Prostate Only Recurrence After Brachy

[Mandelin Rain]

I'm seeing a high PS, 71 yo guy who had I-125 implant in 2002 in another state. Biochemical recurrence (PSA=7) in 2013. Underwent salvage cryo at that time. Nadir 0.06 post cryo. In 2015 had further biochemical progression. Repeat biopsy negative in 2017. Continued rise in PSA to current level of 7.5.

MRI not helpful. Axumin PET shows localized recurrence in what appears to be the central zone just anterior to the urethra. Looks like a dead zone in the seed distribution. No systemic or nodal disease present.

So 17 years post brachy and 5 years post salvage cryo.... rising PSA and apparent localized recurrence on Axumin. I (of course) have no records/dosimetry from the implant. Any call for repeat salvage with EBRT? For some reason, a med onc quoted him a bunch of numbers from the salvage post-prostatectomy literature, which has given him some expectations to manage.

I'm pretty gun shy here. With two previous local therapies I realistically have no idea what his complication rate would be. I would definitely want a positive biopsy prior to doing anything more, but my gut tells me ADT+/- taxane/Zytiga.

What say you group think?

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[Radiator20]

This pt appears to have a persistently local (hence theoretically curable) problem. Systemic tx alone is palliative, which does not feel satisfying in that situation given an otherwise long life expectancy. If it were me, I would ask a urologist I trust to evaluate for salvage RP. If you’re in the community and local urology declines, would refer to an academic center with a strong urology program. I would feel reasonably comfortable with salvage RP after brachy alone. Whether it's still feasible after cryo in addition might be a different question. I agree a biopsy for confirmation is appropriate as long as not otherwise contra-indicated.

 

[medgator]

Salvage RP at tertiary center with a high volume robotic surgeon as the only definitive option, otherwise whatever systemic therapy you prefer

 

[RickyScott]

What is PSA doubling time?

 

[Palex80]

Salvage RP is an option but with high chances of major complications. Evaluate cryotherapy, electroporation? At the end of the day what is the patient willing to accept as potential toxicity?

 

[mavrik13]

Lots of options, none great. The overall picture is one of managing expectations and informing of potential toxicity.

1) Salvage RP - probably very difficult with high complication rates post brachy and cryo. I agree with referral to high volume surgeon who has experience with salvage RP.

2) Salvage RT - there is literature on salvage HDR (focal) which is probably best supported if you wanted to use RT, but I would assume cryo would increase local toxicity. As above, would recommend evaluation by HDR brachy specialist. Preliminary literature on salvage focal SBRT (ie Cyberknife) exists, but limited number of patients post brachy have been treated.

3) I doubt salvage HIFU is worth it.

No one would fault you for recommending palliative treatment with ADT, but the picture you paint suggests further evaluation should be considered. A lot depends on comorbidities, life expectancy, urinary/bowel function, disease trajectory (ie PSA dt), and risk tolerance of the patient.

 

[DoctwoB]

Uro weighing in. Salvage RP after cryo AND brachy sounds extremely hairy with high risk of rectal injury and high likelihood of severe incontinence. If it is really localized to anterior transition zone (which makes sense for a cryo failure) would consider performing a TUR. While not typically a cancer operation it would be low risk and potentially able to completely resect the cold spot in the brachy fields. Also wouldn’t burn any bridges, if inadequate PSA response could always perform salvage prostatectomy after.

 

[cancer_doc]

I would consider attempt to biopsy to confirm recurrent cancer.

If you proceed with some treatment, my top 2 would be:
salvage HIFU under protocol
ADT

other options down the line can be:
salvage cryo, but would think it would be difficult since it is an anterior lesion by urethra
salvage RP, but agree with side effect concerns.

 

[seper]

ADT+/- taxane/Zytiga 100%

 

[evilbooyaa]

Localized disease, treat definitively IMO. His risk of toxicity is high, however, so if he's not willing to accept those then palliative systemic tx is fine. Can send for opinions with urology and HDR brachy docs to consider focal HDR implant. Wouldn't SBRT.

 

[Radiator20]

Localized disease, treat definitively

Agree 100%. If this is not treated definitively, this man likely has a significant risk of dying of his cancer given his relatively low competing risks.

