Follow-up to a negative prostate biopsy
In men who have been referred with suspected prostate cancer, what are the prognostic factors that determine the need for further investigation following a prior negative biopsy? (PICOi question 8.1)
In men with suspected prostate cancer whose initial TRUS biopsy is negative, what should be the next investigation(s)? (PICOi question 8.2)
Guidelines developed in partnership with
This resource has been developed, reviewed or revised more than five years ago. It may no longer reflect current evidence or best practice.
Published: 2015
National Health and Medical Research Council 
These guidelines (recommendations) in the web-version of this guideline were approved by the Chief Executive Officer of the National Health and Medical Research Council (NHMRC) on 2 November 2015 under section 14A of the National Health and Medical Research Council Act 1992 In approving the guidelines (recommendations), NHMRC considers that they meet the NHMRC standard for clinical practice guidelines. This approval is valid for a period of five years. NHMRC is satisfied that the guidelines (recommendations) are systematically derived, based on the identification and synthesis of the best available scientific evidence, and developed for health professionals practising in an Australian health care setting.
This publication reflects the views of the authors and not necessarily the views of the Australian Government.Background
A negative prostate biopsy does not definitively exclude the presence of cancer. Men who have had one negative biopsy may still have prostate cancer. Factors that might indicate undetected prostate cancer include:
- raised PSA
- abnormal digital rectal examination (DRE)
- abnormal results of other PSA-based tests, such as free PSA to total PSA expressed as a percentage (free-to-total PSA%), PSA density and PSA velocity
- novel biomarkers, such as the prostate cancer gene 3 (PCA3) assessed prior to initial biopsy
- specific pathological features of the initial biopsy.
There is a trend towards the use of adjuncts to improve the cancer detection yield following a negative first transrectal ultrasound-guided (TRUS) biopsy. Sampling strategies and imaging techniques currently under investigation for improving prostate cancer diagnosis rates include:
- repeat TRUS biopsy
- multiparametric MRI or magnetic resonance spectroscopy imaging (MRSI) in combination with repeat TRUS biopsy
- extended/saturation TRUS biopsy
- three-dimensional (3D) ultrasound and biopsy
- template (perineal) biopsy
- contrast-enhanced ultrasound and biopsy
- elastography and biopsy
- review of initial biopsy histopathology.
Most of these techniques have been introduced at a local level based on facilities available, rather than according to a systematic approach. The majority of tumours are known to be in the posterior zone of the prostate, but tumours that occur in the anterior zone of the prostate are often missed with TRUS biopsies, particularly in large prostates. Sampling this area is improved with template (perineal) biopsies or with saturation biopsies. Multiparametric MRI localises the lesion(s) of interest in the prostate to permit more accurate placement of the biopsy needle. Template biopsies cannot be performed under local anaesthesia, so there are cost implications compared with transrectal biopsy or transrectal saturation biopsies under local anaesthetic.
The goals of imaging are:
- to reduce the number of patients requiring biopsy while minimising the risk of missing significant cancers
- to require fewer biopsies to be taken in men in whom significant lesions are detected. (This is an appropriate goal, provided that the treatment team is not considering offering focal therapy).
Thus, the overall aim of imaging is to lessen the rate of over-diagnosis.
Evidence
Prognostic factors that determine the need for further investigation following a negative biopsy
In developing a recent UK National Institute for Health and Care Excellence (NICE) clinical guideline for the diagnosis of treatment of prostate cancer,[1] the UK National Collaborating Centre for Cancer undertook a systematic review to identify the prognostic factors that determine the need for further investigation following a prior negative biopsy in men who have been referred with suspected prostate cancer. The review included retrospective and prospective cohort studies that reported on the following potential prognostic factors: age, ethnicity, family history of prostate cancer, DRE, total PSA, free-to-total PSA%, PSA density, PSA velocityii and PCA3 score at the time of initial biopsy, and histopathological features reported on initial biopsy (high-grade prostatic intraepithelial neoplasia [PIN] or atypical small acinar proliferation [ASAP]iii).
The NICE systematic review classified the results of relevant predictive studies into two broad groups: results of univariate analyses (no control for potential confounding) and results of multivariate analyses (some control for potential confounding). The multivariate analyses are likely to provide more reliable evidence, because they reduce the risk of bias due to confounding variables. The most frequently addressed potentially confounding variables were age, DRE, PSA, free-to-total PSA%, PSA density, PSA velocity, high-grade PIN, ASAP and prostate volume.
