PSA time to nadir as a prognostic factor of first-line docetaxel treatment in CRPC

[pjoshea13]

New Chinese study below [1].

It's tempting to think of a short time to PSA nadir (lowest point) as being indicative of a robust respose to treatment. (Of course, the nadir itself is important, but see # below.)

"Patients with a TTN {time to nadir} ≥ 15 weeks had a longer OS {overall survival} and PFS {progression-free survival} compared to those with a TTN < 15 weeks (43 vs. 15 months {&} 24 vs. 6 months.., respectively)."

"Patients with a TTN ≥ 15 weeks and PSA nadir <4.55ng/ml were associated with longer OS than others"

# "patients with a PSA nadir <4.55 ng/ml had longer OS and PFS compared to other patients when TTN was ≥15 weeks."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/316...

Urol Oncol. 2019 Oct 28. pii: S1078-1439(19)30291-1. doi: 10.1016/j.urolonc.2019.07.014. [Epub ahead of print]

PSA time to nadir as a prognostic factor of first-line docetaxel treatment in castration-resistant prostate cancer: Multicenter validation in patients from the Chinese Prostate Cancer Consortium.

Pei X1, Wu K1, Sun Y2, Gao X2, Gou X3, Xu J4, Gao F5, He D6, Li L7; Chinese Prostate Cancer Consortium.

Author information

1

Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China.

2

Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, PR China.

3

Department of Urology, First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China.

4

Department of Urology, Huadong Hospital of Fudan University, Shanghai , PR China.

5

Department of Clinical Research Center, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China.

6

Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China. Electronic address: [e-mail].

7

Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China. Electronic address: [e-mail].

Abstract

OBJECTIVE:

Docetaxel-based chemotherapy remains the first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) in China. We have previously shown that time to nadir (TTN) of prostate-specific antigen (PSA) is an important prognostic factor in patients from a single center in Northwestern China. In this study, we performed a multicenter validation of the prognostic role of TTN in additional Chinese patients with mCRPC receiving docetaxel treatment.

MATERIALS AND METHODS:

The data were gathered from 170 eligible Chinese patients who received docetaxel chemotherapy from January 2007 to October 2018 in 11 Chinese Prostate Cancer Consortium member hospitals in China. TTN was defined as the time from start of chemotherapy to the nadir of PSA level during the treatment. Multivariable Cox regression models and Kaplan-Meier analysis were used to predict overall survival (OS) and progression-free survival (PFS).

RESULTS:

Patients with a TTN ≥ 15 weeks had a longer OS and PFS compared to those with a TTN < 15 weeks (43 vs. 15 months, P < 0.001; 24 vs. 6 months, P < 0.001, respectively). In addition, Patients with a TTN ≥ 15 weeks and PSA nadir <4.55ng/ml were associated with longer OS than others (HR 0.093, 95% CI 0.044-0.188, P < 0.001; HR 4.002, 95% CI 1.890-8.856, P = 0.001, respectively) and TTN, PSA nadir, PSA baseline (optimal threshold 56.07 ng/ml), and PSA reduction (optimal threshold 50%) were associated with PFS (HR 0.238, 95% CI 0.149-0.382, P < 0.001; HR 1.676, 95% CI 1.033-2.722, P = 0.037; HR 1.770, 95% CI 1.134-2.763, P = 0.012; HR 0.573, 95% CI 0.428-0.756, P < 0.001; respectively). Furthermore, patients with a PSA nadir <4.55 ng/ml had longer OS and PFS compared to other patients when TTN was ≥15 weeks.

CONCLUSION:

In this multicenter validation study, TTN and PSA nadir remain important prognostic markers in predicting therapeutic outcomes in Chinese men who receive chemotherapy for mCRPC.

Copyright © 2019 Elsevier Inc. All rights reserved.

KEYWORDS:

Castration-resistant prostate cancer (CRPC); Chemotherapy; Docetaxel; PC-follow; PSA nadir; Time to nadir (TTN); survival

PMID: 31672485 DOI: 10.1016/j.urolonc.2019.07.014

[Jlcwonderboy]

Thanks for sharing this PJ

I’ve long put great hope in the results of this sort of study. Not least because of my Dad’s results since his diagnosis in Aug 2017 - see below - which has indicated a long time (pretty much a year) to PSA nadir.

Aug-17 PSA: 29 ALP: 160

Aug-17 PSA: 2.7 ALP: 136

Sep-17 PSA: 1.2 ALP: 75 TES: <0.4 E2: 676

Oct-17 PSA: 0.4 ALP: 62

Oct-17 PSA: 0.2 ALP: 66 TES: <0.4 E2: 239

Nov-17 PSA: 0.2 ALP: 72 TES: <0.4 E2: 311

Dec-17 PSA: 0.2 ALP: 62 TES: <0.4 E2: 237

Feb-18 PSA: 0.2 ALP:59 TES: <0.4 E2: 566

May-18 PSA: 0.1 ALP: 52 TES: <0.4 E2: 614

Jul-18 PSA: <0.03 ALP: 44 TES: <0.4 E2: 403

[AlanMeyer in reply to Jlcwonderboy]

That is indeed an outstanding response to treatment. I'm hopeful of a very long remission.

