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Today we are honored to welcome Dr.

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Demetris PKIs

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for a lectured entitled a deep dive into PSMA

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PET interpretation.

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Dr. PKIs is a nuclear medicine consultant at the University

0:36

College London Hospital.

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His clinical practice includes a wide range

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of isotope based imaging

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and therapeutic applications with special clinical interest

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and research interest in prostate cancer theranostics.

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At the end of the lecture, please join him in a q

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and a session where he will address questions you

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may have on today's topic.

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Please remember to use the q

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and a feature to submit your questions so we can get to

0:59

as many as we can before our time is up.

1:02

And with that, we are ready to begin today's lecture. Dr.

1:04

Prita is, please take it from here.

1:07

Hello. Welcome everyone to this non-conference,

1:10

and thank you for the kind introduction.

1:12

Uh, today's topic is PSMA PET interpretation.

1:16

And, uh, let me start by saying that this, uh,

1:19

presentation is, uh, the product of, uh,

1:21

my participation in a very busy, uh, uh, prostate cancer

1:27

MDT, uh, where, uh, we have worked, uh,

1:32

very, very hard to optimize, uh, the, um, utility

1:37

of A-P-S-M-A PET for prostate cancer and, um,

1:42

but also where the limits

1:43

of PSMA PET are constantly challenged.

1:47

Um, so these are my disclosures.

1:53

Uh, we'll start with the PSMA tracers,

1:56

which are available for imaging.

1:58

And, um, there are different, uh, flavor of tracers.

2:02

Some of them are, um, labeled

2:06

with Gallium 68, some of them with, uh, fluoride 18.

2:10

And, uh, I'm sure in, uh, different parts

2:12

of the world there are different, uh, tracers

2:14

that are accessible.

2:16

So here in our department, we are using,

2:18

obviously gallium 68, PSMA 11, which was the first

2:21

to gain FDA approval.

2:23

And for, um, some time it was

2:27

considered the default tracer.

2:30

And, uh, we are also using 18 F-P-S-M-A 1007,

2:33

but, uh, um, also, uh, D-C-F-B-Y-L

2:38

and this newer tracer are, uh, are, are quite popular.

2:43

So, uh, in this slide you can see, um, uh, the different,

2:48

uh, types of, uh, excretion of these tracers.

2:51

Um, so all these tracers on the left, uh, have

2:55

so kidney dominant excretion

2:58

and, uh, essentially, uh, have a similar physiological, uh,

3:02

biodistribution, um, which includes, uh, uh,

3:06

part glands kidney, uh, kidneys Yeah, and bladder

3:10

and, uh, liver, spleen, and, um, bowel.

3:14

And, uh, the only, uh, liver, the only tracer, which shows,

3:19

uh, liver dominant excretion is the 18 F PSMA 1007,

3:24

uh, which, um,

3:26

has some difference in the normal blood distribution.

3:29

Um, one theoretical advantage is that, uh, there is, uh,

3:32

limited excretion in the urine.

3:34

So, um, the, this region is clear,

3:39

uh, and um, may allow for, um, better, um,

3:45

sensitivity, um, prostate, uh, disease, um,

3:51

while, um, there is, uh, um, higher liver,

3:56

uh, uptake, um, but also the physiological distribution.

4:00

This, particularly with this tracer may look something like

4:04

this, um, with these areas of, uh, uh,

4:08

heterogeneity bone uptake.

4:09

And we know that, uh, uh, this trace, uh,

4:13

has a higher rate of, of false positives, uh, in the bones,

4:18

uh, which is, uh, uh, usually, uh, an issue

4:22

for interpreting PET with his tracer,

4:24

uh, at the first stage.

4:26

But, uh, as, um, experience grows

4:29

and we get past the learning curve, then, uh, the, there is,

4:33

uh, we, we get more courage to, um, to say

4:37

to the clinicians in the MDT that, uh, this is physiological

4:41

and it doesn't amount to disease.

4:45

Um, I'm going to talk about a little bit of, um, principles

4:50

of PSMA physiology, normal and, uh, abnormal.

4:54

Um, these are things from, uh, the basic sciences

4:57

that we need to, uh, have in mind

4:59

because, um, this knowledge sometimes helps us

5:02

with the interpretation.

5:04

So we must know that the PSMA, um,

5:07

is a membrane lic glycoprotein.

5:10

This is the target of our, uh, tracer.

5:13

And, uh, this, uh, glycoprotein is fixed on,

5:16

um, on the membrane.

5:18

It attacks glutamate, propoxy pep on multiple substrates,

5:23

and, uh, there is physiological expression in a number

5:25

of tissues, including obviously the prostate,

5:28

but other tissues as well.

5:30

And, uh, the excretion is trace dependent,

5:32

as we've already seen now in disease.

5:37

Um, we know that, uh, PSA is, uh,

5:41

this glycoprotein is, uh,

5:43

over expressed specifically in process cancer cells, um,

5:48

but not in 100% of prostate cancer cells.

5:52

So we know that, uh, around 10% of, um,

5:56

um, of patients with, uh, um,

6:02

with, uh, prostate cancer may have, uh, a negative scan, um,

6:08

or lower lower activity in the disease.

6:12

And, uh, the current hypothesis of, uh, how it works,

6:16

how we, why, what's, what's it, what SMAs role is, um,

6:21

in, um, prostate cancer is

6:24

that it plays a role in folate metabolism, which is released

6:27

by dying cancer cells.

6:28

And, um, that, um, um, this

6:33

helps in the transportation of, uh, these four leads to, uh,

6:38

healthy persist cancer cells, uh,

6:40

facilitating further proliferation, um, in, we know that,

6:45

uh, PSMA PET is expressed in other types of, uh,

6:49

that PSA PET can show other types of cancer as well.

6:52

Um, but there's a different, um, biological substrate

6:57

to, to this, uh, imaging.

6:59

And, uh, this is, uh, mainly related

7:01

to neo angiogenesis in the other types of cancer.

7:05

Uh, PSMA expression levels increase according

7:07

to stage tumor grade, um, grade of unemployed

7:12

and BI and, uh, biochemical recurrence patients.

7:15

And the higher PSMA expression is associated

7:18

with poor prognostic outcomes.

7:20

And finally, PSMA expression is upregulated when the

7:25

castrate resistant phenotype evolves.