We updated the NICE systematic review to identify recently published studies. The search strategy, inclusion and exclusion criteria, and quality assessment for the updated NICE systematic review are described in detail in the Technical report. The updated review identified evidence from cohort studies assessing the prognostic value of an additional biomarker: hypermethylation of DNA in three marker genes (GSTP1, APC and RASSF1) in tissue from the initial biopsy. For other parameters of interest included in the update review, such as prostate health index, no studies met inclusion criteria (see Technical report).
The NICE review[1] rated one study as moderate quality and the remainder as low or very low quality. The main weaknesses were that, in many of the studies, the prognostic factor of interest influenced whether patients underwent repeat biopsy and that many of the models did not include important confounding factors such as age, free-to-total PSA%, and prostate volume. In the updated NICE systematic review, all the identified studies were assessed to have a high risk of bias.
Age
The NICE review[1] included 14 studies that examined the relationship of age (as a continuous variable) with risk of prostate cancer at re-biopsy, using multivariate models that adjusted for potential confounders. The review reported odds ratios (ORs) of 1.01–1.10 per year increase in age. In three studies, the relationship between age and prostate cancer risk was statistically significant (p < 0.05).
The updated NICE systematic review found three additional studies that included age in multivariate models. Two studies each reported ORs of 1.01 per year of age as a continuous variable (p > 0.05).[2][3] Another study reported an OR of 1.47 with a 95% confidence interval (CI) of 1.10–1.97 for comparison of the 75th with 25th percentiles of age as a continuous variable.[4]
Ethnicity
The NICE review[1] included one study that examined relationship of ethnic background with risk of prostate cancer at re-biopsy in a multivariate model. It reported an OR of 0.8 (95% 0.4–1.6) for men of Caucasian ethnic origin, relative to those of other ethnic origins.
The updated NICE systematic review found two additional studies that examined relationship of ethnicity with risk of prostate cancer at re-biopsy in a multivariate model. In these US cohorts, African-American men had ORs of 1.21 (95% CI 0.63–2.31)[4] and 0.58 (95% CI 0.23–1.45),[2] relative to men of non-black ethnicity.
Family history
Both of two studies included in the NICE review[1] found family history to be a significant predictor of prostate cancer at re-biopsy in multivariate models. One study reported OR 3.1 (95% CI 1.2–8.0), relative to no family history of prostate cancer.
The updated NICE systematic review found two additional studies that examined the relationship of family history with risk of prostate cancer at re-biopsy. These studies observed ORs of 1.33 (95% CI 0.81–2.18)[4] and 0.92 (95% CI 0.50–1.72)[2] in multivariate models.
Digital rectal examination
The NICE review[1] found 13 studies that examined the relationship of abnormal DRE with risk of prostate cancer at re-biopsy in multivariate models. These studies reported ORs of 0.4–6.75 for abnormal DRE relative to normal DRE. Abnormal DRE was a statistically significant predictor of prostate cancer at re-biopsy in five studies, three of which reported ORs (2.63–4.61, relative to normal DRE). Eight studies reported low overall diagnostic accuracy; most reported low sensitivity (range 0–55.9% and less than 26% in six studies) but high specificity (range 56.3–95.9% and greater than 85% in five studies).
The updated NICE systematic review found one additional study, which reported an OR of 1.36 for abnormal DRE relative to normal DRE (p = 0.30) in a multivariate model.[3]
Total PSA
The NICE review[1] found 14 studies that examined the relationship of PSA as a continuous variable with risk of prostate cancer at re-biopsy in multivariate models, and reported ORs of 0.93–1.04 per ng/mL increase in PSA. In three studies, total PSA was a statistically significant predictor of prostate cancer on re-biopsy. Two studies reported multivariate adjusted results for PSA in categories; neither was statistically significant. Sensitivity and specificity were not consistent for similar PSA levels in six studies and showed no clear trend with increasing PSA thresholds.
The updated NICE systematic review found two additional studies that examined the relationship of PSA with risk of prostate cancer at re-biopsy. One study reported a multivariate-adjusted OR of 1.59 for PSA < 10 relative to PSA ≥ 10 ng/mL (p = 0.18).[3] The other study did not report multivariate-adjusted results for PSA.[4]
Free to total PSA percentage
The NICE review[1] found eight studies of the relationship of free-to-total PSA% as a continuous variable with prostate cancer at re-biopsy examined in multivariate models, and reported ORs of 0.87–1.40 per unit increase in free-to-total PSA%. Four of these studies reported statistically significant associations; three reported inverse associations and one reported a direct association. Three reported multivariate adjusted ORs comparing categories of free-to-total PSA%. In each case the OR was less than 1 for the higher category relative to the lower category, but was not statistically significant. Sensitivity and specificity were not consistent for similar free-to-total PSA% levels between five studies and showed no clear trend with increasing cut-off level.
