0:00

So this next section is all about the patient selection,

0:03

preparation and scan protocols for PSMA pet, including some

0:07

of the things that we do in my local practice,

0:09

which may help with imaging interpretation.

0:12

But keep in mind that nuclear medicine is a very variable

0:15

specialty and things are done differently

0:17

from practice to practice.

0:19

So keep in mind that you should check in

0:21

with your local practice, um, in terms

0:23

of your individual protocols and how things are done.

0:28

So we're going to be drawing quite heavily from the PSMA PET

0:31

CT joint EA and M and SNM MI procedure guidelines.

0:35

Um, and these are published within the related readings.

0:38

Um, so if you'd like to go and have a look through.

0:40

And so a lot of the groundwork we will be talking about in

0:43

the upcoming sections is going to be drawn from this paper.

0:48

So starting broadly with indications for PSMA PET ct,

0:51

we think about diagnosis.

0:52

We wanna be looking at patients

0:53

who have already had treatment, be that surgery radiotherapy

0:56

or A DT.

0:58

And also because of the capability of PSMA PET CT

1:01

for combined theranostic therapy

1:04

with gallium 68 PSMA being swapped out for LUTETIUM 1 77.

1:08

We also have a role for PSMA PET in planning of

1:11

that radioligand therapy.

1:13

We're gonna stop through with a couple of definitions

1:15

for some of you might be new to working

1:17

with prostate cancers.

1:18

So we'll go through some of the scores

1:20

and some of the jargon that may come up

1:21

in your patient referrals.

1:22

And the first of that is the Gleason score,

1:24

which is a histological grading of prostate cancer.

1:27

So it's made up of a combination of Gleason grade, um,

1:30

and it's essentially a grading score,

1:32

which is given based on the histological pattern

1:35

of gland arrangement in the biopsy tissues.

1:37

Um, and then going all the way up to level five,

1:40

which is lack of gland formation from, you know,

1:42

that well-formed glands of level one.

1:44

And essentially that grading score going from one up

1:47

to five is giving an indication

1:49

of least aggressive morphology to most aggressive.

1:52

And then the Gleason score is taking two Gleason grades.

1:56

And so you sum the two most common grade patterns.

1:59

So, um, for example, a common one

2:01

that we see is Gleason three plus four equals seven.

2:03

You might have Gleason four plus five

2:05

equals nine, for example.

2:06

And the most common pattern seen within the histological

2:09

sample is given first.

2:11

Now this can be a little bit challenging,

2:13

however, as only Gleason six

2:16

or above is considered really considered clinically

2:18

significant prostate cancer in practice.

2:20

And to be honest, I can't remember the last time I even did

2:22

A-P-S-M-A PET for a patient who had Gleason six disease.

2:26

Really, we are looking at Gleason seven

2:28

or above, so Gleason six being low grade six intermediate,

2:32

and then Gleason eight to 10, that higher grade disease.

2:36

And so the patient base that we typically are seeing

2:38

with our PSMA pets is those patients with intermediate

2:40

to high grade disease.

2:43

And with kind of that in mind, knowing

2:45

that Gleason six is kind of, you know, your lowest risk,

2:47

you know, what is the implications of Gleason one to five?

2:51

And that was kind of a bit of a gray area.

2:53

And so the ISUP prostate cancer grade groups were

2:56

developed to, you know,

2:58

Rationalize this and compress the Gleason scoring into

3:01

more clinically significant

3:02

and clinically applicable grading score.

3:04

So it's almost like a compression.

3:06

And so the grade group one is for those six

3:08

or less ISUP grade two, um, is your Gleason Sevens.

3:12

Then all the way up to five, those who score Gleason nine

3:15

or 10, which would be four plus five, um, five plus four

3:18

or five plus five disease.

3:20

And this kind of grading scale has had, you know,

3:23

been correlated with a prognosis and MA management decisions

3:27

and also looked against patient outcomes.

3:30

So as I mentioned, we should be doing PSMA PET cts in

3:33

patients, um, who have Gleason seven

3:34

or above, which is ISUP grade group two and above.

3:39

Um, and that's at the initial staging.

3:41

So we're talking about new diagnoses

3:42

of prostate cancer here.

3:44

So in these groups we can use

3:46

that also for treatment planning.

3:47

Um, so for suitability for certain modalities,

3:50

including prostatectomy,

3:51

although we did see from that paper in the introductory

3:54

module that there's PSMA doesn't give you too much change

3:58

to prostatectomy rates,

3:59

but it certainly does change radiotherapy fields.

4:02

Um, and it also, there's an application that if you, um, see

4:06

where the greatest tracer accumulation is in the prostate,

4:08

you can actually change your contouring to boost areas

4:12

of greatest PSMA avidity.

4:14

And here's an example of a paper by COI

4:16

and colleagues, which is just really nicely demonstrated

4:19

some radiotherapy contouring as it's been fused

4:21

with the PSMA pet.

