Nadir PSA & time to nadir during initial ADT - & prognosis

[pjoshea13]

New study below.

Adding to the evidence that a slower response to ADT is better.

"We reviewed the Michinoku Japan Urological Cancer Study Group database, including 321 mCRPC patients."

"Median age and follow-up period were 71 years and 35 months, respectively."

"The unfavorable group {PSA nadir > 0.64 ng/mL and time to nadir < 7 months} included 248 patients who had significantly shorter OS after mCRPC."

"Higher PSA nadir and shorter TTN during the initial ADT are poor prognostic factors in patients with mCRPC."

-Patrick

ncbi.nlm.nih.gov/pubmed/307...

World J Urol. 2019 Feb 7. doi: 10.1007/s00345-019-02664-3. [Epub ahead of print]

Impact of nadir PSA level and time to nadir during initial androgen deprivation therapy on prognosis in patients with metastatic castration-resistant prostate cancer.

Hamano I1, Hatakeyama S2, Narita S3, Takahashi M4, Sakurai T5, Kawamura S6, Hoshi S7, Ishida M8, Kawaguchi T9, Ishidoya S10, Shimoda J8, Sato H3, Mitsuzuka K4, Tochigi T6, Tsuchiya N5, Arai Y4, Habuchi T3, Ohyama C1.

Author information

1

Department of Urology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan.

2

Department of Urology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan. [e-mail].

3

Department of Urology, Akita University School of Medicine, 1-1-1, Hondo, Akita, 010-8543, Japan.

4

Department of Urology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.

5

Department of Urology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, Yamagata, 990-9585, Japan.

6

Department of Urology, Miyagi Cancer Center, 47-1, Nodayama, Shiote, Aijima, Natori, Miyagi, 981-1293, Japan.

7

Department of Urology, Yamagata Prefectural Central Hospital, 1800, Aoyanagi, Yamagata, 990-2292, Japan.

8

Department of Urology, Iwate Prefectural Isawa Hospital, 61, Ryugababa, Mizusawa, Oshu, Iwate, 023-0864, Japan.

9

Department of Urology, Aomori Prefectural Central Hospital, 2-1-1, Higashi-tsukurimichi, Aomori, Aomori, 030-8553, Japan.

10

Department of Urology, Sendai City Hospital, 1-1-1, Nagamachi, Asuto, Taihaku-ku, Sendai, Miyagi, 982-8502, Japan.

Abstract

PURPOSE:

We determine whether the nadir prostate-specific antigen level (PSA nadir) and time to nadir (TTN) during initial androgen deprivation therapy (ADT) are prognostic factors in metastatic castration-resistant prostate cancer (mCRPC) patients.

METHODS:

We reviewed the Michinoku Japan Urological Cancer Study Group database, including 321 mCRPC patients. Optimal cutoff values for PSA nadir and TTN on survival were calculated with the receiver operating characteristic (ROC) curve. Patients were stratified into unfavorable (higher PSA nadir and/or shorter TTN) and favorable (lower PSA nadir and longer TTN) groups. The inversed probability of treatment weighing (IPTW)-adjusted Cox proportional hazard model was performed to evaluate the impact of the unfavorable group on overall survival (OS) after CRPC diagnosis.

RESULTS:

Median age and follow-up period were 71 years and 35 months, respectively. ROC curve analysis demonstrated cutoffs of PSA nadir > 0.64 ng/mL and TTN < 7 months. The unfavorable group included 248 patients who had significantly shorter OS after mCRPC. The IPTW-adjusted multivariate model revealed that the unfavorable group had a negative impact on OS in mCRPC patients [hazards ratio (HR) 2.98, P < 0.001].

CONCLUSIONS:

Higher PSA nadir and shorter TTN during the initial ADT are poor prognostic factors in patients with mCRPC.

KEYWORDS:

Metastatic castration-resistant prostate cancer; PSA nadir; Prognosis; Time to nadir

PMID: 30729312 DOI: 10.1007/s00345-019-02664-3

[jdm3]

So I wonder which it is... higher PSA nadir or shorter TTN or both. Also wonder if there is some relationship to what the initial PSA is to begin with. TTN is time from really high PSA to lower as well as low PSA to lower. One would expect a shorter TTN if you start with a PSA of 1 or 10 vs a PSA of 500 or 1,000. There should be data on averages as well as minimum and maximum endpoints.

