In the Netherlands, most men with PCa are treated with radical whole-gland treatment, i.e.
prostatectomy or a form of radiotherapy. The burden of complications such as incontinence and
erectile dysfunction associated with radical treatment is considerable.
A recent systematic review by our group has shown that focal therapy of PCa seems to reduce
the burden of treatment side-effects in men with intermediate-risk disease, maintaining their
quality of life without compromising oncological effectiveness. The costs of side-effects
that can be prevented are estimated at €5456 per patient, resulting in total expected cost
savings of about €22 million per year in The Netherlands. Furthermore, exploration of the
benefit-risk balance under patients showed that they are willing to sacrifice some survival
for an improvement in quality of life (QoL).
Focal therapy comprises a modern alternative to selectively treat a specific part of the
prostate while preserving the rest of the gland. There is, however, a lack of high-quality
evidence, and numerous papers therefore recommend to perform a multicenter randomized
controlled trial (RCT). The RCT should have long-term follow-up, predefined assessment of
cancer-specific and health-related QoL outcome measures, and economic evaluations to inform
policymakers regarding cost-effectiveness. This RCT on focal therapy versus usual care is
urgently needed to enable focal therapy to overgrow the experimental status, provide the
evidence needed for guidelines, and make this available for selected patients who benefit
from this strategy. Because of its promising results in other countries, focal therapy is
increasingly requested by patients, but due to the lack of high-quality evidence, it is not
reimbursed yet. This has been designated by both the PCa patient support group and physicians
as a failure of both the market and the funding agencies.
At present, all devices that are used in the proposed study are CE approved and no safety
issues were reported in IDEAL stage 1 and 2a studies. For high-risk PCa, local radical
therapy has been found to significantly improve oncological endpoints. However, for low- and
intermediate-risk localized PCa, the different recommended options by guidelines (radical
prostatectomy (RP), radiotherapy (RT), or active surveillance (AS)) have similar short- to
medium-term oncological outcomes in randomized studies. A PROZIB database search and a KWF
report showed that about 65% of the intermediate-risk patients that are eligible for focal
therapy currently undergo either RP or RT. Furthermore, brachytherapy is only used to a
limited extent (7%) in intermediate-risk patients in the Netherlands, and since it is not
offered as a treatment option in the participating hospitals in this proposal, the
investigators do not include this option in our study.
Active surveillance is mainly used for low-risk patients rather than for the
intermediate-risk patients the investigators are aiming for in this study. Our systematic
review concluded that more high-quality evidence is required before focal therapy can become
available as a standard treatment. The majority of focal therapy studies were prospective
development IDEAL stage 2a studies (feasibility studies), showing the limited adverse impact
on functional outcomes and favorable oncological outcomes. Overall, focal therapy studies
reported a median of 95% pad-free at 1-year and 85% of the patients had no clinically
significant cancer in the treated area, respectively. High-quality multi-center comparative
clinical trials, however, appear to be lacking. The appropriate management of patients with
recurrent PCa following focal therapy has been an ongoing point of discussion. Marra et al.
showed that evidence from assessments of salvage treatments after focal therapy failure is
low and is derived from four retrospective salvage series. Available salvage options after
focal therapy include RP and RT. Overall oncological outcomes are acceptable, although
biochemical recurrence is slightly higher compared to primary PCa treatment, probably because
of the higher aggressiveness of recurrent/persistent PCa. Functional outcomes and
complications are not markedly worse compared to primary treatment. Salvage RP and salvage
RT, therefore, seem feasible treatment options with acceptable oncological control and
functional outcomes. Thus, re-treatment with salvage radiotherapy or salvage surgery remains
a clinical option after focal therapy failure. Experience from other countries and our
qualitative research on this topic taught us that many patients will consciously opt for an
initial focal therapy to maintain their quality of life and because they can be treated later
when deemed necessary with the other options.
All patients included in our trial will undergo intensive follow-up. Patients undergoing
focal therapy will undergo quarterly PSA measurement and yearly prostate MRI, followed by a
prostate biopsy after 12 months and thereafter if indicated based on the MRI. Since focal
therapy is a one-time intervention, there will be no patients left in treatment or that
require alternative fallback treatments. Ablation devices can be returned after the
completion of the trial. The disposables are single-use and are depreciated. There are no
specific costs associated with the discontinuation of focal treatment after the trial.
The investigators, therefore, aim to perform a high-quality multi-center RCT to provide the
evidence needed to decide on reimbursement and implementation of focal therapy in patients
with intermediate-risk, unilateral clinically localized PCa in the Netherlands. This study is
funded by a national grant (Veelbelovende Zorg) from the Dutch Health Institute
(Zorginstituut Nederland).