In my opinion, cryo, HIFU, TURP, etc are unlikely to be curative, particularly as he's failed focal salvage therapy previously. I also would not SBRT. One could consider partial-gland HDR as a less invasive but less certain attempt at definitive-intent treatment. However, targeting will be an issue given MRI-occult, and even if you did get your dose in the Axumin-positive zone, that's right next to the previously irradiated urethra. I would pursue this only if RP were refused by patient or not recommended by a high-volume tertiary urologist. While the risks of RP cannot be ignored, there are not many other circumstances where we don't recommend the only curative tx in healthy patients due to side effects. And of course, lifelong ADT is a significant hit to QOL itself.

Ultimately I think the key here is patient decision-making. He has one clear curative-intent salvage option, RP, and another clear palliative option, systemic tx. If, despite his relatively young age, good health, and potentially bad disease he doesn't want to accept the risks of the former, then that's certainly his right. But he has to be given the option, and if he were my patient, it would be my strong recommendation if possible.

 

[Mandelin Rain]

Thanks all. Should have added that pt was seen by a high volume private robot guy. Could send him to local academic center, but I've never heard of anybody there doing salvage RPs. I'll poke around a bit. No centers anywhere nearby perform HDR brachy.

 

[scarbrtj]

The only reason you think he has a local recurrence is because of the PET. It, at best, has a positive predictive value of about 60-70%. However, this should be modified in the setting of other clinical info such as PSA doubling time. He has a doubling time (PSA 0.06-->7 from 2015 to 2017) of FAR less than one year meaning in my mind he has a 50/50 pretest chance of occult systemic disease. Maybe worse, but let's go best case. If we use estimated sensitivities/specificities of 88%/33% for the prostate bed, then in this case with a sole local positive Axumin PET....
...........LOCAL.ONLY.DISEASE
...........positive....negative
TEST...........................
positive......44.........33....PPV:44/(33+44)=57%
negative......06.........17....NPV:17/(17+6)=74%
TOTAL.........50.........50....100
He has a ~57% chance right now of local only disease. This means, I think you should be cautious about proceeding with any local-only therapy right now due to unfavorable risk/benefit ratio couple with likelihood of therapeutic futility if he has metastatic disease. With a ~60% positive predictive value right now based on the PET, your clinical estimate of local disease only is only slightly better than coin toss odds. The addition of perhaps a bone scan (negative) and some biopsy attempt (positive) would improve these odds a lot. Keep in mind though this guy had negative local biopsy previously (making my odds guesstimates maybe more believable). A local-only scan like the MRI he had would not budge the needle much IMHO.
TL;DR
four factors non-local: long interval since local tx, failed local salvage, negative 2017 bx, rapid PSADT
one factor local: 2019 PET
EDIT: Of course, goes without saying must discuss with patient. Attempt to contextualize these risks, benefits, etc. The only benefit he can gain is non-soon-death, maybe no bone met hassles. I bet he has local issues already. He could get a lot of risks. By no local therapy, he may have the risks of systemic therapy. Complex discussion but I always feel like you can get a feel of things from folks. For me, in same boat, if I were 71 and truly "high performance" as you say... I'd just take some testosterone.

 

[Radiator20]

The addition of perhaps a bone scan (negative) and some biopsy attempt (positive) would improve these odds a lot

I certainly agree with doing what you can to clarify presence of local disease and/or absence of distant disease prior to treatment.

Can someone educate me - how much does a bone scan add over a negative Axumin PET?

And of course, metastatic disease does not rule out benefit to local therapy. Not equating salvage RP here to primary RT as used in the trial, but just something to consider.

 

[Palex80]

I certainly agree with doing what you can to clarify presence of local disease and/or absence of distant disease prior to treatment.

Can someone educate me - how much does a bone scan add over a negative Axumin PET?

Bone scans in patients with PSA values <10 ng/ml in non-high-gleason tumor patients are generally not recommended. They are a waste of money in my opinion...
At least this is what the evidence says for newly-diagnosed disease (so not your scenario, but probably comparable).
Baseline staging of newly diagnosed prostate cancer: a summary of the literature. - PubMed - NCBI
This study points out at a risk of 2% to get a positive bone scan when performing a bone scan for a patient with a newly diagnosed prostate cancer and a PSA <10 ng/ml.

And of course, metastatic disease does not rule out benefit to local therapy. Not equating salvage RP here to primary RT as used in the trial, but just something to consider.

It does however not justify it either. Not in the setting you are in, which is a salvage therapy after RT with a high chance to cause complications regardless of the type of local treatment you choose.


