New Protocol of Intermittent ADT for Patients With Metastatic PCa

[pjoshea13]

New Chinese study below [1].

"In the 65 metastatic prostate cancer patients in group 1, androgen deprivation therapy was stopped when prostate-specific antigen (PSA) levels reached a nadir and was resumed when PSA levels doubled and ≥ 1.0 ng/mL (new protocol)."

"In the 62 patients in group 2, androgen deprivation therapy was stopped 3 months after PSA = 0.2 ng/mL and resumed at PSA ≥ 4.0 ng/mL (Chinese Urological Association guideline)."

"In groups 1 and 2, the median total IADT durations were 51 and 46.5 months .., median overall on-treatment times were 28 and 27.5 months .., and median overall off-treatment times were 23 and 19 months .., respectively."

"... patients in group 1 had significantly higher progression-free-survival (hazard ratio, 0.634 ...)"

"The new protocol was found to be beneficial, showing less biochemical/clinical progression, satisfactory performance status, and acceptable treatment-related adverse effects."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/315...

Clin Genitourin Cancer. 2019 Aug 5. pii: S1558-7673(19)30243-5. doi: 10.1016/j.clgc.2019.07.015. [Epub ahead of print]

New Protocol of Intermittent Androgen Deprivation Therapy for Patients With Metastatic Prostate Cancer: A Retrospective Study.

Cai J1, Feng G2, Yan Y2, Liu Z2, Jing S2.

Author information

1

Department of Urology, Beijing Shijitan Hospital, Capital Medical University, Capital Medical University School of Oncology, Peking University Ninth School of Clinical Medicine, Beijing, China. Electronic address: [e-mail].

2

Department of Urology, Beijing Shijitan Hospital, Capital Medical University, Capital Medical University School of Oncology, Peking University Ninth School of Clinical Medicine, Beijing, China.

Abstract

BACKGROUND:

The optimal points for halting and resuming treatment in intermittent androgen deprivation therapy (IADT) for metastatic prostate cancer patients are controversial.

PATIENTS AND METHODS:

In the 65 metastatic prostate cancer patients in group 1, androgen deprivation therapy was stopped when prostate-specific antigen (PSA) levels reached a nadir and was resumed when PSA levels doubled and ≥ 1.0 ng/mL (new protocol). In the 62 patients in group 2, androgen deprivation therapy was stopped 3 months after PSA = 0.2 ng/mL and resumed at PSA ≥ 4.0 ng/mL (Chinese Urological Association guideline). The total IADT duration, overall on-treatment and off-treatment time, tumor clinical progression ratio, performance status improvement, and treatment-related adverse effects were retrospectively analyzed.

RESULTS:

In groups 1 and 2, the median total IADT durations were 51 and 46.5 months (significant difference, P = .006), median overall on-treatment times were 28 and 27.5 months (no significant difference, P > .05), and median overall off-treatment times were 23 and 19 months (significant difference, P < .001), respectively. Multivariate Cox regression analysis indicated that patients in group 1 had significantly higher progression-free-survival (hazard ratio, 0.634; P = .014). Two cases of clinical progression occurred group 1 and 5 in group 2; there was no significant difference (P > .05). There were no significant differences between the groups in terms of performance status improvement and treatment-related adverse effects.

CONCLUSION:

The new protocol was found to be beneficial, showing less biochemical/clinical progression, satisfactory performance status, and acceptable treatment-related adverse effects.

Copyright © 2019 Elsevier Inc. All rights reserved.

KEYWORDS:

Treatment reinitiation; Treatment suspension

PMID: 31594735 DOI: 10.1016/j.clgc.2019.07.015

[Grumpyswife]

Such a simple idea that I wish someone had thought of when my husband went through his radiation.

[GP24]

I think a retrospective study with 65 vs 62 patients provides a poor level of evidence. The difference between the protocols was about 10% regarding off-treatment times and on-treatment times. Considering the typical confounders of a retrospective study and the small number of patients, I think this is statistically not significant.

