EURURO Vol. 72 No. 4

subsequent treatment. The analysis of circulating tumor

DNA may provide the same information.

Conflicts of interest:

Advisory Board: Novartis, AbbVie, Astellas, Janssen,

Amgen, Biocancell, Cubist, Sitka, Bayer, Merck, Sanofi, Spectrum, Roche,

Lilly, Ferring; Speaker: AbbVie, Janssen, Ferring, Biosyent; Grant Funding:

New B Innovation, iProgen, GenomeDx; Patent: GenomeDx.

References

[1]

Faltas BM, Prandi D, Tagawa ST, et al. Clonal evolution of chemo- therapy-resistant urothelial carcinoma. Nat Genet 2016;48:1490–9.

[2]

Plimack ER, Dunbrack RL, Brennan TA, et al. Defects in DNA repair genes predict response to neoadjuvant cisplatin-based chemo- therapy in muscle-invasive bladder cancer. Eur Urol 2015;68: 959–67

[3]

Liu D, Plimack ER, Hoffman-Censits J, et al. Clinical validation of chemotherapy response biomarker ERCC2 in muscle-invasive urothelial bladder carcinoma. JAMA Oncol 2016;2:1094–6.

[4]

Van Allen EM, Mouw KW, Kim P, et al. Somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma. Cancer Discov 2014;4:1140–53.

Peter C. Black

Department of Urologic Sciences, University of British Columbia,

Vancouver, BC, Canada

*University of British Columbia, Urological Sciences, Level 6, 2775 Laurel

Street, Vancouver, BC V6N 2W6, Canada.

E-mail address:

peter.black@ubc.ca

http://dx.doi.org/10.1016/j.eururo.2017.05.049

2017 European Association of Urology.

Re: The Prostate Health Index Adds Predictive Value

to Multi-parametric MRI in Detecting Significant

Prostate Cancers in a Repeat Biopsy Population

Gnanapragasam VJ, Burling K, George A, et al

Sci Rep 2016;6:35364

Expert’s summary:

The National Comprehensive Cancer Network guidelines pro-

vide multiple reflex testing options to help with repeat pros-

tate biopsy decisions, including markers and multiparametric

magnetic resonance imaging (mpMRI)

[1] .

The prospective

study by Gnanapragasam et al

[2]

shows that the combination

of the Prostate Health Index (PHI) and mpMRI can avoid

unnecessary repeat biopsies while preserving the detection

of high-grade prostate cancer (PCa). Among 279 men with one

or more prior biopsies, PHI was a significant predictor of

Gleason 7 PCa on targeted transperineal biopsy in a multi-

variable model with MRI findings. PHI plus MRI (area under

the receiver operating characteristic curve [AUC] 0.75) out-

performed PSA plus MRI (AUC 0.69) or MRI alone (AUC 0.64) in

predicting high-grade disease, and was associated with a net

benefit on decision curve analysis. A PHI threshold of 35 had

97% negative predictive value (NPV) for clinically significant

PCa. Among men with negative mpMRI, PHI outperformed

both prostate-specific antigen (PSA) and PSA density to iden-

tify significant PCa. Applying a PHI threshold of 35 among men

with negative mpMRI would have spared 42% of biopsies,

while only missing a single low-volume Gleason 7 tumor.

Expert’s comments:

A recent consensus statement from the American Urological

Association and Society of Abdominal Radiology recom-

mended that when high-quality mpMRI is available, it should

be strongly considered for any patient with a prior negative

biopsy considering repeat biopsy

[3]

. However, there are also

several markers available for this clinical scenario, including

blood (free PSA, 4KScore, and PHI), urine (PCA3) and tissue

tests (ConfirmMDx)

[1] .

Optimal integration of markers and

imaging is therefore a very timely topic. According to the

consensus statement, decisions on whether to perform

mpMRI in this setting should depend on the results for other

biomarkers. In addition, it states that for men with negative or

low-suspicion MRI, ancillary markers may be used to deter-

mine the need for repeat systematic biopsy.

A recent meta-analysis found that mpMRI had a median

NPV of 88% for clinically significant PCa on repeat biopsy

[4]

. The authors concluded that MRI alone cannot exclude

biopsy owing to variable performance. To date, few studies

have examined the added value of markers in an MRI-based

detection paradigm. The data from Gnanapragasam et al

[2]

suggest that in a setting in which high-quality mpMRI is

routinely performed, PHI reliably identifies the remaining

clinically significant tumors in men with a Prostate Imaging

Reporting and Data System (PIRADS) score

3. A recent

Johns Hopkins study similarly reported that no patient with

PIRADS score 3 and PHI

27 had Gleason 3 + 4 PCa,

suggesting that the combination of MRI plus PHI can avoid

unnecessary repeat biopsies without compromising signif-

icant PCa detection

[5]

Conflicts of interest:

The author has received honoraria for lectures from

Astellas, MDx Health, and Boehringer Ingelheim; travel expenses from

Astellas, Sanofi Aventis, Minomic, and Boehringer Ingelheim; and

consulting fees from GenomeDx and Lilly.

Acknowledgments:

The author is supported by The Edward Blank and

Sharon Cosloy-Blank Family Foundation, The Gertrude and Louis Feil

Family, the New York State Department of Health (#105879), and the

National Institutes of Health (Award Number K07CA178258). The

content is solely the responsibility of the author and does not represent

the official views of the NIH.

References

[1] National Comprehensive Cancer Network. Prostate cancer early

detection

2017.

www.nccn.org/professionals/physician_gls/pdf/ prostate_detection.pdf

[1_TD$DIFF]

[2]

Gnanapragasam VJ, Burling K, George A, et al. The Prostate Health Index adds predictive value to multi-parametric MRI in detecting significant prostate cancers in a repeat biopsy population. Sci Rep 2016;6:35364.

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