% and 81%. The positive likelihood ratio was 1.7 at baseline, 1.7 adding standard read, and 6.5 adding specialized read. The negative likelihood ratio was 0.6 at baseline, 0.5 adding standard read, and 0.1 adding specialized read. Standard read modestly improved prediction of pECE, whereas specialized read improved it moderately. Patient summary The incremental benefit of mpMRI over clinical information is small but increases to moderate with a specialized second opinion. This second opinion may be useful when considering active surveillance, nerve-sparing surgery, or focal therapy.
Abstract Background Focal therapy as a treatment option for localized prostate cancer (PCa) is an increasingly popular and rapidly evolving field. Objective To gather expert opinion on patient ...selection, interventions, and meaningful outcome measures for focal therapy in clinical practice and trial design. Design, setting, and participants Fifteen experts in focal therapy followed a modified two-stage RAND/University of California, Los Angeles (UCLA) Appropriateness Methodology process. All participants independently scored 246 statements prior to rescoring at a face-to-face meeting. The meeting occurred in June 2013 at the Royal Society of Medicine, London, supported by the Wellcome Trust and the UK Department of Health. Outcome measurements and statistical analysis Agreement, disagreement, or uncertainty were calculated as the median panel score. Consensus was derived from the interpercentile range adjusted for symmetry level. Results and limitations Of 246 statements, 154 (63%) reached consensus. Items of agreement included the following: patients with intermediate risk and patients with unifocal and multifocal PCa are eligible for focal treatment; magnetic resonance imaging–targeted or template-mapping biopsy should be used to plan treatment; planned treatment margins should be 5 mm from the known tumor; prostate volume or age should not be a primary determinant of eligibility; foci of indolent cancer can be left untreated when treating the dominant index lesion; histologic outcomes should be defined by targeted biopsy at 1 yr; residual disease in the treated area of ≤3 mm of Gleason 3 + 3 did not need further treatment; and focal retreatment rates of ≤20% should be considered clinically acceptable but subsequent whole-gland therapy deemed a failure of focal therapy. All statements are expert opinion and therefore constitute level 5 evidence and may not reflect wider clinical consensus. Conclusions The landscape of PCa treatment is rapidly evolving with new treatment technologies. This consensus meeting provides guidance to clinicians on current expert thinking in the field of focal therapy. Patient summary In this report we present expert opinion on patient selection, interventions, and meaningful outcomes for clinicians working in focal therapy for prostate cancer.
Focal therapy (FT) and partial gland ablation (PGA) are quickly adopted by urologists and radiologists as an option for the management of localized prostate cancer.
To find consensus on a ...standardized nomenclature and to define a follow-up guideline after FT and PGA for localized prostate cancer in clinical practice.
A review of the literature identified controversial topics in the field of FT. Online questionnaires were distributed to experts during three rounds, with the goal to achieve consensus on debated topics. The consensus project was concluded with a face-to-face meeting in which final conclusions were formulated.
Controlled feedback of responses of previous rounds were summarized and returned to the participants allowing them to re-evaluate their decisions. The level of agreement to achieve consensus on a topic was set at 80%.
Sixty-five experts participated in this interdisciplinary consensus study (72% urologists; 28% radiologists). The experts propose the use of the herein standardized nomenclature for ablative procedures. After FT/PGA, the following tests should be performed to assess treatment outcomes: prostate-specific antigen (PSA), imaging, biopsies, and functional outcome assessment. Although not a reliable marker for treatment failure, PSA should be measured every 3 mo in the 1st year and every 6 mo thereafter. Magnetic resonance imaging is the preferred image modality and should be performed at 6 and 18 mo after treatment. A systematic 12-core transrectal ultrasound-guided biopsy combined with a targeted biopsy of the treated area should be performed 6–12 mo after treatment. Functional outcomes should be obtained 3–6 mo after treatment for the first time and until stability is attained.
The panel recommends the use of the proposed nomenclature and follow-up protocols to generate reliable data supporting a broader implementation of FT as a standard of care for select patients with localized prostate cancer.
In this report, we present expert opinion on the use of a standardized nomenclature, and surveillance methodologies after focal therapy and partial gland ablation for localized prostate cancer.
In this report, we present expert opinion on the use of a standardized nomenclature and surveillance methodologies after focal therapy and partial gland ablation for localized prostate cancer. The panel recommends the use of the proposed nomenclature and follow-up protocols to generate reliable data supporting a broader implementation of focal therapy as a standard of care for select patients with localized prostate cancer.
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