[AlanMeyer]

That's important information! I agree with GP24's criticisms of the statistical significance of the study, but I think it does at least indicate that the PSA >= 4 protocol is not necessarily the best one.

I always wondered about the PSA>=4 protocol. If I remember correctly, that protocol was not based on any study of other options. There was a study of intermittent vs. continuous ADT that happened to use PSA >=4. All the doctors and hospitals decided that there's evidence the 4.0 trigger is okay and no evidence for other options, so they took that as an indication that they should follow that protocol.

Clearly, absence of evidence of a better protocol was not evidence of absence.

Personally, I think there are other IADT protocols that are worth exploring. One that comes to my mind is comparing IADT with no treatment during the off period vs. IADT with dutasteride or low dose bicalutamide, or maybe other minimal therapies. It wouldn't surprise me if time off from full ADT and overall survival were increased over plain IADT, and treatment side effects were still greatly lowered as compared to continuous ADT.

Alan

[GP24 in reply to AlanMeyer]

I prefer the study reported by Crook et al.: nejm.org/doi/full/10.1056/N...

This prospective study included 690 versus 696 Patients. They restarted ADT when the PSA value rose above 10 ng/ml.

If you think this is too low for you, you can follow the study reported by Calais et al.:

europeanurology.com/article...

They restarted ADT when the PSA value rose above 20 ng/ml for patients without symptoms.

In my opinion, if you restart ADT when the PSA value rises above 4, you might as well do continuous ADT. The breaks, after T has finally recovered, will be very short.

[tallguy2 in reply to AlanMeyer]

What we patients are missing is research regarding that 4.0 PSA protocol. IMHO scans such as the newer MRIs of the prostate need to be approved by insurance well before PSA hits 4.0, at least for "high risk" patients with family histories.

[In my case waiting until I hit 4.0 was too late. The biopsy was done and after the PR I was already Stage 4. ]

[Hidden in reply to AlanMeyer]

My PSA was 2.7 at diagnosis; gleason 8. If I had to wait until PSA reached 4 to resume ADT I'd be in a world of trouble.

[Break60 in reply to AlanMeyer]

For very high risk guys like me, with Gleason 9 stage IV pca I’ve concluded that IADT doesn’t work. That’s because psa dt is so fast ( in my case two months) that

the ADT off-time is too short to be of any real benefit. That’s why I started using estradiol patches full time instead of SOC ADT. Side effects are virtually eliminated except for Gynecomastia. My PSA is now undetectable unlike my little man boobs but I no longer have joint pain, fatigue, hot flashes, strength loss etc and feel like a man again.

[tallguy2]

Thank you for posting this.

I wasn't in the trial but I essentially followed the second treatment arm in that trial. What a disaster. As my PSA started to accelerate and reached 2.0 I had a chance MRI for a totally unrelated issue and, wham, after a confirming PET/CT with Axumin I was diagnosed with mets in lymph nodes and my lower spine.

IF an ADT holiday is accompanied by frequent PET/CT scans (which few insurance companies are likely to cover) this might be an interesting approach. Anyone with Gleason 9 or 10 disease should be very cautious about taking an ADT holiday, based on my one-off experiment.

[Hidden in reply to tallguy2]

Did the mets disappear after resuming ADT or did you have local radiation?

[tallguy2 in reply to Hidden]

After resuming ADT I did taxotere chemo. Mets still there, but smaller. I then had EBRT. Mets still there, smaller. PSA doubling time 3 months. I am doing Provenge immunotherapy right now. A PET/CT next month will provide data to determine next steps. This disease is relentless.

[j-o-h-n]

I never got the point of why four point zero?

Good Luck, Good Health and Good Humor.

j-o-h-n Friday 10/11/2019 5:36 PM DST

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

Scholarly doctors confusing PSA with GPA?

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

Good thought..... (I missed that cause I was NEVER a 4.0 student)...

Good Luck, Good Health and Good Humor.

j-o-h-n Friday 10/11/2019 6:48 PM DST

[SeosamhM in reply to Hidden]

Wow.... you pulled a j-o-h-n on j-o-h-n!! A+....!