7:29

Um, obviously when, um, uh, reporting, uh, scan,

7:33

we have to take into account, uh, the clinical context.

7:38

And, um, there are the variables that determine, um,

7:41

the pretest probability

7:43

of someone having primary prostate cancer or recurrence

7:46

or, um, nole in distant metastasis.

7:50

So, uh, it's very important to have a history, uh,

7:54

for the patient and, uh, know at which, uh,

7:57

state their disease is, whether it's hormone sensitive,

8:01

whether it's a newly diagnosed cancer,

8:03

or, um, a cancer that has been already treated,

8:06

or, uh, whether it is like, um,

8:10

gastric resistant cancer, uh,

8:13

because then, uh, our interpretation, uh, will be adjusted

8:17

to these clinical disease states.

8:20

And, uh, for this reason, there are, uh, many different, uh,

8:24

appropriate use criteria.

8:26

Um, I'm showing, uh, the criteria by S-N-M-M-I,

8:31

uh, but there are, there are actually criteria, uh, by ASCO

8:35

NCCN and so on.

8:36

And, um,

8:39

and, uh, this, this, uh, criteria guide us on, uh, where,

8:43

uh, which patients are suitable for PSMA PET imaging.

8:48

Um, so there's a score for the appropriateness of, um,

8:52

the scan and of the indication, the scan.

8:55

And there are two extremes.

8:57

Um, the high scores, uh, means that we have enough evidence,

9:01

um, to know that, uh, the PS PET is, uh,

9:05

appropriate in these clinical scenarios.

9:07

The lung scores, uh, show us that, um, we are,

9:11

um, relatively certain

9:13

that the PSMA PET will not help in these, um,

9:17

uh, clinical scenarios.

9:19

And then there are the intermediate scores where we,

9:22

we either don't have enough evidence, um, for the utility

9:26

of PSMA PET or, uh, where the, uh,

9:31

or, uh, where it's, uh, it may be appropriate in individual,

9:36

uh, patients, um, and, uh, clinical scenarios.

9:41

But overall, the established criteria, uh, the things

9:44

that we, we are sure about is that this can be used alone

9:49

or adjunct to, uh, CT bone CT and bone scan.

9:52

Uh, so-called conventional imaging in high risk disease,

9:57

and it's not useful for low risk disease.

10:00

It's, uh, useful for biochemical care, particularly in, uh,

10:05

patients after radical prostatectomy who eligible for, uh,

10:08

cell patch radiotherapy

10:10

and, um, to, uh, assess eligibility, uh, for,

10:15

uh, lutetium PSMA treatments.

10:17

And there are, uh, less certain, um, uses of, uh,

10:22

PSMA pet, uh, for intermediate risk disease staging

10:25

for restaging, uh, progression for advanced disease

10:29

and Fort psm.

10:30

A response in generally, there is a gap, uh, in the,

10:33

in PSA progression response criteria.

10:35

There are, um, there is work and research

10:40

and the way to address this gap.

10:43

Um, we all know that, um, in newly diagnosed patients,

10:48

newly diagnosed patients with, uh, prostate cancer are, um,

10:52

classified stratified, um, according to the risk.

10:55

And the risk depends on usually on,

10:58

um, clinical tumor stage.

11:00

Um, at this stage, essentially on MRI, uh,

11:04

PSA levels at presentation

11:07

and, uh, ian score from the biopsy.

11:09

And there are different, um, classification schemes,

11:14

uh, which are used, um, in, uh, different,

11:17

um, areas of the world.

11:19

But, uh, they all, uh, depend on this same, uh,

11:22

parameters such as, uh, the, which was, um,

11:27

like the, the first or the more class growing one.

11:31

And, uh, here in the uk we use, uh, Cambridge,

11:34

um, group criteria.

11:36

And, uh, there's a couple score

11:37

that is mainly used in the USA

11:40

and, um, there has been, um, we have very,

11:44

uh, good evidence, um, for the utility of PSMA beds, bed

11:49

for staging high risk patients.

11:52

And this comes from this, uh, trial, the prop PSMA trial,

11:55

which was a, um, phase three randomized study.

12:00

Um, and, um, it showed, um, the superior accuracy

12:05

of PSMA PET C, um, in, uh, comparison to, um,

12:10

CT and bone scan, uh, greater treatment impact.

12:13

Uh, so SMA PET CT led to,

12:18

uh, change in management, um, in 28% of,

12:23

uh, the patients and, uh, fewer uncertain, uh, results.

12:29

Um, and then there were secondary findings,

12:32

like less exposure to radiation, high reporter agreement,

12:36

and, uh, um, no adverse effect.

12:39

And, uh, this, uh, superior accuracy of, um, PSA pet,

12:44

uh, in high risk patients.

12:46

Um, uh, in comparison to, um, CT

12:50

and bone scan is highlighted in this first case

12:53

that I'm going to show you.

12:54

So this is a high risk patient, six 5-year-old man.

12:59

Um, you see

13:00

that all the parameters are high risk PSA 57 GLY score four

13:04

plus five RI shows T three A lesion,

13:07

and he's got a ct, which is negative.

13:11

And, uh, bone scan sos a very, um, tiny focus of uptake,

13:15

um, at T six.

13:17

And, uh, this was called equivocal.

13:20

And, um, uh, then we followed up

13:24

with a PSA PET to clarify what, what this is.

13:27

So, PSMA PET showed the disease locally in the prostate.

13:32

Then, uh, it showed some PSMA avid lymph nodes, which were

13:36

below the, um, CT the size threshold that

13:40

used on ct.

13:42

And, uh, then it showed that there was

13:45

uptake in this T six lesion.

13:47

And I also, um, identified another, uh, four lesions,

13:52

which were not there on the CT or on the bone scan.

13:56

So it clearly upstaged the patient to metastatic disease.

14:01

And then, uh, the patient at the benefit of, uh,

14:04

getting the appropriate, uh, oncological treatment in, uh,

14:09

the, uh, the biochemical recurrence setting, um,

14:14

uh, after radical prostatectomy, uh,

14:18

the main question is which PSA threshold, uh,

14:21

should be used, um, uh, to trigger, uh, p

14:25

to trigger an investigation with PSMA pet.

