Pseudoprogression.

[pjoshea13]

New term to me.

New study [1], below.

From a recent paper [2]:

"Tumor osseous pseudoprogression (PP), defined as an imaging-based transient increase in tumor size following treatment ..."

From the new paper:

"For men with metastatic castration-resistant prostate cancer (mCRPC) whose condition is responding to enzalutamide, new unconfirmed bone lesions detected at posttreatment scinitigraphy may reflect an osteoblastic reaction that represents healing, known as pseudoprogression, which can lead to premature discontinuation of therapy."

...

"...new unconfirmed lesions detected on follow-up bone scans may represent pseudoprogression in men with mCRPC and are indicative of a favorable treatment response to enzalutamide. The detection of new unconfirmed bone lesions in men with mCRPC that responded to treatment with enzalutamide after docetaxel appears to be associated with worse overall survival and may represent true progression, thus highlighting the need for improved functional bone metastasis imaging."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/318...

JAMA Oncol. 2019 Dec 12. doi: 10.1001/jamaoncol.2019.4636. [Epub ahead of print]

Association Between New Unconfirmed Bone Lesions and Outcomes in Men With Metastatic Castration-Resistant Prostate Cancer Treated With Enzalutamide: Secondary Analysis of the PREVAIL and AFFIRM Randomized Clinical Trials.

Armstrong AJ1, Al-Adhami M2, Lin P3, Parli T4, Sugg J5, Steinberg J6, Tombal B7, Sternberg CN8, de Bono J9, Scher HI10, Beer TM11.

Author information

1

Division of Medical Oncology and Urology, Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, North Carolina.

2

Biostatistics, Pfizer Inc, Cambridge, Massachusetts.

3

Biostatistics, Pfizer Inc, San Francisco, California.

4

Clinical Development, Pfizer Inc, San Francisco, California.

5

Biostatistics, Astellas Pharma Inc, Northbrook, Illinois.

6

Clinical Development, Astellas Pharma Inc, Northbrook, Illinois.

7

Division of Urology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

8

Medical Oncology, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, New York.

9

Division of Clinical Studies, The Institute of Cancer Research, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom.

10

Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York.

11

Division of Hematology/Medical Oncology, OHSU Knight Cancer Institute, Oregon Health & Science University, Portland.

Abstract

IMPORTANCE:

For men with metastatic castration-resistant prostate cancer (mCRPC) whose condition is responding to enzalutamide, new unconfirmed bone lesions detected at posttreatment scinitigraphy may reflect an osteoblastic reaction that represents healing, known as pseudoprogression, which can lead to premature discontinuation of therapy.

OBJECTIVE:

To determine the association between new unconfirmed lesions detected on a follow-up bone scintigram (bone scan) and outcomes in enzalutamide-treated men with mCRPC.

DESIGN, SETTING, AND PARTICIPANTS:

This post hoc, retrospective secondary analysis of 1672 enzalutamide-treated men from 2 phase 3, randomized mCRPC studies (PREVAIL and AFFIRM) before or after treatment with docetaxel was conducted from April 12, 2018, to July 25, 2019. Participants were men from the enzalutamide groups of the 2 studies with a decrease in prostate-specific antigen level at any time or with stable disease or soft-tissue disease responding to treatment based onradiologic findings.

INTERVENTION:

Enzalutamide, 160 mg once daily.

MAIN OUTCOMES AND MEASURES:

The clinical significance of new lesions detected on the first (early) or second (late) posttreatment bone scan, without an unfavorable change in prostate-specific antigen level or soft-tissue progression, was investigated. Associations of new unconfirmed lesions with radiographic progression-free survival, overall survival, decrease in prostate-specific antigen level, objective response in soft tissue, and quality of life were evaluated.

RESULTS:

Among the 643 men (median age, 72 years [range, 43-93 years]) in PREVAIL, early and late unconfirmed lesions were observed in 177 men (27.5%) with stable disease or disease responding to enzalutamide. Among the 404 men (median age, 70 years [range, 41-88 years]) in AFFIRM, early and late unconfirmed lesions were observed in 73 men (18.1%) with stable disease or disease responding to enzalutamide. In PREVAIL, men with new unconfirmed lesions had median radiographic progression-free survival (hazard ratio [HR], 1.37 [95% CI, 0.81-2.30]; P = .23) and median overall survival (HR, 1.25 [95% CI, 0.85-1.83]) in the chemotherapy-naive setting similar to men those of men without such new lesions. In AFFIRM, the median overall survival (HR, 1.94 [95% CI, 1.10-3.44]) was reduced among men with unconfirmed bone lesions, but the median radiographic progression-free survival was not reduced (HR, 1.21 [95% CI, 0.83-1.75]; P = .32). Quality of life over time was similar regardless of the presence of new unconfirmed lesions detected on a follow-up bone scan in either setting.

CONCLUSIONS AND RELEVANCE:

These results suggest that new unconfirmed lesions detected on follow-up bone scans may represent pseudoprogression in men with mCRPC and are indicative of a favorable treatment response to enzalutamide. The detection of new unconfirmed bone lesions in men with mCRPC that responded to treatment with enzalutamide after docetaxel appears to be associated with worse overall survival and may represent true progression, thus highlighting the need for improved functional bone metastasis imaging.

TRIAL REGISTRATION:

ClinicalTrials.gov identifier: NCT01212991 and NCT00974311.

PMID: 31830211 DOI: 10.1001/jamaoncol.2019.4636

[2] ncbi.nlm.nih.gov/pubmed/296...

Neurosurgery. 2019 Mar 1;84(3):647-654. doi: 10.1093/neuros/nyy075.

