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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5209_Библиотеки_им_академика_М_И_Перельмана.pdf
20 Using Multicore, Transperineal Prostate Mapping Biopsy to Detect, Localize, and Treat the mpMRI…
Table 20.1 Patient data and TRUS biopsy results
PSA
Age
(ng/
PGV
Pt #
(years)
mL)
(cc) PSAD TRUS ndings
1 63 23.2 40.0 0.58 4 TRUS biopsies—all negative
2 64 23.0 89.0 0.26 2 TRUS biopsies and one 50 core saturation biopsy—all negative
3 60 4.9 40.0 0.12 5/12 cores positive 3+3(5) bilateral
4 50 3.1 20.0 0.16 2/12 cores positive 3+3(2) right apex and mid
5 56 5.9 36.0 0.16 2/12 cores positive 3+3(2) right apex, lateral apex <5% grade 4 focus
6 74 17.9 28.0 0.64 5 TRUS biopsies—all negative
Table 20.2 Biomarker, mpMRI, and TPMB results
Final
TPBM
PT # Biomarkers ndings MRI
1 PCA3: 18—negative Negative 9/99 cores positive,
2 PCA3: 19—negative
4KScore: 30%—positive HG PCa
PHI: 75—positive
PHID: 0.84—positive HG PCa
SelectMDx: 68% and 39%—
positive HG PCa
3 PHI: 47.7—positive
PHID: 1.19—positive HG PCa
SelectMDx: negative
4 PCA3: 15—negative
PHI: 61.2—positive
PHID: 3.06—positive HG PCa
5 PCA3: 9—negative, SelectMDx:
negative
6 PCA3: 18.5—negative
PHI: 89.17—positive
PHID: 3.18—positive HG PCa
SelectMDx: 78% and 48%—
positive PG PCa
a
Patient had mpMRI (June 2016) after TPMB (May 2016) but before RRP (August 2016)
a
PIRADS 5
lesion
Posterior
apex left
PIRADS 2
lesion
posterior
mid left
Negative 14/46 cores positive
PIRADS 4
left
Negative 5/72 cores positive
G.Sum (# of cancer cores) Treatment
3+3(1) 3+4(2) 4+3(5)
4+5(1)
41/126 cores positive,
3+3(5) 3+4(5) 4+4(1)
5+4(3) 5+5(27)
20/100 cores positive
3+3(6) 3+4(7) 4+3(7)
3+3(12) 3+4(2)
11/34 cores positive
3+3(6) 3+4(5) bilateral
3+3(2) 3+4(2) 4+4(1)
RRP GG5, pT2
RRP GG5, pT3a
RRP GG2, pT2c
Cryotherapy GG2
Undecided GG2
Undecided GG2
pathology -
grade, stage
223
Patient #1 (Pt #1) The patient had four TRUS
biopsies without any evidence of cancer. His
MRI ndings were also negative. T2W, DWI,
and ADC sequences are included in Fig.20.1a–
c, respectively. MRI report notes, “Within the
peripheral zone of the left midportion between 2
and 4 o’clock, there is an area of mild T2
hypointensity measuring 13 x 7mm (image # 18
series 7). This area does not demonstrate
enhancement or restricted diffusion and is
therefore indeterminate. Within the central
gland there are scattered nodular areas of T2
hypointensity and restricted diffusion. However,
these nodules have very discrete margins, which
are more typical for BPH nodules. Otherwise,
no denite focus of malignancy is suspected
within the prostate gland on this examination,
despite of the clinical information of elevated
PSA.”
His PCA3 results were negative, indicating
the absence of any PCa. Histopathology data of
TPMB found 9/99 cores positive with 8 cores
≥GG2. Table 20.3 summarizes histopathology
data for multifocal lesions. 3DTPMB model with
224
E. D. Crawford et al.
a
R
b
d
R
L
L
e
c
Fig. 20.1 MRI and 3DTPMB images for Pt #1—(a)
T2W, (b) DWI, (c) ADC, (d) Front view, (e) Side angle
view, and (f) Top view. Gleason 3+3 cancer 1/99 cores on
the left depicted in purple, Gleason 3 + 4 cancer 2/99
f
cores mid and left depicted in blue, Gleason 4+3 cancer
5/99 cores bilateral depicted in orange, Gleason 4+5 cancer 1/99 cores on the right depicted in green
20 Using Multicore, Transperineal Prostate Mapping Biopsy to Detect, Localize, and Treat the mpMRI…
Table 20.3 Pt #1—Histopathology and MRI ndings of multifocal lesions
Lesion # TPMB side TPMB location TPMB zone Gleason score (GG) MRI ndings and PIRADS score
1 Right Apex Anterior 4+5 (GG5) MRI invisible
2 Left Mid Transition
zone
3 Right Mid Posterior 4+3 (GG3) MRI invisible
4 Left Mid Transition
zone
5 Left Mid Transition
zone
4+3 (GG3) MRI invisible
4+3 (GG3) MRI invisible
3+3 (GG1) MRI invisible
225
histopathology ndings is given in Fig.20.1d–f.
