Bone biopsy failures. Any advice? - Advanced Prostate...

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Bone biopsy failures. Any advice?

MarkEmrys profile image
18 Replies

Hello

I have had two attempts at a bone biopsy for genetic testing to guide future treatment options for M1 mcrpc (no visceral mets). Both failed -- the first because the sample was said to have been contaminated; the second because there was insufficient tissue. Has anyone else had this kind of problem? Any advice on how best to get genetic result from a bone biopsy?

thanks

Mark

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MarkEmrys
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Schwah profile image
Schwah

I wrote about this the other day. The latest scans have become so advanced and see things so small that it is often very difficult to get tissue from such a small site that could be useful. Probably more good than bad though.

Schwah

MarkEmrys profile image
MarkEmrys in reply to Schwah

Thanks SchwahPET-PSMA/CT scan showed the mets. Biopsy via core needle guided by CT, I think. Sedated with Fentonyl. 6 cores from thumbnail size iliac lesion in 1st biopsy, which was somehow contaminated, therefore not useful.

Three months later two cores from 50mm lesion on sacrum turned up insufficient tissue for T 1500 genetic test. Im getting the feeling bone biopsy genetic testing often fails?

Cheers

MarkEmrys

GP24 profile image
GP24

Yes, bone biopsy often fails. Did you try to get your old prostate biopsy probes tested? This is usually done instead of a bone biopsy. There are studies that the results mostly do not differ from a biopsy of mets.

MarkEmrys profile image
MarkEmrys in reply to GP24

Unfortunately MO and Urologist didn’t do a prostate biopsy on dx as M1.

GP24 profile image
GP24 in reply to MarkEmrys

I suggest to get a prostate biopsy now. This way you can be sure to get a sufficient amount of tissue plus your Gleason score.

MarkEmrys profile image
MarkEmrys in reply to GP24

I’ll check this. My understanding is that following 20 hyper fractionated external beam radiation therapy doses to prostate mid-2020 there is not much tissue to extract from prostate.

As part of Lu-617 treatment, which begins tomorrow, there’s a psma/pet/ct scan which might indicate possible biopsy site/s.

Cheers

MarkEmrys

GP24 profile image
GP24 in reply to MarkEmrys

You did not write a profile, so I thought you were treated with ADT only. Yes, if the PSMA SCAN shows no recurrence in the radiated area, it does not make sense to biopsy that.

MarkEmrys profile image
MarkEmrys in reply to GP24

Must complete profile. Sorry to confuse…

Tall_Allen profile image
Tall_Allen

It is often the case that insufficient tissue is collected for a genomic analysis. Was there enough for histology and IHC?

MateoBeach profile image
MateoBeach in reply to Tall_Allen

I’ve been wondering if there is some PSA level or other marker that would suggest successful somatic genomics analysis from cell-free DNA, liquid biopsy, for Guardant360 or similar?

Tall_Allen profile image
Tall_Allen in reply to MateoBeach

They don't usually detect much if there isn't substantial radiographic evidence.

Seasid profile image
Seasid in reply to MateoBeach

If you have bone mets than the PSA should be above 10 in order to have a meaningful liquid biopsy. This information is coming from Tango65. You can message him for more details.

MarkEmrys profile image
MarkEmrys in reply to Seasid

SUV mac for bone mets was aboce 10

Seasid profile image
Seasid in reply to MarkEmrys

You need to have PSA above 5 according to the reasearchers.

Abstract

Background: Liquid biopsy is a powerful tool that can enable treatment decisions for metastatic prostate cancer patients with difficult-to-biopsy tumors. However, the detection of genomic alterations via liquid biopsy is limited by the fraction (tumor fraction [TF]) of circulating tumor DNA (ctDNA) within the total cell-free DNA content. While prior work has preliminarily correlated TF with clinical features of prostate cancer, we sought to validate and provide additional resolution, such that a clinical practitioner might anticipate the probability of successful liquid biopsy profiling leveraging commonly assessed clinical and laboratory features.

Methods: A total of 813 liquid biopsy specimens were assessable, with 545 associated with a PSA prostate specific antigen measurement, collected in standard-of-care settings across approximately 280 US academic or community-based cancer clinics from September 2018 to July 2021. Deidentified data were captured into a real-world clinico-genomic database (CGDB). Comprehensive genomic profiling (CGP) was performed on extracted cell-free DNA from liquid biopsy samples.