The updated NICE systematic review found one additional study that examined the relationship of free-to-total PSA% with risk of prostate cancer at re-biopsy,[4] but it did not report multivariate-adjusted results.
PSA density
The NICE review[1] identified five studies that reported the relationship of PSA density as a continuous or categorical variable with prostate cancer at re-biopsy examined in multivariate models, four of which reported statistically significant results. Where reported, ORs were 1.005 (95% CI 0.998–1.012) per unit of PSA density as a continuous variable, and 2.3 (95% CI 1.4–4.0) and 2.34 (p = 0.012) for a PSA density of > 0.15 relative to less than this value. Test performance characteristics were reported for only one study (sensitivity 66%, specificity 60%).
The updated NICE systematic review found one additional study that examined the relationship of PSA density with risk of prostate cancer at re-biopsy,[4] but it did not report multivariate-adjusted results.
PSA velocity
The NICE review[1] found five studies that examined the relationship of PSA velocity as a continuous or categorical variable with risk of prostate cancer at re-biopsy in multivariate models. Three of these reported statistically significant results. Where reported, ORs were 1.34 (95% CI 1.03–1.74) and 1.58 (95% CI 1.06–2.35) per unit of PSA velocity as a continuous variable. Sensitivity and specificity showed no clear trend with increasing cut-off level and demonstrated low overall diagnostic accuracy in four studies.
The updated NICE systematic review found no additional published results from studies that examined the relationship between PSA velocity and risk of prostate cancer at re-biopsy.
Atypical small acinar proliferation
The NICE review[1] found five studies that examined the relationship between the presence of ASAP and the risk of prostate cancer at re-biopsy in multivariate models. All reported statistically significant associations (p < 0.05). One study that was reported twice (more participants in the second report) reported multivariate adjusted OR of 20.7 (95% CI 4.45–96.4; p < 0.001) in the first report and 17.7 (p < 0.001) in the second. The other four studies reported ORs ranging between 2.97 and 3.65. Two studies that assessed diagnostic accuracy for the presence of ASAP at initial biopsy both reported low sensitivity but high specificity.
The updated NICE systematic review found one additional study that examined the relationship between the presence of ASAP and the risk of prostate cancer at re-biopsy. It reported an OR of 1.92 (95% CI 1.07–3.46).[4]
High-grade PIN
The NICE review[1] found eight studies that examined the relationship between the presence of high-grade PIN and the risk of prostate cancer at re-biopsy in multivariate models, and reported ORs of 0.13–3.2. Only one of these reported an OR of less than 1. Four studies reported a statistically significant relationship. Five studies reported inconsistent test performance characteristics for the presence of high-grade PIN at initial biopsy as a predictor of risk of prostate cancer at repeat biopsy.
The updated NICE systematic review found two additional studies that examined the relationship between the presence of high-grade PIN and the risk of prostate cancer at re-biopsy. These studies reported ORs of 1.87 (1.23–2.85)[4] and 1.25 (p = 0.5).[3]
PCA3
The NICE review[1] found three studies that reported multivariate-adjusted associations of PCA3 score with prostate cancer at re-biopsy. All reported statistically significant associations. One reported an OR of 1.02 (95% CI 1.00–1.03) per unit of PCA3 score as a continuous variable. Another reported an OR of 3.01 (95% CI 1.74–5.23) for a PCA3 score of > 30 relative to < 30. The third reported ORs of 9.44 (95% CI 5.15–17.31) and 9.29 (95% CI 5.11–16.89), respectively, for PCA3 score cut-offs of 39 and 50. In 12 studies that measured sensitivity and specificity, these were not consistent and showed no clear trend with increasing cut-off level, indicating low overall diagnostic accuracy.
The updated NICE systematic review found no additional studies that examined the relationship of PCA3 score with risk of prostate cancer at re-biopsy.
DNA methylation
The updated NICE systematic review found one study[3] that examined the relationship between hypermethylation of three marker genes (GSTP1, APC and RASSF1) evaluated in tissue from the first biopsy, and risk of prostate cancer on re-biopsy. It reported an OR of 3.17 (95% CI 1.81–5.53), adjusted for age, PSA, DRE, and histopathology of first biopsy (benign, atypical cells, high-grade PIN). The sensitivity of the test was 68% and specificity was 64%.