The patient had radical retropubic prostatectomy
(RRP) surgery at UCH. He had Gleason 4 + 5
cancer (GG5) with perineural invasion and was
assigned to AJCC pathologic stage group IIIC
(pT2, N0, M0).
Patient #2 (Pt #2) The patient had a history of
rising PSA which served as precursors to three
successive TRUS biopsies, including one 50-core
saturation biopsy without nding any evidence of
cancer. His Serial PSA values were 11.9 in
November 2013, 13.3 in June 2014, 23.0 in
February 2014, and 24.2in April 2015. He had an
MRI in 2015 from an outside facility which
didn’t nd any suspicious lesions and afterwards
he was referred to UCH.
Based on the patient’s history, the next logical
step was to test PCa biomarkers and all biomarkers except PCA3 indicated incidence of HG PCa
with a very high probability. PHI of 75 was estimated using PSA 13.68, free PSA 1.46, and
p2PSA 29.66. He had TPMB in May 2016. Based
on histopathological ndings of multiple bilateral
GG5 lesions, another MRI was taken in June
prior to his RRP surgery at UCH.
Figure 20.2a–c illustrates post-TPMB MRI
sequences and Fig.20.2d–f illustrates 3DTPMB
model with histopathological ndings.
Histopathology data showed 41/126 cores positive. The disease was multifocal and bilateral
with 7 lesions, including the GG5 index tumor in
the left transition zone extending from the apex,
mid and to the base. Table 20.4 summarizes the
TPMB and MRI ndings of multifocal lesions.
All seven lesions were csPCa, but only the index
lesion was visible and assigned a score of
PIRADS 5 corresponding to biopsy proven
ndings.
Post-TPMB MRI report notes, “The prostate
measures 6.1 x 5.5 x 6.0cm for an estimated volume of 100 cc. The transition zone is enlarged
and demonstrates diffuse intermediate/hypointense T2 signal. Diffuse signal abnormality corresponding to multifocal biopsy-proven
adenocarcinoma (PIRADS 5). There are scattered areas of hemorrhage within the transitional
zone. Capsular bulge is noted at the apex on the
left in series 7. The peripheral zone is thin and
compressed. There is a small 8mm focus of low
T2 signal in the left peripheral zone mid gland
(series 6/image 21) with enhancement in series
1101 but without associated restricted diffusion
corresponding to the indeterminate but may
reect a focus of adenocarcinoma. Seminal vesicles: There is abnormal intermediate/hypointense T2 signal extending into the left seminal
vesicle is asymmetrically and suspicious for
extraprostatic tumor extension.”
The patient had RRP surgery in August 2016.
The nal diagnosis shows prostatic adenocarcinoma overall Gleason grade 5+4 (GG5), multifocal and bilateral disease, 16 mm greatest
dimension, involving approximately 15% of the
prostate; Gleason grade 5 is approximately 60%
of the tumor. Perineural invasion of thick nerves
and extraprostatic extension are present. No evidence of seminal vesicles invasion. Apical and
left peripheral surgical margins involved by
tumor (3 mm and 6 mm). The patient was
assigned to AJCC pathologic stage grouping IIIC
(pT3a, N0, Mx).