Alan

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

Boy! Are those numbers a wonder!!!

Good Luck, Good Health and Good Humor.

j-o-h-n Sunday 11/03/2019 7:44 PM EST

[LearnAll]

Thanks pjoshea for this post. There is confusion regarding PSA nadir and time to nadir issue.

I have read that if PSA Nadir is 0.2 or lower ,time to Nadir is irrelevant....I have also read that

very low PSA Nadir along with > 6 months Time to Nadir both should be taken into account

to predict prognosis.

In my case, in 6 months PSA has come down to 0.7 from 830 and I am castration sensitive.

PSA Nadir has not been completed ..next 3 to 4 months PSA is likely to go further down.

Does this study and its conclusion applicable to castration sensitive men ?

[AlanMeyer in reply to LearnAll]

Hello LearnAll,

The study was specifically looking at chemotherapy, not ADT. However it seems to me that the likely reasons why the study showed what it did also apply to ADT in castration sensitive men. See my comment below on why I thought the result was logical and even obvious.

Alan

[Hidden]

Keep in mind that this and other studies done on the subject were not done with patients taking additional second-line ADT agents such as Zytiga, Xtandi or others. The addition of second-line ADT drugs may effect the PSA nadir and time to nadir.

[LearnAll]

Agree with Nalakrats that there are many different factor which combinedly can give approximate prognosis. Of course PSA Nadir and Time to Nadir are two of those factors

FEATURES of aggressive Prostate cancer: (worse prognosis features)

(1) Small cell/ductal/ neuroendocrine type pathology

(2) Mainly visceral (organ related ) mets

(3)predominantly Lytic bone lesions

(4) Multiple BULKY lymphadenopathy

(5)Gleason Grade above 8

(6) very low PSA

(7) greatly elevated LDH or CEA

(8) short term response to ADT

(9) multiple comorbid medical conditions.

[marnieg46 in reply to LearnAll]

Thank you for this list Learn All. What are Lytic bone lesions and multiple bulky lymphadenopathy. Basically when you read results of PSMA scan how would these two features be described?

[LearnAll in reply to marnieg46]

There are 2 types of bone lesions..(1) osteoblastic and (2) Lytic

Osteoblastic lesions are much more common in prostate cancer. They are caused by

bone erosion and at the same time bone repair. On scan they have "cobblestone " appearance along with dense white areas ,its called "sclerotic" pattern.

On the other hand, Lytic lesion are result of mainly bone destruction and on scans they appear as corroded ,eaten away bone.

Bulky lymphadenopathy is literally multiple large lymph nodes ,sometimes seen as big mass sticking together.

I am not familiar with PSMA scan reading.

[Hidden]

This is all very well to see who got trashed with Docetaxel AFTER they had it. We need better pre-selection of candidates BEFORE treatment. Docetaxel is still killing far too many patients unnecessarily.

[pakb]

I keep a close eye on studies like this- while keeping in mind things such as those brought up by Nalakrats and others brought up. My husband has yet to reach Nadir- diagnosed 8/2017. Age at diagnosis 49. Gleason 9. Mets to pelvic lymph, hip, spine.

*Lupron, Docetaxel were first treatment.

*After chemo ended jan 2018 zytiga+prednisone and continued lupron. Has been on that treatment plan since then.

*Also changed diet and supplements.

*Scans show tumors shrinking.

Sept 2017...He started with PSA >677 (first PSA wasn't done until a few weeks after he started bicalutimide so we don't know what his starting was)

Current PSA (Oct 2017)... 8.4

He got down to 7.9 at lowest then we switched labs. After switching labs has been going down from about 11 to current 8.4.

He feels good- more tired than he was before but works, works out, is active, no pain. Just starting some cognitive issues I've noticed forgetfulness. Very infrequently, but I notice.

Wish someone would do that study with similar diagnosis groups- Gleason, mets, treatments.

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

I'm forgetting what I forgot........

Good Luck, Good Health and Good Humor.

j-o-h-n Sunday 11/03/2019 7:47 PM EST

[AlanMeyer]

It seems to me logical and even obvious that longer time to nadir would indicate longer response, at least on average. If PSA drops quickly and then begins climbing, the drug only suppressed cancer growth for a short time. If it keeps declining over time then it is continuing to suppress cancer growth during that time.

If it happens that nadir is reached quickly and then stays at that level for a long time, then the fact that it happened quickly didn't mean that it stopped working. However if you lump all of the men together whose PSA went down quickly in one group, and all of the men for whom the decline continued over a longer period in another group, it would be very surprising if the first group did better than the second. At least some, and possibly most, of the men in the first group would have a rising PSA shortly after nadir, while all of the men in the second group had a nadir that took longer to reach and so could not have had a rising PSA (i.e., a rising tumor burden) during all of that extra time.

Alan

[tom67inMA in reply to AlanMeyer]

It sort of baffles me why they pick time to nadir instead of time to increasing PSA.