4:24

Um, and here in the same paper,

4:26

it is not only the prostate gland itself

4:28

that we're necessarily looking at, we can also use PSMA PET

4:32

to help our radiotherapy colleagues contour, um,

4:35

targeted radiotherapy to pelvic lymph nodes as well.

4:39

There is also, um, a role for biopsy planning as well,

4:42

particularly if you're combining with MRI guided biopsy.

4:44

However, it's not yet standard in clinical practice.

4:50

I've popped in these two comparison images as well.

4:53

And you can see that we've got a baseline study

4:55

and then 12 months post radiotherapy.

4:57

Um, and there's a trial running at my center,

4:59

which really looks at, um, the role of targeted radiotherapy

5:01

for primary prostate cancer and how it behaves over time.

5:05

And here on the baseline you can see

5:07

that there's intense uptake

5:08

of the radioligand tracer in the left, um,

5:12

prostate right there indicated by the arrow

5:14

and 12 months post radiotherapy.

5:16

We've got a good indication

5:17

that the HER has been a treatment response

5:19

in that site to therapy.

5:22

So moving on to the biochemical recurrence group.

5:25

And I have to say that, you know,

5:26

remembering the definitions is a little bit tricky for me.

5:28

So I've copied them here from the

5:30

guideline that we cited earlier.

5:32

So we think about doing PSMA pets in patients

5:35

with rising PSA in a patient who has been treated

5:37

with surgery or radiotherapy.

5:39

Um, and we can classify them

5:40

as we are looking for recurrence.

5:43

Um, so biochemical recurrence or biochemical persistence.

5:47

So biochemical recurrence being diagnosed

5:49

as PSA greater than or equal to two nanograms per liter.

5:52

Um, and that's six to 13 weeks post prostatectomy.

5:56

Um, and then that's confirmed with the second, um,

5:58

PSA level, again, greater than, um, equal

6:00

to two nanograms per mil.

6:02

And that is in comparison to biochemical persistence,

6:05

where the PSA never really drops down

6:07

and it's remains greater than 0.1 nanograms PLE day greater

6:10

than six weeks after prostatectomy.

6:12

So they never had that drop down to near baseline.

6:16

So for patients who have undergone curative radiotherapy,

6:19

those two that we spoke of earlier were

6:21

for prostatectomy patients,

6:22

the biochemical recurrence is then defined as, um,

6:25

rising PSA of greater than two nanograms per mil

6:28

above the NIR or the lower baseline

6:30

after radiotherapy, which was achieved.

6:33

So you're looking at patients who have had therapy

6:35

and their PSA rises in a way that it shouldn't.

6:39

And if the prostate is resected, you know,

6:41

we shouldn't theoretically have, um, a PSA to measure.

6:45

So if it's going up, that's a concern

6:47

that we've got disease elsewhere.

6:50

Another definition that will, um, just kind

6:52

of briefly pause on here is castrate resistant prostate

6:55

cancer or CRPC.

6:57

Um, and that leverages

6:59

and the understanding that prostate cancer usually requires

7:02

normal levels of testosterone to grow,

7:05

whereas if we deplete the body of testosterone,

7:08

and typically that's through, um,

7:10

androgen deprivation therapy

7:11

or a DT, um, that is an effective way

7:14

of controlling prostate cancer.

7:16

But what do we do if the PSA rises

7:19

or the disease spreads despite, um,

7:21

androgen deprivation therapy

7:22

or, um, that then we will call that castrate resistant

7:25

because it is progressing despite the, um, androgen levels

7:30

and that testosterone level being so low.

7:33

Another application is imaging post or during therapy.

7:36

We saw that post radiotherapy, um,

7:38

images in a few slides before.

7:40

Um, and that is an example of monitoring treatment response.

7:43

Um, and then in that rising PSA,

7:45

so we've looked at our definitions of

7:46

where PSMA PET can come in for evaluating patients

7:50

with biochemical recurrence

7:51

or biochemical persistence to try

7:53

and identify the sites of

7:54

where this persistent abnormal tissue is

7:56

or the disease is recurring.

7:58

And that may be a focus of uptake in the prostatectomy bed

8:01

or small volume lymph nodes in the pelvis,

8:03

or an site of oligometastatic disease

8:05

that wasn't apparent at baseline.

8:07

In some patients, it can be used for monitoring

8:09

of systemic therapy, um, including a DT.

8:12

Um, however, the role in the literature is less clear

8:15

for this particular indication.

8:18

And to throw in here we've got, um, just an example

8:21

of radioligand therapy, which we will come back

8:23

to later in the course.

8:24

That's that determining that suitability

8:26

for LUTETIUM 1 77 PSMA targeted therapy.

8:30

And here, um, there's the gallium 68 PSMA PET labeled a,

8:35

and then after they've had the radio tracer, which localizes

8:37

to those lesions, but we'll revisit this in a few modules

8:40

time.