Bottom line is simple to me:
1. Local treatment now bears the potential to cure the patient. Permanently. It does however involve taking considerable risks.
2. Noone can really tell you which local treatment option is the bed. Salvage prostatectomy is the "clean" solution. It also bears the highest risk for complications probably.
3. You staged quite well so far. I would definetely go for another biopsy before embarking on any local treatment. You could consider to do an MRI-TRUS-fusion biopsy, if you can see the lesion in the MRI.

 

[scarbrtj]

Bone scans in patients with PSA values <10 ng/ml in non-high-gleason tumor patients are generally not recommended. They are a waste of money in my opinion

They are a "waste of money," and rightly so, only because the incidence of bone mets is so low for newly diagnosed PSA<10 patients. With a sensitivity of 90%, it is a horrible screening test when incidence of the disease (having M1 bone mets) is <1-2% for this population. Thus, a positive bone scan for a patient like this has a positive predictive value of ~4%; i.e., it is worthless and truly a waste. Negative predictive value is 99+%, but since you are a good doctor you "already know" it will be negative.

However, for a patient post-tx with rapidly rising PSA and the where incidence of bone mets is >>>1-2%, the test becomes more useful and much less waste of money. There is nothing too magical about the PSA per se; i.e., recommending bone scans for patients with PSA=20 versus not with PSA=5. It's all about the clinical scenario (newly diagnosed or not), odds of mets in different situations, and good old fashioned statistics. Getting a bone scan for a PSA=20 newly diagnosed patient makes more sense, but not much more sense.

Can someone educate me - how much does a bone scan add over a negative Axumin PET?

I will attempt. It's a bit guesswork isn't it.

First off, assume that for a patient 17y out from local therapy, failure of local salvage, PSA rise from 0.06 2015 to ~7 in 2019, negative biopsy 2017... has 50% chance of local disease only. 50% is my clinical guess. This is pretest likelihood. So you run a test, Axumin. It is positive local only. I showed above how now the pretest likelihood now goes up to ~60% from 50%. A 60% local only disease probability equals 40% chance of metastatic disease. Bone scan has sensitivity/specificity of 90%/75% for prostate cancer. So you do a bone scan now in this scenario:
...........BONE.METS
...........positive....negative
TEST...........................
positive......36.........15....PPV:15/(15+36)=29%
negative......04.........45....NPV:45/(45+4)=92%
TOTAL.........40.........60....100
But all Bayesian-like, you don't take these probabilities by themselves. With a negative bone scan/negative Axumin, the likelihood of no mets equals (1-((1-0.92)*(1-0.4))=95%, mets probability 5%. You'd feel real good about saying "no bone mets." With a positive bone scan/negative Axumin, the calculation is not straightforward and would depend on ROCs, the degree of bone scan positivity (clearly mets vs equivocal, etc.). Someone could prob educate me on that. Rough guesstimate for this patient: in the setting of positive bone scan/negative Axumin the chance that disease is metastatic is (1-((1-0.29)*(1-0.6))=72%. The likelihood of local-only disease would go from 60% to 28%. A negative bone scan/negative (metastatic) Axumin gives the highest clinical confidence in no metastatic disease. In reality, negative bone scan on top of a locally-positive PET would not inform the local disease status at all. But it does rule out bone mets quite nicely.

It should be obvious that all these probabilities flow from the initial pre-Axumin assumption that this patient (negative local biopsy and rapid PSADT) had a 50/50 chance of local-only disease. One can argue that my giving the patient 50% chance of local disease with negative 2017 biopsy is very wrong. Pretest probabilities are opinions. And opinions are like a#$holes.

 

[Radiator20]

Bone scan has sensitivity/specificity of 90%/75% for prostate cancer

I definitely appreciate the statistical argument. A key point, however, is that you’re relying on the best case of complete statistical independence between bone scan and Axumin. But alternative is that they’re not independent and Axumin is just more sensitive In every scenario such that with a negative Axumin the bone scan will always be negative. (And of course, statistical independence is a continuum between those 2 extremes). So I’m still not clear—if you don’t see a bone lesion on Axumin PET, is there any data to say significant chance of picking it up on bone scan?

With a positive bone scan/negative Axumin

Not to short circuit your statistical argument, but I think the right answer if you’re in that situation is biopsy

It does however not justify it either. Not in the setting you are in, which is a salvage therapy after RT with a high chance to cause complications regardless of the type of local treatment you choose.

