EURURO Vol. 73 No. 1

The sensitivity of MPMRI and TRUSB depends on their

definitions and cut-offs. An MPMRI cut-off of 2 and above

refers 96% of men to biopsy, but ensures that only 2% of men

with intermediate-risk cancer and none of the men with

high-risk cancer are missed. Furthermore, it means that

most men receive a more sensitive TRUSB, since MRI-

targeted TRUSB is thought to be more sensitive than the

standard

[16]

. The recent guidance based on the Prostate

Imaging Reporting and Data System (PI-RADS) suggests that

men with PI-RADS 1 or 2 should not be referred for biopsy

given concerns about overdiagnosis

[17]

. This may not be

equivalent to the cut-off recommended here, since the

PROMIS diagnostic study did not use PI-RADS, which is a

limitation. Nonetheless, higher MPMRI cut-offs, whilst

reducing the proportion of men receiving biopsy, also

reduce the proportion of CS cancers detected and treated.

This is the first study comparing all possible ways of

using MPMRI, TRUSB, and TPMB to diagnose CS prostate

cancer, using data from PROMIS, the largest study on

MPMRI and TRUSB

[4] .

A limitation of PROMIS, and of this

study, is that it did not include other tests, such as

transperineal biopsies, or the combination of additional

clinical and genetic characteristics for diagnosis and risk

stratification. This is an area for future research. Another

area for future research is the sensitivity of the first and

second MRI-targeted TRUSBs, since these parameters were

key cost-effectiveness drivers. Previous cost-effectiveness

studies compared up to two ways of using MPMRI, either

as a first test to determine which men should receive

MRI-targeted TRUSB

[1,18]

, as MRI-targeted TRUSB for all

men

[1]

, or for men with previous negative biopsy

[19]

. For these reasons, this study is the most comprehen-

sive cost-effectiveness analysis to date of alternative

diagnostic strategies for prostate cancer.

The appropriate MPMRI cut-off, and ultimately the

optimal diagnostic strategy, depends on the cost effective-

ness of early diagnosis and treatment. Although this study

did not include radiotherapy, it tested the impact of changes

on the cost effectiveness of treatment. If cost effectiveness

of radiotherapy is similar to or more favourable than that of

radical prostatectomy, highly sensitive strategies such as

M7 222 are cost effective. Highly sensitive diagnostic

strategies may not be cost effective if radical treatment is

not as cost effective in the manner modelled here. The cost

effectiveness of treatment is less favourable if (1) treatment

is less effective, (2) it impacts negatively on HRQoL, or (3)

it is costlier than that assumed for this study.

Management of men classified as having no cancer or

non-CS cancer also has an impact on the scope for

investment in diagnosis. More sensitive monitoring proto-

cols improve the cost effectiveness of less sensitive and less

costly diagnostic strategies. There is a dearth of evidence on

the effectiveness of repeated testing protocols, which

constitutes an important limitation of the current evidence

base in support of policy, and meant that these analyses

could not formally evaluate the use of such protocols.

In order to evaluate the cost effectiveness of diagnostic

tests, evidence is required on the long-term outcomes of

patients who are correctly diagnosed and those who are

misclassified, given their true disease status. The extensive

literature searches conducted for this study did not identify

evidence on the outcomes of patients and the effectiveness

of treatments when true disease status is known (eg, using

TPMB to identify and risk stratify patients). The existing

studies used TRUSB to diagnose and risk stratify patients

[8,20,21]

; hence, some individuals may have been under-

diagnosed. As a consequence, their long-term quality-

adjusted survival may have been overestimated, and the

cost effectiveness of treatment may have been under-

estimated. This issue can only be resolved with better-

quality evidence on the outcomes of men with prostate

cancer, based on a perfect test such as TPMB for their

diagnosis and classification.

Conclusions

MPMRI is cost effective as the first test for the diagnosis of

prostate cancer, when followed by an MRI-targeted TRUSB

in men in whom the MPMRI suggests a suspicion for CS

cancer, and a second TRUSB if no CS cancer is found, under

the most sensitive CS cancer definitions and cut-offs. These

findings are sensitive to the cost of each test, sensitivity of

MRI-targeted TRUSB, and long-term outcomes of men with

cancer, which warrant more empirical research.

Author contributions:

Rita Faria had full access to all the data in the study

and takes responsibility for the integrity of the data and the accuracy of

the data analysis.

Study concept and design:

All authors.

Acquisition of data:

All authors.

Analysis and interpretation of data:

All authors.

Drafting of the manuscript:

Faria.

Critical revision of the manuscript for important intellectual content:

All

authors.

Statistical analysis:

Faria, Soares, Spackman.

Obtaining funding:

Ahmed, Kaplan, Emberton, Sculpher.

Administrative, technical, or material support:

Faria, Soares.

Supervision:

Soares, Sculpher.

Other:

None.

Financial disclosures:

Rita Faria certi

es that all con

icts of interest,

including speci

nancial interests and relationships and af

liations

relevant to the subject matter or materials discussed in the manuscript

(eg, employment/af

liation, grants or funding, consultancies, honoraria,

stock ownership or options, expert testimony, royalties, or patents

led,

received, or pending), are the following: Rita Faria, Marta O. Soares, Eldon

Spackman, Louise Brown, Richard Kaplan, and Mark J. Sculpher have no

con

ict of interests. Hashim U. Ahmed receives trial funding from

Sophiris Biocorp, Trod Medical, and Sonacare Inc., and fees for lectures

and proctoring from Sonacare Inc. Mark Emberton receives trial funding

from Sophiris Biocorp, Trod Medical, Steba Biotech, Immodulon, and

Sonacare Inc.; fees for lectures and proctoring from Sonacare Inc.; and

consulting fees from Sonacare Inc., Steba Biotech, and Sophiris Biocorp.

Mark Emberton has shares in Nuada Medical Ltd.

Funding/Support and role of the sponsor:

This study was funded by the

UK National Institute for Health Research Health Technology Assessment

programme. The funders had no role in the design and conduct of the

study; collection, management, analysis, and interpretation of the data;

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