Results: In multivariable models, higher PSA level, lower hemoglobin, lower albumin, higher alkaline phosphatase (all p < 0.001), and collection of liquid biopsy blood draw within 60 days of new treatment initiation (p = 0.002) were the most strongly associated features with higher TF. At PSA levels of <5 ng/ml, 43% of patients had a TF of <1% indicating an increased likelihood of unevaluable results. Conversely, at PSA levels of >5 ng/ml, 78% of patients had a TF of at least 1% and 46% had a TF of ≥10%, suggesting improved sensitivity for detection of targetable alterations.

Conclusions: Universal genomic profiling of prostate cancers will require complementary use of liquid biopsy and tumor tissue profiling for suitable patients. The likelihood of adequate ctDNA shedding into plasma is one consideration when deciding whether to pursue CGP via liquid biopsy versus tumor profiling. Our real-world data suggest that PSA < 5 ng/ml is associated with lower ctDNA yield on liquid biopsy, potentially increasing the incidence of negative results or a need for confirmation with tissue testing.

Keywords: ctDNA; genomic profiling; liquid biopsy; mCRPC; tumor fraction.

© 2022 The Authors. The Prostate published by Wiley Periodicals LLC.

Seasid profile image
Seasid in reply to MateoBeach

pubmed.ncbi.nlm.nih.gov/352...

Clinical and pathological features associated with circulating tumor DNA content in real-world patients with metastatic prostate cancer

Emmanuel S Antonarakis et al. Prostate. 2022 May.

Abstract

Background: Liquid biopsy is a powerful tool that can enable treatment decisions for metastatic prostate cancer patients with difficult-to-biopsy tumors. However, the detection of genomic alterations via liquid biopsy is limited by the fraction (tumor fraction [TF]) of circulating tumor DNA (ctDNA) within the total cell-free DNA content. While prior work has preliminarily correlated TF with clinical features of prostate cancer, we sought to validate and provide additional resolution, such that a clinical practitioner might anticipate the probability of successful liquid biopsy profiling leveraging commonly assessed clinical and laboratory features.

Methods: A total of 813 liquid biopsy specimens were assessable, with 545 associated with a PSA prostate specific antigen measurement, collected in standard-of-care settings across approximately 280 US academic or community-based cancer clinics from September 2018 to July 2021. Deidentified data were captured into a real-world clinico-genomic database (CGDB). Comprehensive genomic profiling (CGP) was performed on extracted cell-free DNA from liquid biopsy samples.

Results: In multivariable models, higher PSA level, lower hemoglobin, lower albumin, higher alkaline phosphatase (all p < 0.001), and collection of liquid biopsy blood draw within 60 days of new treatment initiation (p = 0.002) were the most strongly associated features with higher TF. At PSA levels of <5 ng/ml, 43% of patients had a TF of <1% indicating an increased likelihood of unevaluable results. Conversely, at PSA levels of >5 ng/ml, 78% of patients had a TF of at least 1% and 46% had a TF of ≥10%, suggesting improved sensitivity for detection of targetable alterations.

Conclusions: Universal genomic profiling of prostate cancers will require complementary use of liquid biopsy and tumor tissue profiling for suitable patients. The likelihood of adequate ctDNA shedding into plasma is one consideration when deciding whether to pursue CGP via liquid biopsy versus tumor profiling. Our real-world data suggest that PSA < 5 ng/ml is associated with lower ctDNA yield on liquid biopsy, potentially increasing the incidence of negative results or a need for confirmation with tissue testing.

Keywords: ctDNA; genomic profiling; liquid biopsy; mCRPC; tumor fraction.

© 2022 The Authors. The Prostate published by Wiley Periodicals LLC.

MateoBeach profile image
MateoBeach in reply to Seasid

Thanks Seasid, that is just the information I was looking for. Paul

MarkEmrys profile image
MarkEmrys in reply to Tall_Allen

Thanks TAThere was a histology report on first biopsy which I understood simply confirmed pca. No IHC on second biopsy which had insufficient tissue for genomics.

Cheers

Mark

pka21 profile image
pka21

Yes, recently my father had bone biospy to send for HRR testing since our previous biopsy block was old and had failed DNA testing.

But unfortunately, In this bone biospy Dr. did not get any tissue which they could further sent for testing.

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