As I say, not the same situation. But I do think we could allow the strong evidence in the primary setting to somewhat color our thinking here. Given low frequency of post-RT local failures, x low frequency of oligomet disease, doubt we’d ever have prospective evidence for that specific situation. Anyway, he doesn’t have mets that we know of.

2. Noone can really tell you which local treatment option is the bed.

Maybe not, but if you’re going to do local tx, I would strongly favor doing something that’s a standard curative-intent option like RP or HDR. I don’t see how TURP, cryo, HIFU, etc is a good treatment approach here.

 

[scarbrtj]

So I’m still not clear—if you don’t see a bone lesion on Axumin PET, is there any data to say significant chance of picking it up on bone scan?

There is data, and that's the sensitivities/specificities published for the tests. Negative Axumins make negative bone scans more likely, and vice versa; every test either lowers or raises the pretest probability of the next test being positive/negative. That's Bayesian. There is always a chance two tests will conflict. Always, no matter how small. For example, in the OP's case, the patient had a negative biopsy and a positive Axumin in the prostate (although the tests were separated by a good time interval): two conflicting tests. (Rapid PSADT is itself a "test" of metastatic disease.) The idea of running two tests with different sens/spec was useful for early HIV diagnosis e.g. where an ELISA is run (high sensitivity but false positives) and confirmed by western blot (high specificity with low false positives)...

Accordingly, screening tests possess a high degree of sensitivity, whereas confirmatory assays have a high specificity. Tests with high sensitivity produce few false-negative results, whereas tests with high specificity produce few false-positive results. These classes of assays, performed in tandem, produce results that are highly accurate, reliable, and appropriate to protect the blood supply or assist in the diagnosis of HIV infection.
​

Axumin has only a ~33% specificity for local disease but at ~90% sensitivity it is a good screen for local disease. It is thus considered a relatively poor confirmatory test; in general, one would always want to followup with a biopsy. My reasoning for using two high sensitivity tests (bone scan and Axumin) for metastatic disease is "take an outside shot" that is harmless and try and avoid a biopsy which is kinda not too easy in a guy with seeds/radiation, previous cryo, and multiple previous biopsies.

Not to short circuit your statistical argument, but pretty sure the right answer if you’re in that situation is biopsy

You would either accept the bone scan as correct and not offer local therapy (and say "Whew thank goodness!") or have to do a bone biopsy (or maybe MRI of the bone).

 

[maxxor]

Radiology resident doing integrated NM training:

Fluciclovine PET is terrible for osseous lesions and will frequently show a false positive bone lesion because red marrow can have focal uptake. Bone scan could be helpful, especially since this is not a newly diagnosed patient.

As far as the prostate bed, the problem is that even previously irradiated prostate will take up radiotracer. You’d need something really focally elevated to be able call local recurrrence, ideally with MR correlate.

If you could show the images, it would help.

I just reviewed all the cases we have done at our hospital. At PSA 7.5, we’d expect > 90% of cases to have something positive on the scan.

 

[scarbrtj]

Radiology resident doing integrated NM training:

Fluciclovine PET is terrible for osseous lesions and will frequently show a false positive bone lesion because red marrow can have focal uptake. Bone scan could be helpful, especially since this is not a newly diagnosed patient.

As far as the prostate bed, the problem is that even previously irradiated prostate will take up radiotracer. You’d need something really focally elevated to be able call local recurrrence, ideally with MR correlate.

If you could show the images, it would help.

I just reviewed all the cases we have done at our hospital. At PSA 7.5, we’d expect > 90% of cases to have something positive on the scan.

You did with words briefly what I tried to do with numbers lengthily. With a PSA of 7.5 giving a >90% chance of a positive Axumin, not 100% of those >90% of patients will all have prostate cancer in the prostate; i.e., the false positive rate is high. This is predictable given the test's low specificity for local disease. Of those <10% of patients at PSA 7.5 who have a negative Axumin, the negatives are far more believable.

 

[evilbooyaa]

Yes, confirm recurrence at primary with biopsy before proceeding with treatment. OP had said he definitely wants a biopsy prior to considering treatment, so I didn't think that was a point of discussion.

I think if an Auxumin is negative for distant metastatic disease getting a bone scan additionally is a waste of time and resources. False negative rates on Auxumin are lower than on bone scan. False positives are much more likely on Auxumin, so the local area does need to be biopsied, but if it's negative in all other metastatic sites then I don't see how a bone scan adds anything.
It's like getting a CT of the chest for a lung tumor then saying the patient needs an X-ray.