14:29

And, um, the knowledge is that, um, uh,

14:34

the detection rate of recurrence for PSMA PET increases, um,

14:39

uh, while PSA increases.

14:42

But, uh, also that, uh, even at p at low PSAs

14:47

below 0.5,

14:48

and even below 0.2, there is 33 to 50% chance,

14:54

um, to have a positive, uh, pet.

14:57

And, um, this may even get, um,

15:03

higher, uh, with, uh, newer PET technologies that are now,

15:07

uh, introduced in the clinics such as, uh, digital PET

15:11

or, um, uh, PET with, uh, new crystals.

15:16

Um, so this is a case, uh, of, uh, patient

15:20

with biochemical occurrence, such a radical prostatectomy.

15:23

Um, his PSA, um,

15:27

reached 0.46 months

15:30

after his prostatectomy.

15:32

And, um, the PSMA PET revealed, um, uptake,

15:37

uh, quite intense uptake in a very, very small, uh,

15:41

lymph node, as you can see here, uh, which, um,

15:46

would not otherwise, uh, we wouldn't, we wouldn't

15:50

otherwise be able to identify.

15:53

Um, so, so biochemical recurrence

15:57

after pro biochemical recurrence

15:59

after prostatectomy was, uh, the main, um, strong point

16:03

for P sm a pet for a long time, even

16:05

before, um, we got, um, the data for staging.

16:09

Uh, in the meantime, we learned that, uh, um,

16:15

um, the patients, uh, who get the biochemical recurrence,

16:19

um, uh, eligible for salvage, uh, radiotherapy,

16:23

and the sooner we do the s radiotherapy, uh, the better, uh,

16:27

outcome the patient is going to have.

16:29

Um, so, so essentially yes, maybe pet, um,

16:35

uh, does not change the management that much anymore.

16:39

But, uh, there are, there is role in, um, exclusion

16:43

of extra pelvic disease.

16:45

Um, radiation boosted their identified disease

16:49

and, uh, prediction of response to salvage radiotherapy.

16:52

And, um, according to the nuclear medicine, uh, community,

16:57

there's no absolute PSA threshold, uh, um, uh,

17:02

should, uh, be used to trigger, um,

17:06

a P sm a bed in this setting.

17:09

Um, after a radical radiotherapy.

17:14

This is an example of, uh, a six 9-year-old man with,

17:18

um, a rising PSA, uh, four years

17:23

after radiation therapy.

17:24

And he had a quick rise.

17:27

It's a bit short of, uh, the definition

17:30

for biochemical recurrence, which should be, uh,

17:35

two points, um, uh, two points above the,

17:39

the NA PSA, uh, but, uh, essentially

17:43

because of, uh, of the fast, uh, of the,

17:48

of the fast doubling time, um, the patient was investigated,

17:52

um, for, with PSMA pet,

17:55

and we see, uh, recurrence within the prostate, um,

18:00

which had been previously irradiated

18:02

and no disease has, were in the body.

18:04

Uh, while in this case, uh, this is a case, um, again,

18:09

of a patient, uh,

18:11

with rising PS a one here post mutation therapy, again,

18:14

with a very, um, short, uh, doubling time.

18:19

And, um, here we can see, um,

18:22

that there is extra pelvic recurrence, um, in a, uh,

18:26

retroperitoneal lymph nodes even above, uh, the diaphragm.

18:30

Um, there were no bone metastasis.

18:32

And essentially this patient, um,

18:35

previously had a whole body MRI, which was negative

18:38

because, uh, this habit nodes, uh, were, um,

18:43

relatively, uh, small.

18:45

So, so again, we see, um, uh, a superiority of,

18:50

uh, PSMA PET in, uh, this setting.

18:54

Um, the next topic is, um, um,

18:59

the interpretation criteria, um,

19:02

and, um, some, uh, um, essentially,

19:07

uh, classification, uh, schemes that have been proposed, uh,

19:11

for interpreting, uh, PSMA PET scans.

19:14

Um, and, uh, this is one of those is the promise criteria,

19:18

and the other one is the PSMA rats.

19:21

So, promise criteria essentially gives us a guide on how

19:24

to assess the extent of, uh,

19:27

the disease in A-P-S-M-A PET scan, um, based on

19:32

level of uptake.

19:33

And it also gives us, um, uh, certainty, uh, scale,

19:39

um, so that we can add our, our, um,

19:44

uh, certainty, uh, level to our report.

19:47

Um, while it also, it also gives some, um, algorithms, um,

19:53

uh, for, uh, interpretation, which I will, uh, show

19:56

and analyze later.

19:58

Uh, PSMA RADS is, um, more about,

20:03

um, uh, characterizing a, a lesion with, uh, uh,

20:08

PSMA, um, uptake.

20:10

And again, there are, um, there are five, um, uh,

20:15

there's a score from one to five

20:17

and with some, uh, subdivision

20:20

and, um, some, um, uh, proposed,

20:25

uh, phrasing, uh, for, uh, describing these lesions.

20:30

And essentially, um, these, um, um,

20:35

these schemes are not, um, um, are not, uh, uh,

20:40

definitely validated, um, against outcomes, um,

20:45

or, or I guess, uh, uh, golden standard.

20:49

Uh, but, uh, uh, what, um, the, the

20:54

contribution to interpretation is that, uh, um, they reduce,

21:00

uh, disagreement, uh, between, um, the reporters.

21:04

Um, so there is lower inter observer variability

21:08

and higher reproducibility, uh, when we are using, um,

21:12

these, uh, um, uh, criteria.

21:15

And, um, and, uh, even when there is disagreement,

21:20

uh, this has a minor effect on clinical management.

21:24

And the other important thing that was found in this, uh,

21:29

study is that, uh, the highest variation was in,

21:31

in the reporting of intra prostatic distribution.

21:35

So, um, which we'll, we're going to talk,

21:39

talk about in a bit, how to approach this.

21:43

Um, so essentially when we are ready

21:47

to report the scan, we should, uh, um, uh, it's,

21:52

it's better to, to follow our report template.

21:55

And this report template includes, uh, the patient history,

21:57

some technical information like, um, dosing of trace dose

22:01

of tracer used, and, um, uh, image acquisition parameters.

22:06

And then, uh, the reporting of findings,

22:10

um, is better.

