Active surveillance of prostate cancer: a questionnaire survey of urologists, clinical oncologists and urology nurse specialists across three cancer networks in the United Kingdom

In contemporary UK practice LRPC accounts for 20 % of all new prostate cancer diagnoses
6]. The perception that LRPC is over-treated has gained the ascendancy among the urological
community following results from randomised studies such as the European Randomised
Study of Screening for Prostate Cancer (ERSPC) trial 7] and Prostate Cancer Intervention vs Observation Trial (PIVOT) 8]. It is therefore easy to foresee that AS will most likely become the preferred option
of managing patients with LRPC. The UK NICE guidelines define men suitable for AS
as having the following characteristics: clinical stage T1c; a Gleason score of 3?+?3;
a PSA density of ?0.15 ng/mL/mL; and cancer in ?50 % of their total number of biopsy
cores with ?10 mm of any core involved (http://guidance.nice.org.uk/CG175) 5]. These recommendations are very similar to the European, American and Canadian urological
guidelines which universally recommend that AS is suitable for patients with Gleason
score of 6 or less 1], 2], 9]. Our survey demonstrated that the NICE guidelines regarding AS enrolment are generally
followed. However, in certain cases patients are being recruited into AS programmes
with characteristics of intermediate-risk prostate cancer. A significant proportion
of our respondents considered men for AS who had T2b or T2c disease, a PSA of 10–20 ng/ml,
a Gleason score of 7 and patients with tumour involvement of more than 50 % of their
total biopsy cores. This reflects that routine UK practice of AS commonly outstretches
that described in most international published series of AS and also the recommendations
of European, American and Canadian urological guidelines. Encouragingly however, there
was a general agreement between our respondents as to the criteria that would trigger
conversion to radical treatment.

Our survey demonstrated the marked heterogeneity which exists in the practice of AS
across our cancer network. This variability is not unique to our cancer network alone
but also evident in other cancer networks too in geographically distinct areas of
the UK. This striking variability in AS enrolment criteria, follow up and triggers
for intervention is also demonstrated in international and national series of AS (Tables 3 and 4). In these studies, patients were followed up with a combination of repeat biopsies,
serial PSA measurements and clinical examination. The frequency of repeat biopsies
varied widely analogous to our own cancer network. Some carried out biopsies annually
10]–12], while others every 2 or 3 years 13]–16], and in some depending on clinical characteristics 17], 18]. Almost unanimously in the studies we reviewed tumour upgrading on repeat biopsy
would prompt a recommendation for treatment. Some studies also considered an increase
in tumour volume or percentage of core biopsies involved as a trigger to radical treatment.
PSA doubling time or velocity was also sometimes a trigger to proceed to radical treatment.

Table 3. Selection criteria for Active Surveillance in international published series

Table 4. Triggers to treatment used in patients under Active Surveillance

The updated NICE guidance has advocated the use of mpMRI at the time of AS enrolment
followed by a repeat biopsy at year one and has put in place a follow up regime as
its key suggestions. To understand what the impact of these recommendations would
be on routine clinical practice, our survey assessed the current reported patterns
of practice. Amongst our respondents only 40 % of respondents performed a repeat biopsy
at 12 months and only 60 % use mpMRI routinely as a tool for selecting patients suitable
for AS. It should be noted however that although the NICE guidelines have clearly
stated that mpMRI should occur at the time of AS enrolment, the EUA and AUA guidelines
are not so prescriptive. Similarly Canadian urological guidelines from Ontario recommend
that mpMRI may be included in AS protocols but is not currently a necessity 1], 2], 9]. In contrast, the recommendation on 3–4 monthly PSA checks is consistent with current
routine practice in our survey. Even so there will need to be a method to monitor
and track the PSA. Similarly recommendations for DRE every 6–12 months is probably
best combined with clinic reviews. Of note, in our survey there was great variability
in who did the AS follow up including DRE. Moreover 40 % of respondents did not routinely
perform a DRE during the follow up appointment. Again adherence to the NICE guidelines
will require a significant change in practice and ideally necessitate consistency
in AS follow up providers.

From the results of this survey it is quite clear that the implementation of a robust
and consistent AS program according to the recommendations of the NICE guidelines
will prove challenging due to the current variation in its practice. In addition the
burden of follow-up with clinical examinations and serum PSA testing on both men and
healthcare systems is far from cost-neutral. Even more so the use of novel strategies
such as mpMRI at the time of AS enrollment will further put a strain on radiology
providers. It is clear that in addition to reducing the variability in the practice
of AS there is also the need for robust cost-effectiveness studies to ensure that
such novel strategies are both clinically and cost-effective.

This study however does not come without its limitations. Firstly the methodology
of this study is a questionnaire survey study with a total of 35 respondents which
is a low number of participants and may not accurately depict the practice of AS within
the EoE cancer network. Also this study was UK specific and may not mirror the trends
in the world-wide practice of AS though our review of other international published
series of AS did demonstrate variability in its practice. Furthermore the majority
of our respondents were from primarily academic institutions therefore it is likely
that the practice of AS is even more heterogeneous outside the academic setting.