 

[Mandelin Rain]

Yes, confirm recurrence at primary with biopsy before proceeding with treatment. OP had said he definitely wants a biopsy prior to considering treatment, so I didn't think that was a point of discussion.

I think if an Auxumin is negative for distant metastatic disease getting a bone scan additionally is a waste of time and resources. False negative rates on Auxumin are lower than on bone scan. False positives are much more likely on Auxumin, so the local area does need to be biopsied, but if it's negative in all other metastatic sites then I don't see how a bone scan adds anything.
It's like getting a CT of the chest for a lung tumor then saying the patient needs an X-ray.

This was my impression as well.

 

[Radiator20]

This was my impression as well.

Mine too, hence the question.

 

[maxxor]

Fluciclovine is not sufficiently sensitive for sclerotic lesions, which is why MDP bone scan or just regular CT is still recommended for excluding blastic osseous disease.

It's great for lytic or mixed lesions.

 

[scarbrtj]

Yes, confirm recurrence at primary with biopsy before proceeding with treatment. OP had said he definitely wants a biopsy prior to considering treatment, so I didn't think that was a point of discussion.

I think if an Auxumin is negative for distant metastatic disease getting a bone scan additionally is a waste of time and resources. False negative rates on Auxumin are lower than on bone scan. False positives are much more likely on Auxumin, so the local area does need to be biopsied, but if it's negative in all other metastatic sites then I don't see how a bone scan adds anything.
It's like getting a CT of the chest for a lung tumor then saying the patient needs an X-ray.

It's like a lottery ticket purchase in a way. It doesn't add anything... unless you win. The sensitivities of bone scan and Axumin overlap, thus false negative rates overlap. If you're already of a mindset to "lean in" in this case, you skip bone scan and get the biopsy and try a local therapy. If you're more cautious, you explore every avenue possible to try and rule in metastatic disease. Granted, with a negative Axumin, a bone scan is unlikely to be positive. Axumin has an overall true positive rate of about 60%, and a false negative rate therefore of about 40%. For a guy with a rapid PSADT, the true positive rate for bone scan is ~66%. Thus, rough calc, P(Axumin negative=A) and P(bone scan positive=B)=P(A∩B) = 0.26.
You would therefore have to bone scan about 4 Axumin-negative patients to find a bone-scan positive patient in the clinical setting of where distant mets are "somewhat" likely (whatever somewhat means).
Whether that's a waste of time/resources: totally up to the treating physician.

 

[Radiator20]

Fluciclovine is not sufficiently sensitive for sclerotic lesions

This is helpful as it speaks to statistical independence of the two tests.

If you did get a bone scan and found something, I would absolutely biopsy it, however. Both to prove new metastatic prostate cancer and to exclude a second primary.

 

[medgator]

Fluciclovine is not sufficiently sensitive for sclerotic lesions, which is why MDP bone scan or just regular CT is still recommended for excluding blastic osseous disease.

It's great for lytic or mixed lesions.

Aren't you going to pick up those lesions anyways on the ct portion of the study? No one is doing Pet alone these days

 

[maxxor]

Aren't you going to pick up those lesions anyways on the ct portion of the study? No one is doing Pet alone these days

If it’s a diagnostic CT, sure.

The very low mAs attenuation correction CTs that are common with FDG PET may not see them.

 

[scarbrtj]

This is helpful as it speaks to statistical independence of the two tests.

Medical tests are not independent. On average they tend to agree; less commonly they disagree. A heads on one coin toss does not make heads more likely on the next coin toss. If you get 10 heads straight in a row, the odds of heads are 50/50 on the 11th toss. If you get 10 positive tests for a disease, the 11th test is very, very likely to be positive: a positive on one medical test does make a positive more likely on the next. Every test affects the prevalence/population for the next test. (This is also true in randomized trials e.g.: a positive trial makes the next same-styled trial more likely to be positive.)

 

[Radiator20]

Medical tests are not independent. On average they tend to agree; less commonly they disagree. A heads on one coin toss does not make heads more likely on the next coin toss. If you get 10 heads straight in a row, the odds of heads are 50/50 on the 11th toss. If you get 10 positive tests for a disease, the 11th test is very, very likely to be positive: a positive on one medical test does make a positive more likely on the next. Every test affects the prevalence/population for the next test. (This is also true in randomized trials e.g.: a positive trial makes the next same-styled trial more likely to be positive.)