[pjoshea13 in reply to jdm3]

I wonder if there are other biomarkers for those who are going to have this issue? Might call for a more aggressive treatment.

-Patrick

[hansjd]

When I read about these statistics I always wonder how do you take into account the effect on psa nadir and ttn having added chemo / zytiga / other treatment along the way? It seems to me very few would be on adt alone.

[pjoshea13 in reply to hansjd]

They followed these men until death, which suggests to me that the men might have begun ADT-classic some time before the new drugs & new thinking occurred. The full text probably has dates.

{The median follow-up period (after becoming castrate resistant) was 35 months.}

-Patrick

[tom67inMA]

Isn't nadir defined by when PSA eventually starts to rise again, rather than how fast the initial drop was? I try to interpret these studies as "is your PSA still low and dropping 7+ months after beginning treatment? If yes then you have a better prognosis".

[pjoshea13 in reply to tom67inMA]

Tom,

Nadir means the lowest point, i.e. the lowest PSA in this instance.

One could be at the nadir PSA for some time, but the date of the first test at that level would be used to calculate "time to nadir".

A man might feel anxious because he hasn't reached nadir by 7 or more months, but this is a good thing, as long as the PSA trend is heading to a very low nadir (below 0.64 ng/mL, in this study.)

-Patrick

[tom67inMA in reply to pjoshea13]

Hi Patrick,

I might feel anxious because I went from 216 to 0.2 in two months Happily my PSA had eased down even more in the next two months, but as that now includes chemo I'm probably off the reservation as far as these studies are concerned.

- Tom

[pjoshea13 in reply to tom67inMA]

Tom,

I'd take the study as a 'heads-up' rather than a dire prediction. Somewhere out there must be some expert opinion on the phenomenon. I only became aware of the topic two years ago. Talk to your doctor, of course, & I hope you get more than "don't worry" from him. But do some research. The study above is Japanese, but there are others, & you might be able get a response from an author (an email address is often provided). The big question to ask is what you should do to improve your odds.

I can't answer that of course, but staving off resistance to ADT would be my immediate concern. Perhaps you are a good candidate for BAT? There are quite a few threads on the topic. The basic idea is to not allow the cancer cells to adapt to low testosterone [T] levels. A monthly T shot shocks the cells that were getting used to ADT. I have come around to the approach, but I have used a similar therapy for a number of years.

But this is one idea - I'm sure there will be others.

Best, -Patrick

[Darcym1]

Just as importantly, they need to better define the individual influences of nadir level vs. TTN. I was diagnosed with Metastatic PC and a PSA over 100. A few months later, following docetaxel and ADT, my PSA was less than detection and continues that way so long as I stay on ADT. I was diagnosed in fall 2014. So the study results are meaningless to me without some context. I’m still going strong...

[dockam]

PSA @ 840, GL 7(4+3), mets to L ureter lymph nodes in 01/2015, First nadir 08/22/2016 @ 0.2. PSA rose to 0.5 on 06/26/2017 with T @ 30, then 3 months @ 0.1 from 08/2017. Had last Lupron on 03/31/17 after 30 months. So, dunno why PSA rose and dropped again, but I'll take it. PSA dropped from 10.8 to 7.7 after I restarted Lupron on 12/14/18 with from 547 to 20 in that month. Best to y'all

[j-o-h-n]

Mold.... I always thought you were... now you've admitted it...

Good Luck, Good Health and Good Humor.

j-o-h-n Sunday 02/10/2019 6:32 PM EST

[j-o-h-n]

nader? I always thought he was a political activist who drove a chevy corvair.

Good Luck, Good Health and Good Humor.

j-o-h-n Sunday 02/10/2019 6:37 PM EST

[Darcym1]

😎

[billyboy3]

This does create some interesting thoughts, two of them being:

1. using the old fashioned psa test and results of IHT onto themselves, and

2. finding out what the highest level of psa prior to surgery/radiation can be in order to calculate the cure level.

One of the downsides to so much research etc. going on is that we are now lost in really seeing the big picture of what works and how well etc. We are floundering, in my view to having too much and having it so ad hoc and leaving us to attempt to wade thru it all, and make the best call for treatment modality.

It makes one wonder if we will ever put the pieces together and be able to offer a black and white treatment plan.