“Is there a proven benefit to continuing ADT if you have high risk PCa even if your PSA is undetectable after RP and RT?”
I was diagnosed in November 2017 at age 68 after my PSA was found to be 45.5. Biopsy found Gleason 4+5=9, later confirmed by prostate pathology. Bone scan negative. CT scan showed one likely pelvic lymph node. Two Axumin scans (one just before surgery) also showed just the one lymph node.
Had RP in February 2018. Margins negative but PCa was extracapsular with seminal vesicle invasion. Of 69 lymph nodes dissected only the one was positive.
In June I started 30-days of bicalutamide followed by a 6-month shot of ADT (Trelstar). I underwent 37 sessions of IMRT beginning in July.
My post-RP PSA was .01. My post-IMRT PSA is undetectable as of two months ago—I’m scheduled for another test in January.
All this seems like very good news, but I don’t want to let down my guard. My question is should I continue ADT anyway? For me the side effects have been relatively tolerable, mainly hot flashes largely controlled by Estradiol patches Of course, the ED and lack of libido is depressing, but I have many other joys in my life and am in otherwise excellent health, very fit and active
Based on what I’ve read, I believe that continuing ADT now will not improve my survival odds. I’m hoping that one of the smart folks on this forum can confirm that belief with clinical evidence.
Thank you, and Merry Christmas!
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I’m not as smart as some of the experts but I can at least identify with your situation as you can see from my profile.
My observations based on experience:
Gleason 9 is virtually incurable particularly as you’ve had SVI and ECE as did I which necessitated SRT.
ADT is holding your PSA down and will continue to for a while, likely a few years. If you stop ADT, PSA will climb again.
Since mets were found in a lymph node there likely are micromets elsewhere in your pelvic lymph nodes which is where mets are typically found first once they escape the prostate. That’s what happened with me. So I had all my pelvic lymph nodes hit with 75 grays of IMRT.
I’ve had no recurrence in prostate bed or lymph nodes.
I did stop ADT three times and each time I had recurrence in bones. Then I had axumin or PSMA scans to find the mets which I hit with sbrt.
So that’s my experience. Take it for what it’s worth.
Thanks Bob—it does seem that your experience is quite similar to mine except that my RT was ajduntive as opposed to salvage. I primarily base my belief on Dr. Patrick Walsh’s book. He says (in the the current edition, published this year) that he believes “if there is no cancer in your bones and no sign that anything is wrong other than a rising PSA after surgery or radiation...in most cases there is no evidence that starting hormonal therapy immediately as opposed to later will prolong life.”
I know that new studies and treatment options for PCa are rapidly emerging, so I want to see if anyone here can point me to new information on this topic that wasn’t available when the above was written.
I will naturally consult my MO about this, but I have found that being forarmed with good current information makes those conversations more productive.
Tall_Allen, can you point me to any clinical trials or studies that support the benefit of continuing ADT in my circumstance?
My RO did not prescribe tamoxifen and I seem to have already developed gynecomastia. Once again I seem to get more accurate and complete information from this site than from my own doctors ☹️
To my knowledge, there has never been a randomized trial to determine the optimal duration of adjuvant ADT in men with pN1. The adjuvant ADT is thought to clean up any cancer cells that the radiation may have missed. Because it is known to be in the lymph, the risk of systemic mets is increased and I think most ROs would err on the side of longer duration rather than shorter duration. In the following study, "When combined with EBRT, the median duration of ADT was 5.9 yr (interquartile range [IQR]: 3.55–8.91), 10% of the patients received ADT for less than 1 yr, 15% for 1–3 yr, and 75% for more than 3 yr."
However, development of castration resistance becomes a factor at more than 3 years, so if ADT hasn't killed off the errant cells by then, it probably never will. Also, the long term effects of ADT on overall health becomes a bigger factor (in that study, overall survival decreased even while prostate-cancer-specific survival benefitted from life-long ADT).
If you already have gynecomastia, you may be able to reverse it with 20 mg daily tamoxifen. Although the following trial discusses bicalutamide-induced breast events, the same is true for estrogen patches -- they both increase estrogen levels. Tamoxifen blocks estrogen only in breast tissue (it is estrogenic in other tissues and the brain, so it should not impact the positive effect of reducing hot flashes.)
This discussion caused me to return to Dr Walsh’s book to review his rationale about when to start ADT.
He discusses this topic at length in chapter 12. He emphatically states that starting ADT before there is evidence of PCa progression after RP or RT has no survival benefit, but does have significant detrimental impact on quality of life and causes other health issues. He focuses in particular on the long-term Veterans Administation Cooperative Urological Research Study 1 of 954 men with PCa.
Men were randomly assigned to either immediate surgical castration or a placebo treatment and then followed closely until cancer progression, at which time they received comprehensive ADT.
There was NO difference in survival between the two groups.
If there’s no survival benefit to starting ADT earlier, it seems rational to delay starting it until it’s actual needed and enjoy life more until then.
Which gets me back to my original question—what if anything to do next? I’m still learning and listening.