I agree with what you've written and perhaps I wasn't clear but what I'm getting at is whether the failure modes are independent.

Not independent: CT chest and CXR for lung nodules. There is essentially no situation in which a lung nodule will be detected on CXR but not on CT. The ROC curve for CXR is entirely "under" that of CT. It adds no marginal value for detecting lung nodules. Likewise: CT head and MRI for intracranial mets.

Vs., per Maxxor, the situation here, where there is a class of lesions not well detected by Axumin that may be better detected by bone scan.

 

[Mandelin Rain]

Just FYI, plugged in his 8 most recent PSAs. Doubling time is right at 12 months. Velocity right about 2.

 

[scarbrtj]

Just FYI, plugged in his 8 most recent PSAs. Doubling time is right at 12 months. Velocity right about 2.

Ha. Well, tons of lackluster and/or conflicting info here. On one hand, negative previous biopsy two years ago. On the other, intermediate PSADT. And finally, an Axumin whose false positive rate is too high to make a definitive call, locally, and a possible false negative systemically. Now we must guesstimate the false negative rate of re-biopsy in the setting of previous negative biopsy but positive local Axumin Do you believe a negative re-biopsy? Of course, in this case. There's no choice really. Although that decision, maybe, would be as likely wrong as believing the positive Axumin! Dammit.

 

[evilbooyaa]

Fluciclovine is not sufficiently sensitive for sclerotic lesions, which is why MDP bone scan or just regular CT is still recommended for excluding blastic osseous disease.

It's great for lytic or mixed lesions.

Any data to support this statement?

 

[maxxor]

Any data to support this statement?

Published comparative data is not that well available because in most of the trials that evaluated Fluciclovine a positive bone scan was an exclusion criteria. One of the multi center trials that led to Fluciclovine's approval was published in J Urology. In their reading protocol, they explicitly call out that sclerotic lesions without uptake do not exclude metastasis. They also excluded patients with positive bone scans prior to scanning with Fluciclovine. This is on Supplemental Material, Table 2. The Impact of Positron Emission Tomography with 18F-Fluciclovine on the Treatment of Biochemical Recurrence of Prostate Cancer: Results from the LO... - PubMed - NCBI

Here's a review article that talks about some performance for bone lesions: Update on 18F-Fluciclovine PET for Prostate Cancer Imaging

18F-fluciclovine has been shown to accumulate in osteolytic and osteoblastic lesions, including early-stage osteoblastic bone metastatic lesions that have abundant cellular components (31). Additionally, 18F-fluciclovine has been shown to have uptake in osseous lesions before morphologic changes can be detected by CT. 18F-fluciclovine typically demonstrates intense focal uptake in lytic prostate metastatic osseous lesions, moderate uptake in mixed sclerotic lesions, and mild to no uptake in dense sclerotic lesions (Fig. 3). Because there may be little to no 18F-fluciclovine activity in dense sclerotic lesions, skeleton-specific imaging to supplement 18F-fluciclovine PET/CT is recommended in these cases.

Compared with standard osseous scintigraphy, 18F-fluciclovine demonstrated equivalent or better results in limited studies. A phase 2A clinical trial of 10 patients with untreated prostate cancer found that 7 patients had increased 18F-fluciclovine uptake in osseous metastatic lesions—a finding that was comparable to those of conventional imaging (32). In a study involving 68 patients, 18F-fluciclovine PET/CT had moderate concordance with combined bone scintigraphy and contrast-enhanced CT for osseous metastatic disease; however, 7 patients did have positive 18F-fluciclovine findings that were negative on the combined modality (16). Although it might be concluded that a dedicated bone scan may not be necessary if a patient has definitively positive osseous disease on 18F-fluciclovine PET, most early clinical trials used a positive bone scan as an exclusion criterion. Thus, it is not recommended at this time that 18F-fluciclovine PET replace dedicated bone scintigraphy.

These are in agreement with what we've all been saying in various ways. If the question is "are there metastases?", then a positive Fluciclovine finding in the bone obviates the need for a bone scan. However, a negative Fluciclovine scan does not necessarily exclude distant osseous metastatic disease.

Fluciclovine performance correlates with PSA. Our center's data lines up with published work where roughly 30% of cases will have findings when PSA is 0.3-1.0, with an increasing percentage of positive cases approaching >95% when PSA > 5.