Choice of further investigation following a negative biopsy
In developing the NICE clinical guideline[1] for the diagnosis of treatment of prostate cancer, the UK National Collaborating Centre for Cancer undertook a systematic review to identify adjuncts following a negative first TRUS biopsy to improve cancer detection in men who have been referred with suspected prostate cancer. The review identified two systematic reviews[5][6] and one randomised controlled trial[7] of enhanced ultrasound. It also included case series studies (level IV evidence) and comparative studies.[1] Included studies reported the following tests at repeat biopsy: repeat TRUS biopsy, multiparametric MRI (or MRS) in combination with repeat TRUS biopsy, extended/saturation TRUS biopsy, 3D ultrasound and biopsy, template biopsy, contrast-enhanced ultrasound and biopsy, elastography-guided biopsy, and review of the initial biopsy histopathology.
The NICE systematic review[1] assessed the risk of bias using the QUADAS-2 checklist.[8] Namely, risk of bias in patient selection (whether the sample was representative and whether the selection criteria were clearly described) and risk of bias in the index test (whether the repeat biopsy protocol was described in sufficient detail). Risk of bias was deemed to be low in the majority of studies.[1]
The NICE systematic review[1] was updated by the Guidelines’ Expert Advisory Panel (see Technical report). The updated NICE systematic review was restricted to level II evidence: studies that directly compared different investigations post negative biopsy (i.e. sequential sampling studies or randomised controlled trials). Eight additional level II evidence sequential sampling studies were found.34-41 All eight update studies were assessed to be at moderate risk of bias using a modified QUADAS-2 quality appraisal tool.[9][10][11][12][13][14][15][16] The quality assessment criteria, including those for assessing risk of bias, are described in the Technical report).
Multiparametric MRI targeted biopsy
The NICE systematic review included four level II studies[17][18][19][20] that assessed multiparametric MRI-guided biopsy in men with a previous negative biopsy undergoing repeat biopsy. These studies used repeat standard biopsy protocols that ranged from 6 to 12 cores. Among those with positive findings on multiparametric MRI imaging, adding multiparametric MRI-targeted biopsy to a repeat 12-core biopsy improved the cancer detection rate. In one study, adding multiparametric (T2W + DWI + DCE) MRI increased the cancer detection rate by 14.3 percentage points,[20] while adding multiparametric (T2W + DWI) MRI increased the cancer detection rate by 45.2 percentage points.[17]
The updated NICE systematic review identified another two studies[10][11] in which multiparametric MRI-targeted biopsy was performed in addition to a 12-core random or systematic biopsy in men with a previous negative biopsy. One reported that multiparametric (T2W + DCE) MRI improved the cancer detection rate by 6.4 percentage points,[10] while the other reported that unspecified multiparametric MRI improved the cancer detection rate by 10.1 percentage points.[11]
The updated NICE systematic review identified one study that assessed the addition of multiparametric MRI-targeted biopsy to repeat saturation biopsy.[13] It found that adding multiparametric (T2W + DWI + DCE + MRS) MRI-targeted biopsies to the saturation biopsy improved the cancer detection rate by 5.1 percentage points for all men undergoing biopsy regardless of MRI findings, and by 8.7 percentage points for the subgroup of men who underwent targeted biopsy.
There were no included studies in which all participants underwent an initial biopsy using 21–24 cores.
Enhanced ultrasound-targeted biopsy
Studies included in the NICE systematic review found that adding enhanced ultrasound targeted biopsy to TRUS grey-scale schematic biopsy resulted in cancer detection rates similar to those using the TRUS grey-scale schematic biopsy method alone. In the only relevant level II study, the addition of enhanced ultrasound (colour Doppler)-targeted biopsy to a TRUS grey-scale 13-core systematic biopsy improved the cancer detection rate by 2–3 percentage points.[1]
Saturation or extended biopsy
Studies included in the NICE systematic review found that increasing the number of biopsy cores increased cancer detection rates.[1] Transrectal 12–14 core biopsies had a cancer detection rate of 15%–25%. Transrectal saturation biopsies had a cancer detection rate of 11%–45%, and transperineal saturation biopsies had a cancer detection rate of 23%–72%.
The most common complication was haematuria, which occurred in 8.8% of men undergoing transrectal saturation biopsy and 23.4% of men undergoing transperineal biopsy.