Incidence and Time of Onset of Osseous Pseudoprogression in Patients With Metastatic Spine Disease From Renal Cell or Prostate Carcinoma After Treatment With Stereotactic Body Radiation Therapy.

Jabehdar Maralani P1, Winger K1, Symons S1, Machnowska M1, Heyn C1, Helmi A1, Chan A1, Tseng CL2, Sahgal A2.

Author information

1

Department of Medical Imaging, University of Toronto, Toronto, Canada.

2

Department of Radiation Oncology, University of Toronto, Toronto, Canada.

Abstract

BACKGROUND:

Tumor osseous pseudoprogression (PP), defined as an imaging-based transient increase in tumor size following treatment, was recently described in patients with spinal metastases following stereotactic body radiation therapy. Distinguishing PP from true tumor progression is critical.

OBJECTIVE:

To describe the incidence, time of onset, and time range of PP following stereotactic body radiation therapy in patients treated for spinal metastases from either prostate cancer (PC) or renal cell carcinoma (RCC), and associated predictive factors.

METHODS:

A retrospective study was conducted on our institution's cancer database from 2009 to 2015. Selection was based on single level, no prior radiation or surgery, ≥2 follow-up spine magnetic resonance imaging (MRI), and metastases arising from either PC or RCC. Gross tumor volume was contoured on pre- and up to 5 posttreatment MRIs. Patients were sorted into groups depending on gross tumor volume response: PP, non-PP, or progressive disease. Clinical and dosimetric variables were compared using either Fisher's exact test or Kruskal-Wallis analyses.

RESULTS:

Forty-three spinal segments from 31 patients were analyzed. RCC and PC patients showed similar incidence of PP (∼37%). Whether the primary was lytic or sclerotic was a significant predictive factor with more PP in the lytic group (P = .0208). There was a trend of earlier PP onset in RCC (within 6-18 mo) as compared to PC; however, PC segments showed more time-confined presentation of PP (9-12 mo).

CONCLUSION:

There was a higher incidence of PP in lytic compared to sclerotic primary tumor type. PP in spinal metastatic sites may have variable presentations depending on the primary cancer.

Copyright © 2018 by the Congress of Neurological Surgeons.

KEYWORDS:

Prostate carcinoma; Pseudoprogression; Renal cell carcinoma; Stereotactic body radiation therapy

PMID: 29618107 DOI: 10.1093/neuros/nyy075

[LearnAll]

Psudo= false ….false progression! This is similar to bounce of ALP which in my case shot up from initial 191 to 491 within 14 days of being on Bicalutamide and then, ALP dropped continuously ending up at 59. I think that ALP flare was pseudo progression.

MO said "don't worry.. this is a very good response"

[pjoshea13]

Actually, I was up at 3 am to bake some New York-style bagels. My son & granddaughter love them (as do I), but it's a lot of work. I shall have to teach my son the arcane procedures.

-Patrick

[j-o-h-n in reply to pjoshea13]

You need New York water to make good bagels....

Good Luck, Good Health and Good Humor.

j-o-h-n Saturday 12/14/2019 10:55 AM EST

[monte1111 in reply to j-o-h-n]

Yes. Hudson River Specials. Bet you can't eat just one.

[j-o-h-n in reply to monte1111]

Yep and you can find them in the dark.............

Good Luck, Good Health and Good Humor.

j-o-h-n Sunday 12/15/2019 2:01 PM EST

[cesces]

This seems to be real important:

"follow-up spine magnetic resonance imaging (MRI), and metastases arising from either PC or RCC. Gross tumor volume was contoured on pre- and up to 5 posttreatment MRIs. Patients were sorted into groups depending on gross tumor volume response: PP, non-PP, or progressive disease. Clinical and dosimetric variables were compared using either Fisher's exact test or Kruskal-Wallis analyses."

Does anyone know

1. Why MRI and not pet scans?

2. What contrast agent did they use

3. "up to 5 posttreatment MRIs" makes it like something far more than a temporary flare up?

4. Am I reading this correctly that it is basically about taxotere treatment?

[pjoshea13 in reply to cesces]

Full text: jamanetwork.com/journals/ja...

[cesces in reply to pjoshea13]

Thanks, but the writing is too thick for me to translate into what they are attempting to say.

[addicted2cycling in reply to cesces]

Clear as mud.

[pjoshea13 in reply to addicted2cycling]

I think that the take-home message is clear, though. Don't automatically give up on Enzalutamide if scans appear to show progression but PSA is indicative of a treatment response - unless Docetaxel was previously used.

-Patrick

[cesanon in reply to pjoshea13]

"unless Docetaxel was previously used"

So if Docetaxel was previously used followed by Enzalutamide and an MRI scan shows subsequent progression that should raise a red flag. But not so if there is no history of Docetaxel treatment?

And what is the significance of the MRI scan. Does this apply to situations where a PET scan is used? My understanding is that because of cost, MRI scans are seldom used.

And aren't MRI scans not very good for looking at bone mets? Or is it that PET scans are not so good for looking at bone mets?

[MateoBeach]

I suppose an F18 PET scan would also show enhancement of lesions during pseudo-progression?

But perhaps the increased bone turnover from healing could be a window that might enhance the effectiveness of R223 Xofigo to those lesions (?) Would be interesting to explore in a trial.

[PhilipSZacarias]

After long term use enzalutamide is associated with progression to neuroendocrine type PCa which does not release much PSA. Is the progression in bone lesions indicative of a subpopulation neuroendocrine PCa? Cheers, Phil