Thanks to all of you who have chimed in with their thoughts and experience.
I don't know if you have an older edition of Walsh (it was updated this year), but be careful in drawing any conclusions from that very old study for several reasons:
1. Patients were treated 1960-1967. It was before PSA testing. The men in that study were mostly newly diagnosed because of symptoms.
2. They only found metastases that were large enough to be detected by X-rays or biopsy. Many would have detectable metastases even with today's Bone scans/CTs.
3. Most men were excluded for any previous treatment, because they were in poor health, or because they had a second malignant lesion (on X-ray). Only men with a DRE showing extracapsular extension (Stage III) or distant metastases (Stage IV) were selected for treatments (placebo, DES or orchiectomy).
4. Table 4 shows that among those men with EPE getting orchiectomies (+placebo) 13% died of prostate cancer (63% overall mortality), but among men getting no treatment initially (placebo) 18% died of prostate cancer (61% overall mortality). So there was actually an advantage to early orchiectomy.
There was a more recent randomized clinical trial (TOAD), that found with 5 years of follow-up that among men with BCR (mostly), overall mortality was cut in half by early use of ADT (mostly iADT). However, there were very few deaths and no prostate cancer deaths in that time, and accrual was less than expected, so we will probably have to wait another 5 years for clearer findings. At the least, it shows there is no advantage in waiting for a clear sign of metastases (radiographic, fast PSADT, or high PSA), and there was no long-term QOL difference (see below). The reduction in micrometastases using ADT seems to be a more important effect than selective pressure for castration resistance.
Not stupid at all-- use of the terms is inconsistent. Androgen Deprivation Therapy (ADT) usually means chemical castration using a GnRH agonist (like Lupron) or antagonist (Firmagon), but I've seen it used sometimes for antiandrogen monotherapy (e.g. 150 mg daily Casodex). This is because it was found that GnRH agonists alone were more effective than Casodex alone. Some use the term ADT2 or Complete Androgen Blockade (CAB) to refer to a GnRH agonist + an antiandrogen (like Casodex).
I had my RP and Rd in 2002. My PSA stayed below for until 2012
I have now been on casodex for 6 years 50 mg day. My PSA is now 1.5. Trying to make the agonizing decision to start Lupron. I feel so good on casodex versus my friends that are on Lupron. How much longer should I let it go
I spoke with my RO at Emory about this yesterday. He recommends that I stop ADT at this time, because he believes the benefit is maximum during the first six months. He did acknowledge that there is some disagreement regarding the benefits of continuing ADT for a longer period, but he feels that stopping now is the right choice in my case because of my low post-RP PSA, negative margins, and only one lymph node positive out of 69 removed. Note that my radiation treatment was adjunctive, not salvage. He mentioned a French study that supported his recommendation: the GETUD(sp?) Study. I have not been able to locate that online so far so I may have the spelling wrong.
In answer to your question about the Walsh book, I do have the new (4th) edition published this year, so Dr. Walsh still stands by that recommendation and apparently feels the VA study does support his position.
I still plan on consulting an MO at Emory, and another MO at one of the top hospitals before finalizing my decision.
Thank you again for the effort you put into this forum and the excellent advice you dispense.
It proved that 6 months is better than no adjuvant ADT. It did not try to find the optimal duration of ADT, so it is very possible that results may have been improved by, say, 2 years of adjuvant ADT. They also specifically excluded men with positive lymph nodes.
Just a couple of months ago, the results of RTOG 0534 were revealed. The purpose was to prove that whole pelvic salvage radiation improved outcomes compared to prostate bed-only. It did. 5-year freedom from progression was 89% among men who received whole pelvic salvage radiation with just 4-6 months of ADT. While they did not test a longer duration of adjuvant ADT, 89% is a very good outcome - how much higher could it get? As with GETUG-AFU-16, they EXCLUDED men with positive pelvic LNs.
So you see that there is really no data on optimum duration of adjuvant ADT in men with positive lymph nodes. I agree that you have several factors that argue that less ADT may suffice - only one detected positive node out of many dissected, adjuvant rather than salvage RT, and low post-RP PSA. You also had several risk factors - positive node (pN1), EPE and SVI. Those who argue for longer duration of ADT with pN1 argue that lymph is a fluid and that metastatic cells are easily carried away in it, and that the only hope of cure is long-term adjuvant ADT. Your RO is quite right that MOST of the cancer cells are killed early. But "most" is not "all." In fact, the most ADT-resistant ones may take longer to kill (they may have to enter a more vulnerable cell-cycle phase). Up until a few years ago, men with positive pelvic LNs were considered to be incurable and were only given life-long ADT. I know this is a difficult decision. There is little data. You have to balance the tolerability of ADT with the risk of incurable PC.
BTW - what was the radiation dose to your pelvic LNs and to your prostate bed? Did the pelvic LN radiation field include expansion to your common iliac nodes?
What is tamoxifen and what is gynecomastia? I have been on only Cassodex now for 6 years and my psa is now at 1.4 to 1.6 the last 4 months. Should I look at starting Lupron?