22:12

And it is suggested, uh, to, to follow, um, the,

22:17

uh, clinically relevant sites in the order of, uh,

22:20

prostate bed first pelvic

22:23

and extra pelvic lymph nodes, ous disease,

22:25

and then non nauseous disease

22:28

and incidental findings, rather than go going with, um,

22:32

um, head to toe, um, anatomical, uh, approach.

22:37

And then in the conclusion, we do our interpretation

22:41

of the scan, essentially.

22:42

And, uh, the final recommendations.

22:45

So now we're going to talk, uh, about, um, uh,

22:50

reporting findings, uh, per, um, uh, site

22:55

of interest, and we'll start

22:56

with a prostate and prostate bed.

22:59

Essentially, what we need to, uh, report in our scan is,

23:04

uh, whether the disease is unifocal

23:07

or multifocal, uh, whether it's unilateral

23:11

or bilateral, uh, the localization of, um,

23:16

the, uh, PSMA uptake and the lesions.

23:19

And, uh, we can, uh, follow, um, a simple, um,

23:25

sex division, uh, with, uh, base Midland,

23:30

Midland, and Apex, uh, left

23:32

and right, um, uh, particularly when we don't have,

23:38

uh, an MRI, um, substrate for, for accurate localization,

23:43

um, suspicion of extra capsular extension wherever possible.

23:47

So, um, that's I think something where, um,

23:52

PSMA pet, um, is not very good at particularly

23:57

for, uh, T three disease,

23:59

but it is, uh, good for seminal, uh, physical invasion

24:02

for T three B disease.

24:04

And it, it is, uh, marginally more sensitive than MRI.

24:09

Um, I'm saying this, usually what happens is that, uh,

24:13

it highlights an area in the second physical where, where,

24:17

um, then, uh, it may,

24:22

it may highlight, uh, areas in the seminal basic course

24:24

where, um, when we go back

24:27

and, uh, see the MRI again, um, may, we may see

24:31

that there have been change, small changes

24:34

that haven't been reported.

24:36

And, uh, for, uh, our recurrence, uh, patient

24:41

again, we have, uh, to report laterality localization

24:46

and, uh, unifocal versus multifocal disease.

24:49

Um, and always, um, check the concordance

24:53

with MRI, if there is one available.

24:57

And this is the kind of algorithm that promise criteria,

25:02

uh, provide us with.

25:03

And, um, I'm not gonna go into, uh, details,

25:07

but essentially you see that, uh, these are, um,

25:10

mainly based on imaging criteria.

25:13

So, uh, previous imaging CT or MRI appearance

25:16

or, um, appearance on the ct, uh,

25:20

or MRI, component of the PET ct

25:22

or PET MRI, um, then the level of uptake.

25:26

And, um, then it propose based on, on this,

25:31

um, uh, this parameters, it proposes, um,

25:35

a diagnosis helps us make a call, uh,

25:38

whether this is positive or negative.

25:40

And again, there are some gray areas

25:42

where these are equivocal, so it doesn't, uh,

25:47

resolve all the uncertainty, but it is,

25:51

and, uh, again, I I remind you that it's not, uh, validated,

25:55

uh, versus gold standard,

25:57

but, um, it, uh, works, uh, well most of the time.

26:02

And, um, the other, um, in, uh, the other,

26:08

um, uh, scoring that has been, uh, proposed for,

26:13

um, the intra prostatic, uh, lesion, um,

26:18

reporting is this primary score.

26:20

And essentially, um, the interesting part here is

26:24

that there is, like, this is the, um, uh,

26:29

the negative, uh, the, the, um, uh, negative pet,

26:34

uh, in the prostate.

26:35

And these, these are, uh, different types of positive pet.

26:38

But there is, um, the, the importance of this slide is

26:42

to remind you that, uh, there may be this, uh,

26:48

uh, bilateral uptake in the, uh, TZ, um,

26:53

the transitional zones, which is physiological

26:56

rather than pathological and

26:59

or, um, this bilateral low grade,

27:03

relative low grade uptake in the, um, central, uh, zones,

27:07

which again, is physiological and not pathological.

27:11

And, uh, um, we can, uh, compare always with MRI,

27:16

um, and see it's rare, um,

27:21

because sometimes it happens that we say, oh,

27:23

but there are more lesions on, uh, PSMA pattern on MRI,

27:28

but that is not true.

27:29

It's just, um, some patterns of physiological take, uh,

27:33

that is not completely, uh, homogeneous as in this case.

27:38

Um, other thing that, uh, we need to have in mind,

27:42

bear in mind, for a local assessment

27:45

of the prostate is previous therapies.

27:47

And this is an example of a patient who had a pet

27:51

after, um, haifu

27:53

and, uh, sometimes, uh, with fut cavity, which communicates,

27:57

uh, with the urethra,

27:58

and there is urine accumulation in there.

28:00

So this focal uptake, uh, essentially does not, um,

28:04

correspond to a pathological condition,

28:07

but it does correspond to urine within this cavity.

28:10

So this is a pitfall, uh, that we should avoid.

28:13

And in patients post, uh, focal therapy, uh, we should

28:19

go back and, uh, check, uh, the localization on the MRI.

28:23

Um, this is a case of a patient, uh,

28:27

who has a high grade, um, disease,

28:32

and we said that, uh, the higher the grade, the, uh,

28:35

the higher the PSMA, uh, uptake,

28:38

but, uh, we said also that, um, up to 10%, um,

28:43

of, uh, patients

28:45

with high grade disease may have a negative pet.

28:47

And this is one of these cases.

28:49

Um, so, um, here we,

28:54

we can't see any uptake, um, in the,

28:57

the area of the disease.

28:58

And we also noticed that the PSA is relatively, uh, low,

29:02

and there may be, uh, correlation,

29:05

although not proven, um, in patients who are called non-SEC

29:09

non PSA secrets and, uh, the low, um, PSMA activity.

29:16

Um, then, uh, the, except for the process there is,

29:20

there is also, uh, the seminal les in this area.

29:24

And, uh, as we said, um,

29:26

we can assess PSMA uptake in the seminal les,

29:30

as in this case where, uh, you can, uh, see on, uh,

29:35

the right, the image on the right, uh, the, uh,

29:39

uptake, unilateral uptake, um, in the seminal physical.