Elastography targeted biopsy
Studies included in the NICE systematic review found no relevant evidence.[1] The updated NICE systematic review found that the addition of elastography targeted biopsies to a 10-core TRUS biopsy increased cancer detection rate by 8.2 percentage points.[16]
Review of initial biopsy
A study included in the NICE systematic review found that review of initial biopsy reclassified 1.2% of benign biopsies as cancerous and 0.4% of positive biopsies as benign.[1]
Evidence summary and recommendations
| Evidence summary | Level | References |
|---|---|---|
| Age
There is consistent evidence that each additional year of age at an initial negative biopsy predicts a 1–10% greater risk of prostate cancer at re-biopsy. |
II, III-3 | [1], [4], [2], [3] |
| Ethnicity
There is consistent evidence in three studies (two including African American men) that ethnicity at an initial negative biopsy is not associated with prostate cancer at re-biopsy. |
II, III-3 | [1], [4], [2] |
| Family history of prostate cancer
There is inconsistent evidence in four studies that family history of prostate cancer at an initial negative biopsy is associated with risk of prostate cancer at re-biopsy. |
II, III-3 | [1], [4], [2] |
| DRE
There is moderately consistent evidence that an abnormal DRE at an initial negative biopsy predicts a higher risk of prostate cancer at re-biopsy, with high specificity but low sensitivity. |
II, III-2, III-3 | [1], [3] |
| Total PSA
There is little evidence that a higher total PSA at an initial negative prostate biopsy predicts a higher risk of prostate cancer at re-biopsy. |
II, III-2, III-3 | [1], [4], [3] |
| Free to total PSA%
There is inconsistent evidence that a higher free-to-total PSA% at an initial negative prostate biopsy predicts a lower risk of prostate cancer at re-biopsy. |
II, III-2, III-3 | [1], [4] |
| PSA density
A moderately consistent association of PSA density at an initial negative biopsy with risk of prostate cancer at re-biopsy is rendered uncertain by the few studies that adjusted for possible confounding and incomplete reporting of key results. |
II, III-2, III-3 | [1], [4] |
| PSA velocity
A moderately consistent association of PSA velocity at an initial negative biopsy with risk of prostate cancer at re-biopsy is rendered uncertain by the few studies that adjusted for possible confounding and incomplete reporting of key results. |
II, III-2, III-3 | [1] |
| Atypical small acinar proliferation
There is consistent evidence that a finding of ASAP at an initial negative biopsy predicts with high specificity but low sensitivity a higher risk of prostate cancer at re-biopsy. |
II, III-2, III-3 | [1], [4] |
| High-grade PIN
There is moderately consistent evidence that high-grade PIN at an initial negative biopsy predicts a higher risk of prostate cancer at re-biopsy, but with low diagnostic accuracy. |
II, III-2, III-3 | [1], [4], [3] |
| PCA3
The three studies that adjusted for potential confounding found significantly positive associations of PCA3 at an initial negative biopsy with prostate cancer at re-biopsy. However, the sensitivity and specificity PCA3 for prostate cancer at re-biopsy were not consistent in 12 studies in which they were measured and showed no clear trend with increasing cut-off level. |
II, III-2, III-3 | [1] |
| DNA methylation
The only available study found that methylation of three marker genes in tissue from an initial negative biopsy was a moderately strong predictor of prostate cancer at re-biopsy. |
II, III-2, III-3 | [3] |
| Multiparametric MRI-targeted biopsy
Studies included in the NICE systematic review found that, compared with 12-core biopsy protocols, adding multiparametric MRI (T2W+ DWI +DCE)-targeted biopsies improved cancer detection rates by 14.3 percentage points and adding T2W + DWI multiparametric MRI improved cancer detection rates by 42.6 percentage points. For men with positive findings on multiparametric MRI, adding multiparametric MRI-targeted biopsies to 12-core biopsies improved cancer detection rates by 6.4, 10.1, 14.3 and 45.2 percentage points. A single study from the updated NICE systematic review showed that a repeat saturation biopsy on its own had a cancer detection rate of 35.9%. Adding 3–4 multiparametric MRI-targeted biopsies increased the cancer detection rate by an additional 5.1 percentage points. |
II, IV | [9], [19], [11], [12], [17], [13], [18], [10], [14], [20], [15], [1] |
| Enhanced ultrasound-targeted biopsy
Studies included in the NICE systematic review found that adding enhanced ultrasound targeted biopsy to TRUS grey-scale schematic biopsy resulted in cancer detection rates similar to those using the TRUS grey-scale schematic biopsy method alone. |
II, IV | [1] |
| Saturation or extended biopsy
Studies included in the NICE systematic review found that increasing the number of biopsy cores increased cancer detection rates. Transrectal 12–14 core biopsies had a cancer detection rate of 15–25%. Transrectal saturation biopsies had a cancer detection rate of 11–45%, and transperineal saturation biopsies had a cancer detection rate of 23–72%. The most common complication was haematuria, reported in 8.8% of men undergoing transrectal saturation biopsy and 23.4% of men undergoing transperineal biopsy. |
