Androgen Deprivation Therapy & Gleason 8 Versus Gleason 9-10.

[pjoshea13]

New study below.

The Gleason scoring system has been around for fifty years & ADT since before I was born. So hasn't the question been asked before? Not much of a surprise to find that the Gleason score might affect treatment success. The higher the Gleason, the greater the case for a more aggressive therapy from the start.

"A retrospective cohort study of 20,139 men from the National Cancer Database with localized or locally advanced, Gleason 8-10 PCa who received EBRT. Data were collected from 2004 to 2012."

"In contrast to the significant survival advantage of ADT for Gleason 8 disease, our results suggest that Gleason 9-10 disease derives less survival benefit from ADT and that a higher Gleason score predicts lesser benefit. Consideration should be given to treatment intensification for Gleason 9-10 patients through enrollment in clinical trials or potentially adding novel antiandrogens or docetaxel, which have shown efficacy in both castration-resistant and castration-sensitive settings."

-Patrick

ncbi.nlm.nih.gov/pubmed/305...

Eur Urol. 2019 Jan;75(1):35-41. doi: 10.1016/j.eururo.2018.08.033. Epub 2018 Oct 24.

Androgen Deprivation Therapy and Overall Survival for Gleason 8 Versus Gleason 9-10 Prostate Cancer.

Yang DD1, Mahal BA1, Muralidhar V1, Martin NE2, Orio PF2, Mouw KW2, King MT2, Choueiri TK3, Trinh QD4, Hoffman KE5, Spratt DE6, Feng FY7, Nguyen PL8.

Author information

1

Harvard Medical School, Boston, MA, USA; Harvard Radiation Oncology Program, Boston, MA, USA.

2

Harvard Medical School, Boston, MA, USA; Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA.

3

Harvard Medical School, Boston, MA, USA; Department of Medical Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA.

4

Harvard Medical School, Boston, MA, USA; Division of Urological Surgery, Brigham and Women's Hospital, Boston, MA, USA.

5

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

6

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.

7

Departments of Radiation Oncology, Urology & Medicine and Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA.

8

Harvard Medical School, Boston, MA, USA; Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA. Electronic address: [e-mail].

Abstract

BACKGROUND:

While the addition of androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) is known to improve overall survival (OS) in Gleason 8-10 (Grade Group 4-5) prostate cancer (PCa), it has been hypothesized that Gleason 9-10 disease, which is less differentiated than Gleason 8 disease, may be less sensitive to ADT.

OBJECTIVE:

To examine the association between ADT and OS for Gleason 8 versus Gleason 9-10 PCa.

DESIGN, SETTING, AND PARTICIPANTS:

A retrospective cohort study of 20 139 men from the National Cancer Database with localized or locally advanced, Gleason 8-10 PCa who received EBRT. Data were collected from 2004 to 2012.

INTERVENTION:

ADT.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

Cox proportional hazards regression was used to examine the association between ADT and OS.

RESULTS AND LIMITATIONS:

Overall, 9509 (78%) of the 12 160 men with Gleason 8 disease and 6908 (87%) of the 7979 men with Gleason 9-10 disease received ADT. On multivariable analysis, ADT was associated with a significant improvement in OS for Gleason 8 patients (adjusted hazard ratio 0.78, 95% confidence interval 0.70-0.87, p<0.001) but not for Gleason 9-10 patients (adjusted hazard ratio 0.96, 95% confidence interval 0.84-1.11, p=0.6), with a significant interaction (pinteraction=0.020). A higher Gleason score (8, 9, 10) correlated with an increased adjusted hazard ratio for the association between ADT and OS (pinteraction=0.042). Our study may be limited by the relatively short follow-up (median of 4.0 yr).

CONCLUSIONS:

In contrast to the significant survival advantage of ADT for Gleason 8 disease, our results suggest that Gleason 9-10 disease derives less survival benefit from ADT and that a higher Gleason score predicts lesser benefit. Consideration should be given to treatment intensification for Gleason 9-10 patients through enrollment in clinical trials or potentially adding novel antiandrogens or docetaxel, which have shown efficacy in both castration-resistant and castration-sensitive settings.

PATIENT SUMMARY:

In this study, we examined the effect of androgen deprivation therapy (ADT) for Gleason 8 (Grade Group 4) versus Gleason 9-10 (Grade Group 5) prostate cancer. We found that Gleason 9-10 disease may derive a smaller survival benefit from ADT than Gleason 8 disease.

Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

KEYWORDS:

Androgen deprivation therapy; Gleason score; High-grade; Prostate cancer; Prostate-specific antigen

PMID: 30554605 DOI: 10.1016/j.eururo.2018.08.033

[Mkeman]

I am Gleason 9. Have been on Eligard, Zytiga and prednisone for 14 months and my PSA is undetectable. My MO sees me every three months and says she expects me to be around for a long time. Every case is different and there are many, many variables.

[gusgold in reply to Mkeman]

A GL9 is a lot worse then a GL8 if the 9 is 5+4

[VHRguy in reply to gusgold]

It has long disturbed me that the G9/10 cases were blurred in with G8. I've seen a very few studies separating those, in part due to the newer Gleason Grade Group 5 designation for G9/10.

My biopsy had 6 of 12 positive cores, all G9, a couple of them 5+4, and they ranged from 60% to 100% involved. So, these studies are of great interest to me! I think the G9 cases merit some very, very aggressive treatments right up front.