29:44

And, um, there is, uh, there is, um,

29:48

another structure, the past difference, which, uh, is, uh,

29:52

sometimes overlooked, uh,

29:54

but, uh, it may be, um, side of, uh,

29:58

recurrent disease

30:00

and, um, as in, in this, uh, case,

30:05

and, um, essentially this is, uh, the normal anatomy

30:10

of the vast difference, which comes over, uh,

30:14

the ureter and into the medial, um,

30:19

medial aspect of the seminal physical.

30:21

And this is how the area looks

30:25

after, uh, prostatectomy.

30:27

And, um, here, there is a case again, of,

30:32

um, um, disease in the, uh, medial aspect

30:37

of the seminal physical, which corresponds to the,

30:43

uh, vast difference, uh, in this area.

30:46

And here, uh, more distal, uh, focus of uptake, uh,

30:51

in the vast difference, uh, the distal, um, uh, aspects

30:55

of the vast difference may be hard

30:56

to see on the CT component.

30:59

And, uh, for example, in this case,

31:01

we saw this focal uptake,

31:03

and, uh, uh, we were not, uh,

31:06

sure whether there was a small lymph node with, uh,

31:09

very intense uptake like, uh, uh, um, uh,

31:14

external IAC lymph node.

31:15

But essentially, uh, we registered again with, uh, an MRI,

31:20

and, uh, we saw that this was part of the vast difference,

31:25

um, course.

31:27

So going to lymph nodes.

31:31

Um, so here I say the size does not matter much

31:36

because, uh, PSMA pet is very sensitive for, uh,

31:40

even small lymph nodes.

31:42

And, uh, it can detect lymph nodes down to, uh,

31:44

three millimeters.

31:46

Um, so essentially an intense uptake in a very

31:51

small lymph node is, uh, very characteristic

31:54

for, uh, disease.

31:55

But, um, there, um,

31:59

there may be false negative findings inside

32:01

of microscopic metastasis.

32:03

Um, staging, I think, um, in the literature,

32:07

there is a variation of, uh, the sensitivity of, uh,

32:11

p the reported sensitivity of PSA pet, uh, for, uh,

32:15

lymph node, um, involvement, um, um,

32:22

identification, uh, which, uh, does not sound great.

32:25

It's between 40 to 60 or 65%.

32:29

Uh, but essentially, uh, the key question is what, um, size

32:34

of lymph nodes are we referring to?

32:35

And it's, uh, definitely better, uh, than a CT

32:38

or MRI, where we only have the size criteria.

32:41

Um, we have to be careful

32:43

for false positive uptake in lymph nodes,

32:46

and obviously we have to report the exact location

32:48

of the lymph nodes and the short axi size,

32:52

whether the lymph nodes are, uh, within the surgical

32:54

or radiotherapy field,

32:55

because that, this, again, um, it's important for, uh,

33:00

management planning and, um,

33:02

there are quantitative measurements.

33:05

We have to report the quantitative measurements

33:06

and reader reduce confidence.

33:08

And in cases of, um, borderline findings,

33:13

and again, we have the algorithm, uh, from promise criteria,

33:19

um, uh, which, uh, depends a lot on the, so,

33:23

so calling a a node positive

33:25

or negative depends, uh, a lot on where the node is.

33:29

So it's, uh, there's aro, um, lower threshold, uh,

33:34

for, for pelvic, uh, for calling, uh, pelvic,

33:39

uh, lymph nodes and, uh, higher threshold

33:42

for calling extra pelvic lymph nodes.

33:45

And again, it, uh, reminds us to think

33:48

of common pitfalls such as, um, uh, reactive nodes,

33:52

inflammatory nodes, or notes,

33:54

or suspected non prostate cancer malignancy.

33:58

And, uh, uh, this is an example.

34:00

So on the top, um, right, uh, image,

34:05

you see that, uh, there are, uh, there is, uh,

34:10

PSMA uptake, which is higher than, uh, the blood pool, um,

34:14

um, background.

34:15

But, um, these lymph nodes are bilateral.

34:20

Uh, they have reactive appearances on ct,

34:23

so there's metrical with reactive appearances on ct,

34:27

and actually they're quite distal.

34:29

So in areas where it is rare at primary staging to, um,

34:34

find involved, no.

34:36

And, uh, bear in mind that, um, finding, uh,

34:41

there's a, a less than 1% chance to have a distal external,

34:46

uh, lymph node involved at primary staging.

34:49

Um, there are, on the bottom, uh, image,

34:54

you can see that, uh, there are other lymph nodes

34:57

that don't have this symmetry.

35:00

Yeah, so they are asymmetrical, they are in areas, uh,

35:04

which are, uh, uh, where, which are typical

35:09

for nodal involvement.

35:11

And, um, uh,

35:13

they do not have the typical reactive morphology on ct.

35:18

So these are at least, uh, suspicious.

35:21

But obviously this is a tricky case where, uh, we have both,

35:26

um, um, reactive

35:29

and suspicious notes.

35:32

Uh, this is another case.

35:34

So we have, um, a patient with a,

35:38

a relatively low lesion score, three plus four.

35:41

And, um, there, there is low grade activity in the primary,

35:45

and there is no pelvic, uh, lymphadenopathy, but,

35:47

but there are, um, p sme, avid,

35:52

uh, lymph nodes, uh, in the retroperitoneum and abdomen.

35:58

And essentially, uh, it didn't fit with, uh,

36:02

the clinical context of the patient, the low grade disease,

36:05

and, um, the discrepancy of activity between the,

36:10

the primary tumor and this

36:12

and, um, uh, the lack of, uh,

36:15

pelvic lymph nodes.

36:17

So essentially there was further investigation

36:19

and, uh, uh, um,

36:22

eventually there was a biopsy from this paric lymph nodes,

36:24

which showed granuloma to lymphadenitis.

36:27

So, again, other, uh, um,

36:31

pathologists may give us false positive results.

36:35

Um, another pitfall, potential pitfall is, uh,

36:39

that there is physiological PSMA uptake in the sympathetic

36:42

ganglia, which may be misinterpreted

36:45

for positive lymph nodes.

36:46

Here, I remind you the, um, uh, anatomy

36:49

of the sympathetic ganglia.