Gynecomastia means growth of breast tissue in men. Tamoxifen is a medicine that prevents it. With metastases, you should definitely discuss Lupron with your oncologist - it provides more powerful androgen deprivation than 150 mg Casodex.
Thanks so much for the explanation. I have taken the Cassodex, 50 mg daily, for 6 years and really do not have any soreness in my nipples any more. PSA no higher than 1.5.
If a biopsy of my met on my hip bone could be done, do you think a genomic test would help? That spot is about the size of a quarter, do you think it would help to radiate it. I have no soreness.
Unfortunately, there are very few medicines so far that treat aberrant genomic characteristics of tumors, and even those are rare. Clinical trials may reveal more someday.
While there is no compelling data indicating that SBRT of such mets has any effect on survival, I can't think of any reason not to do it, other than safety.
In a randomized clinical trial of intermittent ADT, continuing with avodart provided no benefit. But that was with ADT3. If you're accumulating testosterone due to Casodex, it may be a good idea to prevent DHT formation. Which ADT to take and how much is up to your judgment, balancing side effects with progression. If you're on iADT, I can see that there might be a benefit during the vacations.
As Tall Allen says, ADT for at least 2 years would be the usual standard of care at your stage. However, an option might be bicalutamide monotherapy using the 150 mg dose.
I recollect a 1996 paper asserting the equivalence of such an antiandrogen monotherapy with standard ADT (zolodex, lupron etc). I didn't keep the reference but this is a more recent one implying the same.
My RO originally wanted me on ADT for 18 months, but he accepted my decision to do just 6 months and then revisit my options. I’m transitioning to MO care this month since I’m now at the end of my ADT shot. I will keep this discussion updated as I learn more from my doctors.
Wow! Now we have a clear understanding of the “correct” ADT strategy!
In my odd case I’ve been on and off ADT for 4 1/2 years: Lupron for 6 months, off adt for 9 months , bcr , RT to pelvic nodes, 13 mos ADT3 , off adt for 6 mos, bcr, SBRT to femur, xgeva 12 mos, 13 mos ADT3, off adt for 4 mos, bcr, SBRT to rib and scapula, resume trelstar only , resume xgeva every 3 mos.
So my adt vacations were quite short because I had quick bcr after stopping adt and therefore went back on adt. My vacations could have been longer if I waited for Psa to go higher ( which I’ve read that some guys do) but my short doubling times (2mos) led me to act quickly to get scans when Psa was 1-2 and then use RT to zap oligomets.
This practice has allowed me to remain castrate sensitive using only first line adt ( thereby extending its efficacy) while killing off visible oligomets.
Now I need to consider whether or not to continue with this adt strategy although I have stopped taking casodex and avodart. My sense is if it’s not broke don’t fix it.
I take metformin, cabergoline, Crestor, celecoxib and use estradiol patches changed twice weekly for hot flashes. I hope the patches aren’t a problem! All Snuffy Recs per my RO. I will go back on avodart. How about casodex? Should I go back on that 50mg dose? Should I get estradiol level tested along with Psa and T?
When I mentioned this to my MO, he more or less dismissed it and said “ I can manipulate the psa if I want to too”. Avery well known and respected MO in New York.
I was diagnosed a little of 7 years ago with cores of 7, 8, and 9. I had a RP in Jan of 2012. My PSA was 1.9 after surgery. The MO / URO called PC particularly aggressive. I was graded as T3C N1 M0 after surgery. The ADT I went on after a few weeks past surgery took me down to undetectable. So the MO / URO said "Let's do a vacation and see what happens." It wasn't pretty. My PSA quickly went to 1.2, and 3 months later to 10.2 UGH!! My other MO (I have sideroblastic anemia he was treating) when ballistic when he saw those numbers and insisted and immediate scans and a return to ADT. The scans showed the same 4 lymphnodes (I think they were / are the same) as showed up in my pre-RP scans. I have been on Trelstar every since. I moved to another city when the URO told me to never change a thing - let sleeping dogs lie. My PSA is still undetectable. My newest URO was given lots of APC training (they established a center for Prostate Cancer Excellence) added Xtandi (4 capsules a day) as a safe guard. (4 was too many - eventually dropped to 2.) So I continue, after 7+ years on ADT and have learned to live with the side effects. I am convinced that without it, I would have been dead for a few years by now.
tl;dr --- ADT is good for controlling APC. Standards of care change. I recommend ADT.
Nalakrats, thank you for your very thoughtful and detailed response. I have learned so much from your replies to me as well as the others you have posted to.
You had RP three years ago. Did you have any urinary function problems before the RP/ Specifically, weak stream.? Did the RP correct the weak steam problem?? My Uro wants me to do ADT with Orgovyx. Scares the life out of me. Side effects include fatal heart attack or stroke. I would like to find a "cure" for my PC that would ALSO "cure" my weak stream. I had a TURP 10 months ago that only helped for a few months. Some RP guys say that since their RP, they have No problems with weak stream?? What was your story?
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