This modified Delphi study sought to address current issues surrounding the consistency and quality of care for men with prostate cancer who could potentially benefit from active surveillance as a treatment modality. The panel considered a range of issues relating to AS, including underlying principles of treatment, diagnostic information, and risk assessment. The agreed consensus statements outline a relatively flexible approach to offering AS, reflecting the current uncertainties and evolving evidence around the optimal use and delivery of AS.
Key principles of Active surveillance
There were a number of key principles on which the participants held clear agreement. The panel agreed that a patient with prostate cancer should be in a reasonable state of health in order to benefit from active surveillance, and that their life expectancy, medical co-morbidities, suitability for radical treatment, and treatment preferences should all be taken into consideration for management decision-making. In the context of the known limitations of the current prostate cancer diagnostic patient, with the potential for over-diagnosis and misclassification of prostate cancer, a rigorous approach to AS is critical to avoid over-treatment and the associated adverse effects for men. The panel also felt that an optimal AS follow-up protocol would be able to accurately identify disease progression to inform decisions about switching to radical treatment.
Diagnostic information
The importance of accurate diagnostic information was discussed at length by the panel, underlying the key role that this data plays in identifying men who are potentially appropriate for AS. This is exemplified in the two cases captured in Table 3. The index of suspicion following a negative mpMRI and the need to consider biopsy in these men with some similar characteristics is clinically different, and underlines the importance of thorough investigation to make a clear diagnosis of prostate cancer. There was strong consensus on the minimum set of diagnostic tests needed to inform the decision about offering AS (see Table 2), however other available tests such as Free:Total PSA ratio and the number of positive cores were more contentious. Multiparametric MRI was felt to be of high importance, and is increasingly being used as a diagnostic test for prostate cancer; however pre-biopsy mpMRI has not yet been recommended in many national level guidelines(17,22).
|
Patient 1
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Patient 2
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Age
|
50
|
50
|
PSA
|
10
|
10
|
PIRADS 2.1
|
1
|
1
|
Free:Total PSA
|
Low
|
High
|
Family history of prostate cancer
|
Negative
|
Negative
|
Prostate volume
|
20cc
|
120cc
|
Table 3 – Clinical scenarios of two similar patients with different prostate cancer risk
The number of positive cores and positive core length can be influenced by the location of the biopsy sampling and the total number of cores taken, and the relative importance of these factors was not agreed upon by the panel. Most prostate cancer guidelines do not include the number of positive cores or the percentage of cancer per core in prostate cancer risk definitions, although many individual centres still include these measures in their AS eligibility criteria(17,18). The panel generally felt that Transrectal Ultrasound-guided biopsy (TRUS) alone was not sufficiently accurate to be used as the basis for histopathological assessment of a prostate cancer, and ideally a Transperineal (TP) biopsy approach was followed. This reflects the general trend towards increasing use of TP biopsy due to its lower adverse effect profile and ability to access all areas of the prostate(23). The need for a confirmatory biopsy in tertiary centre referrals was also debated, with no clear opinion reached; however the importance of concordance between mpMRI and biopsy findings was felt to be vital in reassuring the clinicians and the patient that an accurate diagnosis has been made.
Prognostication of localised prostate cancer
A clear challenge for clinicians treating men with localised prostate cancer at the present time is accurately assessing the risk of disease progression in men with Gleason score 3 + 4 / Gleason Grade Group 2, and recommending the appropriate treatment. The risks of morbidity from radical treatment versus the risks of disease progression on AS are often finely balanced. This was a particularly contentious issue for the panel, and no consensus was reached. The agreed statements in Table 2 could be considered conservative in their approach, but the majority of panel members were more comfortable with not recommending AS as the optimal treatment option to this patient given there is currently no reliable way of distinguishing lethal from non-lethal prostate cancer for these men.
Strengths and limitations
This modified Delphi study was conducted in a methodologically rigorous manner. A diverse panel of international prostate cancer experts was assembled, with an optimal number of participants who engaged throughout the whole process. Agreement was achieved on the consensus statements through robust discussion and iterative work over two rounds of questionnaires, followed by a face-to-face workshop to refine the statements(24). The panel has developed a set of practical recommendations that take into consideration the latest evidence in the field. The role of certain tests, including number of positive cores and Free:Total PSA ratio, in patient selection for AS was not agreed by the panel, although this could be considered to be a reflection of the current state of the evidence in these areas(15).