Docetaxel & PSA time to nadir.

[pjoshea13]

New study below [1].

Here is another of those studies that associate a longer time to lowest PSA with a significantly longer survival.

"170 eligible Chinese patients who received docetaxel chemotherapy from January 2007 to October 2018 in 11 Chinese Prostate Cancer Consortium member hospitals in China."

Patients with a time to nadir ≥ 15 weeks had a longer overall survival compared to those with a time to nadir < 15 weeks (43 vs. 15 months).

& a longer progression-free survival compared to those with a time to nadir < 15 weeks (24 vs. 6 months).

In addition, a time to nadir ≥ 15 weeks & PSA nadir <4.55ng/ml were associated with longer overall survival.

-Patrick

[1] sciencedirect.com/science/a...

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

XinqiPeiM.D.a1KaijieWuM.D.a1YinghaoSunM.D.bXuGaoM.D.bXinGouM.D.cJunXuM.D.dFanGaoM.D.eDalinHeM.D.aLeiLiM.D.aChinese Prostate Cancer Consortium

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.

[6357axbz]

Nice summary, as usual. Thanks Patrick!

[LearnAll]

Thanks. Some previous studies have also reached to similar conclusion...Lower PSA Nadir and longer Time To Nadir ensures longer survival and delayed progression.

In other studies ,they say that anything longer than 6 months to Nadir is good enough.

Patrick, does it matter how PSA was lowered by chemo or radiation or ADT ?

[pjoshea13 in reply to LearnAll]

You asked: "does it matter how PSA was lowered by chemo or radiation or ADT ?"

Seemingly not. Here is an observation regarding time to nadir for ADT:

"The relationship between TTPN {time to the prostate-specific antigen nadir} and survival beyond TTPN consisted of three phases. In the first phase (<3 months for PFS and <6 months for OS), the survival beyond TTPN increased with TTPN. In the second phase (3-17 months for PFS and 6-20 months for OS), the survival beyond TTPN remained relatively static. In the third phase (>17 months for PFS and >20 months for OS), the survival beyond TTPN increased exponentially with TTPN."

ncbi.nlm.nih.gov/pubmed/252...

I can live with "exponential".

I once knew a girl called Nadir.

That sounds like the start of a limerick. I leave it to J_O_H_N to complete.

-Patrick

[Hidden in reply to pjoshea13]

This is for patients doing chemotherapy when castrate resistant vs early chemo, correct?

[pjoshea13 in reply to Hidden]

Gregg,

Yes - "Chinese men who receive{d} chemotherapy for mCRPC".

-Patrick

[Pleroma]

Thanks, Patrick. It took me 60 weeks to reach nadir (undetectable), so I will really be putting these clinical observations to the test in the years (hopefully) to come.

[pjoshea13 in reply to Pleroma]

Best of luck! -Patrick

[Lynsi13 in reply to Pleroma]

Took my dad 48 weeks! Like you, hoping this slow decline provides lots of added years! Good luck!

[tom67inMA]

I don't like these studies. Please correct me if I'm wrong, but the short time to nadir group will include a number of patients whose PSA will start increasing immediately after reaching nadir. Of course these men won't do as well, they're showing signs of progression while the other group's PSA is still dropping.

[dentaltwin in reply to tom67inMA]

I read this and had to look back to see if this was an example of lead-time bias, but the survival is measured from PSA nadir, so it is not.

[tom67inMA in reply to dentaltwin]

Thanks for that very important detail. This is how I learn

[Hawk56]

One study, 170 people and not a lot of information about their clinical history...

In making my decision to do combined therapy my search indicated the more rapid the decline in PSA the longer the progression free survival period.

In my case after BCR 18 months after surgery then SRT failed, with rapid PSADT and PSAV and GS 8 I elected to do 18 months of Lupron, six cycles of taxotere and 26 more radiation treatments as the C11 Choline scan showed four pelvic lymph nodes but no organ or bones involved. PSA dropped to <.1 with the first Lupron and taxotere treatment after 49 days. It has stayed there. Last Lupron was May 18, it cleared my system by October when T was 135. In February this yea it was 482. PSA remains undetectable. Next labs are coming up on 3 January.

Thanx for the post but for me the study was too small and lacked detail to be of use in decision making.

[MateoBeach]

Makes sense that when there is more surviving cancer cells that begin to contribute to the PSA level, that it will overtake the otherwise very slow descent to nadir seen without that contribution. Hence the earlier nadir. Still I'm curious about the continued decline for over 3 years when the chemo has been most successful. Why so long?