36:51

And, uh, in the middle there is a map where you see, um,

36:56

these spots along, um, um, uh,

37:00

along the neck bilaterally.

37:02

And, uh, essentially this is a common area where, where, uh,

37:07

ganglia are seen.

37:09

And also there is, um, there are the, um,

37:14

celiac ganglia in this area

37:17

that should not be misinterpreted for, um,

37:21

retroperitoneal lymph nodes.

37:23

And, uh, again, uh, sacral ganglia, um, which are close to,

37:29

uh, the exit of the sacral for fora.

37:33

Um, and again, uh, this could, this

37:38

may, may give us some, a hard time to,

37:42

to figure out if there is a small lymph node

37:45

or, um, a ganglion there.

37:47

And, uh, usually, uh, the symmetry of uptake is

37:51

what, uh, guides us.

37:54

Um, finally, for the skeleton, uh,

37:59

um, so we have to always, uh, think

38:04

of false positives.

38:05

Uh, it's, uh, one of the trickier, um,

38:10

parts of PSMA, uh, reporting

38:13

and, um, the false positive rate, different difference

38:16

between PSMA ligands, as we said,

38:18

and, um, solitary bone lesions detected in patients

38:23

with no nodular involvement should be interpreted

38:25

with caution, especially in, uh, the primary staging setting

38:29

where, uh, it might make the difference between a radical,

38:33

um, management

38:35

or oncological management system with systemic treatment.

38:39

And, um, we have to

38:41

take the con the clinical context into account, again,

38:44

with clinical semiology, the pain, the PSA kinetics

38:48

and, uh, available imaging, uh,

38:50

where possible CT bone scan, MRI.

38:54

And, uh, if we are in a dead end

38:57

and, um, we can't make a call, first thing is,

39:02

uh, first thing we should do is to discuss in an MDT.

39:07

Most of the times the MDT uh,

39:12

uh, gives, uh, an accurate, um, estimation of, uh,

39:16

whether this is positive

39:18

or negative based on the clinical context.

39:20

And, um, uh, there may be, uh, the benefit

39:25

of the doubt or, um,

39:28

or, um, a reasonable suspicion in other cases,

39:34

um, where, uh, which will guide,

39:39

uh, the management

39:40

and, uh, the patient will get the, uh, best management.

39:44

Um, but if not, then, uh, there are other options such as

39:48

to do a dedicated MRI, uh, to be reviewed by a, um,

39:52

an MSK specialist

39:54

or to recommend histopathological confirmation if feasible.

39:58

And, um, another, uh, thing that is sometimes used is, uh,

40:03

uh, the patient is starting on hormones

40:06

and gets a very close follow up to see if, um,

40:10

there is any response.

40:12

Um, uh, so this is again, uh,

40:16

the algorithm and again, the,

40:22

um, the probability depends on,

40:26

on whether there is a single focus or multiple foci.

40:29

And whether there is, um, a CT or MRI, uh, finding

40:34

or not, uh, remember that, uh, PSMA PET is, um, uh,

40:40

identifying, um, is more sensitive essentially than a ct.

40:44

So, um, so, uh, uptake

40:49

in, um, a city, uh,

40:53

negative side, uh, may be a metastasis.

40:57

So this is a case of a typical, uh,

41:00

false positive uptake, uh, in the ribs.

41:04

So it's, uh, quite rare that, um, there is a solitary, uh,

41:09

rib metastasis at staging.

41:11

And, um, then, uh, this uptake corresponds to, uh,

41:16

this CT finding, which shows, uh, uh, Lucent Center

41:20

and, uh, sclerotic cream.

41:22

And this is, um, fibrous, um,

41:27

uh, this is a fibro dysplasia essentially,

41:30

and it is positive

41:31

and quite characteristic for a false, uh, positive.

41:35

Um, again, here, uh, the,

41:39

the reconstruction that you use

41:41

for viewing your PSMA PET may, uh, change, um,

41:46

uh, the way that, um,

41:49

the false positives are, um, seen.

41:52

So in, uh, T-F-S-P-S-F, you might get, um,

41:57

accentuation of this heterogeneity

42:00

and the ribcage, uh, that is, uh, characteristic

42:04

of imaging with 18 F-P-S-M-A 1007.

42:09

And, um, I've got, uh, three cases, uh, for,

42:15

um, um, the promise criteria

42:18

and how, uh, how far they can go and how the MDT

42:22

and the clinical context of the patient can, um, like, um,

42:26

improve, um, essentially the interpretation.

42:30

Um, so this is, um, high risk patient,

42:33

but with a low grade of disease, three plus four.

42:37

And, um, there was a suspicious, um, sclerosis

42:41

with, uh, a level of uptake.

42:45

Um, so according to the promise, this, uh, uh, would be

42:50

positive lesion, but this is a solitary lesion, uh,

42:53

in the thoracic spine, in a patient with a non noal disease.

42:57

Um, so essentially we doubted that, uh, this, um, was, uh,

43:03

actually, um, metastasis,

43:04

and we did a ized spine, which showed an INTS hemo.

43:08

So remember that the solitary bone focus

43:11

of increased PSMA in the thoracic spine is often,

43:14

often benign despite high risk disease.

43:18

Um, the second case is a case, again, high risk,

43:22

but again, with, um, relatively low, uh,

43:27

grade G score.

43:28

And there is a very intense lesion,

43:34

uh, focus of uptake, essentially with no, uh, CT correlate.

43:39

And, um, again, we had doubts about this

43:42

because of the low Gleason score

43:43

and, uh, uh, no nodal involvement.

43:46

So we did a, a biopsy,

43:49

and this turned out to be, uh,

43:52

multiple myeloma in this patient.

43:53

So a synchronous cancer expressing PSMA is a possibility,

43:58

and the third case is the opposite.

44:01

Yeah. So here we have a patient with high grade disease

44:05

and particularly high Gleason score.

44:08

And, um, there is,

44:10

there was some indeterminate uptake in one of the ribs

44:13

with low expression, low grade expression, which, uh,

44:18

according to promise criteria would be, uh, negative.

44:21

But because of the high risk of the patient, we, um,

44:24

assumed it was positive.

44:26

And then, um, this was actually confirmed, uh,

44:30

later on as the patient, um, quickly developed, uh,

44:35

cast castrate resistant breast cancer, uh,

44:37

with an NCI lesion at the same site about,

44:41

uh, two years later.