IV | [1] |
| Elastography targeted biopsy
Studies included in the NICE systematic review found no relevant evidence. NICE update review found that the addition of elastography-targeted biopsies to a TRUS 10-core biopsy increased cancer detection rate by 8.2 percentage points. |
II, IV | [16], [1] |
| Review of initial biopsy
A study included in the NICE systematic review found that review of initial biopsy reclassified 1.2 % of benign biopsies as cancerous and 0.4% of positive biopsies as benign. |
IV | [1] |
Note: The additional studies identified in the update review (those published after the NICE systematic review and before 1 March 2014) did not materially alter the evidence on which the recommendations in the NICE guideline[1] were based. Therefore we have chosen to adapt the NICE 2014 recommendations with minimal changes. The NICE guideline recommended that clinicians should advise men whose initial biopsy is negative for prostate cancer that there is still a risk that prostate cancer is present, and that the risk is higher if any of the following conditions apply: the initial biopsy showed high-grade prostatic intraepithelial neoplasia, the initial biopsy showed atypical small acinar proliferation, or their digital rectal examination before the initial biopsy was abnormal.
Evidence-based recommendation
|
Grade |
|---|---|
 Monitor more closely men with abnormal findings on pre-biopsy digital rectal examination, and those whose biopsy findings included either atypical small acinar proliferation or high-grade prostatic intra-epithelial neoplasia. In addition to further PSA testing and digital rectal examination, consider prostate imaging with investigations that can help to localise the site of cancer within the prostate, and repeat biopsy using a targeted approach. |
D |
| Evidence-based recommendation
|
Grade |
|---|---|
Do not offer another biopsy if the multiparametric MRI (using T2- and diffusion-weighted imaging) is negative, unless any of the following risk factors are present:
|
D |
| Practice point
|
|---|
|
Multiparametric MRI should be used only in centres with experienced radiologists appropriately trained in the use of multiparametric MRI to aid urologists in the management of individual patients.iv iv Refer to Urological Society of Australasia position statement: Status of mp-MRI prostate 2012: report from the MRI Prostate Working Party (available at www.usanz.org.au). |
| Practice point
|
|---|
|
Clinicians and other staff performing multiparametric MRI should do so in accordance with appropriate standards and guidelines for its use.v v See Moore CM, Kasivisvanathan V, Eggener S, et al. Standards of reporting for MRI-targeted biopsy studies (START) of the prostate: recommendations from an International Working Group. European urology 2013; 64: 544-552. |
| Practice point
|
|---|
|
The recommendations for multiparametric MRI apply only to its use in patients who have already undergone biopsy. Primary healthcare professionals should not order multiparametric MRI in the initial investigation of suspected prostate cancer in men with raised PSA levels. |
| Practice point
|
|---|
|
Advise patients not undergoing repeat biopsy after a normal multiparametric MRI that there is a 10–15% chance of missing a significant cancer and that further follow-up is recommended. |
| Practice point
|
|---|
|
For men at average risk for prostate cancer whose initial biopsy is negative for prostate cancer, and who have a life expectancy of less than 7 years (e.g. due to their age or due to other illness), advise that no further action is recommended unless they develop symptoms that suggest prostate cancer. |
Health system implications
Clinical practice
Implementation of the recommendations for advising men with a negative initial biopsy about their risk of prostate cancer would not necessitate significant changes to usual care or changes in the way care is organised.
The use of multiparametric MRI after an initial biopsy would affect the patient’s pathway through the healthcare system and would alter the way clinical decisions are made about further biopsies.
Resourcing
Implementation of the recommendation for the use of multiparametric MRI would lead to an increase in referrals for this imaging procedure before clinical decisions are made about further biopsies and would therefore increase the cost of care, but may reduce the number of further biopsies. If a man chooses to have multiparametric MRI after a negative biopsy, this will incur significant costs, which may not be offset by the reduced need for biopsies.
Implementation of the recommendations for advising men with a negative initial biopsy about their risk of prostate cancer would not have any important resource implications.
Barriers to implementation
At present, facilities for performing multiparametric MRI and expertise in its interpretation are limited to major metropolitan centres.