 

[evilbooyaa]

These are in agreement with what we've all been saying in various ways. If the question is "are there metastases?", then a positive Fluciclovine finding in the bone obviates the need for a bone scan. However, a negative Fluciclovine scan does not necessarily exclude distant osseous metastatic disease.

Fluciclovine performance correlates with PSA. Our center's data lines up with published work where roughly 30% of cases will have findings when PSA is 0.3-1.0, with an increasing percentage of positive cases approaching >95% when PSA > 5.

Thanks for the links, I'll take a look. However, my (and I believe others') question, primarily in regards to the bolded, is given that these two tests are not giving results independent of each other, is there any subset of the population that has a negative Fluciclovine but a positive (and biopsy confirmed) bone scan? Even in sclerotic bone lesions? If they're not bright enough for Fluciclovine will some proportion of them still show up on bone scan?

 

[maxxor]

Thanks for the links, I'll take a look. However, my (and I believe others') question, primarily in regards to the bolded, is given that these two tests are not giving results independent of each other, is there any subset of the population that has a negative Fluciclovine but a positive (and biopsy confirmed) bone scan? Even in sclerotic bone lesions? If they're not bright enough for Fluciclovine will some proportion of them still show up on bone scan?

We have seen these patients. There is no published data doing head to head comparisons as far as I am aware, mainly because trials required negative bone scans as an inclusion criteria. This implies the patients tested were enriched for Tc99 MDP negative lesions.

To be honest, Ga68 PSMA will completely replace Fluciclovine once it is approved in the US. It has superior lesion detection at lower PSA. You can also swap out the Ga68 with Lu177 and given IV PSMA-based radiotherapy, much like with advanced Neuroendocrine tumors.

68Ga-PSMA PET/CT Replacing Bone Scan in the Initial Staging of Skeletal Metastasis in Prostate Cancer: A Fait Accompli? - PubMed - NCBI

 

[scarbrtj]

Fluciclovine performance correlates with PSA. Our center's data lines up with published work where roughly 30% of cases will have findings when PSA is 0.3-1.0, with an increasing percentage of positive cases approaching >95% when PSA > 5.

Positive in prostate, extra-prostatic, or either/or? This in and of itself suggests a kind of high false positive rate because I wouldn't guess >95% of men with PSA>5 have prostate cancer. What you're saying is, save money when the PSA is >5: just predict a positive Axumin if that is the answer you're looking for.

 

[maxxor]

1. Positive in prostate, extra-prostatic, or either/or? This in and of itself suggests a kind of high false positive rate because I wouldn't guess >95% of men with PSA>5 have prostate cancer. What you're saying is, save money when the PSA is >5: just predict a positive Axumin if that is the answer you're looking for.

   It depends on what you’re looking for with the test.
   
   Is it biochemical recurrence and looking for a potential site to target therapy?
   
   Is it initial staging?
   
   The vast majority of our patients have had prior prostatectomy. Maybe 20% have had prior radiation as the primary treatment. That’s just our referral pattern. For the prior radiation, fluciclovine is really bad at assessing the prostate because even previously irradiated prostate takes up the tracer, so you have to hope whatever recurrent disease there is takes it up to an even higher degree than background. I’ve personally found this very challenging for prostatic assessment. Extraprostatic non osseous, works fine whether primary treatment was radiation or surgery. Osseous, lytic and mixed lesions are fine. Subtle blastic lesions, really bad. This is where an atomic CT or bone scan are better. Osseous disease also is plagued by false positives from red marrow.
   
   Fluciclovine has really only been validated in one setting so far:
   
   Patients who have had definitive primary therapy (with a bias towards prostatectomy) with subsequent biochemical recurrence and a negative bone scan and now we are looking for targetable lesions for potential targeted cure.
   
   Our RadOncs use it to see if there is somewhere they can target their salvage radiation fields. Everything else we have been discussing is beyond what the tracer was originally approved to do.
   
   Personally, as someone who reads these scans, I find it a crappy agent. The target to background is not great. A lot of the interpretation is handwavy according to the protocols from Emory is based on “expected nodal drainage pathways”. For example, we often see intense inguinal uptake. Their protocols said it’s an unlikely path of spread so that is most likely inflammatory. We aren’t recommending biopsy so who knows why there’s so much frequent inguinal uptake. The tracer is technically challenging to inject and image; if the techs mess up the acquisition by a few minutes, they can miss the peak activity as the tracer redistributes to muscle tissues quickly. If the patient exercises at all, the sensitivity is greatly reduced.
   