44:43

So PSMA allows for early detection of bone ASCE

44:46

before developing typical appearance.

44:50

And, um, uh, the last, um, case on,

44:55

uh, on, uh, false positive, uh, bone lesions is this case

45:00

where there was this, uh, uptick in a single, uh,

45:04

thoracic vertebra with, which was diffused, uh,

45:09

with sclerosis,

45:10

but, um, with extension to the posterior elements.

45:14

And this was considered as disease.

45:19

And again, it was confirmed that, um, this

45:24

after, uh, radical prostatectomy

45:26

with almost undetectable PSA, um, this,

45:31

uh, remain the same.

45:34

So, um, lastly, we have, uh, visceral metastasis.

45:38

They are not frequent. Uh, we have

45:40

to include in the report visual

45:41

and quantitative description, uh,

45:43

anatomical information, obviously.

45:46

And we have to take into account the clinical status,

45:49

whether it's a known metastatic prostate cancer

45:52

or not, whether it's hormone sensitive

45:55

or, um, gastric resistance and so on.

45:59

And, um, uh, keep in mind

46:01

that the synchronous cancers may be false positive,

46:04

and this is a case of a patient with, uh,

46:07

A-P-S-M-A AVID lung nodule.

46:10

Um, this may either be a metstro synchronous primary.

46:13

It's not easy, um, to say

46:17

unless the patients have a biopsy.

46:20

So these, uh, patients are usually referred to the lung MDT,

46:24

for example, and they go into the, um,

46:29

uh, investigation of these, uh, lesions.

46:33

And just as a reminder of how many, uh, pathologies, uh, can

46:38

actually give us false positives on PSMA.

46:43

So in conclusion, um,

46:47

this is a short survival guide, uh, for, uh,

46:51

PSMA PET reporters.

46:53

Uh, PSMA PET is very good and very accurate,

46:56

but it doesn't hold all the answers.

46:59

And, uh, the better the patient selection, uh, then, uh,

47:03

the better, um, the results.

47:06

And, uh, we have less biblical, uh, results.

47:10

Um, if, uh, we select, uh, appropriately the patients

47:15

and we have appropriate clinical questions,

47:17

there will always be uncertainty.

47:20

Uh, but we don't, uh, have to, as reporters, we don't have

47:25

to, to make the calls on our own.

47:27

We can, uh, address our concerns to the MTT

47:31

and then all together, uh, with, uh, the clinical, uh,

47:35

context of the patient, we can, uh, make the decisions

47:39

and never forget to involve the patients in, uh, this,

47:44

in this process and this decisions

47:45

and respect, um, the patient's preferences.

47:49

Thank you.

47:54

Thank you so much for that lecture.

47:56

Um, and at this time, we will open the floor

47:58

for some questions, and you've got a few in there

48:01

already, if you can Yes. Pop that open.

48:04

Okay. Um, yeah, I'll start with the first question.

48:08

Um, it says, uh, what is the diagnostic, uh,

48:13

in, uh, 18 F PSMA one 1007?

48:15

What is the diagnostic algorithm in case

48:18

of doubtful positive bone lesion in your hospital?

48:21

So, um, we, we start

48:26

with the promise algorithm, essentially.

48:28

Yeah, that's a starting point,

48:30

and it's, uh, it's quite good.

48:33

And usually, um, it's, um, uh,

48:38

giving us a correct direction.

48:40

And, uh, essentially we have, um, if we go back

48:44

and I can, um,

48:49

depending whether it's single focus

48:51

or multiple foci, uh, we have different, um, thresholds.

48:55

Obviously we take into account, um, uh,

48:58

whether there is a lesion on CT or MRI

49:02

and, um, uh, essentially depending on the level

49:06

of uptake in comparison, uh, to deliver

49:11

or, uh, uh, uh, essentially to the liver,

49:16

uh, this is, uh, called as positive or negative.

49:20

Um, and then if there,

49:24

it's still borderline, we take it to the m mt, um,

49:30

and we discuss, um, these, uh, cases.

49:37

I hope that covered the question.

49:40

Next question is how to differentiate metastasis

49:42

and fibrous dysplasia.

49:45

So, um, I think this is, um,

49:50

if we have like a good,

49:53

a relatively good city on the pet city,

49:55

and we see a relatively low grade uptake in an area

50:00

where there is, um, uh,

50:03

where there is this typical lesion with a lucent center

50:06

and, um, uh, sclerotic, uh, rim, uh,

50:11

then this is most likely, uh, fibrous dysplasia.

50:14

In other bones, it might be more difficult.

50:18

Um, and it might, um, we might need

50:22

to investigate further, uh, for example, with, uh,

50:25

an M-R-I-M-S-K-M-R-I.

50:30

Um, and next

50:34

question was, uh,

50:36

can you please elaborate on the urine cavity slide?

50:39

How do we differentiate that, the uptake from malignancy?

50:44

So I think, um,

50:48

referring to this one, so, so in this patient,

50:52

there has been, uh, focal treatment, uh, in the history,

50:56

yeah, uh, in this area.

50:58

And, um, on PET ct, it's impossible to know.

51:03

And obviously the clinical indication is either the PSA, uh,

51:07

is rising, and, uh, we want to check whether there is

51:10

a recurrence, um, not on pet.

51:13

It's because we see a focal uptake in this area.

51:16

Um, we may see in the notes of the history that, uh,

51:20

there is, um, um, um,

51:25

there, there has been a high in this particular area

51:28

and for example, not the other side

51:31

or a different area in the prostate.

51:34

And, um, we can't say unless we, we look at the MRI

51:38

and, um, see, so this is a T two MRI

51:43

and, uh, with high T two signal,

51:46

and this shows us that there is fluid in there.

51:48

So some of these cavities, as I said, communicate

51:51

with the urethra and, uh, there is, uh, urine there.

51:55

So then we know that this is uptake, um, from the urine

52:00

and likely not, um, that's, uh, not metastatic.

52:07

Um, then next question

52:12

says, uh, to be considered positive node

52:15

or local lesion, do you decide by above hepatic uptake?

52:19

Um, so it's different for nodes

52:22

and, um, um, uh, it's different for notes

52:26

and different for, um, it's, uh, part of the body.