[NPfisherman]

Thanks Patrick, I am Gleason 8.... informative...appreciate your posts...Merry Christmas

[Shooter1]

Gleason 9/10 here. Hit it hard, hit it fast, hit it longer than standard. ADT after RP with rising PSA after prostate removal. 10pts in 6 weeks. ADT started, chemo for 9 cycles, Xtandi added after cycle 5 pretest showed PSA again rising. Pushed on until side effects had turned me into and invalid. Cut dosage of Xtandi 60 days after end of taxotere. Slow recovery Orchiectomy and thumb rebuild during recover time. (75 days before return to work). PSA in 0.130 range, but invalid from excess toxicity to Xtandi. Worked 3 1/2 mo. to pay back company for health benefits, then retired and transferred meds to VA. Working at regaining strength and getting used to new normal. Long hard year and a half, but now well past drs first expiration date for what I have. Advice hitting Gleason 8 as hard as you can right now.

[Harry_B]

I'm 5+4 diagnosed in April 18 with PSA 58. ADT + docetaxel (6 sessions). Pelvic lymph node involvement and three bone mets close by. PSA now 0.02. Just done RP and lympadenectomy and surgeon confirmed cancer in remission. Pathology to come. My view is to hit hard and hit early then use data to assess accompanied by continued agression. I agree with Shooter1. I'm 71, also Vietnam veteran (260 combat missions) and spent my life as developmental test pilot so figure I'm living on bonus time anyway.

[Fitzbruce1 in reply to Harry_B]

Thanks for your service! Sounds like u have lived a very exciting life! Good luck to you!!

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

260 combat missions? Sounds like my wife and I.

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 12/19/2018 10:46 PM EST

[charlesmeyers1964]

make it short for u. my gleason score was before treatment. i had i believe not sure 8. there are two scores the size of the tumor/the growth rate. now for me once treated no more Gleason score

charlie

[Break60]

I believe that tumor burden is also a key factor even for gl 9-10. I’m a 9 (4/5) with low burden thankfully and have treated my oligomets with IADT and SBRT successfully. I’ve reserved more intensive systemic tx for “down the road “.

[Stegosaurus37]

I was diagnosed with Gleason 9 and just got Lupron for 6 months until they found I was castrate-resistant and then they started chemo. I agree with the other posts that the tougher the cancer the harder you should hit it. But my quacks apparently didn't think so - try one thing and if that doesn't work, try something else and I was too trusting at the time to question that. I've since gotten religion (in large part thanks to my brothers here) and question everything. Wish I'd been insistent a year ago. I'd probably be better of now. But what is, is and I'll just deal with it.

[pjoshea13 in reply to Stegosaurus37]

A theme in Dr. Myers vlog posts on durable remission is that no other type of serious cancer has been successfully managed with a single drug.

Of course, when you go back a dozen years, the PCa treatment options were few & unchanging year after year. Use 3 drugs & there would be nothing left in one's back pocket. A scary prospect for both doctor & patient.

Now that we have an embarrassment of riches, there is interest in combinations, but it's still early days. In the meantime, men who are at greater risk need doctors who are willing to think beyond established protocols with their dismal statistics.

-Patrick

[monte1111]

Gleason 9. Immediate lupron + 8 cycles taxotere + xgeva. There are some impressive men on this site. Gusgold with 3 silver stars, Harry_B with 260 combat missions, me with 6 months in the brig. I vote we rename it Mad Men.

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

I double your vote! And me just a U.S.O. commando....

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 12/19/2018 10:48 PM EST

[Hidden]

Well I was labeled gleason 8. Five of 12 cores positive: One 8, one 6 and the other three 7's. I hope that shades me towards being more hopeful. I guess we'll find out. Meantime staying dialed in to latest therapies and advice discussed on this site.

[adlerman]

I was told to get 13 months of ADT prior to my cryotherapy for Gleason 8 in 2001.

In June 2002 the cryotherapy was done and my PSA has never been above 0.1 since then,

One case is not a verification of anything but it beats all the failed RP's.

[j-o-h-n]

It's that fat Jackie who's to blame.... AND AWAY WE GO.

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 12/19/2018 10:49 PM EST

[leswell]

I wrote the following, Nalakrats, before reading the above. It is most relevant to the 23andMe report I just read from my “double nephew.” Will fill you in on that, but yours is crucial follow-up. Thanks as always. Mr. and Mrs. S.

"Hello to family, friends, and right now, especially, to our recent friends on the APC site on Health Unlocked. I, Leswell’s spouse (Mrs. S, Jan) am writing to apologize for my limited replies recently which is because I must now assume most of what we have previously accomplished as a couple.

Leswell has increasing memory loss due, not to familial DNA variants, but rather to cancer treating drugs—primarily ADT.

As of Tuesday, December 18th, my husband is no longer permitted to drive. I will drive when and if necessary, but our choice is now between that and paying for Uber, Lyft, or deliveries. This, as you know, is a life-altering edict.

Also, in January we will need to pay new deductibles for drugs (Xtandi) and also have much higher premiums on uCare, i.e. over $400 per month. That total could amount to half of our income for a couple of months.

Our physicians have been wonderful to us and are honorable in every respect. We also like our insurance which is uCare, but the above expenses will be unsustainable for long. It’s all about how many months are worth a life without being who one was.

P.S. Possibly my near-final “contribution” will be to Nalakrats whom we both love and trust. The question is about genetics and will be in a separate post. Love to all. Mrs. S"