226
E. D. Crawford et al.
a
R
b
d
R
L
L
e
c
Fig. 20.2 MRI and 3DTPMB images for Pt #2—(a)
T2W, (b) DWI, (c) ADC, (d) Front view, (e) Side angle
view, and (f) Top view. Atypical small acinar proliferation
(ASAP) in 2/126 cores bilateral depicted in gray, Gleason
3 + 3 cancer 5/126 cores bilateral depicted in yellow,
f
Gleason 3 + 4 cancer 5/126 cores bilateral depicted in
orange, Gleason 4 + 4 cancer 1/126 cores on the left
depicted in blue, Gleason 5+4 and 4+5 cancer 3/126
cores bilateral depicted in red, Gleason 5+5in 27/126
cores bilateral depicted in green
20 Using Multicore, Transperineal Prostate Mapping Biopsy to Detect, Localize, and Treat the mpMRI…
Table 20.4 Pt #2—Histopathology and MRI ndings of multifocal lesions
Gleason score
Lesion # TPMB side TPMB location TPMB zone
1 Left Apex, mid and
base
2 Left Mid Posterior 5+5 (GG5) MRI invisible
3 Left and
middle
4 Right Apex, mid Posterior, and
5 Right Mid Transition zone 5+4 (GG5) MRI invisible
6 Right Mid Transition zone 5+5 (GG5) MRI invisible
7 Right Mid Anterior 4+3 (GG3) MRI invisible
Table 20.5 Pt #3—Histopathology and MRI ndings of multifocal lesions
Lesion # TPMB side TPMB location TPMB zone Gleason score (GG) MRI ndings and PIRADS score
1 Left Mid Posterior 3+4 (GG2) MRI invisible
2 Left and
middle
3 Right Mid, base Transition
4 Right Apex, mid Transition
5 Right Mid Posterior 3+4 (GG2) MRI invisible
6 Right Apex Anterior 3+3 (GG1) MRI invisible
7 Midline Mid Posterior 3+3 (GG1) MRI invisible
Apex, mid Posterior 5+5 (GG5) MRI invisible
Mid, base Transition
Transition zone 5+5 (GG5) MRI visible—5
transition zone
zone
zone
zone
(GG)
5+5 (GG5) MRI invisible
3+4 (GG2) MRI invisible
3+4 (GG2) MRI invisible
3+4 (GG2) MRI invisible
MRI ndings and PIRADS
score
227
Patient #3 (Pt #3) The patient had a TRUS
biopsy due to elevated PSA and was diagnosed
with GG1 bilateral cancer. PHI and PHID results
indicated the presence of ≥GG2 cancer, but not
SelectMDx. PHI score 47.6 calculated for PSA
6.41, free PSA 0.82, and p2PSA 15.4. He had an
MRI to rule out incidence of csPCa and the ndings were negative. His PSAD was 0.12 and did
not meet the normal cutoff ≥0.15 for STRB in
case MRI is negative. He then continued for a
TPMB to determine whether his treatment
options could be watchful-waiting or targeted
focal therapy. TPBM histopathology results conrmed incidence of multifocal GG2 lesions as
summarized in Table20.5. Figure20.3a–c shows
mpMRI sequences and Fig. 20.3d–f shows the
3DTPMB model with csPCa.
MRI report notes, “The prostate gland mea-
sures 5.2 x 3.5 x 3.1 cm, giving a volume of 30cc.
The heterogeneous decreased signal in the
peripheral zone on T2 but no focal suspicious
lesion identied (PIRADS 2). A focal area of
decreased T2 signal left peripheral zone image
19/5, mildly decreased signal on the ADC map.
Area favored to represent brosis, no signicant
enhancement here and no convincing increased
signal on DWI images. No evidence of extracapsular extension.”
The patient had RRP surgery, and the nal
pathology report showed Gleason score 3 + 4
(GG2) multifocal bilateral disease. Index tumor
in the right lobe, Gleason grade 3+4 (grade 4 is
about 5%), 14mm greatest dimension, with additional multifocal and bilateral foci of Gleason
grade 3+3 (GG1), with overall tumor involvement of ~10% of the prostate with perineural
invasion. No evidence of extraprostatic extension
or invasion of seminal vesicles. Surgical margins
with no evidence of malignancy; tumor cells are
focally approaching the right peripheral margin
and present within microns of inked margin;
228
E. D. Crawford et al.
d
a
R L
b
c
R L
e
f
Fig. 20.3 MRI and 3DTPMB images for Pt #3—(a)
T2W, (b) DWI, (c) ADC, (d) Front view, (e) Side angle
view, and (f) Top view. Atypical small acinar proliferation
(ASAP) in 1/100 cores on the right depicted in dark
orange, High-grade prostatic intraepithelial neoplasia
Patient assigned to AJCC pathologic stage grouping IIB (pT2c, N0, Mx).
Patient #4 (Pt #4) Patient was diagnosed with
Gleason 3 + 3 cancer from a TRUS biopsy.
Tested PCa biomarkers were negative except
PHI score 61.2 and PHID 3.06 both indicated
(HGPIN) in 1/100 cores on the left depicted in red,
Gleason 3+3 cancer 4/100 cores midline and on the right
depicted in orange, Gleason 3+4 cancer in 11/100 cores
bilateral depicted in blue, Gleason 4 + 3 cancer 2/100
cores on the left depicted in green
incidence of GG2 or higher cancer. PHI was
estimated for PSA 3.1, free PSA 0.09, and
p2PSA 3.13. MRI ndings were also negative.