   The data on PSMA based agents coming out of Europe looks way better and will make Fluciclovine obsolete.

 

[scarbrtj]

1. 
   It depends on what you’re looking for with the test.
   
   Is it biochemical recurrence and looking for a potential site to target therapy?
   
   Is it initial staging?
   
   The vast majority of our patients have had prior prostatectomy. Maybe 20% have had prior radiation as the primary treatment. That’s just our referral pattern. For the prior radiation, fluciclovine is really bad at assessing the prostate because even previously irradiated prostate takes up the tracer, so you have to hope whatever recurrent disease there is takes it up to an even higher degree than background. I’ve personally found this very challenging for prostatic assessment. Extraprostatic non osseous, works fine whether primary treatment was radiation or surgery. Osseous, lytic and mixed lesions are fine. Subtle blastic lesions, really bad. This is where an atomic CT or bone scan are better. Osseous disease also is plagued by false positives from red marrow.
   
   Fluciclovine has really only been validated in one setting so far:
   
   Patients who have had definitive primary therapy (with a bias towards prostatectomy) with subsequent biochemical recurrence and a negative bone scan and now we are looking for targetable lesions for potential targeted cure.
   
   Our RadOncs use it to see if there is somewhere they can target their salvage radiation fields. Everything else we have been discussing is beyond what the tracer was originally approved to do.
   
   Personally, as someone who reads these scans, I find it a crappy agent. The target to background is not great. A lot of the interpretation is handwavy according to the protocols from Emory is based on “expected nodal drainage pathways”. For example, we often see intense inguinal uptake. Their protocols said it’s an unlikely path of spread so that is most likely inflammatory. We aren’t recommending biopsy so who knows why there’s so much frequent inguinal uptake. The tracer is technically challenging to inject and image; if the techs mess up the acquisition by a few minutes, they can miss the peak activity as the tracer redistributes to muscle tissues quickly. If the patient exercises at all, the sensitivity is greatly reduced.
   
   The data on PSMA based agents coming out of Europe looks way better and will make Fluciclovine obsolete.

Thanks for your tips & tricks. I learned something. For rad oncs who are using Axumin to target fields or change what would be sort of the standard RT volume(s), that doesn't seem the wisest. Any time you're doing what one would term salvage RT for CaP, you're going to treat the entire prostate bed (or prostate) and +/- nodes depending on clinical risk, personal MD preference. If I saw a +Axumin in the pelvis, I wouldn't target that with high dose RT unless the site was also visible and abnormal on CT or MRI. (And if the Axumin were negative there in that abnormal CT/MRI spot, I'd still target it.)

 

[Radiator20]

Fluciclovine has really only been validated in one setting so far:

Patients who have had definitive primary therapy (with a bias towards prostatectomy) with subsequent biochemical recurrence and a negative bone scan and now we are looking for targetable lesions for potential targeted cure.

This is a helpful reminder/summary statement. Thanks.

 

[maxxor]

Thanks for your tips & tricks. I learned something. For rad oncs who are using Axumin to target fields or change what would be sort of the standard RT volume(s), that doesn't seem the wisest. Any time you're doing what one would term salvage RT for CaP, you're going to treat the entire prostate bed (or prostate) and +/- nodes depending on clinical risk, personal MD preference. If I saw a +Axumin in the pelvis, I wouldn't target that with high dose RT unless the site was also visible and abnormal on CT or MRI. (And if the Axumin were negative there in that abnormal CT/MRI spot, I'd still target it.)

We will be meeting with our RadOncs soon to discuss how they are using the test's results now that we've reviewed all our cases from the past year. From the limited follow up I've seen, it seems our RadOncs use the Fluciclovine findings to decide whether to go after nodes or not.

 

[Mandelin Rain]

I've been ordering them largely post-op in guys with PSA 1-10. That seems to be the sweet spot between which the PET may pick up something traditional modalities probably wouldn't. Maybe that's just me misinterpreting though.

 

[maxxor]

I've been ordering them largely post-op in guys with PSA 1-10. That seems to be the sweet spot between which the PET may pick up something traditional modalities probably wouldn't. Maybe that's just me misinterpreting though.

Sounds like what the test was designed for.