The cost of this imaging procedure may be a deterrent for some men. There is currently no Medicare Item number for multiparametric MRI in assessment of the prostate. However, the Prostate Cancer Foundation of Australia is collaborating with the Australian Government Department of Health, the Urological Society of Australia and New Zealand, and The Royal Australian and New Zealand College of Radiologists to establish item numbers for multiparametric MRI.
Footnotes
i Clinical questions were translated into the PICO framework: population, intervention (or exposure), comparator and outcome (see Appendix 3).
ii Measures of PSA kinetics include absolute increase in serum total PSA per year (PSA velocity) and time to doubling of serum total PSA (PSA doubling time). Both are used as indicators of increased risk of prostate cancer (see Testing with variants of PSA to improve sensitivity after an initial total PSA ≤ 3.0 ng/mL).
iii ‘Atypical small acinar proliferation’ and ‘atypical glands suspicious for carcinoma’ are synonymous classifications.[21][22] Accordingly, we have combined the evidence from published reported using either classification, although each was treated as a separate classification in the NICE systematic review.
iv Refer to Urological Society of Australasia position statement: Status of mp-MRI prostate 2012: report from the MRI Prostate Working Party (available at [1]]).
v See Moore CM, Kasivisvanathan V, Eggener S, et al. Standards of reporting for MRI-targeted biopsy studies (START) of the prostate: recommendations from an International Working Group. European urology 2013; 64: 544-552.[23]
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 1.26 1.27 1.28 1.29 1.30 1.31 1.32 1.33 1.34 1.35 1.36 1.37 1.38 National Collaborating Centre for Cancer. Prostate cancer: diagnosis and treatment. London (UK): National Institute for Health and Care Excellence; 2014 Jan. Report No.: Clinical guideline; no. 175. Available from: http://www.nice.org.uk/guidance/cg175/chapter/the-guideline-development-group-national-collaborating-centre-and-nice-project-team.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Gittelman MC, Hertzman B, Bailen J, Williams T, Koziol I, Henderson RJ, et al. PCA3 molecular urine test as a predictor of repeat prostate biopsy outcome in men with previous negative biopsies: a prospective multicenter clinical study. J Urol 2013 Jul;190(1):64-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23416644.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 3.9 Stewart GD, Van Neste L, Delvenne P, Delrée P, Delga A, McNeill SA, et al. Clinical utility of an epigenetic assay to detect occult prostate cancer in histopathologically negative biopsies: results of the MATLOC study. J Urol 2013 Mar;189(3):1110-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22999998.
- ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 Elshafei A, Li YH, Hatem A, Moussa AS, Ethan V, Krishnan N, et al. The utility of PSA velocity in prediction of prostate cancer and high grade cancer after an initially negative prostate biopsy. Prostate 2013 Dec;73(16):1796-802 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24038200.
- ↑ Mowatt G, Scotland G, Boachie C, Cruickshank M, Ford JA, Fraser C, et al. The diagnostic accuracy and cost-effectiveness of magnetic resonance spectroscopy and enhanced magnetic resonance imaging techniques in aiding the localisation of prostate abnormalities for biopsy: a systematic review and economic evaluation. Health Technol Assess 2013 May;17(20):vii-xix, 1-281 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23697373.
- ↑ Nelson AW, Harvey RC, Parker RA, Kastner C, Doble A, Gnanapragasam VJ. Repeat prostate biopsy strategies after initial negative biopsy: meta-regression comparing cancer detection of transperineal, transrectal saturation and MRI guided biopsy. PLoS One 2013;8(2):e57480 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23460864.
- ↑ Taverna G, Morandi G, Seveso M, Giusti G, Benetti A, Colombo P, et al. Colour Doppler and microbubble contrast agent ultrasonography do not improve cancer detection rate in transrectal systematic prostate biopsy sampling. BJU Int 2011 Dec;108(11):1723-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21756276.
- ↑ Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 2011 Oct 18;155(8):529-36 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22007046.
- ↑ 9.0 9.1 Abd-Alazeez M, Ahmed HU, Arya M, Charman SC, Anastasiadis E, Freeman A, et al. The accuracy of multiparametric MRI in men with negative biopsy and elevated PSA level--can it rule out clinically significant prostate cancer? Urol Oncol 2014 Jan;32(1):45.e17-22 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24055430.