However, TPMB histopathology results show
14/46 cores positive with Gleason 3+4 (GG2)
cancer. The Gleason 4 pattern represents
approximately 5% in each core and Gleason 3
20 Using Multicore, Transperineal Prostate Mapping Biopsy to Detect, Localize, and Treat the mpMRI…
229
a
R R R
b
d
L
e
c
Fig. 20.4 MRI and 3DTPMB images for Pt #4—(a)
T2W, (b) DWI, (c) ADC, (d) Front view, (e) Side angle
view, and (f) Top view. Gleason 3+3 cancer 12/46 cores
bilateral depicted in yellow, Gleason 3+4* cancer 2/46
pattern constitutes 95%. Figure20.4a–c shows
MRI sequences and Fig. 20.4d–f shows
3DTPMB with bilateral multifocal disease. The
index lesion located on the right side extended
f
cores on the right depicted in green (*Gleason 4 pattern
represents approximately 5% in each core, Gleason pattern 3 constitutes 95%)
from apex, mid to base within the transition
zone. There were three small GG2 lesions, two
on the right side and one on the left.
230
E. D. Crawford et al.
MRI report notes, “The prostate gland mea-
sures approximately 4.3 x 3.2 x 2.3cm. No abnor-
mal T2 hypointensity or diffusion restricted
lesion/mass identied within the peripheral zone.
No abnormal enhancement. No signicant central gland hypertrophy. A few tiny T2 hyperintense probable periurethral glands/cysts noted
along the right lateral margin of the inferior
prostatic urethra wall. Foci of increased signal
intensity on diffusion weighted images are not
truly restricted on ADC mapping and therefore
likely reect evidence of T2 shine through or
other artifacts. The patient chose whole-gland
cryotherapy for treatment.”
Patient #5 (Pt #5) Initial TRUS biopsy nding
due to elevated PSA show GG1 disease with a
small Gleason grade 4 focus <5% on right side.
PCa biomarkers were negative. The patient had
an MRI for further evaluation. MRI report notes,
“Small T2 hypointense nodule demonstrating
enhancement and restricted diffusion in the left
mid peripheral zone, suspicious for prostate cancer (PIRADS 4). No evidence for extracapsular
extension or neurovascular bundle involvement.
Three small T2 hypointense foci in the peripheral
zone that do not demonstrating enhancement or
denite restricted diffusion are indeterminate but
may still represent neoplasm.”
Patient had TPBM also targeting PIRADS 4
lesion. Histopathology data showed PIRADS 4
lesion was a false positive but found Gleason
3 + 4 (GG2) multifocal bilateral cancer elsewhere. Figure20.5a–c shows MRI sequences and
Fig.20.5d–f shows 3DTPBM models with several multifocal lesions. The index lesion with
GG2 cancer was located anterior on the right side
extending from apex to mid. The patient was an
outside referral and has not returned to discuss
treatment options after TPBM ndings.
Patient #6 (Pt #6) Patient had a history of rising
PSA and consequently had a total of ve TRUS
biopsies. Figure20.6 illustrates his PSA prole
including dates for three TRUS biopsies. Two
other TRUS biopsies were done in 2011 (not
shown). All TRUS biopsy ndings were negative.
However, PHI, PHID, and SelectMDx all indicated incidence of ≥GG2 cancer with high probability. PHI score 89.17 was calculated for PSA
32.28, fPSA 8.15, and p2PSA 127.91. An MRI
was recommended to identify the GG2 and higher
cancer. However, MRI ndings were inconclusive without any PIRADS scores assigned to suspicious lesions.
The MRI report notes, “Somewhat subopti-
mal examination due to artifacts from the bilateral hip prostheses. A focal area at the 2 to 3:00
position in the left mid gland peripheral zone is
concerning for malignancy. There is an adjacent
continuous indeterminate area of low T2 signal
extending to the 12:00 position as well as focal
separate indeterminate area in the anterior left
apex. The focal area within the left central gland
is concerning for malignancy, although benign
prostatic hypertrophy can appear similarly in
the central gland. Fluid and debris in the right
hip joint with capsular enhancement may reect
particle disease or other hip joint related
pathology.”
Histopathology data from his TPMB shows
5/72 cores positive with GG2 and GG4 cancer.