52:30

So essentially again, uh,

52:33

our starting point is the prompts algorithm.

52:36

And, uh, so there are so many, uh,

52:38

subdivisions depending on, um,

52:42

imaging characteristics.

52:45

Uh, but for nole, uh, for positive nodes, we,

52:48

apart from the level of uptake,

52:50

we also consider the imaging features.

52:53

So, and the look, the location of, uh, the node.

52:56

So if it's a node distal, externally node with, uh,

53:01

or inguinal node

53:02

or, uh, symmetrical uptake, um,

53:07

and so on, then we have, uh, yeah,

53:11

we may call them reactive,

53:12

and they have reactive, um,

53:17

characteristics on ct.

53:20

Uh, what is your interpretation of small pet cleanness

53:23

with SUV max between four five in 1007 psma?

53:27

I think similar question,

53:29

and I think I can show this

53:34

by slide, you see here on the mip, this is, um, uh,

53:39

18 f um, 1007 PS MA, you see

53:44

bilateral symmetrical uptake, um, uh,

53:49

in the inguinal areas, distal external areas,

53:54

and, uh, excellent.

53:56

So that is likely, um, reactive uptake.

54:01

Um, it should v max plays a role,

54:05

but it's not the only thing

54:08

that we take into account, as I already said.

54:12

Um, how do we assess response when there is

54:17

discordance between PSMA PET and PSA levels?

54:21

Uh, so response, yes, I haven't touched on that.

54:25

It's, uh, it's a whole different, uh, field

54:29

and response, uh, to treatment on, uh, PSMA.

54:34

And it depends, obviously on the therapy,

54:36

we don't have enough data.

54:39

Uh, there has been, there is some work being done,

54:43

and there, there are some, um, criteria, um,

54:48

uh, which are based on patients

54:50

who had lutetium PSMA treatment.

54:51

And, uh, there is, uh, uh, there has been, um, um,

54:58

uh, sort of, uh, um,

55:03

um, like, um, criteria for, for calling progression

55:08

or response, uh, et cetera.

55:11

Um, but essentially we are in the dark, obviously,

55:15

what we need to assess is if there is a, an increase

55:19

or reduction in the tumor volume

55:21

and, uh, if there are new lesions or not,

55:25

and, uh, take it from, take it from there.

55:28

But we don't have specific criteria yet that are, um,

55:33

sort of applicable to all types of treatments.

55:38

Maybe I have a little bit more time

55:40

for a few, for a couple more.

55:42

Um, how would you handle a clinically high risk patient

55:45

with a positive PSMA scan in the distribution

55:48

of pelvic nodes versus sympathetic ganglia?

55:52

Yeah, so obviously, yeah, we have, we know

55:57

that the, the anatomical allocation

55:58

of the sympathetic ganglia,

56:00

and there are some easy, easy things

56:04

to exclude such as this or this.

56:07

Yeah, these are quite typical

56:09

and they are, uh, most of the time symmetrical.

56:12

Uh, the, the most tricky part is this presacral area.

56:17

So yeah, we have to be a little bit,

56:21

bit more careful if we see the symmetry

56:24

and this uptake is, uh, this area is close to,

56:29

to the, uh, sacred forfor.

56:33

Uh, then, uh, we might say that it's likely, uh,

56:37

ganglion, we sometimes scrolling through the city helps us

56:41

and we might see a small filament, uh, that is, uh,

56:46

actually the nerve leading to that.

56:48

Uh, but it gets trickier in this area.

56:52

And, uh, I think there are two more.

56:56

Um, what about reporting small,

56:57

non avid adrenal lesion should request follow up?

57:01

Yes. Uh, adrenal lesions require follow up

57:05

because, um, they're, they're likely

57:10

to be something else.

57:11

Yeah. Um, so, uh,

57:16

small non-habit, um, I dunno about non avid.

57:19

We would go with what we would do normally, um, with a ct,

57:25

but if it's avid, then definitely we should follow up

57:28

because there might be some, um, benign

57:32

or malignant adrenal pathology.

57:35

And last question is, uh, what do you think about the role

57:39

of PSMA PET in initial staging?

57:41

Is the higher sensitivity

57:43

of PSMA really changing the management of the patients,

57:45

even if upstage down stage?

57:49

Um, yes. So that's a very good question actually.

57:54

And it's, uh, uh, obviously, so,

57:58

so from my experience, uh, I think,

58:01

and from the, from from the data that, um, uh,

58:06

I've seen there is,

58:07

and from the data that are published,

58:09

there is a approximately 30% management change, um,

58:13

in high patients as in prop PSMA trial.

58:17

Now, there are not, uh,

58:20

what we lack is whether this change in management, uh, leads

58:23

to a change in the outcome, uh, of,

58:28

uh, of the disease.

58:29

And that's much, much harder, uh, to, to address.

58:34

But, uh, I know that there are trials trying to, to see, uh,

58:38

the value of PS MA pet.

58:40

Definitely it has changed, um, um, uh, the field

58:45

and, uh, um, the clinicians trust, um,

58:50

PSMA pet, uh, a reliable PSMA PET service if, if you want,

58:55

but obviously PSMA PET alone is not what, um,

59:01

uh, is not what, uh, definitely,

59:05

um, guides the treatment.

59:08

And last one may be for, if it's a few seconds, how

59:11

to evaluate focal PSMA accumulation in the ribs,

59:14

for example, which are not visible on ct.

59:18

Yeah, so ribs, again, it depends, uh,

59:21

if it's not visible on ct, if it's, um, initial staging,

59:27

uh, then the level of uptake is important

59:29

and the, the existence of other, um, areas

59:34

of skeletal uptake.

59:35

So if, uh, if there is, especially for, um, disease,

59:40

uh, overall, um, or, or not.

59:44

So, but what we know is that a so solitary, uh,

59:47

rib metastasis is very rare at initial stage.

59:51

And I hope I covered you with my answers, so

59:56

I think you got 'em all.

59:58

Yeah. Thank you so much, Dr. AKAs. That was wonderful.

60:02

Thank you so much. And thank you for everyone else

60:05

for participating in this NOOM conference

60:07

and asking all those wonderful questions.

60:10

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60:11

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60:16

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60:19

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60:22

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60:26

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60:28

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60:31

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60:35

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