Correspondence
Diagnostic accuracy of TMM received a research grant from MDxHealth. SSS,
the PROMIS study
We commend Hashim Ahmed
and colleagues (Jan 19, p 815)1 for
their rigorous evaluation of multi-
parametric MRI (MP-MRI), which
indicated that prostate biopsy
can potentially be avoided in
approximately 27% of patients with
a negative MP-MRI result. Deciding
how to proceed with a patient who
has a positive MP-MRI result is equally
important. Notably, the authors
did not compare histopathological
correlation for MP-MRI with template
prostate mapping biopsy (TPM) to
assess whether disease was found in
the region of interest. Additionally,
the authors reported that 50% of
patients with a positive MP-MRI result
had no cancer or clinically insignificant
cancer, including 19% of patients
with MRI 5 lesions, and one of every
ten patients with a negative MP-MRI
result had clinically significant cancer.
Intriguingly, the performance profile of
MP-MRI for prostate cancer detection
is similar to that of prostate-specific
antigen-based screening, which has
many limitations, including poor
specificity, and thus supports further
efforts to improve the performance of
MP-MRI.2
When considering MP-MRI as
a biomarker for prostate cancer
detection, it is important to note that
the biological and clinical significance
of MRI-detected disease is unknown—
ie, the survival benefit of treating MRI-
detected prostate cancers has not been
shown. Furthermore, several large
active surveillance studies, including
the ProtecT trial,3 indicate that patients
under active surveillance can do well
without MP-MRI for at least a decade
after diagnosis. Certainly, the presence
of a cancer core length of 6 mm or more
does not necessarily denote cancer that
requires primary therapy. The PROMIS
study represents a vital first step
towards avoiding the limitations that
are associated with prostate-specific
antigen-based screening.
362
whether diagnosed initially or even
AKG, JSM, and GSP declare no competing interests.
*Simpa S Salami, Arvin K George,
Jeffrey S Montgomery,
Todd M Morgan, Ganesh S Palapattu
simpa@med.umich.edu
Department of Urology (SSS, AKG, JSM, TMM, GSP)
and Comprehensive Cancer Center (AKG, JSM, TMM,
GSP), University of Michigan, Ann Arbor,
MI 48109, USA
1 Ahmed HU, El-Shater Bosaily A, Brown LC,
et al. Diagnostic accuracy of multi-parametric
MRI and TRUS biopsy in prostate cancer
(PROMIS): a paired validating confirmatory
study. Lancet 2017; 389: 815–22.
2 Thompson IM, Ankerst DP, Chi C, et al.
Operating characteristics of prostate-specific
antigen in men with an initial PSA level of
3·0 ng/ml or lower. JAMA 2005; 294: 66–70.
3 Hamdy FC, Donovan JL, Lane JA, et al. 10-year
outcomes after monitoring, surgery, or
radiotherapy for localized prostate cancer.
N Engl J Med 2016; 375: 1415–24.
Authors’ reply
We thank Simpa S Salami and col­
leagues for raising three important
issues.
First, the primary role of a triage test is
to rule out clinically significant prostate
cancer and by doing so help the patient
avoid an unnecessary biopsy. If the MRI
does reveal an abnormality with a high
probability of prostate cancer it should
be targeted. The PROMIS1 study did not
address the issue of targeting because it
was a blinded study. Other studies have
investigated this and several others are
currently recruiting.2
Second, we disagree that the
performance of multi parametric
MRI parallels that of prostate-specific
antigen. In PROMIS, prostate-specific
antigen did not contribute to the
prediction of clinically significant
prostate cancer. By contrast, the
MRI-derived Likert score was closely
correlated with clinically significant
prostate cancer.
Third, we agree that our prevailing
assumptions about clinically significant
prostate cancer should be questioned.
Nonetheless, increasing evidence
suggests that lesions with a Gleason
score of 6 do not have hallmarks of
malignancy3 and that many tumours
with a Gleason score of 3 + 4 = 7 do
well without immediate treatment,4
if missed by a transrectal ultrasound-
guided prostate biopsy.5 One of the
most striking attributes of MRI within
PROMIS was the complete absence of
any misclassification of cancers with
Gleason grade group III, IV, or V.
HUA received a grant from TROD Medical, and grants
and personal fees from Sonacare, Sophiris, and Galil
Medical, outside the submitted work. HUA also runs a
private medical practice for the treatment of patients
with potential prostate cancer. ME received grants
and personal fees from STEBA Biotech, and grants
and non-financial support from Sophiris, TROD
Medical, and Sonacare, during the conduct of the
study; and received consultancy fees from NUADA
Medical, outside the submitted work. ME is also
employed at a private medical practice (London
Urology Associates) and reports a pending patent for
computer-assisted diagnosis. CP received personal
fees from Advanced Accelerator Applications and
Janssen, and grants and personal fees from Bayer,
outside the submitted work. LCB and RK declare no
competing interests.
*Hashim U Ahmed, Louise C Brown,
Richard Kaplan, Chris Parker,
Mark Emberton
hashim.ahmed@imperial.ac.uk
Division of Surgery and Interventional Science,
Faculty of Medical Sciences, University College
London, London, UK (HUA, ME); Department of
Urology, University College London Hospitals NHS
Foundation Trust, London, UK (ME); Department of
Academic Urology, Royal Marsden Hospital, Sutton,
UK (CP); Medical Research Council Clinical Trials
Unit at University College London, London, UK
(LCB, RK); Division of Surgery, Department of
Surgery and Cancer, Imperial College London,
London W6 8RF, UK (HUA); and Imperial Urology,
Imperial College Healthcare NHS Trust, London,
UK (HUA)
1 Ahmed HU, El-Shater Bosaily A, Brown LC,
et al. Diagnostic accuracy of multi-parametric
MRI and TRUS biopsy in prostate cancer
(PROMIS): a paired validating confirmatory
study. Lancet 2017; 389: 815–22.
2 Porpiglia F, Manfredi M, Mele F, et al.
Diagnostic pathway with multiparametric
magnetic resonance imaging versus standard
pathway: results from a randomized
prospective study in biopsy-naïve patients
with suspected prostate cancer. Eur Urol 2016;
published online Aug 27. DOI:10.1016/j.
eururo.2016.08.041.
3 Ahmed HU, Arya M, Freeman A, Emberton M.
Do low-grade and low-volume prostate
cancers bear the hallmarks of malignancy?
Lancet Oncol 2012; 13: e509–17.
4 Ahmed HU. Prostate cancer: time for active
surveillance of intermediate-risk disease?
Nat Rev Urol 2013; 10: 6–8.
5 Klemann N, Røder MA, Helgstrand JT, et al.
Risk of prostate cancer diagnosis and
mortality in men with a benign initial
transrectal ultrasound-guided biopsy set:
a population-based study. Lancet Oncol 2017;
18: 221–29.
www.thelancet.com Vol 390 July 22, 2017