Figure 20.7a–c shows MRI sequences and
Fig. 20.7d–f shows 3DTPMB models with
cancer. Two csPCa lesions were on the left side of
the prostate. The index lesion with GG2 cancer
was in the transition zone extending from mid to
base. A smaller second lesion with GG4 cancer
was in the mid peripheral zone. The patient
returned to his urologist from another institution
to discuss treatment options.
Discussion
MRI Invisible Lesions Six patients presented
above highlight the shortcomings of mpMRI,
STRB, and even some PCa biomarkers for failure
to diagnose csPCa whether it is solitary or multifocal. Most of the MRI invisible lesions were
located somewhat anteriorly. MRI has a moderate diagnostic performance for detecting anterior
csPCa with a sensitivity of 78% and specicity of
58% [40]. Anterior tumors were less palpable
20 Using Multicore, Transperineal Prostate Mapping Biopsy to Detect, Localize, and Treat the mpMRI…
231
a
d
R R L L
b
e
c
Fig. 20.5 MRI and 3DTPMB images for Pt #5—(a)
T2W, (b) DWI, (c) ADC, (d) Front view, (e) Side angle
view, and (f) Top view. Gleason 3+3 cancer 6/34 cores
(p<0.001) and require repeat biopsies for diagnosis (p= 0.012) compared to posterior tumors
[40]. Anterior tumors were subjected to upgrading (p=0.003) even though pathological features
did not differ signicantly from posterior tumors.
Due to the multifocality of the disease, there
are differences in the performance parameters of
f
bilateral depicted in blue, Gleason 3+4 cancer 5/34 cores
bilateral depicted in green
mpMRI at the patient level and lesion level. A previously completed study at UCH for a cohort of
47 TPMB patients found PIRADS ≥3 lesions had
a mixed performance in the detection of csPCa
[34]. At the patient level, sensitivity, specicity,
PPV, and NPV were 81%, 32%, 38%, and 77%,
respectively. However, 29 out of 56 biopsy- proven
csPCa lesions were missed on MRI: 10 lesions
232
Fig. 20.6 PSA prole of Pt #6 for a period of 6years prior to mpMRI and TPMB
E. D. Crawford et al.
had ≥GG2 cancer (group 1), and 19 lesions had
GG1 cancer with volume>0.5cc (group 2). The
lesion-level sensitivity for groups 1 and 2 were
68% and 48%, and PPV was 29% and 53%,
respectively. In a similar study, pre- surgery
mpMRI failed to detect more than one- third of the
whole-mount pathology-conrmed csPCa lesions
in 588 patients [19]. The overall sensitivity was
65% and 83% for solitary and multifocal csPCa,
respectively, and overall PPV was 65%.
NPV and Prevalence A major limiting factor to
omit prostate biopsies in patients with negative
mpMRI is the variations in reported NPV (63%
to 98%) that prevent ruling out csPCa [12]. NPV
varied in large parts due to study design, disease
prevalence, and denition of positive mpMRI
and csPCa [20]. European patients are symptomatic [41], whereas the US patients are largely
asymptomatic due to regular PSA/DRE screening, and disease prevalence could be markedly
different [42]. Since the NPV of mpMRI is
dependent on the disease prevalence, mpMRI utilized in cohorts in which the disease (incidence
of csPCa) is rare will always have higher NPVs
than mpMRI applied to cohorts in which the disease is common [43].
PROMIS trial reported that the use of mpMRI
to triage men might allow 27% of patients to
avoid a primary biopsy and diagnosis of 5%
fewer non-csPCa [16]. However, reported NPV
varied from 72–89% depending on the denition
of csPCa and corresponding disease prevalence.
A major aw of the PRECISION trial design was
the failure to biopsy 71/252 (28%) of men who
avoided biopsy because of negative MRI [44].
Without a conrmatory biopsy, it was not possible to rule out csPCa among these men as in the
PROMIS trial. For comparison, TPMB has ≥95%
NPV to rule out csPCa [22]. Since cancer prevalence is highly variable in different populations,
dening those who can avoid biopsy when
mpMRI is negative should be supported by risk
stratication of patients [20].
Limitations of MRTB and STRB MRTB is
becoming the accepted diagnostic pathway for
prostate biopsies due higher detection rate of
csPCa compared to STRB [14]. A case-controlled multicenter randomized clinical trial
results with 453 patients found MRTB targeting
lesions with a PIRADS ≥3 (35% detection of
≥GG2) is non- inferior to initial STRB (30%
detection of ≥GG2) [45]. Hence, many studies
have recommended the inclusion of STRB in
addition to MRTB [46, 47]. One study found
omitting STRB in 16% of patients in the
European cohort with a calculated risk of <15%
would have missed 7% of csPCa, and ndings