Context: The clinical effectiveness of focal therapy (FT) for localised prostate cancer (PCa) remains controversial.
Objective: To analyse the evidence base for primary FT for localised PCa via a systematic review (SR) to formulate clinical practice recommendations.
Evidence acquisition: A protocol-driven, PRISMA-adhering SR comparing primary FT (sub-total, focal, hemi-gland, or partial ablation) versus standard options (active surveillance [AS], radical prostatectomy [RP], or external beam radiotherapy [EBRT]) was undertaken. Only comparative studies with >= 50 patients per arm were included. Primary outcomes included oncological, functional, and quality-of-life outcomes. Risk of bias (RoB) and confounding assessments were undertaken. Eligible SRs were reviewed and appraised (AMSTAR) and ongoing prospective comparative studies were summarised.
Evidence synthesis: Out of 1119 articles identified, four primary studies (1 randomised controlled trial [RCT] and 3 retrospective studies) recruiting 3961 patients and ten eligible SRs were identified. Only qualitative synthesis was possible owing to clinical heterogeneity. Overall, RoB and confounding were moderate to high. An RCT comparing vascular-targeted focal photodynamic therapy (PDT) with AS found a significantly lower rate of treatment failure at 2 yr with PDT. There were no differences in functional outcomes, although PDT was associated with worse transient adverse events. However, the external validity of the study was contentious. A retrospective study comparing focal HIFU with robotic RP found no significant differences in treatment failure at 3 yr, with focal HIFU having better continence and erectile function recovery. Two retrospective cohort studies using Surveillance, Epidemiology and End Results data compared focal laser ablation (FLA) against RP and EBRT, reporting significantly worse oncological outcomes for FLA. The overall data quality and applicability of the primary studies were limited because of clinical heterogeneity, RoB and confounding, lack of long-term data, inappropriate outcome measures, and poor external validity. Virtually all the SRs identified concluded that there was insufficient high-certainty evidence to make definitive conclusions regarding the clinical effectiveness of FT, with the majority of SRs judged to have a low or critically low confidence rating. Eight ongoing prospective comparative studies were identified. Ways of improving the evidence base are discussed.
Conclusions: The certainty of the evidence regarding the comparative effectiveness of FT as a primary treatment for localised PCa was low, with significant uncertainties. Until higher-certainty evidence emerges from robust prospective comparative studies measuring clinically meaningful outcomes at long-term time points, FT should ideally be performed within clinical trials or well-designed prospective cohort studies.
Patient summary: We examined the literature to determine the effectiveness of prostate-targeted treatment compared with standard treatments for untreated localised prostate cancer. There was no strong evidence showing that focal treatment compares favourably with standard treatments; consequently, focal treatment is not recommended for routine standard practice. (C) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Bibliographical noteFinancial disclosures: Thomas B.L. Lam certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Thomas B.L. Lam is a company consultant for and has received company speaker honoraria and travel grants from Pfizer, GSK, Astellas, IPSEN, and Consilient Health. Nicolas Mottet is a company consultant for Janssen, GE, BMS, Sanofi, and Astellas; has received speaker honoraria from Astellas, Pierre Fabre, Steba, Janssen, and Ferring; and has received fellowships and travel grants from Astellas, Ipsen, Sanofi, Janssen, and Roche. Erik Briers has received grants and research support from IPSEN, the European Association of Urology, and Bayer; is an ex officio board member for Europa UOMO; is an ethics committee and advisory group member for REQUITE; is a patient advisory board member for PAGMI; and is a member of SCA and EMA PCWP. Maria De Santis is a company consultant for Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene, Dendreon, Eisai Inc., ESSA, Ferring, GSK, Incyte, IPSEN, Janssen Cilag, Merck, MSD, Novartis, Pfizer, Pierre Fabre Oncologie, Roche, Sanofi Aventis, SeaGen, Shionogi, Synthon, Takeda, Teva, OncoGenex, and Sandoz; receives speaker honoraria from Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Ferring, GSK, IPSEN, Janssen Cilag, Merck, MSD, Novartis, Pfizer, Pierre Fabre Oncologie, Roche, Sanofi Aventis, Synthon, and Takeda; participates in trials run by the Technical University Munich, Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene, Dendreon, Eisai Inc, Ferring, GSK, IPSEN, Incyte, Janssen Cilag, Merck, MSD, Novartis, Pfizer, Pierre Fabre Oncologie, Roche, Sanofi Aventis, SOTIO, and Cancer Research UK; and as a member of the EORTC GU group participates in various trials. She has received research grants from Pierre Fabre Oncologie, and travel grants from Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene, Dendreaon, Ferring, GSK, IPSEN, Incyte, Janssen Cilag, Merck, MSD, Novartis, Pfizer, Pierre Fabre Oncologie, Roche, Sanofi Aventis, SeaGen, Shionogi, Synthon, Takeda, and Teva/OncoGenex. Stefano Fanti is a company consultant for Bayer and ANMI; has received speaker honorarium from Bayer, Genzyme, ANMI, and GE Healthcare; and participates in trials by Amgen, Bayer, BMS, Genzyme, Janssen, Merck, and Novartis. Silke Gillessen is a company consultant for AAA International, Astellas Pharma, Bayer, Bristol-Myers Squibb, Clovis, CureVac, Ferring, Innocrin Pharmaceuticals, Janssen Cilag, MaxIVAX SA, Orion, Roche, Sanofi Aventis Group, Nectar, and ProteoMediX; has received speaker honoraria from Janssen and Novartis; and participates in multiple trials sponsored by different companies. Jeremy P. Grummet has received a speaker honorarium from Mundipharma, a travel grant from Astellas, and a research grant from Cancer Australia; and is the owner of MRI PRO Pty Ltd., an online training platform. Ann M. Henry is a company consultant for Nucletron-Elektra; participates in trials by Cancer Research UK and the National Institute of Health Research (UK); has received travel grants from the Medical Research Council, the National Institute of Health Research (UK), and Cancer Research UK; and has received research grants from Cancer Research UK and the Sir John Fisher Foundation. Malcolm D. Mason is a company consultant for Ellipses Pharma and Oncotherics. Darya Tilki has received speaker honoraria from Astellas and a travel grant from Janssen. Henk G. van der Poel is a company consultant for Intuitive Surgical; has participated in trials for Astellas and Steba Biotech; and has received grant and research support from Astellas. Thomas Wiegel is an advisory board member for IPSEN; receives company speaker honoraria from IPSEN and Hexal; is a member of the Janssen Steering Committee; and has participated in the ATLAS/AUO trial. Philip Cornford is a company consultant for Astellas, Ipsen, and Ferring; has received company speaker honoraria from Astellas, Janssen, Ipsen, and Pfizer; has participated in trials run by Ferring; and has received fellowships and travel grants from Astellas and Janssen. The remaining authors have nothing to disclose.
- Systematic review
- Evidence synthesis
- Focal ablative therapy
- Radical treatment
- Localised prostate cancer
- Oncological and functional outcomes
- Limitations of evidence base
- Clinical practice guidelines and recommendations
- ACTIVE SURVEILLANCE