The Role of Focal Therapy in the Management of Localised Prostate Cancer: A Systematic Review

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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.

Take Home Message

The functional outcomes of focal therapy are encouraging, but there is a lack of high-quality evidence of long-term disease-control outcomes. Although this strategy could decrease the treatment-related side effects of men requiring active treatment, further robust comparative effectiveness research is required.

Related collections

Most cited references 110

Record: found
Abstract: found
Article: not found

Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference.

Mack Roach, Gerald Hanks, Howard Thames … (2006)

In 1996 the American Society for Therapeutic Radiology and Oncology (ASTRO) sponsored a Consensus Conference to establish a definition of biochemical failure after external beam radiotherapy (EBRT). The ASTRO definition defined prostate specific antigen (PSA) failure as occurring after three consecutive PSA rises after a nadir with the date of failure as the point halfway between the nadir date and the first rise or any rise great enough to provoke initiation of therapy. This definition was not linked to clinical progression or survival; it performed poorly in patients undergoing hormonal therapy (HT), and backdating biased the Kaplan-Meier estimates of event-free survival. A second Consensus Conference was sponsored by ASTRO and the Radiation Therapy Oncology Group in Phoenix, Arizona, on January 21, 2005, to revise the ASTRO definition. The panel recommended: (1) a rise by 2 ng/mL or more above the nadir PSA be considered the standard definition for biochemical failure after EBRT with or without HT; (2) the date of failure be determined "at call" (not backdated). They recommended that investigators be allowed to use the ASTRO Consensus Definition after EBRT alone (no hormonal therapy) with strict adherence to guidelines as to "adequate follow-up." To avoid the artifacts resulting from short follow-up, the reported date of control should be listed as 2 years short of the median follow-up. For example, if the median follow-up is 5 years, control rates at 3 years should be cited. Retaining a strict version of the ASTRO definition would allow comparisons with a large existing body of literature.

0 comments Cited 644 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: not found

The Mutational Landscape of Lethal Castrate Resistant Prostate Cancer

Catherine S. Grasso, Yi-Mi Wu, Dan R Robinson … (2012)

Characterization of the prostate cancer transcriptome and genome has identified chromosomal rearrangements and copy number gains/losses, including ETS gene fusions, PTEN loss and androgen receptor (AR) amplification, that drive prostate cancer development and progression to lethal, metastatic castrate resistant prostate cancer (CRPC) 1 . As less is known about the role of mutations 2–4 , here we sequenced the exomes of 50 lethal, heavily-pretreated metastatic CRPCs obtained at rapid autopsy (including three different foci from the same patient) and 11 treatment naïve, high-grade localized prostate cancers. We identified low overall mutation rates even in heavily treated CRPC (2.00/Mb) and confirmed the monoclonal origin of lethal CRPC. Integrating exome copy number analysis identified disruptions of CHD1, which define a subtype of ETS fusionnegative prostate cancer. Similarly, we demonstrate that ETS2, which is deleted in ~1/3 of CRPCs (commonly through TMPRSS2:ERG fusions), is also deregulated through mutation. Further, we identified recurrent mutations in multiple chromatin/histone modifying genes, including MLL2 (mutated in 8.6% of prostate cancers), and demonstrate interaction of the MLL complex with AR, which is required for AR-mediated signaling. We also identified novel recurrent mutations in the AR collaborating factor FOXA1, which is mutated in 5 of 147 (3.4%) prostate cancers (both untreated localized prostate cancer and CRPC), and showed that mutated FOXA1 represses androgen signaling and increases tumour growth. Proteins that physically interact with AR, such as the ERG gene fusion product, FOXA1, MLL2, UTX, and ASXL1 were found to be mutated in CRPC. In summary, we describe the mutational landscape of a heavily treated metastatic cancer, identify novel mechanisms of AR signaling deregulated in prostate cancer, and prioritize candidates for future study.

0 comments Cited 511 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: not found

No surgical innovation without evaluation: the IDEAL recommendations.

Peter McCulloch, Douglas G. Altman, W Campbell … (2009)

Surgery and other invasive therapies are complex interventions, the assessment of which is challenged by factors that depend on operator, team, and setting, such as learning curves, quality variations, and perception of equipoise. We propose recommendations for the assessment of surgery based on a five-stage description of the surgical development process. We also encourage the widespread use of prospective databases and registries. Reports of new techniques should be registered as a professional duty, anonymously if necessary when outcomes are adverse. Case series studies should be replaced by prospective development studies for early technical modifications and by prospective research databases for later pre-trial evaluation. Protocols for these studies should be registered publicly. Statistical process control techniques can be useful in both early and late assessment. Randomised trials should be used whenever possible to investigate efficacy, but adequate pre-trial data are essential to allow power calculations, clarify the definition and indications of the intervention, and develop quality measures. Difficulties in doing randomised clinical trials should be addressed by measures to evaluate learning curves and alleviate equipoise problems. Alternative prospective designs, such as interrupted time series studies, should be used when randomised trials are not feasible. Established procedures should be monitored with prospective databases to analyse outcome variations and to identify late and rare events. Achievement of improved design, conduct, and reporting of surgical research will need concerted action by editors, funders of health care and research, regulatory bodies, and professional societies.

0 comments Cited 332 times – based on 0 reviews      Review now

All references

Author and article information

Contributors

Massimo Valerio

Journal

Journal ID (nlm-ta): Eur Urol

Journal ID (iso-abbrev): Eur. Urol

Title: European Urology

Publisher: Elsevier Science

ISSN (Print): 0302-2838

ISSN (Electronic): 1873-7560

Publication date PMC-release: 1 October 2014

Publication date (Print): October 2014

Volume: 66

Issue: 4

Pages: 732-751

Affiliations

[a ]Division of Surgery and Interventional Science, University College London, London, UK

[b ]Department of Urology, University College Hospitals NHS Foundation Trust, London, UK

[c ]Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

[d ]Department of Surgery, University of Melbourne; and Ludwig Institute for Cancer Research, Austin Hospital, Melbourne, Australia

[e ]Department of Urology, Ospedale San Raffaele Turro, San Raffaele Scientific Institute, Milan, Italy

[f ]Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy

[g ]Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Centre, Harvard Medical School, Boston, MA, USA

[h ]Division of Urology, Department of Surgical Oncology, University Health Network; and Department of Surgery, University of Toronto, Toronto, ON, Canada

[i ]Division of Urology, Department of Surgery, and Duke Cancer Institute, Duke University Medical Centre, Durham, NC, USA

Author notes

[* ]Corresponding author. Division of Surgery and Interventional Science, University College London, London W1P 7NN, UK. Tel. +44 (0) 20 3447 9194; Fax: +44 (0) 20 3447 9303. massimo.valerio@ 123456chuv.ch

[†]

Joint first authors.

Article

Publisher ID: S0302-2838(13)00557-5

DOI: 10.1016/j.eururo.2013.05.048

PMC ID: 4179888

PubMed ID: 23769825

SO-VID: d78774aa-1cf8-4824-8352-cae4bc9ff3c8

History

Date accepted : 24 May 2013

Comments

Comment on this article

Cited by 112

See all cited by