- ↑ 10.0 10.1 10.2 10.3 Sonn GA, Chang E, Natarajan S, Margolis DJ, Macairan M, Lieu P, et al. Value of targeted prostate biopsy using magnetic resonance-ultrasound fusion in men with prior negative biopsy and elevated prostate-specific antigen. Eur Urol 2014 Apr;65(4):809-15. Epub 2013 Mar 17. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23523537.
- ↑ 11.0 11.1 11.2 11.3 Cornelis F, Rigou G, Le Bras Y, Coutouly X, Hubrecht R, Yacoub M, et al. Real-time contrast-enhanced transrectal US-guided prostate biopsy: diagnostic accuracy in men with previously negative biopsy results and positive MR imaging findings. Radiology 2013 Oct;269(1):159-66 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23657887.
- ↑ 12.0 12.1 Costa DN, Bloch BN, Yao DF, Sanda MG, Ngo L, Genega EM, et al. Diagnosis of relevant prostate cancer using supplementary cores from magnetic resonance imaging-prompted areas following multiple failed biopsies. Magn Reson Imaging 2013 Jul;31(6):947-52 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23602725.
- ↑ 13.0 13.1 13.2 Pepe P, Garufi A, Priolo G, Candiano G, Pietropaolo F, Pennisi M, et al. Prostate cancer detection at repeat biopsy: can pelvic phased-array multiparametric MRI replace saturation biopsy? Anticancer Res 2013 Mar;33(3):1195-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23482802.
- ↑ 14.0 14.1 Tang S, Lawrence E, Koo B, Nelson A, Wadhwa K, Barrett t et al. Performance of MRI-TRUS fusion in transperineal template prostate re-biopsy. European Urology Supplements 2013;12:e142-e143.
- ↑ 15.0 15.1 Yerram N, Volkin D, Nix, J, Vourganti S, Hoang A, Ahmned F et al. Multiparametric Magnetic Resonance Imaging and Ultrasound fusion biopsy detects prostate cancer in patients with prior negative TRUS biopsies. J Urol. 2012 May 23;187(supplement):4S.
- ↑ 16.0 16.1 16.2 Salomon G, Drews N, Autier P, Beckmann A, Heinzer H, Hansen J, et al. Incremental detection rate of prostate cancer by real-time elastography targeted biopsies in combination with a conventional 10-core biopsy in 1024 consecutive patients. BJU Int 2014 Apr;113(4):548-53 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24128330.
- ↑ 17.0 17.1 17.2 Lee SH, Chung MS, Kim JH, Oh YT, Rha KH, Chung BH. Magnetic resonance imaging targeted biopsy in men with previously negative prostate biopsy results. J Endourol 2012 Jul;26(7):787-91 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22122555.
- ↑ 18.0 18.1 Portalez D, Mozer P, Cornud F, Renard-Penna R, Misrai V, Thoulouzan M, et al. Validation of the European Society of Urogenital Radiology scoring system for prostate cancer diagnosis on multiparametric magnetic resonance imaging in a cohort of repeat biopsy patients. Eur Urol 2012 Dec;62(6):986-96 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22819387.
- ↑ 19.0 19.1 Arsov C, Quentin M, Rabenalt R, Antoch G, Albers P, Blondin D. Repeat transrectal ultrasound biopsies with additional targeted cores according to results of functional prostate MRI detects high-risk prostate cancer in patients with previous negative biopsy and increased PSA - a pilot study. Anticancer Res 2012 Mar;32(3):1087-92 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22399637.
- ↑ 20.0 20.1 20.2 Vourganti S, Rastinehad A, Yerram NK, Nix J, Volkin D, Hoang A, et al. Multiparametric magnetic resonance imaging and ultrasound fusion biopsy detect prostate cancer in patients with prior negative transrectal ultrasound biopsies. J Urol 2012 Dec;188(6):2152-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23083875.
- ↑ Epstein JI, Netto GJ. Biopsy interpretation of the prostate. 4th Ed, Biopsy interpretation series. Philadelphia: Lippincott Williams and Wilkins; 2008. p. 203-204.
- ↑ Paner GP, Magi-Galluzi C, Amin MB, Srigley JR. Adenocarcinoma of the prostate. In: Amin MB, Grignon DJ, Srigley JR, Eble JN, editors. Urological Pathology. Philadelphia: Wolters Kluwer; 2014. p. 604.
- ↑ Moore CM, Kasivisvanathan V, Eggener S, Emberton M, Fütterer JJ, Gill IS, et al. Standards of reporting for MRI-targeted biopsy studies (START) of the prostate: recommendations from an International Working Group. Eur Urol 2013 Oct;64(4):544-52 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23537686.
Discussion
Supporting attachments
